Framework for Predictive Analytics with Complex Event Processing

Event processing is a technique of tracking and scrutinizing of information about the events that happen and deriving a conclusion from them. Complex Event Processing(CEP) is a technology which allows combining of data from multiple sources and infers complicated patterns from the events. Complex events require real time detection in order to have time for appropriate reactions. However, there are several events which should be prevented rather than responding to them after they have occurred. This can be achieved using Predictive analysis. Predictive analysis(PA) enhances the performance of CEP. In this paper, we define CEP and PA technology and provide a conceptual framework which provides synergy between CEP and PA. This framework can be the basis of general design pattern in future

"Harnessing genomics to improve health in India" – an executive course to support genomics policy

BACKGROUND: The benefits of scientific medicine have eluded millions in developing countries and the genomics revolution threatens to increase health inequities between North and South. India, as a developing yet also industrialized country, is uniquely positioned to pioneer science policy innovations to narrow the genomics divide. Recognizing this, the Indian Council of Medical Research and the University of Toronto Joint Centre for Bioethics conducted a Genomics Policy Executive Course in January 2003 in Kerala, India. The course provided a forum for stakeholders to discuss the relevance of genomics for health in India. This article presents the course findings and recommendations formulated by the participants for genomics policy in India. METHODS: The course goals were to familiarize participants with the implications of genomics for health in India; analyze and debate policy and ethical issues; and develop a multi-sectoral opinion leaders' network to share perspectives. To achieve these goals, the course brought together representatives of academic research centres, biotechnology companies, regulatory bodies, media, voluntary, and legal organizations to engage in discussion. Topics included scientific advances in genomics, followed by innovations in business models, public sector perspectives, ethics, legal issues and national innovation systems. RESULTS: Seven main recommendations emerged: increase funding for healthcare research with appropriate emphasis on genomics; leverage India's assets such as traditional knowledge and genomic diversity in consultation with knowledge-holders; prioritize strategic entry points for India; improve industry-academic interface with appropriate incentives to improve public health and the nation's wealth; develop independent, accountable, transparent regulatory systems to ensure that ethical, legal and social issues are addressed for a single entry, smart and effective system; engage the public and ensure broad-based input into policy setting; ensure equitable access of poor to genomics products and services; deliver knowledge, products and services for public health. A key outcome of the course was the internet-based opinion leaders' network – the Indian Genome Policy Forum – a multi-stakeholder forum to foster further discussion on policy. CONCLUSION: We expect that the process that has led to this network will serve as a model to establish similar Science and Technology policy networks on regional levels and eventually on a global level

Induction and transcriptional regulation of the co-inhibitory gene module in T cells

Expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated co-inhibitory receptor expression on CD4+ T cells promotes autoimmunity while sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and cancer1,2. Here, we used RNA and protein expression profiling at single-cell resolution to identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, Tim-3, Lag-3, and TIGIT), but also a number of novel surface receptors. We functionally validated two novel co-inhibitory receptors, Activated protein C receptor (Procr) and Podoplanin (Pdpn). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in multiple physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors Prdm1 and c-Maf as cooperative regulators of the co-inhibitory module, which we validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies novel regulators of T cell function with the potential to regulate autoimmunity and tumor immunity

The Endocannabinoid System Acts As A Regulator Of Immune Homeostasis In The Gut

Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipids. Endogenous intestinal cannabinoids such as Anandamide (AEA), control appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a novel role for AEA and its vanilloid receptor (VR1) in the regulation of immune tolerance in the gut and the pancreas. This is the first demonstration of a major immunological role for an endocannabinoid. Capsaicin (CP), a vanilloid, with which AEA shares VR1, acts similarly. Specifically, we show that the engagement of the cannabinoid/vanilloid receptor augments the number and immune suppressive function of the regulatory CX3CR1hi macrophages, which express the highest levels of such receptors among the gut immune cells. Additionally, mice that are genetically deficient in VR1 have reduced proportions of CX3CR1hi macrophages in the gut under normal homeostatic conditions. Treatment of mice with CP also leads to differentiation of a regulatory subset of CD4+ T cells called Tr1 cells in an IL27 dependent manner both in vitro and in vivo. In a functional demonstration, tolerance elicited by engagement of VR1 can be transferred to naïve NOD mice (model of type 1 diabetes) by transfer of CD4+ T cells. Further, oral administration of AEA to NOD mice provides protection from type 1 diabetes. Our study unveils a novel role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas, and reveals a new conversation between the nervous and immune systems, using distinct receptors

Tim-3 finds its place in the cancer immunotherapy landscape

The blockade of immune checkpoint receptors has made great strides in the treatment of major cancers, including melanoma, Hodgkin’s lymphoma, renal, and lung cancer. However, the success rate of immune checkpoint blockade is still low and some cancers, such as microsatellite‐stable colorectal cancer, remain refractory to these treatments. This has prompted investigation into additional checkpoint receptors. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a checkpoint receptor expressed by a wide variety of immune cells as well as leukemic stem cells. Coblockade of Tim-3 and PD-1 can result in reduced tumor progression in preclinical models and can improve antitumor T-cell responses in cancer patients. In this review, we will discuss the basic biology of Tim-3, its role in the tumor microenvironment, and the emerging clinical trial data that point to its future application in the field of immune-oncology

Tim-3 finds its place in the cancer immunotherapy landscape

The blockade of immune checkpoint receptors has made great strides in the treatment of major cancers, including melanoma, Hodgkin's lymphoma, renal, and lung cancer. However, the success rate of immune checkpoint blockade is still low and some cancers, such as microsatellite-stable colorectal cancer, remain refractory to these treatments. This has prompted investigation into additional checkpoint receptors. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a checkpoint receptor expressed by a wide variety of immune cells as well as leukemic stem cells. Coblockade of Tim-3 and PD-1 can result in reduced tumor progression in preclinical models and can improve antitumor T-cell responses in cancer patients. In this review, we will discuss the basic biology of Tim-3, its role in the tumor microenvironment, and the emerging clinical trial data that point to its future application in the field of immune-oncology

Two-symbol FPGA architecture for fast arithmetic encoding in JPEG 2000

JPEG 2000 is one of the most popular image compression standards offering significant performance advantages over previous image standards. High computational complexity of the JPEG 2000 algorithms makes it necessary to employ methods that overcomes the bottlenecks of the system and hence an efficient solution is imperative. One such crucial algorithms in JPEG 2000 is arithmetic coding and is completely based on bit level operations. In this paper, an efficient hardware implementation of arithmetic coding is proposed which uses efficient pipelining and parallel processing for intermediate blocks. The idea is to provide a two-symbol coding engine, which is efficient in terms of performance, memory and hardware. This architecture is implemented in Verilog hardware definition language and synthesized using Altera field programmable gate array. The only memory unit used in this design is a FIFO (first in first out) of 256 bits to store the CXD pairs at the input, which is negligible compared to the existing arithmetic coding hardware designs. The simulation and synthesis results show that the operating frequency of the proposed architecture is greater than 100 MHz and it achieves a throughput of 212 Msymbols/sec, which is double the throughput of conventional one-symbol implementation and enables at least 50% throughput increase compared to the existing two-symbol architectures

Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function

Dendritic cells (DCs) sense environmental cues and adopt either an immune-stimulatory or regulatory phenotype, thereby fine-tuning immune responses. Identifying endogenous regulators that determine DC function can thus inform the development of therapeutic strategies for modulating the immune response in different disease contexts. Tim-3 plays an important role in regulating immune responses by inhibiting the activation status and the T cell priming ability of DC in the setting of cancer. Bat3 is an adaptor protein that binds to the tail of Tim-3; therefore, we studied its role in regulating the functional status of DCs. In murine models of autoimmunity (experimental autoimmune encephalomyelitis) and cancer (MC38-OVA–implanted tumor), lack of Bat3 expression in DCs alters the T cell compartment—it decreases TH1, TH17 and cytotoxic effector cells, increases regulatory T cells, and exhausted CD8+tumor-infiltrating lymphocytes, resulting in the attenuation of autoimmunity and acceleration of tumor growth. We found that Bat3 expression levels were differentially regulated by activating versus inhibitory stimuli in DCs, indicating a role for Bat3 in the functional calibration of DC phenotypes. Mechanistically, loss of Bat3 in DCs led to hyperactive unfolded protein response and redirected acetyl–coenzyme A to increase cell intrinsic steroidogenesis. The enhanced steroidogenesis in Bat3-deficient DC suppressed T cell response in a paracrine manner. Our findings identified Bat3 as an endogenous regulator of DC function, which has implications for DC-based immunotherapies.</jats:p