This paper traces the cooperative efforts of scientists at the National Oceanic and Atmospheric Administration (NOAA) and the National Institute of Standards and Technology (NIST) to improve the calibration of operational satellite sensors for remote sensing of the Earth’s land, atmosphere and oceans. It gives a chronological perspective of the NOAA satellite program and the interactions between the two agencies’ scientists to address pre-launch calibration and issues of sensor performance on orbit. The drive to improve accuracy of measurements has had a new impetus in recent years because of the need for improved weather prediction and climate monitoring. The highlights of this cooperation and strategies to achieve SI-traceability and improve accuracy for optical satellite sensor data are summarized From the beginning of the era of meteorological satellites, a remarkable goal-oriented interaction between scientists and engineers of the National Oceanic and Atmospheric Administration (NOAA), the National Aeronautics and Space Administration (NASA) and the National Institute of Standards and Technology (NIST)  has been taking place to reduce measurement uncertainties and improve the quality of observations. Reports and papers published in the literature document this effort. This paper traces the NOAA and NIST cooperation for eliminating the discrepancies in the measurements of NOAA operational sensors in orbit and developing strategies to enable their radiometric calibration to meet international standards, with the ultimate goal of improved weather prediction and climate change monitoring. It gives a chronological perspective of the growth of the cooperation between the agencies, rather than a specific technical discussion. The section, “Legacy of the Early Interval,” discusses the events at the beginnings of the weather satellite program and the development of the state of the art with respect to calibration methodology. Both NASA and NOAA worked with National Bureau of Standards (now NIST) for the development of advanced lamp standards, radiometers, artifact standards and methodologies for calibrations of space-bound optical sensors and their components to quantify and reduce uncertainties in remote sensing data. These capabilities enabled other satellite launching agencies, such as the Department of Defense (DOD) and the United States Geological Society (USGS), to support and use NIST for the characterization and pre-launch calibration of sensors to be launched into space. The following section, “Legacy of Recent Interactions,” covers the cooperation between NOAA and NIST to address issues connected to the calibration of NOAA’s operational sensors to meet the current goals at NOAA for improved weather prediction and climate monitoring. A similar collaborative effort between NASA and NIST, preceding this work, was established in the 90s to support NASA’s Earth Observing System (EOS). This collaboration provided the foundation of NIST’s modern capabilities and facilitated the NOAA/NIST work described here. NASA continued to provide a supporting role for the important achievements in the NOAA and NIST cooperation described in Sec. 3.5.From the beginning NASA has been in the forefront of developing the technology for satellite-based remote sensing, and NOAA has worked with NASA to apply this technology for observing the weather and the global environment. The satellite series, Television Infrared Observation Satellite (TIROS), starting in 1960, and NASA Meteorological satellite (Nimbus), starting in 1964, were launched and operated over many years with the participation of scientists from both agencies. These programs advanced the technology used to observe the weather and the environment . By 1970NESS became involved in ocean color measurements in the late 70s through Warren Hovis, formerly of NASA’s Goddard Space Flight Center (GSFC). Hovis, with colleagues at NASA, developed a satellite sensor, the Coastal Zone Color Scanner (CZCS), which was flown on Nimbus 7 in 1978. AVHRR and CZCS sensors proved capable of providing reliable data. Scientists then faced the challenge to radiometrically calibrate the sensors and improve their on-orbit radiometric accuracy.The launch of CZCS in 1978 for ocean color measurements was based on many observations by NASA from aircraft platforms as a proof-of-principle ,4. The mThe requirement of adapting laboratory standards for remote sensing measurements at the NBS was at its infancy during the beginning of this period. Ralph Stair, William (Bill) Schneider, William Fussell and Henry Kostkowski and co-workers at the NBS received partial funding from NASA to develop radiometric standards for calibrations of satellite sensors. They established a tungsten halogen lamp and a tungsten strip lamp as field-deployable irradiance and radiance secondary standards traceable to blackbodies at NBS. The uncertainties in the radiometric output were in the 1 % range for these transfer standards. Their work and that of other leaders in the field at that time were summarized in Ref. .As Warren Hovis and John Knoll put it in Ref. , “calibr® powder and Allied’s Halon G-80™. The research at NBS showed that superior reflectance properties are exhibited when PTFE powder was sintered and packed. Based on NBS’s research findings, Art Springsteen at Labsphere, Inc., produced the commercial grade of the sintered PTFE called Spectralon™, which became the material of choice for reflectance measurement instrumentation around the world [Warren Hovis actively led a program at NESS Satellite Experiment Laboratory to develop high efficiency integrating spheres. According to one of us (Weinreb), “The laboratory was overrun with integrating spheres, some big, some small, in various stages of development with white paints coating their inside walls. The place had a reputation throughout NESS for looking as if it housed a family of shmoos.”  The significance of establishing a white diffuse material with a flat response across the solar reflective region also became an important area of research at NBS during this period. Various grades of barium sulfate were found to satisfy the primary requirement of stability of diffuse reflectance over time under ambient conditions. The inside of the Goddard sphere was painted with barium sulfate. Drawing from the reports of Frank Grum of Eastman Kodak and Max Saltzman of University of Los Angeles (UCLA) of a new superior white material, NBS researchers Jack Hsia and Vic Weidner thoroughly characterized the material known as PTFE (polytetrafluoroethylene) . It is ahe world .Hovis and Knoll  brought The set up was used for calibrating sensors to be flown on aerial platforms or launched into space on satellites. The aerial platform sensors are flown as under-flights to the sensor on orbit for simultaneously measuring and comparing the reflectance of potential calibration sites on the earth. The use of potential known targets for calibrating the sensor is called vicarious calibration. The pre-launch calibration of sensors need to be validated post-launch to achieve accurate radiometric field measurements from space as the sensor characteristics change due to the stress of the launching process and continued exposure to the space environment . The useThe sensor for whose calibration NOAA sought guidance from NIST in the early period was the AVHRR, which was used operationally in the POES program. The vendor for the AVHRR, ITT, followed the procedures of Hovis et al. , which eIn August 1990, Abel left NESDIS and was succeeded on the AVHRR work by Nagaraja Rao, an expert on atmospheric radiation. Earlier, as a contractor to NESDIS, Rao had written NOAA Technical report NESDIS 36 , which bThe thermal channels of the AVHRR  are calibrated on orbit from views of cold space and a blackbody in the instrument itself. Before launch, the calibration was performed by the instrument vendor, ITT, in their thermal vacuum chamber with a honeycomb-cavity laboratory blackbody equipped with platinum resistance thermometers whose temperature calibration is traceable to NBS. They claimed ±0.35 K absolute uncertainty for the calibration of the laboratory blackbody , based oThe other satellites that NASA developed for weather monitoring with NOAA funding were the Geostationary Operational Environmental Satellites (GOES). The initial GOES series were spin stabilized and viewed the earth only 10 % of the time. The development of the GOES I-M series, the first three-axis stabilized geostationary satellites to view the earth 100 % of the time, began in the mid-1980s, directed by NASA/GSFC and funded by NOAA. The first of the new series was launched on April 13, 1994, and was renamed GOES-8 on achieving geostationary orbit. The GOES satellite sensor configuration is shown in The primary instruments on the GOES I-M satellite are the Imager and the Sounder. The Imager and Sounder are manufactured by ITT Industries, Inc. The Imager is a 5 channel scanning radiometer with one visible (550 nm to 750 nm), one shortwave (3.80 μm to 4.00 μm), two midwave  and one longwave (11.50 μm to 12.50 μm) infrared channels. It senses radiant energy and reflected solar energy from the Earth and produces visible and infrared images of earth’s surface, oceans, cloud cover, hurricanes and severe storms. The Sounder is also a scanning radiometer featuring nineteen spectral channels  that yield the sounding products of vertical atmospheric temperature and moisture profiles, surface and cloud top temperatures. The other instruments monitor the space environment (SEM) and provide data on solar flares, solar wind and high energy particle storms that affect space navigation, communication and electrical power transmission. The SEM data helps industries  to modify their operations as needed and mitigate the effects of Coronal Mass Ejections (CME) from the Sun reaching the earth causing geomagnetic storms.NOAA began interacting with NIST for resolving certain calibration anomalies in the GOES observations. Before the launch of each of these satellites, its Imager and Sounder were thoroughly tested by ITT, their manufacturer. These tests were carried out in the 1990s, beginning with GOES-I in 1993. They included calibration and characterization of the thermal-infrared channels, performed in a thermal-vacuum chamber. One of the puzzling results of the calibrations was that, for each instrument, the brightness temperature of its internal calibration target (ICT), determined radiometrically by the instrument itself after it had been calibrated against ITT’s laboratory blackbody, differed from its temperature as indicated by the PRTs embedded in it. These differences, termed “ICT errors,” were of the order of 0.5 K to 1.0 K and varied over both channel  and the instrument’s operating temperatures. This was not the first appearance of ICT errors. They were also observed earlier  in the pA sufficient (but not necessary) hypothesis that could explain the ICT errors and the shortwave non-linearity was offered by Edward Wack of MIT Lincoln Laboratory in 1996 . He suggIn May 1998, yet another problem in GOES calibration surfaced, giving NESDIS/ORA additional motivation to seek cooperation from NIST—in this case to validate the spectral response functions of the GOES instruments. In early 1998 it was noticed that the simultaneous brightness-temperature observations of the same scenes on the Earth by the Sounders on GOES-8 and GOES-10 disagreed by up to 5 K. Later that year it was also found that there was poor agreement between the measured brightness temperatures in those channels and the brightness temperatures calculated – using spectral response functions provided by the filter vendor (OCLI) – from in-situ temperature and water-vapor profiles. These discrepancies threw suspicion on the accuracy of the spectral response functions provided by the GOES filter vendor. The GOES Program approved the recommendation of the NESDIS ORA to subject some of the witness samples of these filters to the NIST measurement process.The NBS was reorganized in the late 1980s to form the NIST through Congressional legislation to emphasize technology development and standards to forge US innovation and industrial competence. Under the reorganization, NIST expanded the radiometry and optical characterization facilities. NIST developed the High Accuracy Cryogenic Radiometer (HACR) as the NIST primary standard for optical power with 0.01 % uncertainties on par with an international effort to reduce uncertainties in radiometric calibrations of optical radiation detectors . The HACThe first transfer standard radiometer at NIST was developed by one of us (Carol Johnson) in the 1990s to transfer SI-traceable radiance scales to the SeaWiFS project at NASA. It is called the SeaWiFS Transfer Radiometer (SXR) . NASA deNOAA/NESDIS and NIST also collaborated to provide SI-traceable radiance and irradiance calibrations for the MOBY program developed by NOAA and NASA for obtaining ground “truth” for vicarious calibration of ocean color satellite sensors, SeaWiFS and MODIS. As discussed in Sec. 2.1., for the case of the CZCS sensor, the removal of atmospheric radiance is an essential part of ocean color measurements and as such the instruments in space are vicariously calibrated. The MOBY deployed near Hawaii in the Pacific uses the Marine Optical System (MOS) fiber-coupled to sensor fore-optics to measure the upwelling radiances and down welling irradiances within the ocean . The higTo transfer the radiometric scale in the infrared from NIST to customer facilities, one of us at NIST (Joe Rice) developed the Thermal-infrared Transfer Radiometer (TXR) under funding from NASA’s EOS project. The TXR, shown in For infrared calibrations beyond 2 μm, DoD support enabled NIST to build the Low Background Infrared (LBIR) facility, consisting of two cryogenic chambers and two absolute cryogenic radiometers, for the calibrations of cryogenic blackbodies from facilities of DoD and its missile defense contractors ,32. In bThe formal procurement process within NOAA to seek cooperation from NIST began in July 1999 under the technical direction of one of us (Weinreb), who was the GOES calibration scientist at the NESDIS Office of Research and Applications. He wrote a requirements document that began with the truism that accurate calibration is needed if GOES is to provide atmospheric observations that satisfy its users’ stated uncertainty requirements. It alluded to previously observed inconsistencies in NOAA’s satellite measurement from GOES and POES satellites, attributing them to inadequacies in calibration. It mentioned the specific difficulties, described above, in the pre-launch calibration of the GOES I-M instruments. It concluded with the recommendation for the establishment of a long-term collaboration with NIST for support of pre-launch calibration, beginning with TXR measurements of ITT’s laboratory blackbody.On August 12, 1999, NIST responded with a proposal that offered a program of continuing support for calibration of NESDIS’s POES as well as GOES sensors. The goal would be to reduce calibration uncertainties to 0.1 K in radiance temperature. The planned work would be the TXR measurements of ITT’s laboratory blackbody for the GOES Imagers. But the program would also include such other tasks as end-to-end reviews of the calibration procedures of the instrument vendors, measurements of the spectral response functions of the GOES instruments’ bandpass filters, participation on NESDIS calibration panels, and collaboration with NESDIS in developing a long-term program of pre-launch calibration support. These tasks were modeled upon ongoing efforts for NASA EOS and DoD projects.The first measurements made by NIST for NOAA were interferometer measurements of the spectral response functions of witness bandpass filters for selected channels of the GOES-8 and -10 Imagers and Sounders. These measurements were carried out by Simon Kaplan of NIST in March and April 2001 . In someThe TXR measurements of the radiances and emissivities of ITT’s laboratory blackbody were performed by one of us (Joe Rice) of NIST during a two-week period in July 2001 using the NIST TXR. The laboratory blackbody at ITT, called External Calibration Target (ECT), had been in regular usage at ITT for the pre-launch calibration of operational GOES imagers. The TXR data analysis was structured to infer an (non-unity) emissivity and any temperature gradients in ITT’s laboratory blackbody that would allow the radiances of the blackbody computed from its temperature sensors to be in accordance with the TXR radiance observations. The analysis also produced corrections to each temperature of the laboratory blackbody, which could be used with an emissivity of unity to calculate corrected radiances . These cNOAA participated in funding the Committee on Earth Observing Satellites (CEOS) intercomparison of blackbodies used to calibrate radiometers deployed on ships to measure sea surface temperature. The NASA EOS Project also sponsored the event. NIST participated in the comparisons held at the University of Miami’s Rosenstiel School of Marine and Atmospheric Science (RSMAS) in 2001. NIST employed the TXR for this purpose; consequently, this study provided an independent experimental check of the SI-traceability of sea surface temperature measurements . The NISFollowing the successful NIST measurements of GOES filters mentioned earlier, NESDIS employed NIST to measure the spectral response functions (SRF) of the HIRS (High-Resolution Infra-Red Sounder) instruments on the POES series. Since the beginning of the POES series in 1978, radiances observed in some HIRS channels differed significantly from the radiance values produced by forward calculations based on coincident measurements of atmospheric temperature and humidity profiles. These differences, similar to the ones affecting the GOES Sounders, led such data users as the National Weather Service to apply large bias corrections to the measured radiances before assimilating them into its forecast models. The question was, “Could the differences be the result of incorrect knowledge of the spectral response functions used in the forward calculations?” In 2001, one of us (Weinreb) proposed that NIST verify the spectral response functions of the HIRS’s bandpass filters. Funded by the NESDIS Office of System Development, Simon Kaplan of NIST measured the spectral response functions of witness samples of the bandpass filters for a HIRS instrument . The meaIn March 2007, NOAA scientists Timothy Schmit and Mathew Gunshor observed a 2.4 K cold bias, relative to observations with well-calibrated instruments on other satellites, in the observations from channel 6 (13.3 μm) of the GOES-12 and -13 Imagers . They hyGOES-R  is the next generation of geostationary weather satellites. The first satellite with its sensors is scheduled to be launched in 2015. The ABI is the primary sensor on GOES-R for imaging Earth’s weather, climate and environment with advanced capabilities compared to the previous GOES imagers. It has 16 different spectral bands spanning the visible to thermal infrared and will provide more spectral, spatial and temporal coverage than the current GOES system. A workshop was held on October 20, 2003, at NIST with the participation of researchers from NASA , NIST  and NOAA (Weinreb) on the services NIST could offer to a satellite remote sensing program such as GOES-R. In January 2004 one of us (Weinreb) retired from NOAA but returned in March 2004 as a part-time contractor, with responsibility to organize the GOES-R calibration activities. That included starting a management-level calibration steering committee, starting a working-level calibration working group, initiating a relationship with NIST to verify the traceability of the GOES-R sensors’ calibration, and acting as liaison with NIST. In December 2004 one of us (Johnson) at NIST wrote a five-year statement of work for NIST support of GOES-R. It contained tasks in two areas: 1) reviewing GOES-R calibration plans and participating on panels and committees, and 2) carrying out measurements to verify the traceability of GOES-R calibration, e.g., the use of VXR and TXR to characterize ABI laboratory calibration sources, measurements of spectral response functions of the ABI, and experiments to assess vendors’ claims of traceability. Later, space weather monitoring instruments on the GOES-R satellite platform were also included by NOAA for traceability verification.The External Calibration Target (ECT) developed by ITT for the pre-launch calibration of the ABI sensor has been tested and validated by NIST for its performance. For this purpose, the NIST TXR was deployed to the ITT cryogenic chamber in Rochester for in situ measurements of the ECT. The TXR was located in the chamber at the same physical location where the ABI sensor was located for its testing. The geometry of the set up was to emulate the conditions of ABI testing and validate the performance of the ECT to meet the requirements. The emissivity of the ECT was measured and the ECT radiance temperature scale was validated .Two FEL lamps that illuminate the ABI’s solar port for pre-launch testing were validated by NIST for their spectral irradiance scale. These lamps were calibrated at NIST. To establish the on orbit traceability of the radiometric response of the ABI sensor solar reflective channels, the sun is used to illuminate an on-board diffuse reflectance standard that is sub-entrance pupil for ABI. The lamp standard for spectral irradiance (type FEL) serves to illuminate the ABI solar port during pre-flight calibration and validate the spectral irradiance responsivity assigned on orbit using the sun .The spatial uniformity of FEL-based irradiance scale is tested at NIST to use the FEL at distances other than the nominal 50 cm to enable the use of FEL lamp to fill the field-of-view of the ABI sensor. NIST performed the measurements using the gonio filter radiometer (GOFR) and validated those measurements using the NIST gonio-spectroradiometer facility. NIST provided the test results with quantified uncertainties to help the use of FELs at desired distances for pre-launch testing of ABI .NIST (Keith Lykke and Steven Brown) performed calibration and characterization studies for end-to-end testing of the ABI Prototype Model (PTM) at ITT/Fort Wayne, IN using the NIST Travelling SIRCUS . The resThe 165 cm diameter large sphere at ITT, Ft. Wayne, IN, which is used to illuminate the ABI earth-port for determination of its visible-near infrared spectral radiance response functions, was measured in April 2013 by NIST (Carol Johnson and Steve Maxwell) to validate its radiance scale. This scale is established using a NIST-calibrated integrating sphere and a scanning monochromator. NIST used the VXR and two spectrophotometers to perform the measurements. A NIST Portable Radiance (NPR) source developed by Steven Brown served as the radiance standard for this validation activity.The filters for the 6 witness samples of the VIS-Near IR bands and the 10 witness samples for the IR bands for the ABI sensor have been characterized at NIST at high spectral resolution for various incident angles at specific temperatures meeting the ABI sensor operational requirements. The results were provided with uncertainty budgets to help compare with vendor-provided measurements for the real ABI filters .The first flight unit of EXIS has been calibrated at the Spectrometer Calibration Beamline (BL-2) of the NIST Synchrotron Ultraviolet Radiation Facility (SURF III). Several more units are planned to be calibrated in the near future. Calibrations already completed for the EXIS project include the engineering test unit, rocket underflight unit, and flight unit of the X-Ray Sensor and the flight unit of the Extreme Ultraviolet Sensor .NIST staff has been working closely with the SUVI instrument development team in addressing the use of NIST standards to meet the SUVI calibration requirements and in evaluating the metrology done by the vendor. Several calibrations have already been provided at NIST SURF III. The work performed thus far includes 1) Calibration of several transmission gratings using the current BL-7 Beamline in support of end-to-end calibration. 2) Testing of witness samples from the SUVI filter deposition runs by the vendor. The NIST results confirmed the vendor estimates of sample film thickness satisfying the minimum transmission requirements. NIST data provided input on the unexpected large batch to batch variation to be addressed by the vendor .The GOES-R Program at NOAA began funding these activities in fiscal year 2005. The funding was renewed in FY 2006 and FY 2007. It supported work at NIST until FY2009, when a more formal relationship between NESDIS and NIST was established. The thrust of the work before FY2009 consisted of reviewing GOES-R calibration designs and plans, participating in reviews and on committees, and planning the measurements and upgrading equipment and facilities for verifying the radiance scales of the calibration sources of the ABI Vendor, ITTAt the beginning of this century, global climate change became an important issue worldwide, and the absolute accuracy of satellite-based radiometric data of the earth was recognized as a crucial factor in assessing climate change. The three agencies, NASA, NIST, and NOAA, played a pivotal role in bringing the remote sensing community together to address measurement challenges for satellite-based climate observations. Steve Ungar of NASA and one of us (Cao) of NOAA played active roles in CEOS  as chairIn 1994, NOAA, DoD, and NASA had created an Integrated Program Office (IPO) within NOAA to develop, manage, acquire, and operate the National Polar-orbiting Operational Environmental Satellite System (NPOESS). The NPOESS satellite program was intended to reduce costs and increase efficiency by combining NOAA’s POES and DoD’s Defense Meteorological Satellite Program (DMSP) . The NPOSteve Mango, the chief scientist of the NPOESS IPO (1995–2008), promoted the development at NIST of thermal infrared standards and measurement methodologies for high accuracy pre-launch calibration of the NPOESS/NPP Cross-track Infrared Sounder (CrIS) by its contractors ITT and Northrop Grumman. The NIST Optical Technology Division (OTD) received funding from the NPOESS IPO that helped NIST thoroughly characterize the TXR in preparation for field deployment to validate the calibrations of the blackbody targets used by such aerospace contractors as ITT for calibrating remote sensing instruments in the thermal infrared. The successful deployment of the TXR in support of the GOES program, already discussed in Sec. 3, has been an example of the legacy of the cooperation of NOAA and NIST researchers working to resolve operational satellite sensor calibration issues. NOAA is currently sponsoring NIST to calibrate the ECT at ITT, Ft Wayne, IN to support the CrIS FM1 sensor pre-launch calibration for the newly organized Joint Polar Satellite System (JPSS) , which iMango also tasked NIST to determine accuracy requirements for instruments in space to monitor climate change. Sponsored by NPOESS IPO, the NIST OTD collaborated with George Ohring of NOAA and James Butler of NASA to organize the joint workshop, “Satellite Instrument Calibration for Measuring Global Climate Change,” in 2002. This workshop was a grand success, with the active participation of nearly 100 scientists and engineers from the three agencies and major NASA aerospace contractors. The workshop addressed the measurement challenges and instrument calibration needs for the accurate space-based measurement of global climate-change variables such as atmospheric temperature and solar irradiance. These variables are critical for assessing the magnitude of, and determining an effective policy response to, global climate change. The workshop NIST report, NISTIR 7047 , summari3),” sponsored by NOAA, NASA, NIST, NPOESS, and the Space Dynamics Laboratory of the Utah State University was organized in 2007. Its goal was to formulate a national roadmap for developing the calibration systems meeting the requirements identified in the first workshop to monitor long-term global climate change. Two overarching recommendations emerged from the workshop [As a follow up, the second workshop, “Achieving Satellite Instrument Calibration for Climate Change , who first showed that Simultaneous Nadir Overpasses (SNOs) can be utilized for the satellite-to-satellite intercalibration of radiometers . They wiAlso in 2009, NIST, NOAA, and NASA held a workshop at NIST to develop strategies on how to bridge a possible gap in satellite data for climate in case of a launch delay or other failure in maintaining continuous time series of observations from space. The workshop report  was publScientists at the NOAA’s NESDIS began seeking help from NIST with calibration of their laboratory standards from the start of their environmental satellite program. The initial collaborations between the two agencies were confined to the calibration of visible and near-infrared sensors.NIST developed standard lamps early-on that helped NOAA and NASA scientists to develop a pre-launch calibration strategy for visible and near-infrared channels of satellite sensors using lamp illuminated integrating spheres. It has become a standard method around the world.Also early-on, NIST (formerly NBS) characterized the sintered and packed polytetrafluoroethylene (PTFE) as a diffuse reflectance standard that is now widely used to provide reflected solar radiation for the on-orbit calibration of visible channels. The material is called Spectralon™ by its vendor, Labsphere, Inc.In the 1990’s and early 2000’s, NOAA sought and secured assistance from NIST to help diagnose the causes of issues in the performance of the infrared sensors on NOAA’s polar and geostationary meteorological satellites. This cooperation paved the way in 2009 for the generation of a formal Memorandum of Understanding (MOU) between NOAA and NIST for NIST support of the pre-launch calibration in the GOES-R Program. Under this MOU, NIST is validating the calibration of the laboratory calibration standards of GOES-R instrument vendors and the spectral response functions of the GOES-R ABI.NIST and NOAA convened workshops, with the active participation of NASA and industrial and academic institutions, that identified the minimum measurement requirements for detecting and monitoring global climate change, the corresponding instrument capabilities needed to make those measurements, and a road-map for achieving the required capabilities.The NOAA National Calibration Center (NCC) was established to promote best practices and compile a knowledge base for improving the calibration of sensors whose observations are needed to help improve weather prediction and the monitoring of climate change.In a workshop organized by NIST with active participation of NOAA and NASA scientists, calibration strategies were recommended to help bridge gaps in time series of satellite sensor data resulting from launch failures or other operational failures. Responding to the recommendations NIST has built a travelling SIRCUS that is easily deployable at customer sites. NIST proposed the LUSI project to radiometrically characterize the Moon as SI-traceable for use as an on-orbit reference standard for satellites with the required accuracy.The cooperation between NOAA and NIST scientists to increase the accuracy of satellite optical sensor data to improve the prediction of weather and the monitoring of climate change started at the inception of weather satellites and is on-going. Some of the highlights of this article are summarized here:


Omics-technologies  in live science promises highly detailed information about the specific research object and helps to understand molecular changes in response to internal and external environmental factors.Technical progress in the field of next-generation sequencing, mass spectrometry and bioinformatics facilitates the study of highly complex biological samples such as taxonomic and functional characterization of microbial communities that virtually colonize all present ecological niches. Compared to the structural information obtained by metagenomic analyses, metaproteomic approaches provide, in addition, functional data about the investigated microbiota. In general, integration of the main The microbial communities settled in the mammalian gastrointestinal tract are essential for the host metabolism and have a major impact on its physiology and health. The microbiotas of livestock like chicken, pig and ruminants are becoming a focus of interest for veterinaries, animal nutritionists and microbiologists. While pig is more often used as an animal model for human-related studies, the rumen microbiota harbors a diversity of enzymes converting complex carbohydrates into monomers which bears high potential for biotechnological applications.Omics-based research of the microbiota in livestock including its major findings. Differences concerning the results of pre-Omics-approaches in livestock as well as the perspectives of this relatively new Omics-platform will be highlighted.This review will provide a general overview about the recent  Despitevs. long read length (600–800 bp) with 454. The latter one is more feasible in terms of shotgun sequencing studies (see below) Two pyrosequencing techniques, 454 (Roche) and sequencing by synthesis (Illumina), are mainly used for (meta-)genomic and (meta-)transcriptomic projects. Both systems have unique features, such as short paired-end reads (max. 2 × 300 bp) with Illumina in situ hybridization which use the 16S rRNA gene as a target molecule. In this review, we focus mainly on next-generation sequencing methods to describe the microbial community structure. Nowadays the total diversity of a microbiological sample is analyzed preferably by pyrosequencing of the 16S rRNA gene, obtained by amplification of extracted DNA. The active fraction of the community is analyzed using mRNA/cDNA. Subsequent to pyrosequencing, quality filtering and denoising processes have to be applied. The reads should be checked for chimeras and clustered to operational taxonomic units (OTU) in order to assign the respective taxonomies to the sequences. There is a diverse range of bioinformatic tools available in free software platforms such as Mothur, QIIME, RDP pipeline, LIBSHUFF, UniFrac and MEGAN that support data analysis and convert data to formats that can later be used in statistical packages like R, Metastats or Primer-E. A detailed overview of the methods can be found in several review papers The gene of choice to analyze the phylogenetic composition of a microbial community is the 16S rRNA gene, a ribosomal gene in prokaryotes characterized by conserved and variable sequence regions, which is used to calculate evolutionary relationships and similarities between the species In addition to the phylogenetic structure of the community, the analysis of encoded and expressed metabolic pathways is the second objective. Metagenomic or metatranscriptomic data are obtained by shotgun pyrosequencing of the total DNA and cDNA, respectively. Reads have to be quality filtered, assembled to contigs, binned and assigned to taxonomies and possible gene functions. As the assembly requires sequence reads with appropriate length, so far 454 pyrosequencing was the method of choice as it produces reads up to 800 bp (see above). Due to the progress in data generation and bioinformatic processing Illumina pyrosequencing is recently used as well. Several tools are available for the annotation of open reading frames on the contigs, MG-RAST In addition to metatranscriptomic studies, the community activity can be assessed based on expressed proteins and formed metabolites. Metaproteomic studies investigate the protein inventory of a specific sample at a certain point of time Omics-technologies and their importance for the understanding of these niches.The following sections will provide an insight into the ongoing research of the microbiota of the gastrointestinal tract of livestock animals with special emphasis to the use of 2The chicken intestinal environment comprises a vast and diverse assemblage of microorganisms living not as single species populations, but rather in complex communities comprising multiple species that include animal and human pathogens. Intricate networks of interactions between the microorganisms and their environment shape the respective communities and are important for animal welfare and food safety reasons. The chicken GIT consists of more than 900 species of bacteria. This diverse microbiota helps not only the breakdown and digestion of food but also plays an important role concerning the growth and health of the host In the past, the chicken GIT microbial community was studied by culture-based methods. These studies discovered that 10–60% cecal bacteria can be cultured Regarding the research in microbial ecology of the chicken GIT, several studies focused on the influence of diet After hatching, the colonization of the chicken GIT begins. This is a moment of great importance regarding the establishment of the microbial communities. Although the colonization of the chickens by maternally derived bacteria is low, some studies postulated that the microbial community structure of the small intestine settles within two weeks. Older studies showed that cecal bacteria need longer time to develop Lactobacilli, facultative and microaerophilic bacteria are the most dominant bacteria present in this two segments. Other abundant species belonged to Clostridiaceae, Enterococcus and in the case of the crop also Bifidobacterium and Enterobacteriaceae (Lactobacillus as the main colonizer of the jejunum (reaching coverage of up to 99%), Streptococcus was identified as well. Amit-Romach et al. has shown that the relative proportion of Lactobacillus spp. in duodenum and jejunum increases within age Lactobacillus in higher abundance (> 68%) and in lower abundances Streptococcus, Enterobacteriaceae and ClostridiaceaeLactobacilli were dominant The chicken gut is divided in three upper segments: crop, proventriculus and gizzard. The crop is a food storage muscular pouch related to the breakdown of starch and the fermentation of lactate. Digestion starts in the proventriculus while the gizzard grinds food. Because of its lower pH and fermentation activity, the gizzard functions as microbial barrier. Similar microbial communities were found in the crop and gizzard. eriaceae  [25], [4Clostridium, Bacteroidetes, and Bifidobacterium  methods were performed by Collado and Sanz Omics-technologies such as metagenomics Pigs harbor a complex gut-microbiota which establishes strong and complex interactions with the host. Since the importance of these interactions and their implication in nutritional, immunological and physiological functions became more relevant, several research groups started to focus on the characterization of the porcine gut microbiota by using different methods. In the past, members of the porcine gut microbiota were investigated by cultivation attempts that are limited to a small fraction as it is difficult to achieve optimal growth conditions Firmicutes and Proteobacteria, whereas the phylum-level profiles of the caecum and mid-colon are highly congruent and include mainly Firmicutes, Proteobacteria, Bacteroidetes and Spirochetes. Other phyla such as Fibrobacteres, Actinobacteria, Tenericutes, Synergistetes and Planctomycetes are present but their sequences constitute less than 1% of total rRNA gene sequences Bacteroidetes represented about half of the microbiome in large intestine sections and harbored enzymes for polysaccharide degradation. The ileum was enriched in Firmicutes associated genes of numerous bacterial ABC transporters for monosaccharides and amino-acid uptake and bacterial carbohydrate transport phosphotransferase systems showing a preference for the metabolization of easily accessible low molecular weight molecules by Firmicutes species. Therefore, a clear separation of the carbohydrate degradation steps based on the phylogenetic level in the pig GIT can be made, starting with the conversion of polysaccharides to oligosaccharides by pathways encoded in Bacteroidetes and followed by the uptake and fermentation of monosaccharides by metabolic processes encoded in Firmicutes.Most investigated sections within pig's GIT are ileum , caecum and colon (large intestine) . PhylogeFirmicutes and Bacteroidetes. Numerically-abundant bacterial orders revealed that Clostridiales, unclassified Firmicutes, Bacteroidales, Spirochaetales, unclassified Gammaproteobacteria, and Lactobacillales were the top six most abundant bacterial orders. Archaeal sequences constituted less than 1% of total 16S rRNA gene sequences, and were dominated by the Methanomicrobia and ThermococciConcerning fecal-associated microbiota, shotgun metagenomic analysis followed by sequence annotation using both MG-RAST and JGI IMG/M-ER pipelines Firmicutes compared to Bacteroidetes by T-RFLP and qPCR approaches vs. Bt-maize) were determined; moreover no statistical differences occurred in microbiota composition except for the genus Holdemania that was more abundant in isogenic group. However, the authors argued that this difference may be related to the changing of the maize source during the animal's early life, when the gut microbiota has not completely developed Structure and activity of GIT microbiota can differ significantly between animals depending on the breed, diet, health status, age and environment Several other studies investigated how different diet composition can affect porcine gut microbiota in order to draw either a balanced diet able to ensure a higher animal growth rate Since the importance of gut microbiota in animal production was clarified, the study of in-feed antibiotic (AB) effects on porcine gut microbiota is now of great importance. Nowadays various groups focus on understanding how the use of antibiotics promotes animal growth and how it affects the gut microbiota in short- 4http://faostat.fao.org/) constitute a highly significant source of food products to humans. These animals host a complex gut-microbiome  via NMR Along with the microbial community composition two studies analyzed the rumen microbial metabolic profile via pyrosequencing and compared to production parameters and milk composition Firmicutes to Bacteroidetes was clearly associated with milk fat content, but most other taxa were rather related to the residual feed intake phenotype. Elucidating the role of rumen microbiota in shaping host physiological parameters may promote better agricultural yield through modulation of bacterial community structure One study providing valuable information for milk production investigated the bacterial communities of 15 dairy cows 5The most extensive surface in the animal body is the GIT that harbors an immense variety and amount of microorganisms. Internal and external factors can unbalance this dynamic and complex niche and thereby, also disturb or improve the animal's health status.etc.), the experimental setup (feeding and sampling), and used DNA extraction and sequencing method (target region of the 16S rDNA gene sequence). Therefore, it is hard to compare those studies and correlate them with each other. Nowadays, Omics-methods offer the advantage of being able to reliably measure and compare hundreds of samples simultaneously with low costs per sample. The millions of sequence reads available through pyrosequencing methods exceed the depths necessary to describe microbial community compositions of a few samples by far. Therefore, inter- and intra-population similarities, temporal dynamics and effects of external factors on the GIT community of livestock should be addressed with the comparison of a broad array of samples. Requirements to deeply cover the phylogenetic diversity are optimized nucleic acid extraction methods and amplification strategies, especially the choice of the amplification region within the 16S rRNA.Until recently, comparative studies of the microbiota were done between a few points of time and samples, sometimes even pooled samples were used. The results are often contradictory depending on the used animal (breed, age, gender in vivo activity of the communities and of single members. Combination of the collected data will support modeling approaches to detect microbial response mechanisms towards different feeding strategies, pathogens, antibiotics or environmental changes. When compared to the human gut, the analysis of livestock GIT was clearly neglected in the past years, but mainly due to the functional diversity, it should become of interest for future analyses.Metagenomic sequencing and genome assemblies of uncultured prokaryotes already allows the detection of potential functions of the microbiota, but the analysis of the active fraction of the microbiota in the GIT of animals is still in their infancy. Metatranscriptomic and metaproteomic analysis should gain more importance within the next years to grant deeper insights into the expressed pathways and community interaction mechanisms. Labeling and imaging techniques will support the description on the


The current study was conducted to determine the effects of longer steri-strip tape on patient malar and cheek in terms of ecchymosis control and reduction.Early postoperative edema and ecchymosis are the most common factors to complicate initial patient perceptions about rhinoplastyThrough a randomized controlled clinical trial, 64 patients who underwent rhinoplasty were randomly enrolled. One side of the patients’ face was randomly selected for different experience of dressing while the main intervention was different length of tape and steri-strip dressing. In one group, the right side and in the rest, the left side of face was applied with steri-stip from the nose to lateral malar and cheek. In the opposite side of the face, steri-strip taping was done from the nose to medical malar and cheek.The mean area of ecchymosis after rhinoplasty through our trial was 1.55 mm and 2.31 mm, respectively in sides with and without steri-strip which differed significantly. When patients’ age and sex were taken into account, the distribution of ecchymosis had no significant difference in this regard.The present study showed significant reduction in the area of post-rhinoplasty ecchymosis in lower lid, malar and cheek soft tissues as well as the obvious increase in satisfaction rate among intervention side of face in comparison to the control side. But longer steri-strip tape failed to control sub conjunctival bleeding or decrease it. Many researchers and authorities have attempted in this regard to advise following approaches: (i) To use local vasoconstrictive solutions at the site of surgery, (ii) To use micro-osteotomes as rather newly developed tools, (iii) To preserve periosteal attachment, (iv) To prevent transverse osteotomy by medial-oblique approach, and (v) Steroid administration.11-13For the patient, swelling and ecchymosis play the most important role in satisfaction rate and self-confidence after rhinoplasty which are, in turn, resulted by osteotomies through the procedure because of the injured angular vessels which cross the site of osteotomy and fractured bone, in details.8 In spite of the vast number of performances to introduce new ways to control postoperative edema and ecchymosis, there has been no research to work on compressive effects of steri-strip tape on the bleeding sites following rhinoplasty, as far as we know. So, the current study headed to find the results of longer steri-strip tape on patient cheek in terms of edema and ecchymosis control and reduction.The latter item addresses to the effect of glucocorticoids on decreasing vascular permeability to lessen the local exudation and blood accumulation at the site of manipulation.Through a randomized controlled clinical trial, 64 patients who had undergone rhinoplasty were randomly selected to enter the study. Smokers as well as people with hemostatic problems, hypertension and previous rhinoplasty experience were excluded from the study. One side of the patients’ faces were randomly selected to get different length of dressing named Steri-Strip. In one group, the right side and in the rest, the left side of face had steri-stip dressing which was a longer tape application from the nose to lateral malar and cheek. The opposite side had shortey conventional tape dressing from 3 the nose to medial malar and cheek. The participants were followed up for 2 months to assess the outcome of rhinoplasty as well as the complications among which ecchymosis in addition to sub- conjunctival bleeding were most predominant. One week after the surgery, at the first postoperative physician visit, 3M tapes and nasal splints were removed before using a digital camera to get facial photographs at face and bilateral views. Strict protocol was applied to have real size photographs to be compared. A 6 megapixels digital camera was placed in 2 meters far from the subject at 150 centimeters above the floor. The subjects sat on a chair and were fixed at the vertical level of the camera. 2 . When patients’ sex was taken into account, Totally, 64 subjects were enrolled in the study including 11 (17.2%) males and 53 (82.8%) females as can be seen in The participants were divided into two groups regarding their age containing <30 years and >30 years old. Likely, age was not a factor of difference between the patients concerning the mean area of postoperative ecchymosis as We assessed the participants’ satisfaction by dividing them into three levels of low, intermediate and high satisfaction. Forty eight (75%) patients expressed their high satisfaction while 11 (17.2%) and 5 (7.8%) had intermediate and low rates of satisfaction, especially in terms of predominant complications like ecchymosis and sub conjunctival bleeding. .The present study showed significant reduction in the area of post-rhinoplasty ecchymosis in lower lid, malar and cheek soft tissues as well as the obvious increase in satisfaction rate among intervention side of face in comparison to the control side. We found that longer steri-strip tape failed to control sub conjunctival bleeding or decrease it .The present study tried to compare the conventional short tape dressing and long steri-strip tape dressing following rhinoplasty in the prevention or decrease of postoperative ecchymosis which usually occur and disturbs the rate of satisfaction in patients and surgeons. The results showed a significant difference of ecchymosis area between two sides of patients’ faces. Longer tapes had obviously less ecchymosis that confirmed the helpful role of compression on cheek and nasal bone in this matter. Edema and ecchymosis, despite of the usual gentle and careful performances by even the most expert surgeons, are inevitable and could strongly affect the patient and surgeon satisfaction, physically and mentally.14The edema and ecchymosis, which develop around the eyes after rhinoplasty, have been focused by many studies for decades and some techniques have been found to improve compression and dressing techniques in this matter. Many medications are usually used in cosmetic operations, particularly in face such as adrenaline, arnica, lidocaine, and corticosteroids as well as some herbal extracts.15-19 Some also used hypotensive drugs during head and neck surgeries20,21 which are not systematically offensive to be used only to reduce ecchymosis. In a clinical trial by Simsek et al. in Turkey in 2011, two surgical techniques of rhinoplasty with and without osteotomy showed significantly different size and rate of ecchymosis in the patients which suggest the superiority of rhinoplasty without osteotomy in terms of ecchymosis occurrence.22 This confirms that osteotomy; especially transverse osteotomy could potentially direct patients to get edema and ecchymosis following the procedure. However, since all the patients enrolled in our study experienced osteotomy, we through the current trial, tried to assess the effects of simply different dressing techniques on the size of ecchymosis while used in addition to perioperative corticosteroids as the conventional way of control the common complications. As pointed out before, we failed to find any attempts in the literature to assess the compressive aspects of tape and cast to control ecchymosis. As it turns out, there is some herbal extracts which are systematically administered to reduce the edema and ecchymosis following rhinoplasty successfully as Chaiet et al. tried well.23Concerning steroids and their reducer effects on edema and ecchymosis, these medications, with several drug shapes, have been the most group to be studied and used conventionally after surgeries, especially in face, head and neck. Hwang et al. were one of the groups who published even meta-analysis in this matter in 2014.24 They determined that through several studies found in the literature, in more than total 300 patients with rhinoplasty, upper eyelid ecchymosis was significantly decreased by using steroids when compared with the control group. Lower eyelid ecchymosis decreased significantly in the assessed studies but the effect size of steroids in upper eyelid was reported higher. They also advised using multiple doses of steroids instead of single dose to achieve a better control in edema and ecchymosis. We found no effect of age and sex on the rate and size of ecchymosis after rhinoplasty during our trial. Likely, no study explained sex or age different distribution of the named complication. We also found no significant effectiveness of long tape on sub conjunctival bleeding when comparing the intervention and control sides of patients’ faces. This is while Kosucu et al. in Turkey showed significant reduction of bleeding by using hypotensive drug, remifentanil during rhinoplasty.14The present split-clinical trial on patients’ faces provides a reliable way to compare the net effect of different length of steri-strip tapes because of the same physical and physiological base of individuals who each of them was separately a case and at the same time a control. There would be an advice to use long steri-strip tapes from the nose to lateral malar and cheek in both side of the fase in rhinoplasty patients along with topical platelet gels when dressing the operated nose to allow this autologous and homogenous platelet-rich and fibrin-rich gel attract inflammatory cells as well as fibroblasts to stimulate collagen local deposition to prevent or decrease the size of bleeding and ecchymosis following surgery.25-28To conclude, the present study showed significant reduction in the area of post-rhinoplasty ecchymosis in lower lid, malar and cheek soft tissues as well as the obvious increase in satisfaction rate among intervention side of face in comparison to the control side. But longer steri-strip tape failed to control sub conjunctival bleeding or decrease it.The authors declare no conflict of interest.


Ultrasound-guided nerve blocks are becoming more essential for the management of acute pain in the emergency department (ED). With increased block frequency comes unexpected complications that require prompt recognition and treatment. The superficial cervical plexus block (SCPB) has been recently described as a method for ED management of clavicle fracture pain. Horner’s syndrome (HS) is a rare and self-limiting complication of regional anesthesia in neck region such as brachial and cervical plexus blocks. Herein we describe the first reported case of a HS after an ultrasound-guided SCPB performed in the ED and discuss the complex anatomy of the neck that contributes to the occurrence of this complication. A 20-year-old male presented to the emergency department (ED) with right shoulder pain and deformity after falling from his bicycle. Exam was notable for swelling and tenderness overlying the right clavicle with a comminuted mildly displaced clavicular fracture confirmed by plain radiography. The patient complained of severe pain unrelieved by initial parenteral opioids. For improved pain management, an ultrasound-guided superficial cervical plexus block (SCPB) was performed.2The patient was placed on continuous cardiac monitoring. Placement of a high frequency linear transducer  was approximated by palpation of the superior pole of the thyroid cartilage (C4 level), and visual approximation of the midpoint of the sternocleidomastoid muscle (SCM), from mastoid to the clavicle.The superficial cervical plexus was identified as the hyper echoic fascia posterior to the SCM and superficial to the levator scapula muscle (LSM) . The areApproximately 15 minutes after block placement, the patient had complete pain relief, reporting sensory deficit in the cape region of the shoulder, neck, and skin overlying the clavicle without changes in motor function of the arm. Forty-five minutes later, the patient complained of right-sided facial numbness and was noted to have ptosis, miosis, and conjunctival injection on the ipsilateral side of the block . There wPotential complications of a SCPB include Horner’s Syndrome (HS), partial brachial plexus blocks, phrenic and recurrent laryngeal nerve blocks. We believe the HS described here developed as an inadvertent complication of deep spread of local anesthetic after superficial injection, involving the ipsilateral cervical sympathetic chain.6Nash et al.5Finally, it is important to be aware that if HS occurs after the SCPB, providers should consider it self-limiting, requiring only patient reassurance and observation versus urgent neuroimaging to evaluate for an acute stroke.The SCPB is strategy for ED pain management of clavicle fractures. However, emergency clinicians should be aware that similar complications expected of a deep cervical plexus block could occur with the SCPB, such as HS. To minimize risk of complications of the SCPB, in addition to standard precautions for ultrasound-guided nerve blocks, several precautions should be taken. Clinicians should be aware of the anatomy of the superficial cervical plexus and be familiar with the landmarks, ensuring to stay at the level of C4; the injection should be shallow, just under the SCM belly; and appropriate anesthetic volumes (2–5mL) should be used. The development of HS after SCPB can be frightening to patients and the physician should reassure the patient that it is self-limited and not a sign of intracranial pathology or permanent damage.


Plants and microbes interact in various relationships which have both adverse and beneficial effects on plant growth and microbial communities. Many processes of these interactions occur at or near the root–soil interface, which is known as the rhizosphere. The rhizosphere is defined as the soil region under the immediate influence of plant roots. Many studies suggest that the microbial community in rhizosphere inhibits invasion of the plant pathogen to the plant root , 14, 22 Most agricultural soils contain too little available phosphorus for high and stable crop production . TherefoA large portion of phosphorus in most soils is organic forms, and a major component of soil organic phosphorus is phytic acid mainly consisting of inositol penta- and hexaphosphates . Most plet al. focused on phytic acid metabolism in the rhizosphere of Lupinus albus and isolated about 300 strains of phytic acid-utilizing bacteria from the rhizosphere  and metagenomic analysis using pyrosequencing to identify key microbes and to elucidate the processes involved in phytic acid degradation in the rhizosphere. The DGGE analysis showed no clear relationship between the microbial composition and the phytic acid utilization of L. japonicas. Although DGGE analysis is a powerful tool to evaluate the microbial composition in soil environments (Unno and Shinano conducted culture experiments of  strains , to inveronments , 16, 19,ronments , 11. TheAlthough metagenomic DNA-based analysis provides useful information on the phylogenetic and metabolic genes of a microbial community, it cannot be used to estimate the active microbial population size and the expression level of target genes. Metatranscriptomic analysis has significant potential for describing functional processes in complex microbial communities. Analysis of mRNA and 16S rRNA can reveal metabolically active populations. In the past several years, some attempts have been made to investigate microbial gene expression in soils , and rec


Induction and activation of arginase is among the fastest responses of the heart to ischemic events. Induction of arginase expression and enzyme activation under ischemic conditions shifts arginine consumption from nitric oxide formation (NO) to the formation of ornithine and urea. In the heart such a switch in substrate utilization reduces the impact of the NO/cGMP-pathway on cardiac function that requires intact electromechanical coupling but at the same time it induces ornithine-dependent pathways such as the polyamine metabolism. Both effects significantly reduce the recovery of heart function during reperfusion and thereby limits the success of reperfusion strategies. In this context, changes in arginine consumption trigger cardiac remodeling in an unfavorable way and increases the risk of arrhythmia, specifically in the initial post-ischemic period in which arginase activity is dominating. However, during the entire ischemic period arginase activation might be a meaningful adaptation that is specifically relevant for reperfusion following prolonged ischemic periods. Therefore, a precise understanding about the underlying mechanism that leads to arginase induction as well as of it's mechanistic impact on post-ischemic hearts is required for optimizing reperfusion strategies. In this review we will summarize our current understanding of these processes and give an outlook about possible treatment options for the future. Arginase is an enzyme that catalyzes the hydrolysis of L-arginine into urea and ornithine. It is expressed in two different isoforms. Arginase I is located in the cytosol and well-known from hepatic metabolism in which arginase is responsible for the elimination of metabolites from amino acid and nucleotide metabolism. The enzyme is expressed throughout the body in endothelial cells and muscle cells . Therefore, excessive activity of either NOS or arginase reduces substrate availability for the other arginine consumer. In fact, most cells express arginase and NOS isoforms at the same time. In most cells enzymatic activity of each of these enzymes is tightly regulated by direct protein modification or by induction of enzyme expression. In case of arginase an increased activity of arginase has consequences for both pathways: a loss of NO/cGMP signaling and an improvement of polyamine metabolism. Examples for increased arginase activity and expression are found in artherosclerosis, hypertension, inflammation, aging, stroke, myocardial infarction, and heart failure to name just a few  that damages cells and this may be relevant at the onset of reperfusion. In this context it is also likely to understand that ROS stimulates arginase expression as well -α in endothelial cells further decreases the activity of NOS by activation of the transcription factor AP-1 that induces not only the expression of arginase but also that of the up-take of arginine by induction of the expression of CAT-2 transporters  mimetic and radical scavenger . At the same time, the release of polyamines acts via activating of calcium-sensing receptors and this affects the rather sensitive intracellular calcium handling in cells during reperfusion Figure .As mentioned above, arginase activation during hypoxia is not tissue specific. Like the heart, arginase activation occurs in the liver and some other tissues such as the detrusor . However, it remains unclear whether this already clarifies the role of arginase during reperfusion injury of the heart. Pharmacological activation of PKC-ε failed to improve strong end-points such as death and heart failure albeit reduction in infarct size  to inhibit arginase during reperfusion. Nor-NOHA has the advantage not to interfere with NOS. Most but not all data published to date are promising (see above) but it remains unclear whether treatment with an arginase subtype unspecific inhibitor is optimal. Consequently, the development of other arginase inhibitors underway. Congeners of (R)-2-Amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid have been shown to bind preferentially to arginase I, have antagonistic effects and are orally bioavailable (Van Zandt et al., Most studies published to date have used the arginase-specific inhibitor NArginase activation is a common event in hypoxic tissues including the heart. Recent development of reperfusion therapies has led to a situation in which high arginase activity at the onset of reperfusion participates in reperfusion-induced damage. Therefore, there seems to be a therapeutic window by which either attenuation of arginase induction of inhibition of arginase activity attenuates reperfusion damage. The optimal timing of pharmacological interference has still to be defined as well as the optimal time point. Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To assess the prevalence of musculoskeletal disorders (MSDs) as well as the impact of the occupation of waste picking on complaints of MSDs among waste pickers. The study attempts to understand the risk factors for MSDs in various areas of the body.A cross-sectional household survey was conducted using a case-control design. The survey instrument for measuring musculoskeletal symptoms was adopted from a standardised Nordic questionnaire. The impact of the occupation of waste picking on MSDs was analysed using the propensity score matching (PSM) method.The study population consisted of waste pickers (n=200) who had been working for at least a year and a control group (n=213) selected from among or living close to the same communities.The 12-month prevalence of MSDs was higher among waste pickers (79%) compared to controls (55%) particularly in the lower back (54–36%), knee (48–35%), upper back (40–21%) and shoulder (32–12%). Similar patterns were observed in the 12-month prevalence of MSDs which prevented normal activity inside and outside the home, particularly for the lower back (36–21%), shoulder (21–7%) and upper back (25–12%) for waste pickers and controls. Analysis of the impact of waste picking on complaints of MSDs suggests that the occupation of waste picking raises the risk of MSDs particularly in the shoulder, lower and upper back. Older age and longer duration of work are significant risk factors for MSDs.The findings suggest a relatively higher prevalence of MSDs among waste pickers, particularly in the lower and upper back and shoulder, compared to controls. Preventive measures and treatment to minimise the burden of MSDs among waste pickers are strongly recommended. This may be the first study on musculoskeletal disorders (MSDs) among waste pickers.Attempts have been made to assess MSDs which occur due to waste picking.Recall bias in reporting MSDs experienced over the previous year could have occurred.Subjective responses concerning MSDs may have caused bias as the severity of MSDs was not quantified, possibly resulting in underestimation or overestimation of prevalence.Although the study respondents were waste pickers collecting waste from dumps and not from the roadside or community bins, the results may be generalised with caution.Rapid urbanisation has resulted in the production of huge amounts of recyclable waste material in towns and cities. Waste pickers play a important but unrecognised role in solid waste management. They salvage recyclable items and collect rubbish  that can be sold to scrap merchants. This type of work requires no skill and is a source of income for a growing number of the urban poor. It has been estimated that up to 2% of the population in third world countries earn a living through waste picking and recycling.3There is a strong and significant relationship between the working environment and complaints of musculoskeletal disorders (MSDs). Workplace activities such as heavy lifting, manual handling, prolonged bending and repetitive tasks significantly increase the incidence of MSDs.18Many studies on waste pickers and their occupational health risks, such as respiratory illness, skin diseases, stomach problems and eye irritation, have been carried out. However, studies on MSDs among waste pickers have not been published in India. The present study focuses on the relative risk of MSDs among waste pickers compared to individuals engaged in other manual work. An attempt has been made to identify working conditions that increase the risk of MSDs among waste pickers.This study is based on a cross-sectional case–control sampling design and was carried out in one of the oldest and largest dumps in Asia, near Deonar, Mumbai. The exposed population consisted of waste pickers engaged in waste picking for at least 1 year. Workers with occupations other than waste picking for at least 1 year served as the control group and lived in or close to the waste picker areas and in similar socio-economic conditions. Many of these respondents were daily wage labourers engaged in ‘zari’ work (embroidery) and other manual occupations. A community-based organisation working for the health and well-being of waste pickers reported that 30% of households in the study area had at least one waste picker. The estimated sample size was 441 households with a p value 0.30, a response rate of 0.90 and a design effect of 1.25. So that a case–control study could be conducted, the total required sample was divided into two equal parts consisting of cases (waste pickers) and controls (non-waste pickers). A total of 200 waste pickers participated in the study (response rate of 90%) and 213 respondents from the control group were interviewed (response rate of 95%). The data were collected from March to July 2014.The study was approved by the institute research committee.Before data collection, the informed consent of the participants was obtained in the respondent's own language; the interviewer read the consent statement for illiterate respondents. The consent statement identified the researcher and the purpose of study. Respondents were informed that participation was voluntary, that they need not answer any questions they did not want to, and they could leave the study if they so wished. The confidentiality and privacy of the information provided by the respondent was assured.2 test.Our survey instrument for measuring musculoskeletal symptoms was adapted from the Standardized Nordic QuestionnairePrevious studies have reported that individuals engaged in occupations which involved pulling, pushing, carrying loads, manual handling, long hours of continuous bending and repetitive tasks are at higher risk of MSDs.Respondents who reported pain in the neck, hands, upper and lower back, thigh, knees or ankle in the past 12 months were considered to have an MSD. In addition, inability to do normal work (inside or outside the home) in the past 12 months due to an MSD was the response variable.As physical strength declines with age, younger individuals have a lower risk of MSDs than older adults engaged in physical activity.In order to examine the impact of waste picking on MSDs, the study adopted the nearest neighbourhood method of propensity score matching (PSM).The average exposure effect for the exposed (AEEE) was defined as the conditional expectation of the difference in exposure effect for exposed units only:After matching propensity scores, the outcomes of exposed and counterfactual scores of control observations were compared:1) and E (Y0). In this case, difference in MSDs between exposed (exposed to the occupation of waste picking) and control groups (non-exposed to the occupation of waste picking) could have been directly compared to show the impact of exposure on the exposed group, known as AEEE. When the impact of waste picking on MSDs, as well as MSDs that prevented normal work inside or outside the home was calculated, the average effect in both the groups was weighted by the proportion of respondents in the exposed and control groups, which measured the increase/decrease in MSDs due to waste picking as an occupation.The average exposure effect (AEE) has been defined as the expected  difference in potential outcomes across all units in the target population, which was identical to the difference in the expected potential outcomes of the control group, that is, E  on the incidence of MSDs among workers was established by applying multivariate logistic regression. Here, occupation was considered the exposure variable, the confounding factors were duration of work and age, and socio-economic and demographic characteristics were controlled for. Analysis was performed using STATA V.13.1 software.The study examined the impact of waste picking on MSDs by the estimated difference in the outcomes between the exposed workers (waste pickers) and the control group (non-waste pickers) using PSM. PSM reduces the bias found in an estimate of the exposure effect obtained by comparing outcomes among units of an exposed group versus a control group by controlling the demographic and occupational variables. Results from MSDs that prevented waste pickers from doing normal work (inside and outside the home) during the 12-month study period are shown in This study aimed to investigate the prevalence of MSDs among waste pickers compared to a control group of non-waste pickers. Bivariate analysis suggested a high prevalence of MSDs among waste pickers, particularly in the lower back (54%), knee (48%), upper back (40%) and shoulder (32%) compared to the control group . The prevalence of MSDs among waste pickers preventing normal work was higher for the lower back (36%), upper back (25%) and shoulder (21%) compared to the control group .Analysis of the impact of exposure on the waste pickers by matching with the control group using the PSM method, revealed that waste picking increased the prevalence of MSDs of the shoulder (28%), upper back (22%) and lower back (24%). A similar pattern was found for those unable to perform normal activities due to MSDs. When adjusted for demographic and occupational variables in the multivariate logistic regression model, the findings suggested that waste pickers were more likely to have MSDs compared to other occupational groups. For instance, when compared with wage labourers, waste pickers were more likely to complain of shoulder , ankle , hand  and upper and lower back  MSDs. Similarly, shoulder , lower back  and upper back  MSDs preventing normal activity were significantly higher among waste pickers compared to wage labourers. This may be because waste pickers work strenuously throughout the day collecting saleable waste. The work they do is often called ‘3-D work’, that is, dirty, dangerous and demanding.Health issues reported among solid waste workers are also applicable to waste pickers, who are far more vulnerable. Previous studies indicated a relationship between solid waste handling and increased health risk.Previous studies suggested that the prevalence of MSDs was slightly lower among workers with jobs similar to waste picking.The use of a cross-sectional survey to collect data might have underestimated the true prevalence of MSDs. Self-reported MSD results could be biased due to subjectivity in responses, as MSD severity was not quantified. Recall bias may also have affected the estimated prevalence of MSDs. Data were collected from waste pickers who collect waste from dumps and not from the roadside or community bins, and hence, generalisation of the results to similar occupations must be done with caution.Health providers can play a crucial role in reducing the incidence of MSDs through health education and by enhancing awareness of early signs of MSDs.Measures should be taken to promote physical exercise as well as the use of protective equipment to reduce work-related disorders.As waste pickers are unorganised and earn meagre amounts, the development of low cost and easy-to-use tools to minimise the occurrence of MSDs would be helpful.This study recommends both preventive measures and treatment to minimise the burden of MSDs among waste pickers.The work of waste pickers is not always appreciated or acknowledged, although they make a positive contribution to societyThe low socio-economic status, housing conditions and poor household hygiene practices of waste pickers contribute to their health vulnerabilities. In addition, many studies suggest that healthcare expenditure often leads to poverty,This study indicates there is a high prevalence of MSDs among waste pickers, which may increase inpatient and outpatient healthcare costs. It is worth exploring the treatment-seeking behaviours, coping mechanisms and the economic burden of MSDs among waste pickers.


The availability of 3D dental model scanning technology, combined with the ability to register CBCT data with digital models, has enabled the fabrication of orthognathic surgical CAD/CAM designed splints, customized brackets, and indirect bonding systems. In this study, custom lingual orthodontic appliances were virtually designed by merging 3D model images with lateral and posterior-anterior cephalograms. By exporting design information to 3D CAD software, we have produced a stereolithographic prototype and converted it into a cobalt-chrome alloy appliance as a way of combining traditional prosthetic investment and cast techniques. While the bonding procedure of the appliance could be reinforced, CAD technology simplified the fabrication process by eliminating the soldering phase. This report describes CAD/CAM fabrication of the complex anteroposterior lingual bonded retraction appliance for intrusive retraction of the maxillary anterior dentition. Furthermore, the CAD/CAM method eliminates the extra step of determining the lever arm on the lateral cephalograms and subsequent design modifications on the study model. Advances in digital imaging systems, computer-aided design, and computer-aided manufacturing (CAD/CAM) technology are providing new possibilities in orthodontics. The application of CAD/CAM for establishing a virtual setup and fabricating transfer tray/jigs –3 has grAccurate surface imaging is required to digitally manufacture orthodontic appliances. Even when CBCT scans are used for the diagnosis or design of an appliance, separate surface imaging of the dentition is required to compensate for poor surface rendering in the CBCT. Surface images of the dentition are typically obtained from a 3D optical scanner and registered with a CBCT scan. However, taking a CBCT solely for the fabrication of an orthodontic appliance is impractical considering the expense and radiation dose. Recently, 3D dental CAD/CAM solution software utilizing 2D lateral and posteroanterior (PA) cephalograms and 3D virtual dental models  has been introduced. Choi et al. evaluated the accuracy of orthognathic surgical wafers fabricated using the software and concluded that the new method using the cephalograms and surface scan can be regarded as an effective alternative for conventional 3D surface scan and CBCT methods .The lateral cephalogram is important in designing orthodontic appliances for en-masse retraction of the maxillary anterior dentition. The lever arm length of the appliance is determined by the location of the center of resistance of the maxillary anterior teeth on the lateral cephalogram. The appliance design is then drawn on the study model. However, there is room for error when transferring design information from the lateral cephalogram to the actual study model.On the contrary, the CAD/CAM method can precisely transfer the design information from the lateral cephalogram to the final design of the appliance. In order to minimize these errors, this study utilizes merged three-dimensional (3D) model images and cephalograms to virtually design custom lingual appliances. In addition to improving the design accuracy, CAD/CAM technology has simplified fabrication by also eliminating soldering process. It provides a mesh type base in the lingual pads to increase bonding strength of the appliance. Additionally, rapid-prototyping technology makes it possible to support undercuts on the lingual pad base, which are not possible with conventional fabrication methods. This study introduces a technique for CAD/CAM fabrication of lingual orthodontic appliances and assesses the final position of the cemented appliance with the planned position on the lateral cephalogram.This new custom lingual appliance is named kinematics of lingual bar on nonparalleling technique (KILBON). The torque on the maxillary anterior segment is determined by the center of resistance (Cres) and the corresponding retraction force vector. In the sagittal plane, the retraction vector is determined by the vertical position of a palatal temporary skeletal anchorage device (TSAD) and the location of the lever arm –10. WhenThe KILBON system consists of the following components: palatal TSADs, anterior lingual pads connected by archwire, and posterior segments . The antμm). The model image was registered with the lateral and frontal cephalograms using the 3Txer software, as described by Choi and colleagues  and commercial 3D CAD software . The 3D image of the study model was produced using a laser scanner . TheOn the lateral cephalogram, the center of resistance (Cres) was marked using the measurement function within the software. The placement location of the TSADs and lever arm length were determined based on the desired orientation of the retraction vector. The preliminary construction of the appliance was designed using this information . Design Before producing a stereolithographic prototype, any defects or voids were examined with reverse engineering software . A prototype of the KILBON appliance was manufactured using a rapid-prototyping machine . The actual appliance was then manufactured from this stereolithographic prototype using conventional dental casting. The lingual arch component and right and left posterior tube segments were invested using phosphate-bonded investment material and casted with cobalt-chrome alloy. After final finishing and polishing, a transfer jig was fabricated for indirect bonding of the appliance.Prior to trying in the appliance, the tooth surfaces were first etched with 37% phosphoric acid gel  for 30 seconds. In a thin film, a primer  was applied to the etched tooth surface. Then an adhesive paste  was applied, and the appliance was positioned using the transfer jig .To optimize the design with the least distortion during the fabrication process and produce the closest to en-masse anterior retraction, various lever arm designs were applied on five patients. After placing the KILBON appliance, occlusal photographs and lateral cephalograms were taken. Positional accuracy and rigidity of each design were evaluated by comparing the planned design on the 3D model to the new occlusal photograph and through superimposing the new lateral cephalogram on the initial cephalogram containing the design information .The rigidity and stability of the appliance during retraction varied depending on the lever arm design. When 0.8 mm wire was used for the lever arm , the lever arm bent slightly during en-masse retraction Figures . In caseCAD/CAM technology shows a range of promising possibilities in the fabrication of orthodontic appliances. When 3D model and CBCT scans or lateral cephalograms are combined together, the lever arm vector can be virtually designed in the software, and this design information can be saved and exported to the other 3D CAD software. Furthermore, after minor adjustments, this framework design can be used for other patients after minor adjustments. The appliance design can also be converted to fabricate customized brackets following the retraction of the anterior segment. When used with virtual articulation software, premature contacts on the appliance can be eliminated and chair time adjustment is reduced. The treatment result is easily evaluated by comparing registered pre- and posttreatment lateral cephalograms.Another advantage of the CAD design method is improved bonding of the lingual bracket base. One of the most important factors in the bonding of orthodontic brackets is the type of bracket base . The mosThe vertical height of retraction hooks controls the resulting movement of the anterior teeth, resulting in tipping, bodily movement, or lingual root movement during retraction. The double J retractor introduced two lever arm hooks for space closure . The antThe KILBON appliance was fabricated by casting a stereolithographic prototype. During casting, the fragile parts of the appliance are subject to distortion and require reinforcement. In most cases, conventional dental casting utilizes a wax pattern, and distortion of this casting can be attributed to distortion of the wax pattern. The stereolithographic prototype is much more rigid, and therefore distortion is reduced in comparison to the traditional lost wax technique. However, some distortion can be caused by hardening of the investment around the prototype, whereby setting and hygroscopic expansion could lead to uneven deformation of the walls of the prototype. This depends on the thickness and configuration of the prototype. The addition of auxiliary wire and selection of the appropriate wire diameter result in less distortion of the appliance.In this study, the KILBON appliance was applied on five patients. A greater sample size is required for a more thorough evaluation. Further studies are required to optimize the angulation of the lever arm and resulting retraction vectors of the anterior and posterior segments.the use of auxiliary wires reduced the distortion of the appliance during casting;wire diameter should be larger than 0.9 mm to withstand retraction force.CAD technology, equipped with merged image of 3D model image and cephalograms or CBCT scans, enables improved accuracy of orthodontic appliance design. Using computer-assisted design and manufacturing of the KILBON appliance, the following results were obtained:


A visual field defect (VFD) is a common consequence of stroke with a detrimental effect upon the survivors’ functional ability and quality of life. The identification of effective treatments for VFD is a key priority relating to life post-stroke. Understanding the natural evolution of scanning compensation over time may have important ramifications for the development of efficacious therapies.The study aims to unravel the natural history of visual scanning behaviour in patients with VFD. The assessment of scanning patterns in the acute to chronic stages of stroke will reveal who does and does not learn to compensate for vision loss.Eye-tracking glasses are used to delineate eye movements in a cohort of 100 stroke patients immediately after stroke, and additionally at 6 and 12 months post-stroke. The longitudinal study will assess eye movements in static (sitting) and dynamic  conditions.The primary outcome constitutes the change of lateral eye movements from the acute to chronic stages of stroke. Secondary outcomes include changes of lateral eye movements over time as a function of subgroup characteristics, such as side of VFD, stroke location, stroke severity and cognitive functioning.The longitudinal comparison of patients who do and do not learn compensatory scanning techniques may reveal important prognostic markers of natural recovery. Importantly, it may also help to determine the most effective treatment window for visual rehabilitation. Visual field defects (VFD) occur in 20 - 57% of strokes , negativThe identification of the most efficacious treatments for visual problems has been ranked among the top six research priorities concerning life post-stroke . Up to 5While the learning of compensatory scanning techniques towards the side of the VFD is seen as a promising treatment ,6,7, theWe aim to address the issue of the natural history of visual scanning behaviour in patients with VFD. Scanning patterns will be assessed in static (sitting) and dynamic  conditions with eye-tracking glasses. Understanding the natural evolution of scanning compensation over time may have important ramifications for the development of effective treatments.This is an observational, longitudinal study of a cohort of 100 stroke survivors. All patients will receive standard care. The study has been approved by the Southern Adelaide Clinical Human Research Ethics Committee.Fifty stroke patients with visual field defects and a cohort of 50 stroke patients without visual field defects will be recruited at the Flinders Comprehensive Stroke Centre.Subjects will be older than 18 years of age and have the capacity to provide full and informed consent. There is no upper age limit. All patients will have a clinical diagnosis of stroke, defined as the presence of a focal neurological defect due to vascular cause that is present at 24 hours or beyond. Brain imaging (CT or MRI) will confirm the nature of the stroke.Patients must be able to mobilise independently or with minimal assistance during the recruitment period, evidenced by a post-stroke modified Rankin Score greater than three. Moreover, patients with significant medical co-morbidities which preclude participation in the comprehensive clinical and cognitive testing will be excluded.Acute: within the first two weeks of stroke.Subacute: three to six months post-stroke. This is the first follow-up period.Chronic: 12-15 months post-stroke. This is the final follow-up period.Each patient will be assessed at three different time periods:Stroke, ophthalmic, cognitive and eye tracking assessments will be performed . PatienPatients will complete both a stationary and dynamic visual search task while their eye movements are tracked with SMI Eye Tracking Glasses . Eye movements will be separately analysed for each task.The stationary task is adapted from , and is The dynamic search task aims to assess eye movements during walking. Patients will walk a standardized mobility assessment course within the ward corridors (see ), along The primary outcome constitutes the change of lateral eye movements from the acute to chronic stages of stroke. The total time (seconds), number of fixations, number of saccades and saccade amplitudes in the contralesional field relative to the ipsilesional side of space will be used to measure lateral eye movements. We expect to find a relative increase of time spent, fixations and number of saccades in the contralesional field over time.Secondary outcomes include changes of lateral eye movements over time as a function of subgroup characteristics. We will determine whether side of VFD, stroke location, stroke severity, macular sparing, presence of spatial neglect and cognitive functioning influence changes of eye movements from the acute to chronic stages of stroke.Begaze analysis software  will be used to calculate the following quotients of lateral eye movements for each patient: (1) total time spent looking towards the blind side divided by the time looking towards the intact side of space and (2) number of fixations towards blind side divided by number of fixations in intact side. Statistical analyses will be performed using SPSS software .For continuous variables (expressed as a mean and standard deviation) the patients with VFD and patients without VFD will be compared using a mixed-design analysis of variance. In the case of imbalanced group characteristics  we will include them as co-variants in the analysis. An alpha of 0.05 will be considered significant.The study is powered with respect to the primary outcome. Based on previous research , we expeStroke survivors, caregivers and health professionals consider the identification of effective treatments for visual loss as one of the six top priorities relating to life post- stroke . The res


Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS) that has an important neurodegenerative component. The pathological hallmark of MS is the presence of demyelinating lesions  integrity and migration of autoreactive T-cells and monocytes  and secondary progressive (SP) MS. RR-MS represents the initial inflammatory phase of approximately 85–90% of all cases. SP-MS usually develops later in the disease course and is associated with axon degeneration  progression by reducing the frequency of relapses , cells that retain their multipotential capacity in the adult and senescent brain  in rodents and non-human primates  and fibroblast growth factor-2 (FGF-2) (Franklin and ffrench-Constant, in vivo or in vitro models for MS and in human MS brain tissue (Williams et al., Animal studies showed that inflammation and demyelination promote migration of OPCs to the lesions (Nait-Oumesmar et al., Demyelination influences the capacity of OPCs to differentiate by forming a “dysregulated” signaling environment. In chronic MS lesions, OPCs often acquire an immature phenotype which is not permissive for axon remyelination (Wolswijk, In the brain of MS patients, mature oligodendrocytes may undergo demyelination thereby losing capacity to myelinate (Wolswijk, Since sufficient levels of remyelination can repair damaged axons, stimulation of endogenous activity might be beneficial for repair of MS lesions. Besides activation of parenchymal OPCs, generation of new oligodendrocytes for the increase of brain remyelination activity appears a promising perspective for future therapies. This can be achieved with engraftment of transplanted cells or with stimulation of SVZ-derived NSCs by transplanted cells or growth factors to induce differentiation into OPCs.Transplanted stem cells can boost remyelination by cell replacement or bystander neuroprotection and/or immunomodulation (Pluchino and Martino, The new thrust in the treatment of MS is grounded on the discovery that NSCs persist within the adult healthy brain. The human SVZ is located at the lateral wall of the lateral ventricles, thereby providing an accessible route for the intracerebroventricular delivery of growth factors to activate NSC proliferation/differentiation. Newborn cells may theoretically replace the old damaged ones and promote repair in areas with poor regeneration. Intracerebroventricular application of growth factors have revealed multiple beneficial effects in EAE (Tafreshi, The regeneration of MS lesions with new oligodendrocytes depends on the stage and location of the lesion. Although the role of inflammation in remyelination has not yet been clarified, our speculation is that repair of small newly-formed lesions might be advantageous over the repair of chronic lesions, in terms of reparative efficiency and energy consumption. Periventricular lesions are often present in MS and analyses of such lesions showed enhanced number of pro-migratory adhesion molecule PSA-NCAM+ progenitors expressing Sox9, Sox10, and/or Olig2 markers of glial fate. Concomitant enhancement of the PSA-NCAM+ progenitor population at the proximal SVZ suggested increased oligodendrogenesis (Nait-Oumesmar et al., in vivo and in vitro experiments revealed various factors which act on OPCs derived by the adult SVZ, and influence proliferation, migration or differentiation properties (Table Interventions to modulate growth factor signaling for promoting oligodendrocyte replacement and remyelination are nowadays the focus of intense study. Both es Table . An advaes Table . In a pies Table . Since ses Table .The confirmed existence of OPCs in the adult brain as well as the increasing understanding of the pathways regulating endogenous remyelination, are the basic reasons why regeneration of oligodendrocytes is a more well investigated approach compared to regeneration of neurons. Replacement of damaged neurons however, is anticipated to offer intriguing possibilities for the rehabilitation of cognitive disturbances in patients with progressive MS. New neurons may repopulate focal sites of degeneration located near the SVZ, such as the OB or the cingulate gyrus, to induce repair, contributing to the re-growth of nerves that have been lost Figure .Challenges associated with that strategy are linked to the type, density and ability of new neurons to integrate into defined circuits. Acquisition of specific neuronal subtypes is a demanding step for neuronal regeneration of MS lesions since recent evidence indicated heterogeneity and reduced neuropotency in the population of adult SVZ-derived NSCs (Shen et al., Stimulation of endogenous NSCs with growth factors is an interesting approach for treatment of MS and requires more research in order to reveal its entire therapeutic potential. An important question that needs to be addressed is if this approach can repair all or subtypes of MS lesions depending on whether the damage is focal or diffuse. Notably, MS is a complex disease showing activity even in late progressive phases. Therefore, even if regeneration with NSCs proves efficient to revert damage in the CNS of MS patients that today is considered to be irreversible, a combination with disease modifying agents might be needed to halt MS progression.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.