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Gradient platform for combinatorial screening of thermoset polymers for biomedical applications
No full textThe goal of this work was to design a device for rapid screening of crosslinked thermoset polymers. This gradient curing platform is capable of yielding a library of polyesters with systematically varying mechanical and physicochemical properties and the resultant cellular response. A library of poly(xylitolsebacate) polyesters was prepared in this device by differential curing to yield a gradient polymer. The resultant polymer exhibits a gradient in the storage modulus (1 to 5 MPa), wettability (70 degrees < water contact angle < 110 degrees), degree of crosslinking, degradation rate (3-25% in 7 days), drug release and biological response (ability to support stem cell proliferation and differentiation) from one end of the polymer to the other. Primary human mesenchymal stem cells were cultured to assess the cellular response in vitro. Maximal stem cell proliferation and osteogenesis was observed on the highly crosslinked polyester segments that provide high stiffness, are hydrophobic and are slow degrading as compared to the lower cured counterparts. Under in vivo conditions, this material showed differential response across the gradient without displaying significant concerns for inflammation or infection. This gradient curing device is capable of ascertaining suitable curing conditions to obtain appropriate polymers for application specific requirements. This gradient platform was further used to identify optimal processing parameters to prepare three-dimensional tissue scaffolds such as electrospun fiber mats and porous foams. Thus, this versatile combinatorial platform is well suited for rapid screening of thermoset polymers for biomedical applications
Glottal Inverse Filtering Using Probabilistic Weighted Linear Prediction
No full textGlottal inverse filtering is a noninvasive method for getting the glottal flow estimate from the speech. In this paper, we propose a method for glottal inverse filtering based on probabilistic weighted linear prediction (PWLP) in which the speech is assumed to be the output of an all-pole filter with glottal flow as an excitation. First, we introduce a probabilistic interpretation of the WLP, and we propose a probabilistic temporal weighting as convolution of a binary vector and a fixed window. We construct the posterior distribution based on the PWLP likelihood and a Gaussian prior on the filter coefficients. The parameters are estimated using the Gibbs sampling. The experiments are performed using the Lijencrants- Fant (LF) model based synthetic data, a physical model based synthetic data of different vowels and real speech data. Results demonstrate that the proposed method outperforms the best of the existing state-of-the-art methods in terms of the normalized amplitude quotient by 0.035 and 0.12 for the LF model and physical model based synthetic data, respectively. The results based on real speech data show that the glottal flow estimated by the proposed method in the closed phase is flatter and has less formant ripple compared to existing state-of-the-art methods. We also show two key features of the proposed method: first, the proposed method does not need prior detection of glottal closure or opening instants. The temporal weights are learnt in a data-driven manner, which is often found to be high near the closed phase of the glottal cycle, second, the Gaussian prior helps in estimating the filter coefficients when the closed phase duration is small
Testing the gene expression classification of the EMT spectrum
No full textThe epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis and drug resistance-two persistent clinical challenges. Epithelial cells can undergo a partial or full EMT, attaining either a hybrid epithelial/mesenchymal (E/M) or mesenchymal phenotype, respectively. Recent studies have emphasized that hybrid E/M cells may be more aggressive than their mesenchymal counterparts. However, mechanisms driving hybrid E/M phenotypes remain largely elusive. Here, to better characterize the hybrid E/M phenotype (s) and tumor aggressiveness, we integrate two computational methods-(a) RACIPE-to identify the robust gene expression patterns emerging from the dynamics of a given gene regulatory network, and (b) EMT scoring metric-to calculate the probability that a given gene expression profile displays a hybrid E/M phenotype. We apply the EMT scoring metric to RACIPE-generated gene expression data generated from a core EMT regulatory network and classify the gene expression profiles into relevant categories (epithelial, hybrid E/M, mesenchymal). This categorization is broadly consistent with hierarchical clustering readouts of RACIPE-generated gene expression data. We also show how the EMT scoring metric can be used to distinguish between samples composed of exclusively hybrid E/M cells and those containing mixtures of epithelial and mesenchymal subpopulations using the RACIPE-generated gene expression data
Microfluidic-based graphene field effect transistor for femtomolar detection of chlorpyrifos
No full textChlorpyrifos is one of the most widely used pesticides that acts on the nervous system by inhibiting acetylcholinesterase. Prolonged use of chlorpyrifos causes severe neurological, autoimmune, and persistent developmental disorders in humans. Therefore, in this study, a highly sensitive and robust biosensor platform was devised by fabricating graphene field effect transistors (graFET) on Si/SiO2 substrate for the detection of chlorpyrifos in real samples. Anti-chlorpyrifos antibodies were immobilized successfully on the graphene surface. Under optimal conditions, graFET sensor showed an excellent response for chlorpyrifos detection in the linear range of 1 fM to 1 mu M with a limit of detection up to 1.8 fM in spiked samples. The developed graFET biosensor is highly stable, sensitive, and specific for chlorpyrifos as confirmed by its significant ability to detect changes in electrostatic potential. These findings signify useful efficacy of immunobiosensors for the detection of chlorpyrifos and other organophosphates in fruits and vegetables
A Fast and Efficient Two-Dimensional Chien Search Algorithm and Design Architecture
No full textWe develop an efficient procedure for finding the roots of a bi-variate polynomial over GF(q) by extending the Chien search procedure to two-dimensions. The complexity of the Chien search is further reduced to an order of the number of conjugacy classes over GF(q(lambda)) leading to a significant reduction in the computational complexity. We also provide an efficient design architecture for our algorithm towards a circuit realization that produces the roots in `1' clock cycle
Search for pair-produced three-jet resonances in proton-proton collisions at ffiffi s p = 13 TeV
No full textA search has been performed for pair-produced resonances decaying into three jets. The proton-proton collision data used for this analysis were collected with the CMS detector in 2016 at a center-of-mass energy of 13 TeV and correspond to an integrated luminosity of 35.9 fb(-1). The mass range from 200 to 2000 GeV is explored in four separate mass regions. The observations show agreement with standard model expectations. The results are interpreted within the framework of R-parity violating SUSY, where pair-produced gluinos decay to a six quark final state. Gluino masses below 1500 GeV are excluded at 95% confidence level. An analysis based on data with multijet events reconstructed at the trigger level extends the reach to masses as low as 200 GeV. Improved analysis techniques have led to enhanced sensitivity, allowing the most stringent limits to date to be set on gluino pair production
Search for heavy resonances decaying into two Higgs bosons or into a Higgs boson and a W or Z boson in proton-proton collisions at 13 TeV
No full textA search is presented for massive narrow resonances decaying either into two Higgs bosons, or into a Higgs boson and a W or Z boson. The decay channels considered are HHbb+- and VHqq-, where H denotes the Higgs boson, and V denotes the W or Z boson. This analysis is based on a data sample of proton-proton collisions collected at a center-of-mass energy of 13 TeV by the CMS Collaboration, corresponding to an integrated luminosity of 35.9 fb(-1). For the TeV-scale mass resonances considered, substructure techniques provide ways to differentiate among the hadronization products from vector boson decays to quarks, Higgs boson decays to bottom quarks, and quark- or gluon-induced jets. Reconstruction techniques are used that have been specifically optimized to select events in which the tau lepton pair is highly boosted. The observed data are consistent with standard model expectations and upper limits are set at 95% confidence level on the product of cross section and branching fraction for resonance masses between 0.9 and 4.0 TeV. Exclusion limits are set in the context of bulk radion and graviton models:spin-0 radion resonances are excluded below a mass of 2.7 TeV at 95% confidence level. In the spin-1 heavy vector triplet framework, mass-degenerate W and Z resonances with dominant couplings to the standard model gauge bosons are excluded below a mass of 2.8 TeV at 95% confidence level. These are the first limits for massive resonances at the TeV scale with these decay channels at 13 TeV
Structural insights into the activation of metabotropic glutamate receptors
No full textMetabotropic glutamate receptors are family C G-protein-coupled receptors. They form obligate dimers and possess extracellular ligand-binding Venus flytrap domains, which are linked by cysteine-rich domains to their 7-transmembrane domains. Spectroscopic studies show that signalling is a dynamic process, in which large-scale conformational changes underlie the transmission of signals from the extracellular Venus flytraps to the G protein-coupling domains-the 7-transmembrane domains-in the membrane. Here, using a combination of X-ray crystallography, cryo-electron microscopy and signalling studies, we present a structural framework for the activation mechanism of metabotropic glutamate receptor subtype 5. Our results show that agonist binding at the Venus flytraps leads to a compaction of the intersubunit dimer interface, thereby bringing the cysteine-rich domains into close proximity. Interactions between the cysteine-rich domains and the second extracellular loops of the receptor enable the rigid-body repositioning of the 7-transmembrane domains, which come into contact with each other to initiate signalling
Cessation of a dense granular flow down an inclined plane
No full textThe cessation of a dense granular flow down an inclined plane upon decrease in the angle of inclination is studied using particle-based simulations for the linear and Hertzian particle contact models for ordered and disordered flows. The nature of the flow is examined by progressively decreasing the angle of inclination by fractions of a degree, with the objective of examining the range of angles for which the hard-particle model can be used to describe the flow and the nature of the flow dynamics very close to cessation where the hard-particle approximation fails. For a disordered flow, when the angle inclination exceeds the angle for flow cessation by about 0.5 degrees for the linear contact model and about 1 degrees for the Hertzian model, the flow is well described by Bagnold rheology, and the Bagnold coefficients are independent of layer height and the particle stiffness, implying that the flow dynamics is well described by the hard-particle approximation. When the angle of inclination exceeds the angle for flow cessation by less than 0.5 degrees for the linear contact model and 1 degrees for the Hertzian contact model, the flow transitions into a layered state consisting of a faster shearing zone of height about 30 particle diameters atop a bottom slowly shearing zone. There are sinusoidal oscillations in the velocity of the center of mass of the flow, and the period of these oscillations is proportional to the characteristic time for particle interactions, indicating that the particle contact time does affect the dynamics of the layered flow. The flow evolution is qualitatively different for an ordered flow. In this case, there is an abrupt transition from a Bagnold flow to a plug flow with sliding at the base when the angle of inclination is decreased by 0.05 degrees. There is no discernible intermediate flow regime where the particle contact time becomes relevant. We also examine the deceleration of the flow when the angle of inclination is decreased from a flowing state to a final angle below the cessation angle. The initial decrease in the flow velocity is exponential for both contact models and for all final angles of inclination. This is followed by a more rapid decrease to the static state. The time constant for the initial decrease is significantly higher for an ordered flow in comparison to a disordered flow. The time constant is independent of the contact model and particle stiffness, and increases with height proportional to h(3/2), as expected for the hard-particle model
Highly Responsive Fluorescent Assemblies Allow for Unique, Multiparametric Sensing of the Phospholipid Membrane Environment
No full textDespite decades-long extensive research, probes that provide a comprehensive description of the lipid membrane microenvironment are still lacking. Here, a ``smart'' pyrene-terpyridine probe for multiparametric sensing of lipid membranes is reported. The complexity of the associated local microenvironment can be described by the distinct features of the probe fluorescence. The self-assembly of the probe molecules in phospholipid bilayers was sensitive to membrane order and phase state. The self-assembled probes showed a unique emission, influenced by dye-dye interactions and excited-state charge transfer. Moreover, this emission was sensitive to interfacial hydration, with very specific changes in emission wavelengths and fluorescence lifetimes upon variation of lipid compositions and properties. In parallel, changes in the lipid order and hydration affected the ground-state interactions in the dye aggregates and, thus, could be measured through ratiometric changes in the excitation and emission readouts. In addition, fluorescence anisotropy measurements provided another way to study the nature of dye aggregates in lipid bilayers. Overall, this report demonstrates how multiple aspects of the membrane microenvironment can be sensed through the unique fluorescence signatures of this ``smart'' probe in lipid membranes, and it establishes a new paradigm in lipid-membrane sensing