Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies

AbstractWe report two antibodies, scFv 13B1 and MAb PD1.37, against the hinge regions of LHR and TSHR, respectively, which have similar epitopes but different effects on receptor function. While neither of them affected hormone binding, with marginal effects on hormone response, scFv 13B1 stimulated LHR in a dose-dependent manner, whereas MAb PD1.37 acted as an inverse agonist of TSHR. Moreover, PD1.37 could decrease the basal activity of hinge region CAMs, but had varied effects on those present in ECLs, whereas 13B1 was refractory to any CAMs in LHR. Using truncation mutants and peptide phage display, we compared the differential roles of the hinge region cysteine box-2/3 as well as the exoloops in the activation of these two homologus receptors

Policy-aware Distributed and Dynamic Trust based Access Control Scheme for Internet of Things

 The use of smart devices is driving the Internet of Things (IoT) trend today. Day by day IoT helps to support more services like car services, healthcare services, home automation, and security services, weather prediction services, etc, to ease user’s life. Integration of heterogeneous IoT devices and social resources sometimes creates many problems like the privacy of data. To avoid privacy issues, an appropriate access control mechanism is required to check authorized and trusted devices, so that only valid devices can access the data which is only required.  In the sequel, this paper presents implementation of distributed and dynamic trust based access control mechanism (DDTAC) for secure machine to machine communication or distributed IoT environment. Novelty of this mechanism is that, it uses trust calculation and device classification for dynamic access control. The proposed scheme is implemented, tested and deployed on Node MCU and same mechanism is also simulated on NS-2 for large number of nodes. This access control model support Scalability, Heterogeneity, Privacy, Trust, Selective disclosure, Principle of least privileges, and lightweight calculation features. Results of this models proves that it gives good performance as compared to existing scheme in terms of scalability, throughput and delay. As number of devices increase it does not degrade performance. This mechanism is also protected against the Man-in-the-Middle attack, Sniffing attack, Session Hijacking attacks and Injection attacks. It required less time to detect and resist those attacks

An Efficient and Reliable Data Transmission Service using Network Coding Algorithms in Peer-to-Peer Network

Network coding is a progressive enhancement in natural network routing that increases throughput and reliability for unicast, multicast, and even broadcast transmissions. P2P networks are ideal for implementing network coding algorithms for two reasons: I. A P2P network's topology isn't predetermined. As a result, designing a topology that is compatible with the network coding algorithm is much easier. II. Every peer is an end host in this network.  As a result, instead of saving and sending the message, complex network coding operations, such as encoding and decoding, are now easier to perform. The objective of this work is to use the best features of network coding algorithms and properly apply them to P2P networks to create an efficient and reliable data transmission service. The goal of the network coding algorithm is to make better use of network resources and thus increase P2P network capacity. An encoding algorithm that enables an intermediate peer to produce output messages by encoding (that is, computing a function of the data it receives. The decoder's role is to obtain enough encoded packets so that the original information can be recovered. This research work has measured an amount of hypothetical and applied consequences in which the network coding procedure or a variation of it is used to improve performance parameters such as throughput and reliability in P2P network data transmission based on network coding. The comparison of data transmission between network routing and network coding algorithms was the main focus of this paper.  According to our simulations, the new network coding systems can reach 15% to 20% upper throughput than supplementary P2P network routing systems

Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

AbstractBackgroundInsulin resistance heightens the risk for type 2 diabetes mellitus and cardiovascular disease. Amelioration of insulin resistance may reduce this risk. The thiazolidinedone class of insulin sensitizers improves insulin action in individuals with insulin-resistant diabetes and nondiabetic individuals. However, there are few reports on the time of onset of such effects independent of reversal of glucotoxicity.ObjectiveThe goal of our study was to test whether the thiazolidinedione pioglitazone has prominent early metabolic effects that can be detected in an obese, nondiabetic, insulin-resistant population.MethodsWe conducted a randomized, double-blind, placebo-controlled, parallel-group trial in men with nondiabetic insulin resistance using a hyperinsulinemic euglycemic clamp technique (at low and high doses of insulin at 10 and 40 mU/m2/min, respectively). The patients were given 30 mg daily oral pioglitazone or placebo for 28 days. Patients underwent a baseline clamp before initiation of treatment, and again at 14 and 28 days of treatment.ResultsCompared with placebo, under high-dose hyperinsulinemia, pioglitazone led to significant increases in glucose disposal rates (GDR) of 1.29 mg/kg/min (90% CI, 0.43–2.15; 39%; P=0.008) that were detectable at 2 weeks of treatment and persisted at 4 weeks of treatment. Under low-dose hyperinsulinemia, significant increases in GDR of 0.40 mg/kg/min (90% CI, 0.17–0.62; 95%; P=0.003) were observed at 4 weeks of treatment. These responses were accompanied by robust suppression of free fatty acids under hyperinsulinemic conditions, and by significant increases in circulating basal total adiponectin at 2 and 4 weeks of treatment.ConclusionsSignificant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712

Passivation of material using ultra-fast pulsed laser

The surface of a semiconductor material, e.g., gallium arsenide, is passivated by irradiating the surface with ultra-short laser pulses, until a stable passive surface is achieved. The passive surface so prepared is devoid of a superficial oxide layer

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

BACKGROUND Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. METHODS In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. RESULTS Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. CONCLUSIONS These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts

Investigation of Operating Range Capability of Gasoline Fueled Compression Ignition

Diesel engines are extensively used in heavy duty applications owing to their higher efficiency, but they release large amount of nitrogen oxides (NOx) and particulate matter (PM) emissions. Gasoline engines, on the other hand, have lower efficiency, but discharge lower NOx and PM emissions. Strategies like Premixed Charge Compression Ignition (PCCI) and Homogeneous Charge Compression Ignition (HCCI) have a potential of increasing the engine efficiency while simultaneously reducing engine emissions. Alternate Fuel Compression Ignition (AFCI), based on the same principle as PCCI, can be enabled via direct injection of a blend of gasoline and conventional diesel fuel to achieve a premixed combustion. Use of gasoline has an inherent advantage of lower particulate matter emissions. The low reactivity of gasoline also provides ignition delay necessary for premixing, thereby reducing the need for high EGR fractions. In spite of the advantages of AFCI, there are some challenges faced in the practical implementation of AFCI. The main challenge faced is the limited operating range of premixed combustion with gasoline fuel. The lower limit is governed by misfire and the upper limit is characterized by high pressure rise rates and is used in the current study to determine the effectiveness of the combustion. The aim of the present study was to realize maximum torque with AFCI combustion using pure gasoline fuel without violating the constraints on the peak cylinder pressure and pressure rise rate. This effort was carried out using GT-Power simulation software. Calibration of a pre-existing GT-Power model was undertaken as the first step. Experimental data available from a 6.7 liter, six cylinder 2010 Cummins ISB engine, with variable valve actuation (VVA) capability was used for this calibration. This thesis provides details of the GT-Power model calibration procedure and the application of calibrated GT-Power model for range exploration. AFCI range exploration was performed by solving a constrained optimization problem for particular fueling values increased beyond the nominal to obtain the maximum attainable torque at 1200 rpm operating speed. The independent variables or inputs used for this study were EGR fraction, VGT rack position, start of injection and rail pressure. Constraints were imposed on the peak cylinder pressure (PCP) at 2600 psi and on pressure rise rate (dP/dt) at 100, 150, 200 and 300 bar/ms. Four dP/dt constraints were considered to explore the possibility of obtaining an increase in torque on relaxing the constraint. The trends of optimal inputs with increasing quantity of fuel were assessed and were found to match the expected trends. With increase in fueling, the torque increased as expected, but for higher amounts of fueling, the increase in torque was not substantial. This was due to inability to burn the entire quantity of fuel injected. The fraction of fuel combusted decreased as the total quantity of fuel increased, mainly because of lack of air available for combustion. For fueling of 70 mg/stroke, more than 97% of total fuel was combusted and the maximum torque obtained at was 360 ft-lb, while maintaining PCP and dP/dt within the desired constraints