Collaborative Uncertainty Benefits Multi-Agent Multi-Modal Trajectory Forecasting.

In multi-modal multi-agent trajectory forecasting, two major challenges have not been fully tackled: 1) how to measure the uncertainty brought by the interaction module that causes correlations among the predicted trajectories of multiple agents; 2) how to rank the multiple predictions and select the optimal predicted trajectory. In order to handle the aforementioned challenges, this work first proposes a novel concept, collaborative uncertainty (CU), which models the uncertainty resulting from interaction modules. Then we build a general CU-aware regression framework with an original permutation-equivariant uncertainty estimator to do both tasks of regression and uncertainty estimation. Furthermore, we apply the proposed framework to current SOTA multi-agent multi-modal forecasting systems as a plugin module, which enables the SOTA systems to: 1) estimate the uncertainty in the multi-agent multi-modal trajectory forecasting task; 2) rank the multiple predictions and select the optimal one based on the estimated uncertainty. We conduct extensive experiments on a synthetic dataset and two public large-scale multi-agent trajectory forecasting benchmarks. Experiments show that: 1) on the synthetic dataset, the CU-aware regression framework allows the model to appropriately approximate the ground-truth Laplace distribution; 2) on the multi-agent trajectory forecasting benchmarks, the CU-aware regression framework steadily helps SOTA systems improve their performances. Especially, the proposed framework helps VectorNet improve by 262 cm regarding the Final Displacement Error of the chosen optimal prediction on the nuScenes dataset; 3) in multi-agent multi-modal trajectory forecasting, prediction uncertainty is proportional to future stochasticity; 4) the estimated CU values are highly related to the interactive information among agents. The proposed framework can guide the development of more reliable and safer forecasting systems in the future.

CLINICAL OBSERVATIONS OF BEE ENVENOMATION IN TOUCANS.

There are numerous reports on envenomation, even fatal, secondary to bee attacks in humans and other mammals. In birds, reports on those incidents are scarce and there are none regarding honeybee (Apis mellifera) stings in toucans. In the first case presented, an adult female red-breasted toucan (Ramphastos dicolorus) received at least five bee stings in the periophthalmic area. Within 5 h the bird was lethargic and dehydrated. The urates were yellowish. Three days later the bird showed a moderate anemia, but no changes in the leukocyte count, beyond an elevated heterophil: lymphocyte ratio. Blood chemistry showed hyperglycemia, hypoalbuminemia and elevated aspartate aminotransferase and creatine kinase. Alterations in electrolyte values were also noted. Fourteen days later bile acid elevation was observed. Hematocrit levels normalized after 2 wk. A second incident involved a breeding pair of toco toucans (Ramphastos toco). While the female toco toucan received 10 stings and showed mild clinical manifestations, the male toco toucan was more severely attacked, receiving 40 stings, and died overnight. Despite the relative gravity of the attack (in terms of number of stingers in relation to body weight) both surviving birds recovered in less than 2 wk. To the authors' knowledge, fatal bee envenomation in birds has been reported only in pigeons and macaws. The findings described in this report suggest that toucans are less sensitive to bee venom when compared with pigeons and may have higher tolerance to bee venom compared with mammals. Honeybee envenomation must be considered a potential threat when considering toucan husbandry in zoos and collections.

SUCCESSFUL REDUCTION OF FEATHER-DAMAGING BEHAVIOR BY SOCIAL RESTRUCTURING IN A GROUP OF GOLDEN CONURES (GUARUBA GUAROUBA).

A variety of infectious and noninfectious causes may contribute to feather-damaging behavior (FDB) in birds. This paper describes an episode of FDB behavior related to an isosexual group composition in a group of 20 golden conures (Guaruba guarouba) kept in a collective aviary. After ruling out infectious causative agents and analyzing the social bird group composition over a period of 10 yr, the male to female ratio of the group was reduced from 1.7 to 1.0. This intervention resulted in a significant improvement of the feather condition and improved reproduction. Further analysis revealed that FDB was not correlated to age, gender, or origin. In addition, FDB was associated with stress, as reflected by an elevated heterophil : lymphocyte ratio that decreased significantly following social restructuring. This study stresses the importance of an appropriate male to female ratio when golden conures are kept in aviaries.

PRESUMPTIVE PIT VIPER ENVENOMATION IN PSITTACINES IN A BRAZILIAN ZOO.

Snake bites represent a serious public health risk in many regions of the globe, especially in tropical areas. Clinical signs and postmortem changes are well described in human and other mammalian species. However, detailed case reports about venomous snake attacks in avian species are limited. This report describes presumptive fatal envenomations in three psittacines caused by pit vipers in a Brazilian zoo. In one case, a Brazilian lancehead (Bothrops moojeni) was captured in the aviary. In all three cases the dermis around the suspected snake bite area exhibited hemorrhages and edema. Histologically, degeneration and necrosis of subcutaneous musculature were observed. Lung, heart, and kidneys displayed focal hemorrhages. The local changes are similar to those described for mammalian patients including humans. However, except for the parenchymatous hemorrhages, additional external and internal gross and histopathological lesions were missing. After ruling out other causes, such as aggression and dicoumarinic intoxication, the presumptive diagnosis of snake envenomation was made. The smaller size and variabilities of pathophysiological effects of the venom in parrots might explain the different lesion patterns observed, compared with mammals. Possibly, the birds may have reacted differently to envenomation by pit vipers and died before the venom could cause macroscopic and histological changes often observed in mammals.

Immunohistochemical demonstration of connexins in the developing feather follicle of the chicken.

Based on immunohistochemistry, the study demonstrates the varying distribution and reaction intensity of connexins (Cx26 [chicken 31sim], 30 [chicken 31], 31, 32, 43, 45) in the developing feather follicle of the chicken (White Leghorn). The different embryonal stages were identified according to the normal table of Hamburger and Hamilton (1951). The development of the feather follicle complex is closely related to skin layer development, making use of the controlling function of connexins. This was evident during feather follicle differentiation, based on communication between ectomesodermal (fibroblasts) and ectodermal cells (developing epidermis), but also by the subsequent separation of the two cell line types related to their connexin-dependent differentiation degree. With the increase in mesenchymal cell numbers during feather placode development, the multiple connexins Cx26 [chicken 31sim] and 43, supported by Cx30 [chicken 31], 31 and 32, were increasingly activating the fibroblast concentrations as related to epidermal follicle buds, the specific follicle structure, the endothelial cells of capillaries and larger blood vessels, as well as the collagen fiber production and the growing feather musculature shortly before hatching; Cx45 could not be demonstrated. In conclusion, it seems that connexin expression is not only coupled to the origin of embryonic cells, but also connected with tissue formation before the follicle system can be formed.

Scan-based volume animation driven by locally adaptive articulated registrations.

This paper describes a complete system to create anatomically accurate example-based volume deformation and animation of articulated body regions, starting from multiple in vivo volume scans of a specific individual. In order to solve the correspondence problem across volume scans, a template volume is registered to each sample. The wide range of pose variations is first approximated by volume blend deformation (VBD), providing proper initialization of the articulated subject in different poses. A novel registration method is presented to efficiently reduce the computation cost while avoiding strong local minima inherent in complex articulated body volume registration. The algorithm highly constrains the degrees of freedom and search space involved in the nonlinear optimization, using hierarchical volume structures and locally constrained deformation based on the biharmonic clamped spline. Our registration step establishes a correspondence across scans, allowing a data-driven deformation approach in the volume domain. The results provide an occlusion-free person-specific 3D human body model, asymptotically accurate inner tissue deformations, and realistic volume animation of articulated movements driven by standard joint control estimated from the actual skeleton. Our approach also addresses the practical issues arising in using scans from living subjects. The robustness of our algorithms is tested by their applications on the hand, probably the most complex articulated region in the body, and the knee, a frequent subject area for medical imaging due to injuries.

Differential sensitivity of well-differentiated avian respiratory epithelial cells to infection by different strains of infectious bronchitis virus.

Infectious bronchitis virus (IBV) is an avian coronavirus affecting the respiratory tract of chickens. To analyze IBV infection of the lower respiratory tract, we applied a technique that uses precision-cut lung slices (PCLSs). This method allows infection of bronchial cells within their natural tissue composition under in vitro conditions. We demonstrate that IBV strains 4/91, Italy02, and QX infect ciliated and mucus-producing cells of the bronchial epithelium, whereas cells of the parabronchial tissue are resistant to infection. This is the first study, using PCLSs of chicken origin, to analyze virus infection. PCLSs should also be a valuable tool for investigation of other respiratory pathogens, such as avian influenza viruses.

Creating an animatable 3D volume hand model from in vivo MRI.

Volume graphics has obvious benefits to medical visualization, since it represents the complete 3D information of both surface appearance and the underlying anatomical structures. This study presents an approach to rapidly creating an animatable 3D volume from in vivo human hand MRI scans. The result is a fully articulated hand volume driven by intuitive joint control that respects rigid deformation of the bone structures and produces smooth deformations of both the skin surface and the interior soft tissue regions. While the method can potentially be applied to any articulated body region, the human hand is chosen to illustrate the process, both due to its intrinsic interest in medical applications and because of the large number of degrees of freedom and challenging anatomy of the hand.

Infection of the tracheal epithelium by infectious bronchitis virus is sialic acid dependent.

Avian Infectious bronchitis virus (IBV) is a coronavirus that infects chickens via the respiratory epithelium as primary target cells. The binding of coronaviruses to the cell surface is mediated by the viral surface protein S. Recently we demonstrated that alpha2,3-linked sialic acid serves as a receptor determinant for IBV on Vero cells and primary chicken embryo kidney cells. Here we analyze the importance of the sialic acid binding activity for the infection of tracheal organ cultures (TOCs) by different IBV strains. Our results show that alpha2,3-linked sialic acid also serves as a receptor determinant on chicken TOCs. Infection of TOCs by IBV results in ciliostasis. Desialylation induced by neuraminidase treatment of tracheal organ cultures prior to infection by IBV delayed the ciliostatic effect or resulted in partial loss of ciliary activity. This effect was observed with both respiratory and nephropathogenic strains. Inhibition of ciliostasis was also observed when TOCs were pretreated with an alpha2,3-specific neuraminidase. Analysis of the tracheal epithelium for reactivity with lectins revealed that the susceptible cells in the epithelium abundantly express alpha2,3-linked sialic acid. These results indicate that alpha2,3-linked sialic acid plays an important role for infection of the respiratory epithelium by IBV.

Reproducibility of swollen sinuses in broilers by experimental infection with avian metapneumovirus subtypes A and B of turkey origin and their comparative pathogenesis.

Swollen head syndrome (SHS) associated with avian metapneumovirus (aMPV) subtype A or subtype B in broilers and broiler breeders has been reported worldwide. Data about pathogenesis of aMPV subtypes A and B in broilers are scarce. It has been difficult to reproduce swollen sinuses in chickens with aMPV under experimental conditions. In the field, SHS in broilers is suspected to be induced by combined infections with different respiratory pathogens. The objectives of the present study were to compare the pathogenesis of subtypes A and B aMPV in commercial broilers and to investigate the reproducibility of clinical disease. In two repeat experiments, commercial broilers free of aMPV maternal antibodies were inoculated with aMPV subtypes A and B of turkey origin. The clinical signs such as depression, coughing, nasal exudates, and frothy eyes appeared at 4 days post inoculation, followed by swelling of periorbital sinuses at 5 days post inoculation. Higher numbers of broilers showed clinical signs in subtype-B-inoculated compared with subtype-A-inoculated groups. Seroconversion to aMPV was detectable from 10 to 11 days post inoculation. The appearance of serum aMPV enzyme-linked immunosorbent assay antibodies and the clearance of the aMPV genome coincided. Subtype B aMPV showed a broader tissue distribution and longer persistence than subtype A. Histopathological changes were observed in the respiratory tract tissues of aMPV-inoculated broilers, and also in paraocular glands, such as the Harderian and lachrymal glands. Overall, our study shows that representative strains of both aMPV turkey isolates induced lesions in the respiratory tract, accompanied by swelling of infraorbital sinuses, indicating the role of aMPV as a primary pathogen for broilers.

The spike protein of infectious bronchitis virus is retained intracellularly by a tyrosine motif.

We have analyzed the intracellular transport of the spike (S) protein of infectious bronchitis virus (IBV), an avian coronavirus. Surface expression was analyzed by immunofluorescence microscopy, by surface biotinylation, and by syncytium formation by S-expressing cells. By applying these methods, the S protein was found to be retained intracellularly. Tyr1143 in the cytoplasmic tail was shown to be a crucial component of the retention signal. Deletion of a dilysine motif that has previously been suggested to function as a retrieval signal did not abolish intracellular retention. Treatment of the S proteins with endoglycosidases did not reveal any differences between the parental and the mutant proteins. Furthermore, all S proteins analyzed were posttranslationally cleaved into the subunits S1 and S2. In coexpression experiments, the S protein was found to colocalize with a Golgi marker. Taken together, these results indicate that the S protein of IBV is retained at a late Golgi compartment. Therefore, this viral surface protein differs from the S proteins of transmissible gastroenteritis virus and severe acute respiratory syndrome coronavirus, which are retained at a pre-Golgi compartment or transported to the cell surface, respectively. The implications of these differences are discussed.

Expressive facial animation synthesis by learning speech coarticulation and expression spaces.

Synthesizing expressive facial animation is a very challenging topic within the graphics community. In this paper, we present an expressive facial animation synthesis system enabled by automated learning from facial motion capture data. Accurate 3D motions of the markers on the face of a human subject are captured while he/she recites a predesigned corpus, with specific spoken and visual expressions. We present a novel motion capture mining technique that "learns" speech coarticulation models for diphones and triphones from the recorded data. A Phoneme-Independent Expression Eigenspace (PIEES) that encloses the dynamic expression signals is constructed by motion signal processing (phoneme-based time-warping and subtraction) and Principal Component Analysis (PCA) reduction. New expressive facial animations are synthesized as follows: First, the learned coarticulation models are concatenated to synthesize neutral visual speech according to novel speech input, then a texture-synthesis-based approach is used to generate a novel dynamic expression signal from the PIEES model, and finally the synthesized expression signal is blended with the synthesized neutral visual speech to create the final expressive facial animation. Our experiments demonstrate that the system can effectively synthesize realistic expressive facial animation.

Sialic acid is a receptor determinant for infection of cells by avian Infectious bronchitis virus.

The importance of sialic acid for infection by avian Infectious bronchitis virus (IBV) has been analysed. Neuraminidase treatment rendered Vero, baby hamster kidney and primary chicken kidney cells resistant to infection by the IBV-Beaudette strain. Sialic acid-dependent infection was also observed with strain M41 of IBV, which infects primary chicken kidney cells but not cells from other species. In comparison with Influenza A virus and Sendai virus, IBV was most sensitive to pre-treatment of cells with neuraminidase. This finding suggests that IBV requires a greater amount of sialic acid on the cell surface to initiate an infection compared with the other two viruses. In previous studies, with respect to the haemagglutinating activity of IBV, it has been shown that the virus preferentially recognizes alpha2,3-linked sialic acid. In agreement with this finding, susceptibility to infection by IBV was connected to the expression of alpha2,3-linked sialic acid as indicated by the reactivity with the lectin Maackia amurensis agglutinin. Here, it is discussed that binding to sialic acid may be used by IBV for primary attachment to the cell surface; tighter binding and subsequent fusion between the viral and the cellular membrane may require interaction with a second receptor.

Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin.

The anticancer drug rViscumin, currently under clinical development, has been shown in previous studies to be a sialic acid specific ribosome inactivating protein (RIP). Comparative binding assays with the CD75s-specific monoclonal antibodies HB6 and J3-89 revealed rViscumin to be a CD75s-specific RIP due to identical binding characteristics toward CD75s gangliosides. The receptor gangliosides are IV6nLc4Cer, VI6nLc6Cer, and the newly characterized ganglioside VIII6nLc8Cer, all three carrying the Neu5Acalpha2-6Galbeta1-4GlcNAc motif. To elucidate the clinical potential of the rViscumin targets, CD75s gangliosides were determined in several randomly collected gastrointestinal tumors. The majority of the tumors showed an enhanced expression of CD75s gangliosides compared with the unaffected tissues. The rViscumin binding specificity was further investigated with reference glycoproteins carrying sialylated and desialylated type II N-glycans. Comparative Western blots of rViscumin and ricin, an rViscumin homologous but galactoside-specific RIP, revealed specific recognition of type II N-glycans with CD75s determinants by rViscumin, whereas ricin failed to react with terminally sialylated oligosaccharides such as CD75s motifs and others. This strict binding specificity of rViscumin and the increased expression of CD75s gangliosides in various tumors suggest this anticancer drug as a promising candidate for an individualised adjuvant therapy of human tumors.

Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues.

Mistletoe lectin I (ML-I) is a type II ribosome-inactivating protein, which inhibits the protein biosynthesis at the ribosomal level. ML-I is composed of a catalytically active A-chain with rRNA N-glycosidase activity and a B-chain with carbohydrate binding specificities. Using comparative solid-phase binding assays along with electrospray ionization tandem mass spectrometry, ML-I was shown to preferentially bind to terminally alpha2-6-sialylated neolacto series gangliosides from human granulocytes. IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer were identified as ML-I receptors, whereas the isomeric alpha2-3-sialylated neolacto series gangliosides were not recognized. Only marginal binding of ML-I to terminal galactose residues of neutral glycosphingolipids with a Galbeta1-4Glc or Galbeta1-4GlcNAc sequence was determined, whereas a distal Galalpha1-4Gal, GalNAcbeta1-3Gal, or GalNAcbeta1-4Gal disaccharide did not bind at all. Among the glycoproteins investigated in Western blot and microwell adsorption assays, only those carrying Neu5Acalpha2-6Galbeta1-4GlcNAc residues, exclusively, predominantly, or even as less abundant constituents in an assembly with Neu5Acalpha2-3Galbeta1-4GlcNAc-terminated glycans, displayed high ML-I binding capacity. From our data we conclude that (i) ML-I has to be considered as a sialic acid- and not a galactose-specific lectin and (ii) neolacto series gangliosides and sialoglycoproteins with type II glycans, which share the Neu5Acalpha2-6Galbeta1-4GlcNAc terminus, are true ML-I receptors. This strict preference might help to explain the immunostimulatory potential of ML-I toward certain leukocyte subpopulations and its therapeutic success as a cytotoxic anticancer drug.

Lectin histochemistry of the lymphoid organs of the chicken.

Cellular interactions within the immune system are in part mediated via the carbohydrate-rich coat of the cell membrane, the glycocalyx, of which the terminal carbohydrate residues are of particular functional importance. Thus, these carbohydrate residues from thymus, bursa of Fabricius, spleen and bone marrow of 2- and 30-day-old chickens were investigated by lectin histochemistry. In the thymus, mannose as well as N-acetyl-glucosamine (glcNAc)-specific lectins labelled macrophages, epithelial reticulum cells and lymphocytes within the cortex. In the bursa of Fabricius, the brush border of the lining epithelium, the macrophages and the endothelium were labelled by mannose-specific lectins. The follicle-associated epithelium was labelled by a broad spectrum of lectins. Epithelial cells that separated the cortex from the medulla and large mononuclear cells in the cortex were only being labelled by N-acetyl-galactosamine (galNAc)-specific and glcNAc-specific lectins, respectively. In the spleen, lymphocytes of the peri-ellipsoid lymphocyte sheaths and macrophages of the red pulp were labelled by lectins of nearly all sugar specificities. In general, glycotopes of these organs were more intensively labelled in the 2-day-old chicken than in the 30-day-old chicken, indicating changes in glycotope expression during post-hatching development. Thus, cells of the avian immune system are as rich and diverse in their lectin binding sites as their mammalian counterparts, indicating that similar carbohydrate lectin interactions between cells and matrices take place in birds as well.

3D tooth shape from radiographs using thin-plate splines.

Current methods to produce 3-dimensional tooth root models involve conversion from radiographic means (computed tomography) or creation using computer-assisted design (CAD) software. The former lacks detail while the second is manually fabricated and can bear little resemblance to the original. Thin-plate splines have been used in morphometrics to define changes of shape between subjects of the same species. Herein, we use thin-plate splines to deform a 3D geometric prior model of a tooth to match 2D patient radiographs, producing a "best-fit" patient specific 3D geometric polygonal mesh of the tooth.

The virtual craniofacial patient: 3D jaw modeling and animation.

In this paper, we present new developments in the area of 3D human jaw modeling and animation. CT (Computed Tomography) scans have traditionally been used to evaluate patients with dental implants, assess tumors, cysts, fractures and surgical procedures. More recently this data has been utilized to generate models. Researchers have reported semi-automatic techniques to segment and model the human jaw from CT images and manually segment the jaw from MRI images. Recently opto-electronic and ultrasonic-based systems (JMA from Zebris) have been developed to record mandibular position and movement. In this research project we introduce: (1) automatic patient-specific three-dimensional jaw modeling from CT data and (2) three-dimensional jaw motion simulation using jaw tracking data from the JMA system (Zebris).

Preferential binding of the anticancer drug rViscumin (recombinant mistletoe lectin) to terminally alpha2-6-sialylated neolacto-series gangliosides.

Production of biochemically defined recombinant mistletoe lectin was achieved by cloning and separate expression of the single catalytically active A-chain and the B-chain with carbohydrate binding properties in Escherichia coli, yielding an active heterodimeric protein named rViscumin (Eck et al. [1999] Eur. J. Biochem., 265, 788-797). Employing solid phase binding assays, rViscumin was shown to preferentially bind to terminally alpha2-6-sialylated neolacto-series gangliosides IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer isolated from human granulocytes. Only marginal binding of rViscumin to galactose-terminated neutral GSLs was determined, whereas reinvestigation of ricin specificity demonstrated this lectin as a galactose-binding protein. Human promyelotic HL-60 cells exhibited an IC(50) value (half maximum cytotoxicity) of 1.16 pM and human bladder carcinoma 5637 cells of 12.1 pM rViscumin; CHO-K1 cells were resistant to rViscumin treatment up to a concentration of 5.26 nM tested. Quantification of the predominant receptor ganglioside IV(6)Neu5Ac-nLc4Cer by means of a specific anti-Neu5Acalpha2-6Galbeta1-4GlcNAc-R antibody revealed 3.68 x 10(6) and 1.54 x 10(6) receptor molecules per HL-60 and 5637 cell, respectively; CHO-K1 cells were negative, lacking alpha2-6-sialylated gangliosides. The data imply a direct correlation of rViscumin cytotoxicity and the expression of receptor ganglioside. Moreover, CHO-K1 cells were rendered susceptible toward rViscumin cytotoxicity after exogenous application of human granulocyte gangliosides. Thus, (1) rViscumin has to be considered as a sialic acid-specific rather than a galactose-specific type II ribosome-inactivating protein, and (2) neolacto-series gangliosides with Neu5Acalpha2-6Galbeta1-4GlcNAc-terminus are true functional and physiologically relevant rViscumin receptors.