Insulators as mediators of intra- and inter-chromosomal interactions: a common evolutionary theme

Insulator elements mediate intra- and inter-chromosomal interactions. The insulator protein CCCTC-binding factor (CTCF) is important for insulator function in several animals but a report in BMC Molecular Biology shows that Caenorhabditis elegans, yeast and plants lack CTCF. Alternative proteins may have a similar function in these organisms

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation

Notch and Presenilin Regulate Cellular Expansion and Cytokine Secretion but Cannot Instruct Th1/Th2 Fate Acquisition

Recent reports suggested that Delta1, 4 and Jagged1, 2 possessed the ability to instruct CD4+ T cell into selection of Th1 or Th2 fates, respectively, although the underlying mechanism endowing the cleaved Notch receptor with memory of ligand involved in its activation remains elusive. To examine this, we prepared artificial antigen-presenting cells expressing either DLL1 or Jag1. Although both ligands were efficient in inducing Notch2 cleavage and activation in CD4+ T or reporter cells, the presence of Lunatic Fringe in CD4+ T cells inhibited Jag1 activation of Notch1 receptor. Neither ligand could induce Th1 or Th2 fate choice independently of cytokines or redirect cytokine-driven Th1 or Th2 development. Instead, we find that Notch ligands only augment cytokine production during T cell differentiation in the presence of polarizing IL-12 and IL-4. Moreover, the differentiation choices of naïve CD4+ T cells lacking γ-secretase, RBP-J, or both in response to polarizing cytokines revealed that neither presenilin proteins nor RBP-J were required for cytokine-induced Th1/Th2 fate selection. However, presenilins facilitate cellular proliferation and cytokine secretion in an RBP-J (and thus, Notch) independent manner. The controversies surrounding the role of Notch and presenilins in Th1/Th2 polarization may reflect their role as genetic modifiers of T-helper cells differentiation

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Block-based neural network mapping on graphics processor unit

Block-based neural network (BbNN) was introduced to improve the training speed of artificial neural network. Various works had been carried out by previous researchers to improve training speed of BbNN system. Multithread BbNN training on field-programmable gate array (FPGA) limits training speed due to low performance of Nios II software used for communication between central processing unit (CPU) and FPGA. This project aims to improve training speed of multithread BbNN block by mapping BbNN model into Compute Unified Device Architecture (CUDA) core. In this project, each BbNN block is mapped into a CUDA core with each core running on a single thread. The functional verification of BbNN core is carried out based on the BbNN output accuracy value. Near 100 percent accuracy value obtained is used to verify the CUDA mapped BbNN. The performance trade-off analysis had been carried out by comparing the accuracy value obtained from BbNN evolution on GPU versus CPU implementations. From the results obtained, it is found out that the performance of CUDA-mapped BbNN can only be as fast as CPU-mapped implementation. Although CUDA-mapped BbNN implementation run multiple BbNN blocks training in parallel, large data transfer between CPU and GPU dominates the performance gain in training multiple BbNN blocks in parallel. Besides that, a significant gain in training speed can only be seen if the order of complexity for GPU execution is at a higher order compared to the order of CPU-GPU data transfer. The result obtained in this project provides recommendation for future research works on how to further improve the training speed of CUDA-base BbNN implementation

Insulators as mediators of intra-and inter-chromosomal interactions: a common evolutionary theme

Abstract Insulator elements mediate intra-and inter-chromosomal inter actions. The insulator protein CCCTC-binding factor (CTCF) is important for insulator function in several animals but a report in BMC Molecular Biology shows that Caenorhabditis elegans, yeast and plants lack CTCF. Alternative proteins may have a similar function in these organisms. Eukaryotic genomes have developed a variety of strategies for efficiently orchestrating the complex patterns of gene expression required for proper cellular differentiation. Comparative genome analyses suggest that developmental evolution is largely driven by the increase in the complexity of these expression patterns CCCTC-binding factor (CTCF Examples of insulator function The mechanisms of insulator function are best understood from analyses of the gypsy element of Drosophila. Gypsy insulator sites are bound by the Suppressor of Hairy-wing protein (Su(Hw)), in a sequence-specific manner. This protein in turn recruits other factors, including centrosomal protein 190 kDa (CP190), Modifier of mdg4 (Mod(mdg4)2.2), topoisomerase I-interacting RS protein (dTopors) and RNA, to form clusters of 'insulator bodies' (consisting of these proteins and DNA) with multiple gypsy sites The concept of intra-and inter-chromosomal interaction mediated by insulator proteins in Drosophila seems to be applicable to the CTCF insulator in vertebrates, despite the involvement of a different set of protein complexes. The mechanism of CTCF function in vertebrates is best illustrated by the mouse imprinted Igf2-H19 locu

NELF-A controls Drosophila healthspan by regulating heat-shock protein-mediated cellular protection and heterochromatin maintenance

10.1111/acel.13348Aging Cell205e1334

Strengthening performance of PALF-epoxy composite plate on reinforced concrete beams

This paper presents the effective strengthening potential of pineapple leaves fiber (PALF)-epoxy composite plate on reinforced concrete (RC) beam. At first the PALF is treated with alkali (NaOH) and its morphology is observed via scanning electron microscope (SEM).The composite plates made of PALF and epoxy with fiber loading ranging from 0.1 to 0.4 v/v was tested for its flexural behaviour. The composite was then used for external RC beam strengthening. The structural properties of RC beams were evaluated and all the beams were tested under four-point bending. It was found that the flexural strength increased as the fiber volume ratio increases. The maximum flexural strength (301.94 MPa) was obtained at the fiber volume ratio of 40%. The beam strengthened with PALF-epoxy composite plate has a 7% higher beam capacity compared to the control beam. Cracks formed at the edge of the plate of PALF-strengthened beams resulted in diagonal cracking. Result from this work shows that thePALF-epoxy composite plate has the potential to be used as external strengthening material for RC beam