Allosaurus and Australovenator, and a mid-caudal vertebral centrum bearing pneumatic foraminae and extensive camellae that is referrable to Megaraptora and represents the first axial skeletal element of a megaraptorid described from Lightning Ridge.The limited fossil record of Australian Cretaceous theropods is dominated by megaraptorids, reported from associated and isolated material from the Early Cretaceous of Victoria and the ‘Mid’-Cretaceous of central-north New South Wales and central Queensland. Here, we report on new postcranial theropod material from the early Late Cretaceous Griman Creek Formation at Lightning Ridge. Among this new material is an associated set consisting of two anterior caudal vertebrae and a pubic peduncle of the ilium, to which a morphologically similar partial vertebral centra from a separate locality is tentatively referred. These elements display a combination of characteristics that are present in megaraptorid and carcharodontosaurid theropods, including camellate internal organization of the vertebral centra, ventrally keeled anterior caudal centra and a pubic peduncle of the ilium with a ventral surface approximately twice as long anteroposteriorly as mediolaterally wide. Unfortunately, a lack of unambiguous synapomorphies precludes accurate taxonomic placement; however, avetheropodan affinities are inferred. This new material represents the second instance of a medium-sized theropod from this interval, and only the third known example of associated preservation in an Australian theropod. Additional isolated theropod material is also described, including an avetheropodan femoral head that shows similarities to  LRF 3310–3312 were recovered from a one-metre diameter drill shaft in the eastern section of Smiths Field on the Coocoran opal field, approximately 20 km west of Lightning Ridge . Their cb). The posterior articular surface of the centrum is well preserved but is missing a portion of the left rim (figure 2a). The left lateral surface of the centrum has been crushed (figure 2d), resulting in a rightward displacement of the anterior end of the centrum in ventral view (figure 2e). Diagenetic veins of silica have formed in and around the crushed area on the left side of the centrum; this mineralization can also be seen on the neural spine and postzygapophysis (figures 2d and figure 2c).LRF 3310 represents an almost complete centrum, the posterior part of the neural arch, and the base of the right transverse process . The antfigure 2b); no internal structures can be discerned along the plane of the break.LRF 3311 represents the ventral portion of a centrum and a dorsal fragment of the posterior articular surface . The antfigure 4a,b). The ventral surface, where it would have contacted the proximal pubis, is heavily eroded and densely covered in matrix. On the concave posteroventral surface, two subcircular depressions are present (d) that are inferred to be possible bioerosional features, and as such do not represent an original feature of the bone. Only the ventrolateral portion of the acetabular margin is preserved.LRF 3312 is interpreted as representing the ventral end of the pubic peduncle of a right ilium. The broken and exposed dorsal surface is mediolaterally thin, and the interior of the bone appears to have been preserved as a solid mass of opal, obscuring any detail of the original bone texture. The lateral surface is well preserved whereas only the dorsalmost portion of the medial surface of the peduncle is visible through the adherent matrix a,b. The  present d that arAM F106525 is an isolated articular end of a centrum ; only a a,e). The rim of the posterior articular surface is thickened, the dorsal margin of which is depressed in posterior view, forming a trough level with the floor of the neural canal. There is no indication of a chevron facet on the posteroventral part of the centrum . The anterior articular surface is a dorsoventrally elongate ellipse in anterior view. The dimensions of the anterior articular surface are markedly less than those of the posterior articular surface. In lateral view, the ventralmost extent of the anterior articular surface is dorsally offset relative to that of the posterior articular surface . The lateral surfaces of the centrum are smooth, concave anteroposteriorly and convex dorsoventrally, meeting ventrally to form a gently curved surface with no sign of either a ventral keel or midline groove. No pneumatic foramina are visible on the preserved lateral surfaces of the centrum. On the right lateral surface, a slight depression is present at the point of contact between the centrum and the neural arch, associated with traces of the closed neurocentral suture (figure 2b). An oblique fracture at the anterodorsal surface of the centrum reveals polygonal regions bounded by thin septa that represent the camellate internal structure of the centrum (figure 2d).As preserved, the centrum of LRF 3310 is markedly shorter anteroposteriorly than the dorsoventral height of the posterior articular surface . The posfigure 2b,c). The articular surface of the postzygapophysis faces mostly ventrally with a slight posteromedial inclination; it is subrectangular and slightly longer anteroposteriorly than wide mediolaterally. A hyposphene is present immediately ventromedially to the postzygapophysis. The base of the neural spine is positioned towards the posterior end of the centrum and is laterally compressed.The base of the transverse process of LRF 3310 is dorsoventrally compressed and extends laterally and horizontally from the neural arch. A weakly developed posterior centrodiapophyseal lamina is present on the posteroventral surface of the transverse process. A robust postzygadiapophyseal lamina extends between the transverse process and postzygapophysis but is partially broken. The postzygapophysis is robust and extends beyond the posterior articular surface of the centrum b,c. The A depression is present at the base of the neural spine of LRF 3310 on the right side, anterior to the postzygapophysis; this surface is not preserved on the left side. This is interpreted here as representing a postzygapophyseal spinodiapophyseal fossa posdf; . The dora). Immediately anterior to this rim and on the ventral surface of the centrum is a transverse groove which probably represents an articular facet for the chevron . While the anterior articular surface is missing, comparisons with LRF 3310 indicates that the anterior articular surface is likely to have been smaller than the posterior articular surface. In ventral view, the centrum is strongly constricted; the width of the centrum at its narrowest point is approximately one-third of the mediolateral width of the posterior articular surface (figure 4e and figure 4e). The ventral margin of the centrum is concave in lateral view . Anteriorly, the ventralmost preserved point of the centrum extends ventral to the ventralmost point of the posterior articular surface, indicating that the missing anterior articular surface was ventrally offset relative to the posterior articular surface. Dorsally, the ventral outline of the neural canal is visible.The posterior articular surface of LRF 3311 is subcircular and slightly concave with a well-developed rim a. Immedi chevron c,d. Whila,b). The anterior margin is oriented approximately 60° relative to the ventral margin. The posterior (acetabular) margin is subvertical and mediolaterally convex ventrally (in posterior view); however, due to erosion, the shape of the rest of the acetabular margin cannot be determined. In lateral view, the ventral margin forms a sinuous contour, the anterior two-thirds being convex whereas the posterior third is concave. In ventral view, the articular surface forms an isosceles triangle; its mediolaterally widest point forming the posterior end and tapering to its narrowest point anteriorly. The ventral surface is approximately twice as long anteroposteriorly as it is mediolaterally wide. The medial and lateral faces are weakly concave dorsoventrally and divergent towards the ventral surface. The anterior third of the lateral surface is ornamented by a series of parallel striae that extend parallel to the anterior margin of the peduncle in lateral view and are roughly equally spaced, approximately 1.5 mm apart. The striae are most densely packed ventrally (a). There is no evidence of pneumaticity either in the form of internal cavities on the broken dorsal surface or foramina on the medial or lateral surfaces.The pubic peduncle of the right ilium (LRF 3312) is roughly trapezoidal in lateral view a,b. The entrally a. There a). The articular surface is slightly concave mediolaterally and dorsoventrally. A small subcircular convexity is present in the centre of the articular surface, similar to that seen on LRF 3310; this feature occupies approximately 27% of the mediolateral width of the articular surface (figures 2a and figure 6c) and is slightly concave dorsoventrally. The broken lateral edges of the centrum indicate that the centrum became progressively wider dorsally . Ventrally, the surface of the centrum is flattened with no indication of a midline groove or keel .The articular surface of the centrum is subcircular; its dorsoventral height was probably close to that of the mediolateral width when complete, and therefore similar in shape to the articular surfaces of LRF 3310 and LRF 3311 a. The arb,g)—that extend inside the centrum towards the articular surface. As preserved, the more medial of these cavities extends further into the centrum than the lateral cavity; the septa of the former cavity converge to form an acute angle both immediately behind the articular surface and on the ventral floor of the cavity . Another partially preserved septa extends across the dorsal and ventral portions and overlies the cavity, and probably forms the interior boundaries of this cavity (g); thus, the cavities appear to be dorsoventrally elongate but anteroposteriorly narrow. The cavities are delimited mediolaterally by septa, approximately 1–2 mm thick, that radiate dorsolaterally from the ventromedial margin of the centrum, such that the cavities become broader towards the dorsal surface of the centrum. These cavities are interpreted to form part of a system of internal camerae that extend along the length of the centrum.The broken surface of the centrum exposes internal cavities—two of which can be readily distinguished b,g—that e cavity b,f. Anots cavity g; thus, Avetheropoda indet.5.2.Proximal end of a right femur, including the femoral head (caput) and most of the greater trochanter. The exact location at which this specimen was collected is presently unknown.The femur below the distal extent of the metaphysis has been lost. The preservation of the femoral head as a pseudomorph has resulted in the loss of some of the osteological correlates for muscular and cartilaginous attachments typically observed in well-preserved theropod femora.a–c). As the portion of the femur distal to the femoral head is missing, it is not possible to determine the inclination of the head in either the anterior–posterior or dorsoventral planes. However, based on a comparison with the femoral head of Allosaurus [b), at which point the proximal surface curves down onto the posterior surface (d). The proximal surface of the femoral head, extending laterally towards the greater trochanter, is straight in anterior–posterior views, and the surface texture appears to be smooth, with no noticeable rugosities or indication of a cartilage cone trough (b). A deep groove is present on the posterior surface of the femoral head extending ventrolaterally immediately lateral to the articular surface (d); this denotes the passage of the ligamentum capitis femoris. The fovea capitis is present at the dorsal margin of the groove for the ligamentum capitis femoris and is convex as in most theropods in which it is preserved [b–d). The two grooves diverge at an angle of approximately 50°. Anteriorly, the metaphyseal collar extends from the femoral growth plate to the distalmost preserved extent of the femur proximally. The metaphyseal collar is ornamented by striae  that extend roughly perpendicular to the capital-trochanteric axis (a) and represent the extent of the fibrocartilage sleeve on the metaphysis.The femoral head forms an elliptical hemisphere, proximodistally taller than it is anteroposteriorly wide a–c. As tlosaurus  it is mo surface d. The pre trough b. A deep surface d; this dreserved . Howeverric axis a and repMegaraptora ,49Megaraptora indet.5.3.AM F112816 is a mid-caudal vertebral centrum and was recovered from Vertical Bill's near Three Mile, approximately 5 km south-southwest of Lightning Ridge .The articular ends and the bases of the exposed neural arch pedicels have been eroded, the anterior more strongly than the posterior; the neural arch is missing.b,e). The articular surfaces are flat to slightly concave. In the lateral view, the ventral surface of the centrum is slightly concave and the anterior articular surface is slightly elevated dorsally with respect to the posterior surface ; however, this is probably a result of erosional loss of the ventral rim of the articular surface. The posteroventral surface of the centrum is bevelled to form a chevron articular facet, indicating that it comes from the caudal series. The lateral surfaces of the centrum are slightly concave anteroposteriorly and convex dorsoventrally, the lateral surfaces of the centrum converging ventrally to form a well-defined keel (f). Erosion of the articular and dorsolateral surfaces of the centrum exposes large areas of well-defined polygonal cavities delimited by thin septa within the centrum, representative of camellate pneumaticity. The right surface of the centrum is pierced by two anterior and posterior pneumatic foramen (a). The posterior foramina is subdivided by a thin anterodorsally oriented lamina. There are no pneumatic foramina visible on the left side of the centrum.Both articular surfaces of AM F112816 are subtriangular, reaching their widest point dorsally and tapering to a blunt point ventrally b,e. The  surface a,d; howened keel f. Erosio foramen a. The po6.Muttaburrasaurus langdoni from the Albian Mackunda Formation [Wintonotitan wattsi [Savannasaurus elliottorum [Muttaburrasaurus differ from LRF 3310 and LRF 3311  in the considerably less well-developed mediolateral compression of the centra at mid-length, and the presence of paired ventrolateral ridges on the centrum that extend between the anterior articular facet and the posterior chevron facet, delimiting a well-defined midline groove [Wintonotitan have anterior and posterior articular surfaces that are dorsoventrally compressed, a feature common to most neosauropods [Wintonotitan has anterior caudal vertebrae with a solid internal texture and that lack a hyposphene–hypantrum system [Savannasaurus have pneumatic fossae [Muttaburrasaurus [Diamantinasaurus [LRF 3310–3312 is identified as a theropod primarily due to the presence of hyposphene–hypantrum articulations in the anterior caudal vertebrae, dorsoventrally compressed transverse processes elevated above the dorsal margin of the vertebral centra, weakly developed vertebral laminae and fossae, and camellate internal composition of the vertebral centra. The only Australian non-theropod dinosaurs with preserved axial and pelvic elements of comparable size to LRF 3310–3312 are the basal ornithopod ormation  and the n wattsi ,59 and Siottorum  from thee groove . The antc fossae , a featurasaurus , and is nasaurus .A position within the caudal series of the vertebral column for LRF 3310 is inferred based on the weak development of laminae and fossae, contrasting with the cervical and dorsal vertebrae of theropods and sauropomomorphs where these features are better developed  and the Neovenator and the megaraptorids Aerosteon and Orkoraptor (F. E. Novas. pers comm.) and was hypothesized to represent a synapomorphy of Neovenatoridae [The rounded ventral surface of LRF 3310 contrasts with the keeled ventral surface of LRF 3311. In some theropods, the anteriormost caudals have a flattened or gently curved ventral surface that differs from the condition in more posterior caudals in which a ventral groove or keel may be present ,67. A siatoridae ; howeveratoridae ,68,69. Tatoridae ,67,70,71atoridae .Ichthyovenator [Torvosaurus gurneyi [Ichthyovenator and T. gurneyi are more distinctly domed in comparison to the features on LRF 3310 and AM F106525. The variable development (in terms of their relative size and shape) of convex features on centrum articular surfaces advocates for their independent development in each taxon; therefore, this feature is likely to be of little diagnostic utility. As this feature is uncommon within theropods, its presence in both LRF 3310 and AM F106525 is tentatively interpreted as an indication of close affinities between the two specimens.The small circular central convexity on the posterior articular surfaces of LRF 3310 and AM F106525 appear to represent a genuine feature and not a taphonomic artefact. In both centra, the convexity occupies a similar proportion of the mediolateral width of the articular surface . Within theropods, similar convex features have been described in megalosauroid tetanurans: the posterior surface of the 12th dorsal vertebra of the Early Cretaceous Asian spinosaurid ovenator ; and the gurneyi . In bothAnterior caudal neural spines that are mediolaterally narrow and anteroposteriorly short, restricted to the posterior part of the neural arch and extend to or partially overhang the posterior articular surface, are present in many tetanuran theropods, including megalosauroids ,74, alloAccessory hyposphene–hypantrum articulations are present in the anterior caudal series of many theropods, particularly basal tetanurans ,80,82,83In LRF 3310, the preserved base of the transverse process projects essentially horizontally from the neural arch, a characteristic of most theropods with the exception of abelisaurids and some basal tetanurans in which the transverse processes of caudal vertebrae typically are inclined from the horizontal by at least 20°, and sometimes as much as 40° or more . The traNeovenator [An internal structure of the vertebrae consisting of a large number of irregularly shaped chambers delimited by thin septa is termed camellate  and is povenator  and coelovenator . Howeverovenator ,89. In tovenator , or seriovenator . The intovenator ,91, thusTorvosaurus tanneri [Carcharodontosaurus [Aoniraptor lack pneumatic foramina on one or both sides [Majungasaurus [Acrocanthosaurus was considered to be pneumatic [Acrocanthosaurus [Alioramus altai, Monolophosaurus and Garudimimus [Alioramus altai may imply ontogenetic or individual variation, consistent with apneumatic functions such as the sites of axial musculature attachments or fat deposits [Within the axial skeleton, unambiguous pneumaticity in the caudal series, in which pneumatic foramina communicate with internal chambers of the centra, is observed in megaraptorans ,62, the  tanneri , the cartosaurus  and sometosaurus –95 and mtosaurus ; howeverth sides . In LRF gasaurus ,97. A foneumatic ; howeverhosaurus . Variabludimimus ,98–100. deposits ,97.Aerosteon [Allosaurus, megaraptorans  and basal coelurosaurs . In LRFLRF 3312 .On the basis of the characters discussed above, LRF 3310–3312 presents a combination of characters that indicate a probable phylogenetic position within Avetheropoda: camellae in the caudal centra, a ventral keel on the anterior caudal centra and a pubic peduncle approximately twice as long anteroposteriorly as mediolaterally wide. Unfortunately, the absence of any synapomorphies in LRF 3310–3312 precludes referral to a particular avetheropodan clade. LRF 3310 and AM F106525 both have in common a central convexity on the articular surface of the centrum, an uncommon feature among theropods. The shared presence of this unusual characteristic in both vertebrae, together with their relative proximity to each other suggests that they may pertain to the same taxon, or similar taxa, of avetheropodan theropod. The differences in the internal composition of LRF 3310 and AM F106525 would not preclude the possibility of a close relationship as variation in vertebral pneumatic features within and between vertebrae has been documented for a megaraptorid .Australovenator shows evidence of pneumaticity [Australovenator unfortunately limits the extent to which any additional direct comparisons between the three taxa can be made. However, LRF 3310–3312 appears to lack the development of both pelvic and caudal pneumaticity present in almost all megaraptorids in which these elements are preserved.Among Australian megaraptorids, the pubic peduncle of LRF 100–106 bears a pneumatic internal composition; the fragment of the main body of the ilium in maticity , but it Ceratosaurus), allosauroids , tyrannosaurids  and ornithomimids [Ceratosaurus [Masiakasaurus [Cryolophosaurus [Eustreptospondylus [Australovenator [Australovenator differs in lacking transphyseal striations on the anterior surface and having a stronger reduction in anteroposterior width from the capital to trochanteric end. In summary, the combination of characters presented by AM F105662 is indicative of avetheropodan affinities, and is morphologically very similar to the femoral heads of Allosaurus fragilis and Australovenator.AM F105662 can be interpreted as pertaining to a theropod based on the presence of the deep groove for the ligamentum capitis femoris, which first appeared at the common ancestor of Neotheropoda . Within homimids . A cartitosaurus , Masiakakasaurus , Cryolophosaurus  and Eustpondylus , but is pondylus ,75,105, pondylus . In AM Fovenator ,12; howeAM F112816 most probably pertains to a megaraptoran, primarily on the basis of pneumaticity within a mid-caudal centra. The only other theropod clade in which pneumatic mid-caudal vertebrae have been reported, Oviraptorosauria, is unlikely to be a candidate for the affinities of this centrum as the group is likely to have been entirely absent from Gondwana. Restudy of previous material referred to Oviraptorosauria from South America ,108 has To date, a majority of the material of Australian apex theropod predators has been referred to Megaraptora ,5,18,49.7.Allosaurus and Australovenator. AM F112816 is identified as a megaraptorid mid-caudal vertebra due to the presence of pneumatic foramina and camellate internal structure, and is the first reported axial skeletal element of such a theropod recognized from Lightning Ridge.New associated and isolated material from the Upper Cretaceous Griman Creek Formation of Lightning Ridge contributes to the scant fossil record of Australian theropods and underscores the predominance of basal avetheropodan-grade theropods during this interval. LRF 3310–3312, tentatively grouped together with AM 106525, represents axial and pelvic material of an indeterminate medium-sized theropod of indeterminate avetheropodan affinities, and is only the third Australian theropod recognized from associated material. Similarly, AM F105662 is interpreted as the femoral head of an avetheropodan theropod, and shows particular similarities with the femora of


Multiple myeloma (MM) is a hematological malignancy characterized by a high tendency to relapse and to become drug resistant. In the past, melphalan was considered the standard of the treatment for MM patients . FollowiImmunotherapy is part of a concept that goes back to the beginning of 1900. The “magic bullet” opened the way to the objective of having a tool able to selectively eliminate target cells and at the same to modulate the immune response in a beneficial way. It was necessary to wait for several decades and apparently for unrelated findings coming from different fields before having a picture able to frame the view outside a simple anecdotal hope. The objective was initially made possible by combining results from basic science and the availability of mAbs, a reagent made of a homogeneous population of immunoglobulins (Ig), the main difference from the conventional antisera. mAb is hence able to recognize only a single epitope on the molecular target.The second key event derived from the identification of a vast number of soluble factors, which share the feature of transmitting signals in the context of similar or different cells (the interleukins). Using this new tools, Reinherz et al. generated a panel of mAbs specific for surface molecules located on the surface of human T lymphocytes . At the The definition of immune check points molecules lead to the preparation of panels of mAbs able to induce or brake immune responses, according to distinct medical needs. The concept of immune modulation was further completed by the identification of activator effector T and B cells, while other cell subsets produce effects going in opposite directions . The considerations derived from the dissection of the main steps of immune cell defense were indirectly confirmed by studies conducted on the different strategies of immune escape of tumors. Indeed, it emerged that some tumors adopt escape or camouflage strategies, which implement genetic programs driving to metabolic reshaping, secretion of immunomodulatory cytokines, or generation of tolerogenic substances, among the others.At the moment, available to the medical community there is a panel of therapeutic antibodies, which significantly modified the fate of some diseases, especially neoplasies of hematological origin. There is a general agreement that the therapeutic effects are prevalently obtained by means of antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), and concurrently by the induction of signals on cell effectors . These eMorandi et al.). SLAMF7 is a surface glycoprotein receptor expressed on plasma cells (PCs) and on natural killer (NK) cells that is implicated in adhesion to stromal cells and in the activation of NK cell effector function  approved daratumumab (DARA) and elotuzumab (Elo), two monoclonal IgG-k mAbs, specific for CD38 and SLAMF7 , respectively. The approval was for the treatment of relapsed or refractory MM (RRMM) patients, in combination with lenalidomide and dexamethasone . Interestingly, the expression of immunecheckpoint molecules by osteoclast has been recently underlined. However, single-agent studies on PD-1/PD-L1 inhibitors have not demonstrated significant responses in MM patients. On the other hand, other studies have demonstrated the ability of lenalidomide to enhance anti-MM immune activity mediated by PD-1/PD-L1 inhibition despite high grade of toxicity .Both DARA and Elo share the feature to recruit the immune system to enhance cellular cytotoxicity directed against myeloma cells . HoweverThe use of mAbs in therapy now led to the observation of antibody resistance, which may appear at different times. Different approaches were designed in order to answer this issue, which is of critical relevance in clinics. Hypothesis or observations explaining the effects may be referred to down modulation of the target molecule by the neoplastic cells. An alternative is represented by a re-distribution of the target molecule on selected surface domains . Polar aggregation tends to coalescence the CD38 molecule with ectoenzymes involved in the production of adenosine along with inhibitory complement receptors  and PD-L1. The availability now of a second antibody with the same the same specificity but recognizing a different epitope may be proposed when the resistance to the first one is observed. This strategy is expected to bypass the resistance mechanisms and to exert new mechanisms of therapeutic action.The design of innovative strategies in MM therapy is a difficult challenge, since the disease has been adopted as a model where different immunotherapeutic approaches are under evaluation. For these reasons, we would like to focus to some aspects, sometime not considered to design the future of the immunotherapy in MM. Most details and complete authoritative reviews may be found in the manuscripts of this Special Issue.New target markers for mAb therapy. The efforts to identify specific markers exclusively identifying human myeloma cell surface has been quite disappointing. So far, a criteria adopted is quantitative  or based on clear receptorial features . B cell maturation antigen (BCMA) was recently adopted in virtue of a quite restricted expression, along with APRIL, one of its ligand. All the potential targets for antibody-mediated therapy are summarized in a recent and complete reviews  or NK cells are expanding exponentially and analyzed   were likely attributable to negative effects mediated by their interactions with FcRs  cell engagers (targeting NKp46 and CD16 on NK cells) and a tumor antigen on cancer cells have been developed. This approach produced antigens .FcR engagement and effects induced by target ligation. No systematic analysis of this step was conducted on anti-CD38 therapy to date. It is reasonable to expect that the differences in structure between DARA and Isa  may be reflected on the interactions with the IgG FcRs. Results obtained in vitro giving DARA-armed FcR+ cells instead of soluble mAb is followed by a distinct membrane dynamics. Critical here are the effects induced by antibody ligation on the tumor target molecule. It is reported that this event may be followed by internalization of the target/antibody complex or externalization, followed by a release in the biological fluids in the form of microvesicles.Combination therapies. Part of actual therapeutic potential of the different type of antibody approach may be improved by using immune modulators or combination with other mAbs (with similar or different specificities) or recombinant constructs. A limit on the use of reagents targeting one or two different molecules (surface targets or modulators of the immune response) comes from the recent evidence that the MM is characterized by a marked spatial genomic heterogeneity, with an early phase with clonal sweeps followed by a regional evolution in advanced stages of the disease ( disease .NG and FM equally contributed to write the manuscript and made a substantial, direct and intellectual contribution to the work, and approved it for publication.NG received research funding and honoraria from Amgen, Bristol Mayers Squibb, Celgene, Millenium Pharmaceutical, and Janssen Pharmaceutical. FM has received honoraria for lectures and participation on the advisory boards of Janssen, Tusk Therapeutics, Takeda, and Sanofi, along with research agreements from Janssen and Tusk Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.


The ability to tune the composition of nanostructured thin films is a hot topic for the design of functional coatings with advanced properties for sensing applications. The control of the structure at the nanoscale level enables an improvement of intrinsic properties  in comparison with the traditional bulk materials. In this sense, among all the known nanofabrication techniques, the layer-by-layer (LbL) nano-assembly method is a flexible, easily-scalable and versatile approach which makes possible precise control of the coating thickness, composition and structure. The development of sensitive nanocoatings has shown an exceptional growth in optical fiber sensing applications due to their self-assembling ability with oppositely charged components in order to obtain a multilayer structure. This nanoassembly technique is a powerful tool for the incorporation of a wide variety of species  in the resultant multilayer structure for the design of high-performance optical fiber sensors. In this work we present a review of applications related to optical fiber sensors based on advanced LbL coatings in two related research areas of great interest for the scientific community, namely chemical sensing  as well as biological/biochemical sensing . Although the first experiments demonstrating the guiding of light by refraction took place in the XIXth century, the very first optical fibers were reported in the decade of the 1960s , temperaThe irruption of nanotechnology in the decade of the 1990s was, without any doubt, a remarkable milestone in the history of optical fiber sensor research. The appearance of new materials and fabrication techniques that controlled the structure of the matter at the nanoscale level made possible the discovery of new materials with unique properties ,13. In tIn this sense, in order to create new sensitive coatings for optical fiber sensor applications, the layer-by-layer (LbL) technique allows the design and fabrication of ultra-thin films of an enormous variety that can embed nanostructured materials. LbL can create nanofilms starting from a huge variety of materials such as polyelectrolytes, nanoclays, metallic or ceramic nanoparticles, carbon nanotubes, semiconductor quantum dots, chromophores, fluorophores, etc. This gives the opportunity of creating completely new composite nano-assemblies with adjustable properties that make possible the creation of an enormous variety of sensitive coatings. It has been also demonstrated that the LbL nanocoating properties can be adjusted, just by controlling the experimental conditions such as temperature, concentration, ionic strength, bifunctional molecules etc. Such parameters have a dramatic impact on the characteristics of the resultant LbL nano-assemblies (for example thickness and roughness), which are a critical aspect for the sensitivity and response times of the final sensor devices. Further details of the LbL technique and its applications will be commented in the following sections, and can be also be found in .This ability to build highly controllable thin films with customizable composition, regardless of the size or shape of the substrate and using water as the main solvent of the process makes this technique especially attractive for the research of new optical fiber sensors. Given the importance of this topic, in this manuscript an up-to-date review of the main contributions that involve LbL optical fiber sensors is presented. This work has been structured in three different parts; a first one in which the main optical fiber sensor configurations are briefly described, and the two following sections that contain a comparative review on the most relevant works in LbL optical fiber chemical sensors, and optical fiber biological sensors, respectively.In this section a brief description of the main optical fiber sensor (OFS) schemes used with LbL can be found. This will help readers to understand the approaches discussed in Several optical fiber sensor configurations can be made attending to different aspects such as the position of the light source and the detector (transmission vs. reflection), or the nature of the sensing mechanism such as evanescent field, gratings, interferometers, just to mention a few. The information shown in this section is not an exhaustive classification attending to all possible attributes, rather than a brief summary that will be helpful in the following sections devoted to the different LbL optical fiber applications. These configurations are schematically shown in The first type is the intensity-based optical fiber sensors. This kind of structure uses for example a coating that modifies the evanescent field losses of the fiber and most of the times uses U-bent fibers, tapered fibers, or cladding removed optical fibers in order to increase the magnitude of the evanescent field losses. These approaches are also used in fluorescence-based optical fiber sensors, in order to collect the light emitted from the fluorophore  embedded into the LbL coating. In both approaches, the sensor information is coded in the intensity of the light signal.Similar structures, most of the times in their transmission arrangements, are used to create sensors based on optical resonances, such as Surface Plasmon Resonances (SPR), Localized Surface Plasmon Resonance in nanoparticles (LSPR) and Lossy-Mode Resonances (LMR). Those structures have the advantage of their wavelength-based nature, which is more robust than the intensity-based optical fiber sensors . The sensing signal here is coded into the wavelength-shift of the resonance bands, although some intensity-based approaches can be also found.Other approaches use the separation of light into several optical paths, creating an interference pattern when the different paths interact. In reflection arrangements it is very common to find the Fabry-Perot (FP) one, but it is also possible to find an in-line version of the FP interferometer using a short segment of multimode fiber (cavity) inserted between two single mode fibers (SMS structure). A different interferometer can be also found with a Mach–Zehnder (MZ) configuration where the injected light is forced to be guided through the cladding of a short segment of fiber and then refocused into the core again. The change in the optical paths for example due to an external effective index variation through the cavity modify the interference patterns, which give wavelength-dependent signals. Finally it is possible to create sensors with optical fiber gratings. The first Fiber Bragg Grating (FBG) was demonstrated by Hill in 1978 2+ which emits phosphorescence at the wavelength of around 620 nm by means of irradiating blue light at the wavelength of around 450 nm. An interesting work by using this specific luminescent material can be found in n for the detection of three different VOCs  is presented. The experimental results indicate that linear approximations were calculated for each type of alcohol, showing a specific sensitivity of 0.417 nm·ppm−1 (ethanol), 0.520 nm·ppm−1 (methanol) and 0.263 nm·ppm−1 (isopropanol), respectively, with a low hysteresis. Another different organometallic compound with the following chemical structure [Au2Ag2(C6F5)4(NH3)2]n has been used in arene (CA[4]). The presence of CA[4] receptor into the LbL films allows sensitive measurements of VOCs with high reversibility and rapid response times. The sensing mechanism is based on the measurement of the refractive index change induced by the complexation of the VOCs with the CA[4] receptor. This same sensing mechanism has been used in [2 films. As it can be observed in Another interesting work for detection of specific volatile organic compounds (VOCs) such as chloroform and benzene vapors can be found in . In this used in , althougIn order to have a better understanding of the different optical fiber sensors for gas and VOCs detection analyzed in this section, a summary of the different sensitive coatings employed as well as the optical structure and the sensing mechanism for the specific parameter detection can be clearly appreciated in One of the most essential biological materials is deoxyribonucleic acid (DNA) because it controls the heredity of life and the detection of its base sequence is of great importance in many different fields such as criminology, genetics, food safety or pathology, among others ,134. A nOther novel works are based on the development of optical fiber biosensors for the detection of immunoglobulins ,143,144.In  an optic−11 to 10−4 M for variable sizes of the resultant metallic nanoparticles  [A novel fiber-optic IgG biosensor based on the modulation of a LMR by the reaction between an IgG and its corresponding anti-IgG is proposed in , being tctively) .2@AuNPs) can be found in [2@AuNPs  with a detection limit of 15 pg/mm2. In this work [2) and a detection limit of 0.86 pg/mm2, being this limit of detection 22 times lower than the one reported in [2) by using the same optical configuration (LPG), although with a different the functionalization chemical route of the LPG with silica core gold shell nanoparticles. Other LPG configuration for streptavidin detection can be found in [In addition, the transmission spectrum of the LPG sensor at different concentrations of IgM can be appreciated in his work  the sameorted in  (a limitfound in  where a Other work based on LSPR biosensor for streptavidin detection is presented in  where thIn  a novel Other well-known specific biomolecular recognition is produced between concavidin A (Con A) and ribonuclease B (RNase B), and in  a gold nIn addition, optical fiber biosensors for the detection of specific parameters such as glucose , anti-glAdditionally, in order to study the selectivity of the sensor, it has been subjected to different solutions in presence of other molecules, such as urea and creatinine at the same concentrations used with CRP. In In order to have a better understanding of the different optical fiber sensors for biological and biochemical detection analyzed in this section, a summary of the different sensitive coatings employed as well as the optical structure and the sensing mechanism for the specific parameter detection can be clearly appreciated in In this work an overview of the implementation of LbL coatings for the design and development of novel optical fiber devices for the detection of chemical, biological and biochemical parameters is presented. In this regard, the use of optical fiber technology provides a powerful alternative sensing platform due to the inherent potential properties such as easy multiplexing, light weight, small size, immunity to electromagnetic interferences and long-distance transmission, among others. Different optical fiber configurations  are used for the deposition of the sensitive coating by using the LbL technique. It is important to remark that this nanofabrication technique provides a good thickness control and a high versatility due to the possibility of incorporating a wide variety of chemical  or biochemical substances  into the corresponding multilayer structure which can optimize the characteristics of the sensing films such as sensitivity, selectivity, response time or even the range of measurement. This review demonstrates that the LbL technique is a powerful tool to create functional coatings for optical fiber sensors, with enhanced properties respect to the bulk materials, making possible the achievement of highly sensitive optical devices for pH measurement, the identification of gases and volatile organic compounds (VOCs) or even for highly specific biological applications.


Are beauty and goodness the same? The relationship between beauty and goodness has long been a controversial issue in the fields of philosophy, aesthetics, ethics and psychology. Although many empirical studies have explored moral judgment and aesthetic judgment separately, only a few studies have compared the two. Whether these two judgments are two different processes or the same process with two different labels remains unclear. To answer this question, the present study directly compared the influence of facial attractiveness on judgments of moral goodness and moral beauty and revealed distinct contributions of imaging perceptions to these two judgments. The results showed that in the moral beauty judgment task, participants gave higher scores to characters with attractive faces compared with characters with unattractive faces, and larger P200 and LPP were elicited in the unattractive-face condition compared with the attractive-face condition; while in the moral goodness judgment task, there was no significant difference between the two conditions of either behaviour or ERP data. These findings offer important insights into the understanding and comparison of the processes of moral judgment and aesthetic judgment. Many great philosophers have shed light on this question4. For example, Aristotle argued that the goal of all virtue is beauty, while Kant considered beauty a symbol of moral goodness4.Goodness and beauty are two ultimate ends that humankind constantly pursues. These two concepts have been connected to each other since the dawn of civilization, and the debate continues regarding whether the two are the sameThe issue of the relationship between goodness and beauty has not been limited to philosophical discussions in ancient times; people can have their own experiences of this in daily life. Imagine the following scenario: An elderly man falls over the curb of a street, and a young girl passing by immediately runs to him and attempts to help. If you witnessed this, you would probably be impressed by the kindness of the girl’s deed, and it may also occur to you that this girl has a beautiful heart. During this time, you experience two different processes: You make a moral judgment regarding the goodness of the girl’s behaviour; and you make an aesthetic judgment regarding the moral beauty of the girl’s heart. These two judgments are based on the same scene, and both produce positive feelings. This phenomenon raises the following question: Are moral goodness judgments and moral beauty judgments the same process labelled with different names, or are they two different processes?10. Moral judgment, by definition, is a process by which a person makes judgments of particular behaviours or options as being ethical/unethical or correct/incorrect11. This process also involves a tendency to see certain actions and individuals as right, good, and deserving of reward and others as wrong, bad, and deserving of punishment12. Traditional theories of moral psychology have adopted a rational view and suggested that moral judgment is mainly a reasoning process according to social rules6. People may make different moral judgments in response to the same question due to the development of high-level cognitive ability8. However, researchers have recently begun to emphasize the importance of affective processes for moral judgment. Haidt proposed the social intuitionist model and argued that moral judgment is not caused by reasoning but by rapid, affectively based intuitions and that moral behaviour covaries with emotion more than with reasoning14. Both behavioural and brain imaging evidence have confirmed the important role of emotion in moral judgment16. Greene and his collaborators proposed the dual-processing model, a synthetic theory of the above two viewpoints, which argued that social-emotional processing and cognitive processes are two essential elements of moral judgment10. Multiple neuroscientific findings have shown that the brain areas activated during moral judgments involve both areas related to emotion and areas related to cognitive processes, and these two elements both have considerable effects on moral judgment19. Such findings provide support for the above theory. Currently, moral judgment is mainly considered to be the result of both reasoning processing and affective processing.Researchers have conducted extensive empirical studies and accumulated valuable knowledge concerning the separate processes of moral judgment and aesthetics21. According to aesthetic theory, the processes of aesthetic judgment involve a sensory-perceptual process, a cognitive process and an affective process21. In accordance with the above theory, the results of neuroaesthetic studies indicate that the brain areas involved in aesthetic judgment include the ventral visual systems , which are associated with visual processing, the superior frontal gyrus (SFG), which is associated with cognitive processing, and the orbitofrontal cortex (OFC), which is associated with affective processing22. With regard to these different processes, numerous findings emphasize the dramatic effect of objects’ audio-visual features on aesthetic assessment and suggest that the sensory and perceptual processing of an object’s image is not only the primary step in the process but is also crucial for making aesthetic decisions24. According to aesthetic theory, beauty can be further divided into three categories: natural beauty, artistic beauty and moral beauty. The first two, natural beauty and artistic beauty, are external beauty, the judgment of which is directly based on the processing of external auditory and/or visual features21, while the last one, moral beauty, refers to inner beauty21. Although external beauty has been the traditional subject of aesthetic studies, it is noteworthy that more recently, moral beauty has become the focus of a series of studies25. Moral beauty, according to its definition, is mainly the beauty of humanity, virtue and talent, which is evaluated based on the understanding of social regulations and involves social affect and advanced cognition26. In contrast to external beauty, moral beauty involves not only sensory and symbolic elements but also complex social implications26. One representative example of a situation in which the beauty promulgated by the mainstream media was actually moral beauty rather than merely external beauty was when the national television station of the People’s Republic of China, China Central Television, awarded a doctor who provided free treatment for orphans the title of “one of the most beautiful doctors in China”28. This award indicates the admiration of a beautiful inner character rather than an attractive appearance. Wang et al. performed fMRI experiments to explore moral beauty judgments29. Participants were asked to make aesthetic judgments and gender judgments of either face pictures or scene pictures describing good or neutral behaviour. The results showed that during moral beauty judgments, compared with the control condition, stronger brain activation was observed in the OFC (which is associated with affective processing), the ITG , and the SFG (which is associated with cognitive processing)22. These findings suggest that the process of moral beauty judgment, similar to external beauty judgment, also involves sensory-perceptual, cognitive and affective processes22.Similar to the continuous scientific exploration of morality, beauty has been studied extensively31. For instance, when participants were asked to view photographs of individuals first and then evaluate these individuals’ traits, attractive individuals were assumed to be more kind, honest, and moral compared with unattractive persons30. On the other hand, information on internal characteristics also has an impact on the judgment of external appearance, known as the good-is-beautiful stereotype33. For example, when participants were asked to evaluate the physical characteristics of a person shown in a head-and-shoulder photograph before reading a description of either high or low personality traits of the person, the honest target was considered to have a face that looked more attractive than the dishonest target33. Therefore, moral judgment and aesthetic judgment mutually affect each other. With the development of neuroimaging technology, researchers have adopted brain imaging methods to explore the neural features underlying the connection between moral and aesthetic judgments. Tsukiura et al. focused on the medial orbitofrontal cortex and insular cortex and tested whether similar activation patterns were found in these regions in response to two tasks: the attractiveness rating of facial photos and the goodness rating of short sentences that depicted actions34. They found that compared with the control conditions, the medial orbitofrontal cortex showed increased activity and the insular cortex showed decreased activity in both tasks. The researchers inferred that these two regions may underlie the mutual effect between aesthetic and moral judgments. Avram et al. employed one-line poems and short moral statements as stimuli to compare judgments of poetic beauty and judgments of a moral statement’s correctness. They discovered that the orbitomedial prefrontal cortex showed activation in both judgments, while areas such as the posterior cingulate cortex, the precuneus, and the temporoparietal junction were activated specifically in judgments of a moral statement’s correctness22.A number of studies have further investigated the relationship between moral character and physical attractiveness. On the one hand, the results show that physical appearance has an effect on the evaluation of moral character, known as the beauty-is-good stereotype34. However, no previous study has directly compared the process of moral judgment and the process of aesthetic judgment, and it remains unclear whether these two judgments are the same process with two different labels or two different processes. Moral beauty, compared with external beauty, is a type of beauty that is more abstract and more closely related to social affection and social cognition; thus, it is more easily confused with moral goodness25. Hence, an exploration of the similarities and differences between moral beauty and moral goodness will have valuable implications for answering the controversial question of the relationship between beauty and goodness. Based on reviews of previous studies of moral and aesthetic judgments, it can be concluded that moral goodness judgments mainly involve cognitive and affective processes10, while moral beauty judgments mainly involve sensory-perceptual, high-level cognitive and affective processes35. Both judgments include cognitive and affective processes, although the sensory-perceptual process of constructing images of evaluation targets for moral judgments has not been emphasized as much as it has for aesthetic judgment. Notably, a number of studies indicate that the perceived visual features of the input stimuli are decisive for generating aesthetic feelings and that sensory-perceptual processing ranks as a cardinal part of the aesthetic judgment. Thus, the judgment of moral beauty is based on the understanding of social rules, which is equally required in the moral goodness judgment; at the same time, the judgment of moral beauty also depends on the perception of the input stimuli and emphasizes the sensory-perceptual process, which is involved but not decisive in moral goodness judgments29.In summary, abundant scientific investigations have been conducted separately on the processes of moral judgment and aesthetic judgment, and evidence indicates that there may be both similarities and distinctions between the neural bases of moral goodness and beauty36. It typically reflects the perceptual processing of stimuli38. Previous studies have shown that the peak amplitude of P2 is modulated by attention. It is purported that P2 represents the beginning of a central process responsible for stimulus identification and the initiation of decision making41. LPP is a positive component that occurs approximately 600 ms after stimuli onset and is maximal in the central and parietal regions. It is proposed to reflect advanced cognitive processes such as the conscious assessment of targets and deliberate reasoning43. For example, a larger LPP amplitude was found in the moral decision-making process when stronger conflicts existed44. It is hypothesized that for moral beauty judgments, in which the sensation and perception of an image play a decisive role in decisions, facial attractiveness will cause the separation of the P2 and subsequent LPP amplitudes, and the rating scores for attractive-face version stimuli with will be higher than the scores for unattractive-face version stimuli; while for moral goodness judgments, in which the attractiveness of images is not crucial for decisions, there will be no significant difference in P2 amplitudes, LPP amplitudes or rating scores between the two conditions.The present experiment aimed to compare the process of evaluating moral beauty and the process of evaluating moral goodness using event-related potentials (ERPs) to explore similarities and differences between these two judgments. In accordance with the above analyses, we directly test whether different facial attractiveness affects the processes of moral beauty judgments and moral goodness judgments distinctly or similarly through a manipulation of attractive-face-version stimuli and unattractive-face-version stimuli. This exploration will provide new knowledge to resolve the long-standing dispute regarding the relationship between goodness and beauty. The ERP analysis focused on two ERP components, P2 and late positive potential (LPP). The P2 component is a positive component that peaks approximately 200 ms after the presentation of a stimulusFor the behavioural data, analyses of the rating scores and response times (RTs) were performed. With the rating score as the dependent variable, a two-way repeated-measures ANOVA was conducted with the judgment type  and facial attractiveness (attractive face vs. unattractive face) as within-subjects factors. The results, as demonstrated in Fig. With the RTs as the dependent variable, a two-way repeated-measures ANOVA was conducted with judgment type  and facial attractiveness (attractive face vs. unattractive face) as within-subjects factors. The results, as demonstrated in Figs 45, the mean amplitudes of nine frontal and central electrode sites  were measured in a 170–230 ms time window as P2 amplitudes. The P2 results were showed in Figure In accordance with previous studies47, the mean amplitudes of nine central and parietal electrode sites  were measured in a 400–900 ms time window as LPP amplitudes. The LPP results were showed in Figure In accordance with previous studiesThe present study investigated whether judgments of moral goodness and moral beauty are two distinct judgment processes or are actually the same process with two different labels. To answer this question, participants were presented with a series of moral behaviour scene drawings in which the character had either an attractive face or an unattractive face. The participants completed two tasks, the moral goodness judgment task and the moral beauty judgment task, separately while ERP signals were recorded throughout the experiment to compare whether the character’s facial attractiveness had the same impact on the moral goodness judgments and the moral beauty judgments.The results of the rating scores showed that for the moral beauty judgment, although all pictures presented in the experiment depicted positive deeds, scene drawings with attractive-face characters received higher scores compared with scene drawings with unattractive-face characters. In contrast, in the moral goodness judgment, scene drawings with attractive-face characters and scene drawings with unattractive-face characters showed no significant difference. Overall, the behavioural results indicate that the facial attractiveness of the character had a notable influence on the moral beauty assessment but did not have a significant impact on the moral goodness assessment.The results of the two ERP components demonstrated a similar pattern as the behavioural findings, as hypothesized. For the evaluation of moral beauty, the variable of the facial attractiveness of the character caused the separation of the amplitudes of P2 and LPP, while there was no significant difference between the two versions of the material for the moral goodness rating. Both behavioural and ERP data were collected and analysed to maximize the reliability of the present study. The convergence of these two types of evidence validated the findings of this study.48. Its amplitudes are modified by attention and other cognitive variables48. It has been proposed that P2 represents the beginning of a central process responsible for stimulus identification and the initiation of decision making49. The P2 results demonstrated that in the task of moral beauty judgment, the variable of characters’ facial attractiveness modulated the P2 amplitude but showed no significant effect in the same time window in the moral goodness judgment task. These findings indicate that the variable of facial attractiveness affected the processing of moral beauty decisions but showed no evident influence on the processing of moral goodness decisions. Considering the matched stimuli used for these two tasks, this distinction is believed to be due to the different requirements of the moral goodness judgment and the moral beauty judgment. In the former task, when participants integrate the visual information of the scene drawings to make a moral goodness judgment as instructed, whether a character has an attractive or unattractive face may not be the decisive information for evaluating the goodness of the character’s behaviour. Thus, this variable had a limited influence and caused no significant difference in the P2 amplitudes between the attractive-face and unattractive-face conditions. In the latter task, however, when the participants viewed the scene drawings to assess the beauty of the character’s heart as instructed, although the character’s behaviour was one important element to consider, the impression of the character’s appearance was also influential for the final moral beauty rating. Thus, different levels of facial attractiveness caused the separation of the P2 amplitudes. In contrast, for the moral goodness judgment, the attractive-face stimuli and the unattractive-face stimuli showed no evident difference in P2 amplitudes. Previous studies have indicated that facial attractiveness may have an impact on the evaluation of personality traits50. For example, individuals with high attractiveness  are less likely to be considered guilty and more likely to be judged as having positive characteristics, such as kindness and honesty50. However, in the present study, in which the instructions for the moral goodness judgment specifically asked participants to evaluate the goodness of the characters’ behaviour, the influence of facial attractiveness on the goodness judgment was limited and thus caused no significant difference between the two versions of the stimuli.Previous studies have shown that P2 is not only related to the detection of visual features but also reflects higher-order perceptual processing44. LPP is thus considered a neural index of the later cognitive process during reasoning and decision-making that is involved in both moral judgment and aesthetic judgment processes44. In accordance with the above analysis, it is believed that LPP mainly reflects the cognitive reasoning process of moral and aesthetic judgments. In the present experiment, this refers specifically to reasoning and decision making based on the synthetic scene information formed during the perception stage. The present results show that during the task of making moral beauty decisions, the separation of the P2 component indicates that characters’ different external facial attractiveness had an impact on the early stage of the evaluation process. The separation of LPP, similar to the pattern for P2, revealed that the image-constricting process further influences the assessment of moral beauty at later time points. The same variable showed no evident influence on neural responses during moral goodness judgments at either early or late latencies. It is inferred that in the process of moral beauty judgment, the character’s appearance information is especially noticed at the early stage, which produces a significant difference in the P2 amplitude under the two different conditions. When participants further integrated the information on a character’s facial features and information on the character’s behaviour to make a comprehensive moral beauty judgment, different perceptions of the character’s facial attractiveness caused further differences when combined with the same positive behaviour in the final stage of providing a moral beauty score, as demonstrated by the significant difference between the two versions of stimuli in the behavioural results and LPP amplitudes. The relatively larger LPP amplitudes of the unattractive-face condition in the moral beauty judgment were believed to occur because of the inconsistency of information. When evaluating the moral beauty of characters with attractive faces, the participants could smoothly combine an attractive face and good behaviour to obtain positive results through a consistent cognitive reasoning process. In contrast, when evaluating moral beauty with the unattractive-face material, a lack of conformity occurred. If participants were asked to solely assess the beauty of a series of unattractive faces or the goodness of a set of noble deeds, the answer would naturally be negative or positive. However, when participants were required to evaluate the moral beauty of characters with unattractive faces who performed noble deeds, the diversity of the decision tendencies could cause cognitive conflict, which further elicited a larger LPP amplitude compared with the consistent condition in which participants viewed attractive-face characters performing positive behaviours. Previous studies have shown that an inconsistent condition leads to greater LPP amplitudes than a consistent condition53. The findings of this study are in accordance with these findings.The LPP results showed a similar pattern as the P2 results. The characters’ appearance influenced the participants’ neural responses to the moral beauty evaluation of the scene drawings but showed no such effect in the moral goodness rating of matched scene drawings. Previous ERP studies have demonstrated that LPP reflects slow but elaborate moral reasoning processes and aesthetic evaluation processesIn contrast to the moral beauty judgment, for the moral goodness judgment, with external facial attractiveness information did not receive sufficient attention in the early stage, as reflected in the fact that the attractive and unattractive faces did not lead to the separation of P2 components, the further influence of facial attractiveness in the later stage of cognitive processing was limited. Thus, at later time points, the LPP induced by the two different conditions, the attractive-face condition and the unattractive-face condition, demonstrated no significant difference. These distinct results of the LPP amplitudes between moral goodness and moral beauty judgments reveal that perceived facial attractiveness information in the sensation and perception stages influences later stages of moral beauty assessment, but similar effects are not observed in the moral goodness evaluation. This finding indicates the unmatched influence of sensory and perceptual processing on judgments of moral goodness and moral beauty.54. Many studies have accordingly indicated that objective audio-visual feature evaluation occurs first, followed by aesthetic decision making, which is affected by both the result of the former descriptive judgment and a complex set of factors, such as emotional factors and appeals to social status.Combining results of the behavioural and ERP data, it is evident that facial attractiveness has different effects on the processes of moral goodness and moral beauty judgments from the early stage to the late stage. These results indicate the dissimilar influence of the perceived image on the evaluation of moral goodness and moral beauty, suggesting a distinction between the processes of judgments of moral goodness and moral beauty. One crucial factor that distinguishes them lies in the divergent impact of the sensory and perceptual construction of the image on the processes of the two judgments. The salient influence of a character’s facial attractiveness on judgments of moral beauty is consistent with the theory of aesthetic process, which argues that aesthetic judgments engage a two-stage process: the earlier stage is impression formation, and the later stage is evaluative aesthetic categorization57. In contrast to previous studies that presented words, words and facial photographs or facial photographs and scene drawings separately on different slides34, in the present experiment, information on both external facial attractiveness and behaviour was contained in one scene drawing and presented to participants at the same time, which enabled a more natural judgment process. For future studies, more material options, such as photographs of real moral scenes and characters and video clips that record real moral events, could be used to explore whether different types of stimuli affect the results and to test the robustness of the present findings. In addition, as previous studies have demonstrated that multiple factors, such as symmetry, averageness, sexual dimorphism and skin colour/texture, systematically affect the perception of facial attractiveness60, future studies could explore whether these factors function differently with regard to the effect of facial attractiveness on judgments of moral beauty and moral goodness.The present study aimed to directly compare the influence of facial attractiveness on judgments of moral goodness and moral beauty. With this goal, scene drawings were chosen as suitable experimental materials for they have a significant advantage of simultaneously providing information on both characters’ external facial attractiveness and behaviour. Many studies have indicated that both aesthetic judgment and moral judgment can be intuitive processes, and people make these decisions rapidly62, fewer studies focus on people’s positive assessments of morally good behaviours and this process is much less clear63. Studies of judgments of moral goodness and moral beauty are needed to fill this theoretical gap. In addition, such studies have practical significance and can serve as the basis for designing a more scientific and efficient way to conduct moral education63. The investigation of the relationship between moral and aesthetic judgments is far from complete. Previous findings have shown that moral goodness judgments and moral badness judgments may have distinct neural mechanisms and functional connectivity66. For example, one study found that judgments of scenarios classified as morally good  involved greater activity in areas of the middle and inferior temporal gyri, inferior frontal gyrus, dorsolateral prefrontal cortex and precuneus. In contrast, judgments of morally bad scenarios involved greater activity in areas of the hippocampus and midcingulate cortex, superior frontal gyrus, supramarginal gyrus, left inferior and superior parietal lobules, and insula. Thus, it would be interesting and important to further explore whether the influence of facial attractiveness on judgments of moral badness and moral ugliness would show different patterns from judgments of moral goodness and moral beauty and obtain a more comprehensive understanding of moral and aesthetic judgments. Furthermore, with the development of neuroscience technologies such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that temporarily change the brain function of certain areas68, a more thorough investigation could be conducted by specifically changing the function of certain brain areas  and exploring the modulation caused by this manipulation on the processes of moral judgments and aesthetic judgments. This investigation could provide a more advanced way to understand and compare these processes.Another reason why the present study concentrated on the investigation of positive judgments  is that compared to the large numbers of moral judgment studies that focus on participants’ negative evaluations of morally bad behaviours, such as violations of moral norms and maleficent behavioursIn summary, to the best of our knowledge, the present research is the first to use validated scene drawings to present both facial attractiveness information and behavioural information at the same time and to directly compare the processes of moral beauty and moral goodness judgments. With the analysis of both behavioural and ERP data, the present work provides novel and compelling evidence on the difference between judgments of moral goodness and moral beauty and advances current knowledge on the detailed processes of moral and aesthetic judgments. It can be concluded that moral judgment and aesthetic judgment are different processes with two different labels. These findings offer important insights into the ongoing controversial debate about the relationship between beauty and goodness.69 to determine the sample size that would provide sufficient power to detect a large effect size70. In accordance with previous studies, the power analysis revealed that for an effect size (η2) of 0.14 to be detected with an 80% chance of significance with the alpha level set to 0.05, the required sample would be 22 participants. Thus, the sample size of the present study was 22 participants. All participants were assessed before the experiment to ensure that they had normal or corrected-to-normal vision. The study was approved by the ethical review board of the Department of Psychology, South China Normal University and all volunteers gave written informed consent. All methods used in the current study were performed in accordance with the relevant guidelines and regulations of the ethical review board.Twenty-two undergraduate students  with no history of neurological or psychiatric problems were recruited as participants. Prior to initiating data collection, a power analysis was conducted in G*Power72, 80 short sentences that described good deeds, such as taking an injured old man to the hospital and visiting orphans in the orphanage, were collected. Then, black-and-white scene drawings were created based on the content of these sentences , with the characters’ faces blurred to prevent the influence of facial features on the goodness evaluation. According to the results, scene drawings with average scores less than 4 were excluded to ensure that all behaviours described in the scene drawings were positive. The other twenty-two participants were asked to assess the attractiveness of characters’ faces in the scene drawings on a 7-point scale , with other parts of the pictures blurred to avoid the impact of the scene and the characters’ behaviour on the facial attractiveness assessment. Based on the results, drawings with average scores less than or equal to 4 were excluded for the attractive-face version scene drawings, and average scores greater than or equal to 4 were excluded for the unattractive-face version scene drawings. A total of 36 moral scenes were finally selected. Each scene had one attractive-face version and one unattractive-face version, composing 72 validated scene drawings that were used as final stimuli.The 36 moral scenes were then randomly assigned to two sets. Participants made the moral goodness judgment on one stimuli set and made the moral beauty judgment on the other stimuli set to avoid the repeated use of the same stimuli in two different tasks. Each set contained eighteen moral scenes. As each scene had an attractive-face version and an unattractive-face version, each set consisted of 36 moral scene drawings in total. One independent-sample t test was conducted on the scores of the two sets, which were acquired from the first pilot study in which the participants specifically evaluated the goodness of the character’s behaviour described in the scene drawings. The results showed that there was no significant difference between the two sets . This result indicated that with regard to the degree of goodness depicted in the drawings, the two sets were equivalent. Similarly, two more independent-sample t tests were conducted separately on the facial attractiveness scores of the attractive-face-version stimuli of the two sets and the unattractive-face-version stimuli of the two sets. The facial attractiveness scores were the scores acquired from the second pilot study in which participants specifically assessed the facial attractiveness of the character with all content other than the characters’ face blurred. The results showed that there was no significant difference between the attractive-face version of the two stimuli sets  and the unattractive-face version of the two stimuli sets . All of the results showed no significant difference between the two sets, which ensured that the two sets were equivalent.Thus, for each judgment task, eighteen moral scenes were used that contained eighteen attractive-face scene drawings and eighteen unattractive-face scene drawings. Every scene drawing was shown three times. Therefore, there were 54 trials for each experimental condition: The attractive-face-version stimuli in the moral goodness judgment, the unattractive-face-version stimuli in the moral goodness judgment, the attractive-face-version stimuli in the moral beauty judgment and the unattractive-face-version stimuli in the moral beauty judgment.During the experiment, participants were seated in a sound-attenuated, electrically shielded, dimly illuminated chamber. Stimuli were presented in the centre of a 15-inch computer screen at a viewing distance of 85 cm to ensure that both the horizontal and vertical visual angles were less than 3°. The participants were asked to perform two types of tasks. One task was the moral goodness judgment, in which the participants were instructed to look at the scene drawings and evaluate the goodness of the character on a 7-point scale . The other task was the moral beauty judgment, in which the participants were instructed to look at the scene drawings and assess the beauty of the character’s heart on a 7-point scale . Two equivalent sets that were used separately in the moral goodness and moral beauty judgments were balanced across participants. The experiments included 3 runs of moral goodness judgments and 3 runs of moral beauty judgments. The order of the 6 runs was random, and each run consisted of eighteen trials. A single trial began with a fixation cross presented at the centre of the black background for 700 ms. Next, a scene drawing and a 7-point scale were shown on the screen. This slide did not disappear until the participant pressed the number key in response. Then, there was a 1200 ms blank screen before the next trial began  were obtained throughout the experiment using an electrode cap that contained 64 electrodes positioned according to the International 10 ⁄ 20 System. For the purpose of artefact scoring, electrooculograms (EOGs) were also recorded. The horizontal electrooculogram (HEOG) was recorded using two electrodes placed lateral to the right and left eyes. The vertical electrooculogram (VEOG) was recorded with electrodes placed below the right eye.During the off-line analyses, all data were visually scored for artefacts. Ocular artefacts were removed from the data using a regression-based correction algorithm implemented with the Neuroscan software. EEG signals were re-referenced to the average of the left and right mastoid recordings and low-pass filtered below 30 Hz. The EEG was segmented into 1600 ms epochs from 200 ms before to 1400 ms after the scene drawing stimulus onset. The EEG epochs were baseline corrected against the mean voltage during the 200 ms pre-stimulus period. Trials containing EEG sweeps with amplitudes exceeding ± 100 µV were excluded from the analysis.


Light detection and ranging (LiDAR) systems based on silicon single-photon avalanche diodes (SPAD) offer several advantages, like the fabrication of system-on-chips with a co-integrated detector and dedicated electronics, as well as low cost and high durability due to well-established CMOS technology. On the other hand, silicon-based detectors suffer from high background light in outdoor applications, like advanced driver assistance systems or autonomous driving, due to the limited wavelength range in the infrared spectrum. In this paper we present a novel method based on the adaptive adjustment of photon coincidence detection to suppress the background light and simultaneously improve the dynamic range. A major disadvantage of fixed parameter coincidence detection is the increased dynamic range of the resulting event rate, allowing good measurement performance only at a specific target reflectance. To overcome this limitation we have implemented adaptive photon coincidence detection. In this technique the parameters of the photon coincidence detection are adjusted to the actual measured background light intensity, giving a reduction of the event rate dynamic range and allowing the perception of high dynamic scenes. We present a 192 × 2 pixel CMOS SPAD-based LiDAR sensor utilizing this technique and accompanying outdoor measurements showing the capability of it. In this sensor adaptive photon coincidence detection improves the dynamic range of the measureable target reflectance by over 40 dB. To bring autonomous vehicles to the road, a fast and reliable high-resolution perception of the environment is essential. Today, cars include many different driver assistance systems, like adaptive cruise control, lane assist, or emergency braking. However, all these systems are designed to assist the driver and make the journey more comfortable. In case of a system malfunction, it is disabled and the driver has to undertake the task. In self-driving cars there is no human driver to replace non-functional systems and, therefore, much higher reliability requirements are demanded. Different sensors are used for environmental perception : ultrasoDifferent methods for the rejection of high ambient light are used in LiDAR systems. A basic approach is the use of optical bandpass filters adapted to the wavelength of the illumination source ,11. ThesIn this paper we present a technique to improve the measurement performance at high ambient light. This technique can be implemented in addition to the aforementioned techniques for ambient light rejection and is especially suitable for single-photon avalanche diode (SPAD)-based LiDAR sensors. By detecting temporal correlated single photons in each pixel, false detections caused by ambient photons are reduced and, at the same time, an improvement of the signal quality is achieved allowing for higher measureable distances. Since fixed coincidence parameters as usually used in the literature ,17,18 shIn the direct TOF measurement technique the time between emission and reception of a laser pulse is measured by a high precision electronical stopwatch as shown in Unfortunately, background illumination and dark counts are always present in real LiDAR systems; especially in outdoor applications high background light is present. Since background photons impinge the sensor during the whole measurement cycle starting right at the laser pulse emission, there is a certain probability for background photons to arrive at the detector before the reflected laser pulse and cause false detections . The prording to : (1)P1, a higher PDE, which increases the ambient photon rate, could result in a loss of measurement performance if the ambient photon rate is thereby increased above the optimal level. To counteract the high ambient photon rate due to high PDE or high ambient illumination, the rate has to be kept on the optimal level by rate adjustment. In our sensor this is achieved by photon coincidence detection whereas the parameters of the coincidence detection are adjusted to the actual ambient photon detection rate.To reduce the amount of false photon detections in real-time without sacrificing range and precision, photon coincidence detection can be applied. In this technique the measurement is not stopped by the detection of a single photon, but only if at least a defined number of single photons—called coincidence depth—is detected within a defined timespan—called coincidence time. Since the laser photons are confined to the pulse width whereas the background photons are approximately equally distributed in time, the ability to differentiate between ambient and laser signal is improved ,25. CompThe basic idea of this principle is to apply a certain threshold and stop the time measurement as soon as the impinging light intensity and photon rate, respectively, exceeds this threshold. In a best-case scenario this level is set slightly above the ambient light intensity. Since the laser pulse adds to the ambient light, the received light intensity increases, exceeds the threshold, and stops the time measurement. Unfortunately, the photons do not arrive in regular intervals but the inter-arrival time obeys the exponential distribution. Therefore, a total rejection of ambient light is not possible. However, since low photon rates  are more reduced than higher photon rates  this technique increases the ratio of the laser signal and ambient light event rate  allowing a longer distance range at high ambient light . An evenTo investigate the effect of photon coincidence detection on the event detection rate, a model based on statistical calculations has been developed. This model is an advanced version of the model presented in  and addi2 [As an example arbitrary input values are chosen and highlighted in  cps/µm2 , it is nAs can be recognized in With CMOS integrated SPADs the photodetector can be integrated along with the control and processing electronics on a single chip. This allows the realization of application specific sensors with dedicated CMOS circuitry. Additionally, system-on-chip sensors are more durable and can be fabricated more cost-efficiently than sensors built in other technologies or compound sensors. In this technology a LiDAR sensor  based onAs shown in the pixel block diagram in For measurements and demonstration of the sensor we have built the flash LiDAR camera “Owl”. The camera shown in In addition to 2D image acquisition, the event counting mode is used to gain information about the ambient light intensity and event rate, respectively. In counting mode an integrated eight-bit counter is used allowing counting up to 255 events in a single measurement. In counting mode the output of the coincidence detection circuit, which triggers the TDC in the time measurement, is directly fed to the counter as shown in For the implementation of the adaptive coincidence controlling algorithm levels with associated parameters resulting in a decreasing event rate are defined. This is necessary, since increasing the coincidence depth for coarse event rate adjustment and the coincidence time for interpolation results in a non-monotonic behavior of the event rate. The defined coincidence levels and their associated parameters are shown in Assuming the distance measurement works well within the defined range of the event rate, the adaptive photon coincidence detection increases the measureable dynamic range in ambient light conditions and target reflectance by more than 40 dB from 20 dB to over 60 dB. Due to the different slopes of the curves, the step size between the coincidence levels depends on the current single photon detection rate. To reduce the step size between the levels, the coincidence parameters need to be varied in finer steps. Since the coincidence depth can only attain integer numbers, this is only possible for the coincidence time. Unfortunately, this requires more complex circuitry.In In the presented realization the coincidence levels are varied by one step in each cycle only. A cycle corresponds to one frame, which is 40 ms in the typical setup of the camera. Therefore, in fast-changing environments this kind of coincidence adjustment could be too slow to allow a reliable real-time distance measurement. Assuming a large change in reflectance, the system takes 10 cycles corresponding to 0.4 s to adjust the coincidence settings. To increase the adjustment speed, the step size of the parameter adjustment could be increased in case of high divergence between the actual and target event rates. Another method for the parameter adjustment is to use a look-up table. Here, the best suitable coincidence level is directly chosen based on the measured ambient event rate. For this method the coincidence has to be turned off during the counting mode or the look-up table has to include all possible coincidence levels. This reduces the settling time down to just a single cycle.The first measurement is to compare the theoretical coincidence model to actual measurements. In The further measurements are performed with our 192 × 2 pixel LiDAR sensor mounted in the camera “Owl”. The lens and laser sources are chosen according to the description in the previous section. In the outdoor measurements we use Lambertian targets with different reflectance levels.In the next measurement we investigate the effect of varying target reflectance on the system performance. Since the received photon rates of the ambient light and laser signal are proportional to the reflectance, we expect good performance without coincidence only for a limited dynamic range. As a measure of performance, the parameter success probability, defined as the probability to measure the true distance with a maximum deviation of 10%, is calculated from 1000 single distance measurements, whereas each distance is obtained from a histogram filled with 400 timestamps. Obviously, the algorithm to extract the distance from the filled histogram has a major influence on the measurement performance. However, to show the influence of the ambient event rate on the measurement, only the quantitative shape of the measurement curve is of interest and, therefore, an arbitrary algorithm can be applied. We simulate the change in reflectance by adjusting the reception optics aperture. This affects only the absolute intensities of the ambient light and laser while the SBR is kept constant. Assuming a minimum required success probability of 80%, only within a dynamic range of around 12 dB of the ambient photon rate Next, a dark  and a bright  object, 6.5 m distant, at 100 klx ambient sunlight are measured in a scene to show the capability of the on-chip pixel-wise adaptive coincidence parameter adjustment. In ment see , PDF C. In vel case a the eveIn The measurement proves that achieving long range in scenes with high dynamic range in target reflectance and high ambient illumination requires pixel-wise event rate adjustment. The concept of adaptive photon coincidence detection is one promising possibility to fulfill this task and improve the measurement performance. For automotive short and mid-range applications distances up to 50 m are of interest. To extend the range of the shown system several improvements are possible: reducing the width of the optical bandpass filter from 80 nm down to 10 nm reduces the ambient light by a factor of 8. Since the laser pulse intensity scales quadratic with the distance, the range increases by approximately factor 2.5. Another possibility is the usage of laser sources with shorter pulses and higher repetition rates. And also improvements in the histogram processing by the usage of more sophisticated algorithms will extend the system range. Nevertheless, the proposed method of adaptive photon coincidence detection can be implemented in any LiDAR system based on the direct TOF measurement to improve the dynamic range.To enable a reliable distance measurement with CMOS SPAD-based LiDAR systems at strong ambient illumination, background light suppression is essential. Without the application of any ambient light rejection method, an improvement of the SPAD sensitivity is not generally beneficial in the first-photon direct TOF measurement, because higher PDE can imply a higher probability of unwanted background photon detections and, hence, false measurements. The detection of photon coincidences reduces the probability for background generated events and improves the ability to separate between ambient light and laser signal. This allows for a more reliable measurement. Since the best measurement performance is achieved only for a specific and distance dependent ambient event rate, the adjustment of the event rate by varying the coincidence parameters enables the sensor to capture scenes with a high dynamic range in object reflectance. To be applicable in real-world traffic situations, the parameter adjustment needs to be performed in real time. This can be achieved by using dynamic step size of the parameter adjustment or a look-up table approach. Since applying photon coincidence detection reduces the resulting event rates and shows a dead-time induced saturation, a higher SPAD sensitivity and lower dead-time can further improve the advantages of photon coincidence detection.