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Immunological implications of epidermal growth factor receptor signaling in persistent infections
No full textInfectious diseases account for a large proportion of global health emergencies and are rising more so owing to the paucity of effective vaccination and chemotherapeutic strategies. The severity is compounded by the development of antibiotic resistance among major pathogenic strains, capable of residing in the hostile host microenvironment by hijacking its signaling mechanisms and molecular circuitry. Among such processes, studies on epidermal growth factor receptor (EGFR) have revealed specific contributions of this classical oncogenic signaling axis during distinct infection conditions. Here, we review the current status of EGFR family members in the context of host-pathogen interactions and speculate the possible dimensions of exploration and manipulation of the EGFR pathway for host-directed therapeutic purposes
Mapping scroll expander performance for organic working fluids using dimensionless parameters in N-s-D-s diagram
No full textThis paper presents an analysis of single-stage scroll expander performance for pure fluids and their zeotropic mixtures in supercritical conditions using dimensionless parameters, namely specific speed (N-s) and specific diameter (D-s). Scroll geometries with different aspect ratios were modeled for a range of expander inlet temperatures. The expander efficiency was modeled accounting for losses due to leakage, friction, and over- and under-expansion. The expander efficiency was plotted as a function of two dimensionless parameters to analyze the applicability domain of scroll expanders. For a particular expander inlet temperature (T-in), zeotropic mixtures result in more compact scroll geometries than pure fluids, leading to reduced losses and better expander efficiency. Any increase in T-in results in larger scrolls leading to higher leakage and thereby lower efficiency. At suitable operating conditions, an optimized scroll expander design can achieve expansion efficiency as high as 75%. Sub-optimal scroll designs for a given application lead to lower expansion efficiency due to over- or under-expansion losses
Lignin loss under AD in monocot and gymnosperm biomass
No full textLignin degradation in digesting biomass substrates of monocot and gymnosperm feedstocks fed into a biogas plant was studied and is reported for the first time with significant implications on biomethanation and bioethanol production. Around 0.013g/gTS/d lignin loss in monocots and 0.007g/gTS/d in gymnosperms was achieved during 30d. In the case of monocots the lignin degraded from substrate was found to be predominantly from cell wall and vascular bundles while in case of gymnosperms it was only from the cell walls. Changes in FT-IR spectra confirmed the alteration in core structure of lignin characterized by loss of H and S subunits in case of monocot biomass. For gymnosperms only a few S units were lost without bringing any changes to the core lignin structure. A correlation was attempted between lignin loss and loss of other constituents of biomass to understand the changes in the architecture of biomass during AD and its relevance to predicting biogas production potential
A cartridge based Point-of-Care device for complete blood count
No full textWe demonstrate a proprietary lab-on-chip/mu TAS technology platform for a regulatory grade portable instrument for complete blood count (CBC) hematology tests including 3 part differential WBCs, RBCs, platelet and hemoglobin for rapid diagnostics at the point of care in resource-poor settings. Presently, diagnostics based on blood tests are confined to centralized laboratory settings, dependent on large footprint and expensive cytometers or on a microscope, requiring trained laboratory technicians. Consequently, such facilities are not present in rural and semi-urban settings, where there are opportunities and challenges in delivering efficient healthcare infrastructure at an affordable cost in resource-challenged environments. Our proposed design leverages advances in microfluidics and lab-on-chip fabrication techniques to miniaturize the conventional cytometer and bring down the cost significantly. The device can be operated autonomously, without skilled manpower, by primary healthcare professionals in the field and by patients (like glucose self-test devices). The instrument consists of a single-use chip, the size of a credit card, pre-loaded with reagents, in which the sample is loaded, and which is fluidically insulated from the environment. The controller, the size of a toaster, performs the necessary fluid handling and the impedance measurements to deliver the results in minutes
Network utility maximization revisited: Three issues and their resolution
No full textDistributed and iterative network utility maximization algorithms, such as the primal dual algorithms or the network-user decomposition algorithms, often involve trajectories where the iterates may be infeasible, convergence to the optimal points of relaxed problems different from the original, or convergence to local maxima. In this paper, we highlight the three issues with iterative algorithms. We then propose a distributed and iterative algorithm that does not suffer from the three issues. In particular, we assert the feasibility of the algorithm's iterates at all times, convergence to global maximum of the given problem (rather than to global maximum of a relaxed problem), and avoidance of any associated spurious rest points of the dynamics. A benchmark algorithm due to Kelly et al. (1998) involves fast user updates coupled with slow network updates in the form of additive-increase multiplicative-decrease of suggested user flows. The proposed algorithm may be viewed as one with fast user updates and fast network updates that keeps the iterates feasible at all times. Simulations suggest that the convergence rate of the ordinary differential equation (ODE) tracked by our proposed algorithm's iterates is comparable to that of the ODE for the aforementioned benchmark algorithm
Preferential Presentation of High-Affinity Immune Complexes in Germinal Centers Can Explain How Passive Immunization Improves the Humoral Response
No full textPassive immunization (PI) with external antibodies has been used classically for rapid but temporary alleviation of disease. Transcending this role, recent studies have shown PI to induce lasting improvements in natural antibody production, suggesting that PI could become a powerful tool to engineer humoral responses. We propose a mechanism with which PI can alter the humoral response. Antigen-specific B cells evolve and get selected in germinal centers (GCs) on the basis of their ability to acquire antigen from antibody-antigen complexes presented in GCs. When external antibodies of high affinity for antigen are used, they form the majority of the complexes in GCs, letting only B cells with even higher affinities be selected. Using an in silico GC reaction model, we show that this mechanism explains the improved humoral responses following PI. The model also synthesizes several independent experimental observations, indicating the robustness of the mechanism, and proposes tunable handles to optimize PI
Genomic and Functional Characterization of Poultry Escherichia coli From India Revealed Diverse Extended-Spectrum beta-Lactamase-Producing Lineages With Shared Virulence Profiles
No full textExtended-spectrum beta-lactamases (ESBLs) form the most important resistance determinants prevalent worldwide. Data on ESBL-producing Escherichia coli from poultry and livestock are scarce in India. We present data on the functional and genomic characterization of ESBL-producing E. coli obtained from poultry in India. The whole genome sequences of 28 ESBL-producing E. coli were analyzed comprising of 12 broiler chicken E. coli isolates, 11 free-range chicken E. coli isolates, and 5 human extraintestinal pathogenic E. coli. All of the 28 ESBL-producing E. coli isolates were tested for antibiotic susceptibilities, in vitro conjugation, and virulence-associated phenotypic characteristics. A total of 13 sequence types were identified from the poultry E. coli, which included globally successful sequence types such as ST117 (9%), ST131 (4.3%), and ST10 (4.3%). The most common ESBL gene detected in poultry E. coli genomes was bla(CTX-M-15) (17%). Also, FIB (73%) and FII (73%) were the most common plasmid replicons identified. Conjugation experiments demonstrated 54 (7/13), 30 (3/10), and 40% (2/5) of broiler, free-range, and human ExPEC E. coli to be able to transfer their ESBL genes, respectively. The in vitro virulence-associated phenotypic tests revealed the broiler, free-range, and human ExPEC isolates to be comparable in biofilm formation, resistance to serum bactericidal activity, adherence, and invasion capabilities. Our overall results showed prevalence of virulence phenotypes among the diverse ESBL-producing E. coli from poultry; while certain E. coli clones from broiler-poultry may indeed have the potential to cause infection in humans
Turbulence Amplitude Amplification in an Externally Forced, Subsonic Turbulent Boundary Layer
No full textExperimental studies of the changes in turbulence characteristics inside a boundary layer due to external forcing were performed using hot-wire anemometry. The forcing was created by a periodically forced shear layer that was external to a compressible subsonic turbulent boundary layer. The convecting coherent structures in the shear layer create a concomitant unsteady pressure and velocity field and provide an external disturbance for the turbulent boundary layer on the wall of the tunnel close to the forced shear layer. Both the pressure and velocity fluctuations inside the boundary layer were simultaneously measured along with the forcing signal, and a phase-locked analysis was performed. Regions of amplified turbulence inside the boundary layer were observed. Near the wall, the region of amplified turbulence was slightly upstream or lagging of the external forcing and away from the wall it was downstream or leading the forcing signal. Analysis of the convective speeds in the region of amplified turbulence supported the existence of the critical layer inside the wake region of the boundary layer, and the critical layer is believed to be responsible for the amplified levels of the turbulence in the wake region. Various modulation and amplification correlation coefficients were computed and analyzed, and the results also indicated the presence of the critical layer. Examination of the phase-locked turbulence revealed similarities between the turbulence amplitude amplification results due to these externally forced experiments and modulation response of an internally forced, subsonic boundary layer in the literature
Experimental signatures of a nonequilibrium phase transition near the crossover point of a Langmuir monolayer
No full textWe investigate the response of the two-dimensional (2D) continuous non-particulate film of surfactant sorbitan tristearate confined at the air-water interface under oscillatory shear deformation. The time dependence of various rheological parameters show critical-like behavior at a value of strain amplitude close to the crossover point of elastic (G') and viscous (G `') shear moduli. Imposing oscillatory shear of different strain amplitudes (gamma(0)) above and below the crossover strain amplitude (gamma(f)) over a large number of cycles, we quantify the temporal dependence of interfacial viscous modulus, phase angle (G `'/G') as well as higher harmonic components of stress. The number of shear cycles (tau(R)) required for these quantities to reach the steady state value diverges near gamma(f). The steady state values of the third harmonic (I-3/I-1) show order parameter like behavior indicating the importance of higher order harmonics near the nonequilibrium transition. We further show that the energy dissipation per cycle per unit volume has a marked change near gamma(f), consistent with continuum level nonequilibrium shear-transformation-zone model of amorphous viscoplasticity
Computational and Microstructural Stability Analysis of Shock Wave Interaction with NbB2-B4C-Based Nanostructured Ceramics
No full textDespite extensive research on developing different transition metal boride composites for aero-thermostructural applications, the understanding of the shockwave interaction using high pressure shock testing facilities and computational simulation of such interactions are much less explored. This aspect is even more important for much less explored ceramics, like NbB2-based materials. While addressing this aspect, the present investigation reports the thermostructural stability of spark plasma sintered NbB2-(0-40) mol % B4C composites under the hypersonic aero-thermodynamic conditions using a miniature detonation-driven shock tube facility. All the ceramic discs underwent mild surface oxidation, as a consequence to impulsive load together with the thermomechanical shock. Using the in situ recorded pressure pulse data together with conjugate heat transfer analysis, spatiotemporal evolution of ceramic surface temperature was computationally analyzed for the given test conditions. Importantly, the NbB2-(0 and 20) mol % B4C composite retained structural integrity even after exposure to 10 shock pulses with maximum reflected shock temperature and pressure of 5000 K and 37.5 MPa, respectively. In contrast, NbB2-40 mol % B4C underwent structural failure by shattering to pieces. An attempt has been made to rationalize such results on the basis of thermal shock resistance parameters, estimated using the Kingery and Hasselman model. It is observed that NbB2-(0 and 20) mol % B4C shows higher crack propagation resistance, that is, 20 and 30%, respectively, under thermal shock (R `') than NbB2-40 mol % B4C. Interestingly, all the shock exposed NbB2-B4C ceramics show a measurable increase in hardness, which is attributed to transient melting and solidification of constituent phases due to interaction with shock heated gas, for a short duration of similar to 5 ms. Taken together, the present study establishes the potential of NbB2-B4C composites for aero-thermostructural applications