Himanshu Kumar - Academia.edu (original) (raw)

Papers by Himanshu Kumar

The present subject matter discloses a system (104) and a method for managing a connection betwee... more The present subject matter discloses a system (104) and a method for managing a connection between a client (102) and an application (214) within a server (104) in a network (106). In one implementation, the method includes receiving a connection request from the client (102). The method further includes associating with a worker thread (228), a unique identifier (UID) that uniquely identifies the received connection request. Further, the method involves, communicating a message that includes client data associated with the connection request to the application by the worker thread. The method also includes obtaining, by a reverse worker thread (230), a reply message (218) associated with the UID from the application. The reverse worker thread is configured to communicate the reply message (218) to the client (102).

Molecular Biology Reports, 2012

Oxidative stress is one of the major causes of degenerative conditions occurring at cellular leve... more Oxidative stress is one of the major causes of degenerative conditions occurring at cellular level with serious health implications. This study was aimed at investigating the antioxidative potentials of probiotic lactobacilli of Indian gut origin and their ability to augment antioxidant defense enzyme systems in the host cells under oxidative stress conditions. A total of 39 Lactobacillus cultures were assessed for their resistance against reactive oxygen species. Most of the cultures were moderately to strongly resistant towards 0.4 mM H 2 O 2. The Lactobacillus isolate CH4 was the most H 2 O 2 resistant culture with only 0.06 log cycle reduction. Majority of the cultures demonstrated high resistance towards hydroxyl ions and Lp21 was the most resistant with log count reduction of 0.20 fold only. Almost all the cultures were also quite resistant to superoxide anions. Lp21 also showed the highest superoxide dismutase content (0.8971 U). Amongst the 39 cultures, Lactobacillus spp. S3 showed the highest total antioxidative activity of 77.85 ± 0.13 % followed by Lp55 (56.1 ± 1.2 %) in terms of per cent inhibition of linolenic acid oxidation. Lp9 upregulated the expression of superoxide dismutase 2 gene in HT-29 cells both at 0.1 mM (1.997 folds) and 1.0 mM H 2 O 2 (2.058 folds) concentrations. In case of glutathione peroxidase-1, Lp9, Lp91 and Lp55 showed significant (P \ 0.001) up-regulation in the gene expression to the level of 5.451, 8.706 and 10.083 folds, respectively when HT-29 was challenged with 0.1 mM H 2 O 2. The expression of catalase gene was also significantly up-regulated by all the cultures at 0.1 mM H 2 O 2 conditions. It can be concluded that the antioxidative efficacy of the putative probiotic lactobacilli varied considerably between species and strains and the potential strains can be explored as prospective antioxidants to manage oxidative stress induced diseases.

General Relativity and Gravitation, 2012

With an aim to include the contribution of surface tension in the action of the boundary, we defi... more With an aim to include the contribution of surface tension in the action of the boundary, we define the tangential pressure in terms of surface tension and Normal curvature in a more naturally geometric way. For a thin shell approximation of a static spherically symmetric surface and for weak and slowly varying fields, the negative tangential pressure is chosen to be analogous to S , where S is the classical surface tension. First, by a suitable choice of the enveloping surfaces, we show that the negative tangential pressure is independent of the four-velocity of a very thin hyper-surface. Second, using suitable definition of the normal curvature for such a surface layer, we relate the 3-pressure of a surface layer to the normal curvature and the surface tension. Third, using the fact that the tangential pressure on the surface layer is independent of the four-velocity and a central force interaction, we relate the surface tension S to the energy of the surface layer. Four, we show that the delta like energy flows across the hypersurface will be zero for such a representation of intrinsic 3-pressure. Five, for the weak field approximation and for static spherically symmetric configuration, we deduce the classical Kelvins relation between surface tension, pressure difference and mean curvature from this sort of representation of negative tangential pressure in terms of surface tension S and the normal curvature. Six, using the representation of tangential pressure in terms of surface tension and normal curvature, we write a modified action for the boundary having contributions both from surface tension and normal curvature of the surface layer. Also we propose a method to find the physical action assuming a reference background, where the background is + not flat. (The g or just g has been chosen to represent the metric coefficent of the hypersurface of V+ space which is time-like surface layer here. The g represents the metric coefficient of the space like hypersurface of V space.

Nature Immunology, 2005

Type I interferons are central mediators for antiviral responses. Using high-throughput functiona... more Type I interferons are central mediators for antiviral responses. Using high-throughput functional screening of interferon inducers, we have identified here a molecule we call interferon-b promoter stimulator 1 (IPS-1). Overexpression of IPS-1 induced type I interferon and interferon-inducible genes through activation of IRF3, IRF7 and NF-jB transcription factors. TBK1 and IKKi protein kinases were required for the IPS-1-mediated interferon induction. IPS-1 contained an N-terminal CARD-like structure that mediated interaction with the CARD of RIG-I and Mda5, which are cytoplasmic RNA helicases that sense viral infection. 'Knockdown' of IPS-1 by small interfering RNA blocked interferon induction by virus infection. Thus, IPS-1 is an adaptor involved in RIG-I-and Mda5-mediated antiviral immune responses.

The Journal of Immunology, 2009

Plasmacytoid dendritic cells (pDCs) recognize RNA virus infection via TLRs and consequently produ... more Plasmacytoid dendritic cells (pDCs) recognize RNA virus infection via TLRs and consequently produce vast amounts of type I IFN. Because nucleic acid-sensing TLRs reside in the intracellular membrane compartment, it is presumable that pDCs do not require cytoplasmic viral replication to recognize the infection. By checking Newcastle disease virus (NDV) RNA abundance in GFP+ and GFP− pDCs from Ifna6gfp mice, we found that NDV replication was not detected in IFN-producing pDCs. GFP+ pDC was induced in response to replication-incompetent NDV. In contrast, the replication-incompetent NDV failed to induce IFN-producing pDCs in type I IFNR-deficient mice. The lack of IFNR signaling led to the replication of NDV and the subsequent RIG-I-like helicase-dependent IFN-α production in pDCs. These results showed that detection of viruses via TLRs together with a type I IFN feedback system circumvents the requirement for viral replication-dependent recognition in pDCs.

The Journal of Immunology, 2007

The innate immune system recognizes influenza A virus via TLR 7 or retinoic acid-inducible gene I... more The innate immune system recognizes influenza A virus via TLR 7 or retinoic acid-inducible gene I in a cell-type specific manner in vitro, however, physiological function(s) of the MyD88- or interferon-β promoter stimulator 1 (IPS-1)-dependent signaling pathways in antiviral responses in vivo remain unclear. In this study, we show that although either MyD88- or IPS-1-signaling pathway was sufficient to control initial antiviral responses to intranasal influenza A virus infection, mice lacking both pathways failed to show antiviral responses, resulting in increased viral load in the lung. By contrast, induction of B cells or CD4 T cells specific to the dominant hemagglutinin or nuclear protein Ags respectively, was strictly dependent on MyD88 signaling, but not IPS-1 signaling, whereas induction of nuclear protein Ag-specific CD8 T cells was not impaired in the absence of either MyD88 or IPS-1. Moreover, vaccination of TLR7- and MyD88-deficient mice with inactivated virus failed to c...

Journal of Experimental Medicine, 2007

Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream sig... more Toll-like receptors (TLRs) recognize a variety of microbial components and mediate downstream signal transduction pathways that culminate in the activation of nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases. Trib1 is reportedly involved in the regulation of NF-κB and MAP kinases, as well as gene expression in vitro. To clarify the physiological function of Trib1 in TLR-mediated responses, we generated Trib1-deficient mice by gene targeting. Microarray analysis showed that Trib1-deficient macrophages exhibited a dysregulated expression pattern of lipopolysaccharide-inducible genes, whereas TLR-mediated activation of MAP kinases and NF-κB was normal. Trib1 was found to associate with NF-IL6 (also known as CCAAT/enhancer-binding protein β). NF-IL6–deficient cells showed opposite phenotypes to those in Trib1-deficient cells in terms of TLR-mediated responses. Moreover, overexpression of Trib1 inhibited NF-IL6–dependent gene expression by down-regulating NF-IL6 prot...

Immunity, 2007

Type I interferons (IFNs) are critical for antiviral responses. Here we generated a knockin mouse... more Type I interferons (IFNs) are critical for antiviral responses. Here we generated a knockin mouse in which green fluorescence protein (GFP) was expressed under the control of the Ifna6 promoter. Virus-induced expression of GFP recapitulated various IFN-a subtypes. Systemic infection of the mice with Newcastle disease virus (NDV) increased GFP + plasmacytoid dendritic cells (pDCs) via the Toll-like receptor system, and GFP + conventional dendritic cells (cDCs) and macrophages via the RIG-I-like helicase system. By contrast, lung infection with NDV led to IFN-a production in alveolar macrophages (AMs) and cDCs, but not in pDCs. Specific depletion of AMs caused a marked defect in the initial viral elimination in the lung. pDCs produced IFN-a in the absence of AM-mediated viral recognition, suggesting that pDCs function when the first defense line is broken. Thus, AMs act as a type I IFN producer that is important for the initial responses to viral infection in the lung.

Cell Host & Microbe, 2011

Secondary bacterial infection is a common sequela to viral infection and is associated with incre... more Secondary bacterial infection is a common sequela to viral infection and is associated with increased lethality and morbidity. However, the underlying mechanisms remain poorly understood. We show that the TLR3/MDA5 agonist poly I:C or viral infection dramatically augments signaling via the NLRs Nod1 and Nod2 and enhances the production of proinflammatory cytokines. Enhanced Nod1 and Nod2 signaling by poly I:C required the TLR3/MDA5 adaptors TRIF and IPS-1 and was mediated by type I IFNs. Mechanistically, poly I:C or IFN-b induced the expression of Nod1, Nod2, and the Nod-signaling adaptor Rip2. Systemic administration of poly I:C or IFN-b or infection with murine norovirus-1 promoted inflammation and lethality in mice superinfected with E. coli, which was independent of bacterial burden but attenuated in the absence of Nod1/Nod2 or Rip2. Thus, crosstalk between type I IFNs and Nod1/Nod2 signaling promotes bacterial recognition, but induces harmful effects in the virally infected host. Cell Host & Microbe Crosstalk between Nod1/Nod2 and Type I IFNs

Biochemical and Biophysical Research Communications, 2009

Toll-like receptors (TLRs) are the best-characterized membrane-bound receptors in innate immune c... more Toll-like receptors (TLRs) are the best-characterized membrane-bound receptors in innate immune cells, including macrophages and dendritic cells. Upon recognition of specific ligands originating from pathogen-and modified selfderived molecules, TLRs trigger intracellular signaling cascades that involve various adaptor proteins and enzymes, resulting in the generation of proinflammatory and antimicrobial responses through the activation of transcription factors such as nuclear factor-κB. TLR-dependent signaling pathways are tightly regulated during innate immune responses by a variety of negative regulators. This review focuses on the newly described regulation of TLR-dependent signaling pathways, and emphasizes the roles of TLRs in innate immunity. Efforts to modulate these regulatory pathways and signaling molecules may result in the development of new therapeutic strategies through TLR-based therapy.

European Journal of Human Genetics, 2005

Single nucleotide polymorphisms (SNPs) in the regulatory region shared by PARK2 and PACRG have be... more Single nucleotide polymorphisms (SNPs) in the regulatory region shared by PARK2 and PACRG have been identified as major risk factors for leprosy susceptibility in two ethnically distinct populations. We investigated the association of six SNPs present in this regulatory region with leprosy susceptibility in an Indian population. Genotyping was performed by direct PCR sequencing in 286 leprosy patients and 350 healthy controls. Our results showed that T allele of SNPs PARK2_e01 (À2599) and 28 kb target_2_1 was significantly associated with susceptibility to leprosy per se (P ¼ 0.03 and 0.03, respectively). The T allele of SNPs PARK2_e01 (À2599) showed a significant recessive effect (P ¼ 0.04) in susceptibility to leprosy in Indian population as against the dominant effect of haplotype T-C of the major risk SNPs PARK2_e01 (À2599) and rs1040079 in Brazilian and Vietnamese population. However, after bonferroni corrections, these significant differences disappeared. Haplotype analysis also showed a lack of significant association of any haplotype with cases or controls. The noninvolvement of major risk SNPs in the regulatory region of PARK2 and PACRG locus with leprosy susceptibility in Indian population highlights the differential effect of these SNPs in regulating genetic susceptibility to leprosy in different populations.