1,335 research outputs found

    Solvent Evaporation Technique Of Microencapsulation: A Systemic Review

    Get PDF
    Solvent evaporation is one of the most widely employed and investigated technique in pharmaceutical industries and research area for microencapsulation process.Microspheres are particles coated with a continuous film of polymeric material, having a diameter in range of 1 to 1000 ?m and are widely used as drug carriers. This technique provides a controlled drug release, having various clinical benefits. While initial lab scale experiments are carried out in simple beaker, stirrer setups, clinical trials and market introduction needs more sophisticated technologies, permitting economic robust, well-controllable and aseptic production of microspheres. In this review article our aim is to review and compile recent research work on solvent evaporation technique while focusing on different methods of above said technique and various factors affecting microencapsulation prepared by solvent evaporation technique

    The Hyaluronan Receptor for Endocytosis (HARE) Activates NF-ÎșB-mediated Gene Expression in Response to 40–400-kDa, but Not Smaller or Larger, Hyaluronans

    Get PDF
    Background: HARE mediates systemic clearance of hyaluronan (HA), which turns over continuously in tissues. Results: HARE uptake of 40–400-kDa, but not larger or smaller, HA stimulated NF-ÎșB activation. Conclusion: HA-HARE signal complexes activate NF-ÎșB and gene transcription only with optimally sized HA. Significance: HARE responsiveness to a narrow size range ofHAdegradation products may be a sensing system to detect tissue ECM stress

    The Hyaluronan Receptor for Endocytosis (HARE) Activates NF-ÎșB-mediated Gene Expression in Response to 40–400-kDa, but Not Smaller or Larger, Hyaluronans

    Get PDF
    Background: HARE mediates systemic clearance of hyaluronan (HA), which turns over continuously in tissues. Results: HARE uptake of 40–400-kDa, but not larger or smaller, HA stimulated NF-ÎșB activation. Conclusion: HA-HARE signal complexes activate NF-ÎșB and gene transcription only with optimally sized HA. Significance: HARE responsiveness to a narrow size range ofHAdegradation products may be a sensing system to detect tissue ECM stress

    Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21

    Get PDF
    Meta-AnalysisThis is the final version of the article. Available from the American Diabetes Association via the DOI in this record.Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻âč). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻ÂčÂČ) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.The major funding for this work comes from Council for Scientific and Industrial Research, Government of India, in the form of the grant “Diabetes mellitus—New drug discovery R&D, molecular mechanisms, and genetic and epidemiological factors” (NWP0032-19). R.T. received a postdoctoral fellowship from the Fogarty International Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (D43-HD-065249)

    Activation of ERK and NF-ÎșB during HARE-Mediated Heparin Uptake Require Only One of the Four Endocytic Motifs

    Get PDF
    We thank Bruce A. Baggenstoss and Jennifer L. Washburn for technical support in many experiments and Emma K. Blank, Andrew W. Egger, Brianna M. Kellar and Helen T. Russom for assistance with experiments supporting Fig 2.Fifteen different ligands, including heparin (Hep), are cleared from lymph and blood by the Hyaluronan (HA) Receptor for Endocytosis (HARE; derived from Stabilin-2 by proteolysis), which contains four endocytic motifs (M1-M4). Endocytosis of HARE‱Hep complexes is targeted to coated pits by M1, M2, and M3 (Pandey et al, Int. J. Cell Biol. 2015, article ID 524707), which activates ERK1/2 and NF-ÎșB (Pandey et al J. Biol. Chem. 288, 14068–79, 2013). Here, we used a NF-ÎșB promoter-driven luciferase gene assay and cell lines expressing different HARE cytoplasmic domain mutants to identify motifs needed for Hep-mediated signaling. Deletion of M1, M2 or M4 singly had no effect on Hep-mediated ERK1/2 activation, whereas signaling (but not uptake) was eliminated in HARE(ΔM3) cells lacking NPLY2519. ERK1/2 signaling in cells expressing WT HARE(Y2519A) or HARE(Y2519A) lacking M1, M2 and M4 (containing M3-only) was decreased by 75% or eliminated, respectively. Deletion of M3 (but not M1, M2 or M4) also inhibited the formation of HARE‱Hep‱ERK1/2 complexes by 67%. NF-ÎșB activation by HARE-mediated uptake of Hep, HA, dermatan sulfate or acetylated LDL was unaffected in single-motif deletion mutants lacking M1, M2 or M4. In contrast, cells expressing HARE(ΔM3) showed loss of HARE-mediated NF-ÎșB activation during uptake of each of these four ligands. NF-ÎșB activation by the four signaling ligands was also eliminated in HARE(Y2519A) or HARE(M3-only;Y2519A) cells. We conclude that the HARE NPLY2519 motif is necessary for both ERK1/2 and NF-ÎșB signaling and that Tyr2519 is critical for these functions.Yeshttp://www.plosone.org/static/editorial#pee

    Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21

    Get PDF
    Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 3 1029 ). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P , 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

    Combined searches for the production of supersymmetric top quark partners in proton–proton collisions at √s=13Te

    Get PDF
    A combination of searches for top squark pair production using proton–proton collision data at a center-of-mass energy of 13TeV at the CERN LHC, corresponding to an integrated luminosity of 137fb−1^{-1} collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on the model, the combined result excludes a top squark mass up to 1325GeV for a massless neutralino, and a neutralino mass up to 700GeV for a top squark mass of 1150GeV. Top squarks with masses from 145 to 295GeV, for neutralino masses from 0 to 100GeV, with a mass difference between the top squark and the neutralino in a window of 30GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420GeV

    Search for a vector-like quark Tâ€Č → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

    Get PDF
    A search for the electroweak production of a vector-like quark Tâ€Č, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first Tâ€Č search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet Tâ€Č states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a Tâ€Č quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength ÎșT = 0.25 and a relative decay width Γ/MTâ€Č < 5%

    Measurement of the top quark mass using events with a single reconstructed top quark in pp collisions at s\sqrt{s} = 13 TeV

    Get PDF
    A measurement of the top quark mass is performed using a data sample enriched with single top quark events produced in the t channel. The study is based on proton- proton collision data, corresponding to an integrated luminosity of 35.9 fb−1^{-1}, recorded at s\sqrt{s} = 13 TeV by the CMS experiment at the LHC in 2016. Candidate events are selected by requiring an isolated high-momentum lepton (muon or electron) and exactly two jets, of which one is identified as originating from a bottom quark. Multivariate discriminants are designed to separate the signal from the background. Optimized thresholds are placed on the discriminant outputs to obtain an event sample with high signal purity. The top quark mass is found to be 172.13+0.76^{+0.76}−0.77_{-0.77} GeV, where the uncertainty includes both the statistical and systematic components, reaching sub-GeV precision for the first time in this event topology. The masses of the top quark and antiquark are also determined separately using the lepton charge in the final state, from which the mass ratio and difference are determined to be 0.9952+0.0079^{+0.0079}−0.0104_{-0.0104} and 0.83+1.79^{+1.79}−1.35_{-1.35} GeV, respectively. The results are consistent with CPT invariance
    • 

    corecore