Exploiting Inferential Structure in Neural Processes

Neural Processes (NPs) are appealing due to their ability to perform fast adaptation based on a context set. This set is encoded by a latent variable, which is often assumed to follow a simple distribution. However, in real-word settings, the context set may be drawn from richer distributions having multiple modes, heavy tails, etc. In this work, we provide a framework that allows NPs’ latent variable to be given a rich prior defined by a graphical model. These distributional assumptions directly translate into an appropriate aggregation strategy for the context set. Moreover, we describe a message-passing procedure that still allows for end-to-end optimization with stochastic gradients. We demonstrate the generality of our framework by using mixture and Student-t assumptions that yield improvements in function modelling and test-time robustness

The Use of Growth Factors and Mesenchymal Stem Cells in Orthopaedics

Stem cell therapy is an exciting and upcoming branch of tissue engineering with application in the field of orthopaedics. The most commonly used type of stem cells, mesenchymal stem cells (MSCs), can be easily isolated from bone marrow or synovium and cultured in vitro. Newer techniques using tissue engineering to regenerate musculoskeletal tissue by using biomimetic materials are now being studied. These osteoconductive three dimensional constructs seeded with MSCs are highly porous, biodegradable and biomechanically stable scaffolds which do not evoke an immunogenic host cell response. Research has shown the importance of growth factors in guiding and modulating the differentiation of MSCs in order to obtain the required cell type. Gene-based delivery systems have aided the delivery of sustained quantities of these growth factors. The evidence from growth factor enhanced tissue engineering studies for tissue healing looks very positive. This is a multi-disciplinary approach that integrates molecular, biochemical and clinical techniques with developmental and engineering processes. Initial studies indicate an immense potential for cell based strategies to enhance current orthopaedic approaches in skeletal tissue reconstruction. Ultimately, there is a need for randomised controlled trials on human populations to apply these findings to a clinical setting. Nevertheless, stem cell based tissue engineering in orthopaedics shows a promising future

Relook at Foundation Design of RE Structures in Indian Environment Based on Case Study

India has massive infrastructure development plan in next decade. The safety, cost optimization saving construction time is challenges to engineers. The mass communication progress of 11th & 12th five year plans involves design and execution of large number of underpasses/flyovers through out country. The problems faced by adoption of foundation practice in India based on interpretation of BS 8006 / 1995 during execution are analyzed. Though not widely publicized, failures of walls or part of facial block wall are reported. To avoid contract schedules quick remedial measures are adopted, which based on consultants and facilities includes stone columns, lime piles, CC slab cover over foundation trench etc. A relook at entire problem for RE walls or steep slope foundation is reported. The site specific parameters namely construction season, rains during execution, desiccated expansive soils, settlement of parent subsoil for long life, environment – flood ponding are ignored. A sand-gravel 1.5 m pad foundation cannot take above factors in to account. The soil below the pad is rarely evaluated for differential settlement. Cyclically flooded poorly drained geographical areas particularly for long life structures, needs to be looked into. For Indian fast developing zones a common approach is evolved. This includes specific shallow depth exploration of RE wall foundations, environmental data collection of drainage, flooding and settlement analysis. Depth of trench is site specific depending on desiccated depth and permissible settlement. A model profile of subsoil, replaced relatively impervious fill in trench with or without Geofabrics is presented. The relook of site specific factors and control of settlement in present practice is justified by case studies presented

Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations

One less visited area in musculoskeletal stem cell research is the effects of donor age on quality of stem cells. The prevalence of degenerative orthopaedic conditions is large, and the older population is likely to receive great benefit from stem cell therapies. There are many known growth factors involved in controlling and influencing stem cell growth which are also related to cell senescence. Of which, expressions are found to be altered in mesenchymal stem cells from older donors. Considerations must also be taken of these mechanisms which also have a role in cell cycle and tumour suppression

Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations

One less visited area in musculoskeletal stem cell research is the effects of donor age on quality of stem cells. The prevalence of degenerative orthopaedic conditions is large, and the older population is likely to receive great benefit from stem cell therapies. There are many known growth factors involved in controlling and influencing stem cell growth which are also related to cell senescence. Of which, expressions are found to be altered in mesenchymal stem cells from older donors. Considerations must also be taken of these mechanisms which also have a role in cell cycle and tumour suppression

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche.

A major challenge in stem cell differentiation is the availability of bioassays to prove cell types generated in vitro are equivalent to cells in vivo. In the mouse, differentiation of primordial germ cell-like cells (PGCLCs) from pluripotent cells was validated by transplantation, leading to the generation of spermatogenesis and to the birth of offspring. Here we report the use of xenotransplantation (monkey to mouse) and homologous transplantation (monkey to monkey) to validate our in vitro protocol for differentiating male rhesus (r) macaque PGCLCs (rPGCLCs) from induced pluripotent stem cells (riPSCs). Specifically, transplantation of aggregates containing rPGCLCs into mouse and nonhuman primate testicles overcomes a major bottleneck in rPGCLC differentiation. These findings suggest that immature rPGCLCs once transplanted into an adult gonadal niche commit to differentiate towards late rPGCs that initiate epigenetic reprogramming but do not complete the conversion into ENO2-positive spermatogonia

TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1

Ubiquitin E3-ligases are recruited at different steps of TNF-α-induced NF-κB activation; however, their role in temporal regulation of the pathway remains elusive. The study systematically identified TRIMs as potential feedback regulators of the TNF-α-induced NF-κB pathway. We further observed that TRIM15 is “late” response TNF-α-induced gene and inhibits the TNF-α-induced NF-κB pathway in several human cell lines. TRIM15 promotes turnover of K63-linked ubiquitin chains in a PRY/SPRY domain-dependent manner. TRIM15 interacts with TAK1 and inhibits its K63-linked ubiquitination, thus NF-κB activity. Further, TRIM15 interacts with TRIM8 and inhibits cytosolic translocation to antagonize TRIM8 modualted NF-κB. TRIM8 and TRIM15 also show functionally inverse correlation in psoriasis condition. In conclusion, TRIM15 is TNF-α-induced late response gene and inhibits TNF-α induced NF-κB pathway hence a feedback modulator to keep the proinflammatory NF-κB pathway under control