gebhart/patrepeval huggingface dataset:
Recombinant DNA/MVA/ChAdV-63-elicited T cells specific for conserved regions of the HIV-1 proteome recognize HIV-1 infected cells and suppress HIV-1 (2012)

Results HIV-1 infection kinetics is influenced by the multiplicity of infection (MOI) used to infect autologous CD4+ cells, with rapid kinetics observed at higher MOIs. For HIV-1 BaL optimal infection of autologous CD4+ cells was achieved at MOI of 0.05. In the VSA, HIV-1 BaL virus replication was shown to be sensitive to the chemokines MIP-1a and RANTES added in the absence of effector cells. Pre-activated effector cells indicated increased nonspecific background suppression in healthy controls, which was reduced following a prolonged rest before coculture with autologous CD4+ targets, but led to marked proliferation of the CD8+ T cell effectors. Preliminary investigations in vaccinees show that HIV-1 suppression mediated by CD8+ T cells can be detected in vitro following vaccination and that P24 ELISA has higher sensitivity than flow cytometry. As an alternative to the VSA, an IFN-g ELISpot assay has also been optimized for the use of autologous HIV-1-infected CD4+ cells. Using both of the above assays, preliminary characterization of T cell responses induced in volunteers receiving pSG2.HIVconsv DNA, MVA.HIVconsv and ChAdV63.HIVconsv vaccines will be shown.
Synthesis of<i>N</i>‐Octyl‐2,7‐dimethoxy‐1,8‐bistrimethylsilyl‐3,6‐dibromocarbazole (2004)

Abstract Starting with 2,7‐dimethoxycarbazole, a N‐alkyl‐hexafunctionalized carbazole derivative has been synthesized in only three steps with a good overall yield. N‐Octyl‐1,8‐bistrimethylsilyl‐3,6‐dibromo‐2,7‐dimethoxycarbazole is a new synthon that could be useful for the synthesis of conjugated polymers or bioactive compounds.
Quantified elasticity mapping of ocular tissue using acoustic radiation force optical coherence elastography (Conference Presentation) (2017)

Age-related macular degeneration and keratoconus are two ocular diseases occurring in the posterior and anterior eye, respectively. In both conditions, the mechanical elasticity of the respective tissues changes during the early onset of disease. It is necessary to detect these differences and treat the diseases in their early stages to provide proper treatment. Acoustic radiation force optical coherence elastography is a method of elasticity mapping using confocal ultrasound waves for excitation and Doppler optical coherence tomography for detection. We report on an ARF-OCE system that uses modulated compression wave based excitation signals, and detects the spatial and frequency responses of the tissue. First, all components of the system is synchronized and triggered such that the signal is consistent between frames. Next, phantom studies are performed to validate and calibrate the relationship between the resonance frequency and the Young’s modulus. Then the frequency responses of the anterior and posterior eye are detected for porcine and rabbit eyes, and the results correlated to the elasticity. Finally, spatial elastograms are obtained for a porcine retina. Layer segmentation and analysis is performed and correlated to the histology of the retina, where five distinct layers are recognized. The elasticities of the tissue layers will be quantified according to the mean thickness and displacement response for the locations on the retina. This study is a stepping stone to future in-vivo animal studies, where the elastic modulus of the ocular tissue can be quantified and mapped out accordingly.
Asynchronous Magnetic Bead Rotation (AMBR) Microviscometer for Label-Free DNA Analysis (2014)

We have developed a label-free viscosity-based DNA detection system, using paramagnetic beads as an asynchronous magnetic bead rotation (AMBR) microviscometer. We have demonstrated experimentally that the bead rotation period is linearly proportional to the viscosity of a DNA solution surrounding the paramagnetic bead, as expected theoretically. Simple optical measurement of asynchronous microbead motion determines solution viscosity precisely in microscale volumes, thus allowing an estimate of DNA concentration or average fragment length. The response of the AMBR microviscometer yields reproducible measurement of DNA solutions, enzymatic digestion reactions, and PCR systems at template concentrations across a 5000-fold range. The results demonstrate the feasibility of viscosity-based DNA detection using AMBR in microscale aqueous volumes.
Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops (2012)

The HIV-1 envelope (Env) spike (gp120(3)/gp41(3)) undergoes considerable structural rearrangements to mediate virus entry into cells and to evade the host immune response. Engagement of CD4, the primary human receptor, fixes a particular conformation and primes Env for entry. The CD4-bound state, however, is prone to spontaneous inactivation and susceptible to antibody neutralization. How does unliganded HIV-1 maintain CD4-binding capacity and regulate transitions to the CD4-bound state? To define this mechanistically, we determined crystal structures of unliganded core gp120 from HIV-1 clades B, C, and E. Notably, all of these unliganded HIV-1 structures resembled the CD4-bound state. Conformational fixation with ligand selection and thermodynamic analysis of full-length and core gp120 interactions revealed that the tendency of HIV-1 gp120 to adopt the CD4-bound conformation was restrained by the V1/V2- and V3-variable loops. In parallel, we determined the structure of core gp120 in complex with the small molecule, NBD-556, which specifically recognizes the CD4-bound conformation of gp120. Neutralization by NBD-556 indicated that Env spikes on primary isolates rarely assume the CD4-bound conformation spontaneously, although they could do so when quaternary restraints were loosened. Together, the results suggest that the CD4-bound conformation represents a "ground state" for the gp120 core, with variable loop and quaternary interactions restraining unliganded gp120 from "snapping" into this conformation. A mechanism of control involving deformations in unliganded structure from a functionally critical state (e.g., the CD4-bound state) provides advantages in terms of HIV-1 Env structural diversity and resistance to antibodies and inhibitors, while maintaining elements essential for entry.
A common haplotype in the complement regulatory gene factor H ( <i>HF1/CFH</i> ) predisposes individuals to age-related macular degeneration (2005)

Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of approximately 900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2 = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.
Multiple roles for HIV broadly neutralizing antibodies (2019)

Potent broadly neutralizing antibodies may be used to treat or prevent HIV and to help guide HIV vaccine design.
ChemInform Abstract: Asymmetric Amino Acid Synthesis by the Asymmetric Alkylation of Glycine Derivatives with Chiral Spiro‐Type and Simplified Phase‐Transfer Catalysts (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Multifunctional Liposomes Reduce Brain β-Amyloid Burden and Ameliorate Memory Impairment in Alzheimer's Disease Mouse Models (2014)

Alzheimer's disease is characterized by the accumulation and deposition of plaques of β-amyloid (Aβ) peptide in the brain. Given its pivotal role, new therapies targeting Aβ are in demand. We rationally designed liposomes targeting the brain and promoting the disaggregation of Aβ assemblies and evaluated their efficiency in reducing the Aβ burden in Alzheimer's disease mouse models. Liposomes were bifunctionalized with a peptide derived from the apolipoprotein-E receptor-binding domain for blood-brain barrier targeting and with phosphatidic acid for Aβ binding. Bifunctionalized liposomes display the unique ability to hinder the formation of, and disaggregate, Aβ assemblies in vitro (EM experiments). Administration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 weeks (three injections per week) decreased total brain-insoluble Aβ1-42 (-33%), assessed by ELISA, and the number and total area of plaques (-34%) detected histologically. Also, brain Aβ oligomers were reduced (-70.5%), as assessed by SDS-PAGE. Plaque reduction was confirmed in APP23 transgenic mice (aged 15 months) either histologically or by PET imaging with [(11)C]Pittsburgh compound B (PIB). The reduction of brain Aβ was associated with its increase in liver (+18%) and spleen (+20%). Notably, the novel-object recognition test showed that the treatment ameliorated mouse impaired memory. Finally, liposomes reached the brain in an intact form, as determined by confocal microscopy experiments with fluorescently labeled liposomes. These data suggest that bifunctionalized liposomes destabilize brain Aβ aggregates and promote peptide removal across the blood-brain barrier and its peripheral clearance. This all-in-one multitask therapeutic device can be considered as a candidate for the treatment of Alzheimer's disease.
Rapid Software‐Based Design and Optical Transient Liquid Molding of Microparticles (2015)

Microparticles with complex 3D shape and composition are produced using a novel fabrication method, optical transient liquid molding, in which a 2D light pattern exposes a photopolymer precursor stream shaped along the flow axis by software-aided inertial flow engineering.
Specific immunotherapy of experimental myasthenia gravis by a novel mechanism (2009)

Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially-expressed human muscle AChR cytoplasmic domains for antigen-specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe.
Pharmacological targeting of apelin impairs glioblastoma growth (2017)

Glioblastoma are highly aggressive brain tumours that are associated with an extremely poor prognosis. Within these tumours exists a subpopulation of highly plastic self-renewing cancer cells that retain the ability to expand ex vivo as tumourspheres, induce tumour growth in mice, and have been implicated in radio- and chemo-resistance. Although their identity and fate are regulated by external cues emanating from endothelial cells, the nature of such signals remains unknown. Here, we used a mass spectrometry proteomic approach to characterize the factors released by brain endothelial cells. We report the identification of the vasoactive peptide apelin as a central regulator for endothelial-mediated maintenance of glioblastoma patient-derived cells with stem-like properties. Genetic and pharmacological targeting of apelin cognate receptor abrogates apelin- and endothelial-mediated expansion of glioblastoma patient-derived cells with stem-like properties in vitro and suppresses tumour growth in vivo. Functionally, selective competitive antagonists of apelin receptor were shown to be safe and effective in reducing tumour expansion and lengthening the survival of intracranially xenografted mice. Therefore, the apelin/apelin receptor signalling nexus may operate as a paracrine signal that sustains tumour cell expansion and progression, suggesting that apelin is a druggable factor in glioblastoma.
Referencing Earlier Communications in SIP Requests (2009)

This document defines a SIP header extension that refers to earlier
SIP or non-SIP communication in SIP requests. For example, this
extension allows users to correlate a SIP session with earlier
sessions or email exchanges.
A technique for reducing rectifier reverse-recovery-related losses in high-voltage, high-power boost converters (2002)

A circuit technique that reduces the boost power converter losses caused by the reverse-recovery characteristics of the rectifier is described. The losses are reduced by inserting an inductor in the series path of the boost switch and the rectifier to control the di/dt rate of the rectifier during its turn-off. The energy from the inductor after the boost switch turn-off is returned to the input or delivered to the output via an active snubber. The same technique can be extended to any member of the PWM power converter family.
Derivative Synthesis toward Enhancement of the Biophysical Properties of 2′,4′-Bridged Nucleic Acids (2019)

Over the past few decades, a number of modified oligonucleotides have been synthesized and evaluated their biophysical properties. Modified oligonucleotides having high enzymatic stability, high duplex-forming ability toward single-stranded RNA (ssRNA), high sequence specificity, and good pharmacokinetic profiles, are highly desirable for therapeutic applications. We previously demonstrated that oligonucleotides modified with 2′-O,4′-C-methylene bridged nucleic acid/locked nucleic acid (2′,4′-BNA/LNA) have extremely high duplex-forming ability toward ssRNA. In recent years, we have been focusing on developing further strengthened bridged nucleic acids, e.g. 2′,4′-BNA/LNA analogues showing high enzymatic stability, high sequence specificity, high efficacy, and low toxicity. We herein report several promising bridged nucleic acids developed recently for therapeutic applications, especially in antisense and splice-switching oligonucleotides.
Cross-conservation of T-cell epitopes (2014)

A novel avian-origin H7N9 influenza strain emerged in China in April 2013. Since its re-emergence in October-November 2013, the number of reported cases has accelerated; more than 220 laboratory-confirmed cases and 112 deaths (case fatality rate of 20-30%) have been reported. The resurgence of H7N9 has re-emphasized the importance of making faster and more effective influenza vaccines than those that are currently available. Recombinant H7 hemagglutinin (H7-HA) vaccines have been produced, addressing the first problem. Unfortunately, these recombinant subunit vaccine products appear to have failed to address the second problem, influenza vaccine efficacy. Reported unadjuvanted H7N9 vaccine seroconversion rates were between 6% and 16%, nearly 10-fold lower than rates for unadjuvanted vaccine seroconversion to standard H1N1 monovalent (recombinant) vaccine (89% to pandemic H1N1). Could this state of affairs have been predicted? As it turns out, yes, and it was. In that previous analysis of available H7-HA sequences, we found fewer T-cell epitopes per protein than expected, and predicted that H7-HA-based vaccines would be much less antigenic than recent seasonal vaccines. Novel approaches to developing a more immunogenic HA were offered for consideration at the time, and now, as the low immunogenicity of H7N9 vaccines appears to indicate, they appear to be even more relevant. More effective H7N9 influenza vaccines can be produced, provided that the role of T-cell epitopes is carefully considered, and accumulated knowledge about the importance of cross-conserved epitopes between viral subtypes is applied to the design of those vaccines.
Synthesis and Oxidation Behavior of Nanocrystalline MCrA1Y Bond Coats - eScholarship (2002)

Thermal barrier coating (TBC) systems protect turbine blades against high-temperature corrosion and oxidation. They consist of a metal bond coat (MCrAIY, M = Ni, Co) and a ceramic top layer (ZrO2/Y2O3). In this work the oxidation behavior of conventional and nanostructured HVOF NiCrAIY coatings has been compared. Commercially available NiCrAIY powder was mechanically cryomilled and HVOF sprayed on a nickel alloy foil to form a nanocrystalline coating. Free-standing bodies of conventional and nanostructured HVOF NiCrAIY coatings were oxidized at a 1000oC for different time periods in order to form the thermally grown oxide (TGO) layer. The experimants show an improvement in oxidation resistance in the nanostructured coating when compared to that of the conventional one. This behavior is a result of the formation of a continuous AI2O3 layer on the top surface of the nanostructured HVOF NiCrAIY coating. This layer protects the coating from further oxide protrusions present in the conventional coating.
Low-Cost Sorting Network Circuits Using Unary Processing (2018)

Sorting is a common task in a wide range of applications from signal and image processing to switching systems. For applications that require high performance, sorting is often performed in hardware with application-specified integrated circuits or field-programmable gate arrays. Hardware cost and power consumption are the dominant concerns. The usual approach is to wire up a network of compare-and-swap units in a configuration called the Batcher (or bitonic) network. Such networks can readily be pipelined. This paper proposes a novel area-efficient and power-efficient approach to sorting networks, based on “unary processing.” In unary processing, numbers are encoded uniformly by a sequence of one value (say 1) followed by a sequence of the other value (say 0) in a stream of 0's and 1's with the value defined by the fraction of 1's in the stream. Synthesis results of complete sorting networks show up to 92% area and power saving compared to the conventional binary implementations. However, the latency increases. To mitigate the increased latency, this paper uses a novel time-encoding of data. The approach is validated with two implementations of an important application of sorting: median filtering. The result is a low cost, energy-efficient implementation of median filtering with only a slight accuracy loss, compared to conventional implementations.
Chimeric  2 microglobulin/CD3  polypeptides expressed in T cells convert MHC class I peptide ligands into T cell activation receptors: a potential tool for specific targeting of pathogenic CD8+ T cells (2003)

CD8(+) T cells are key mediators of transplant rejection and graft-versus-host disease and contribute to the pathogenesis of autoimmune diseases. We tested whether TCR ligands can be converted into T cell activation receptors, redirecting genetically modified T cells at pathogenic CD8(+) T cells. For this purpose we exploited the ability of the non-polymorphic beta(2) microglobulin light chain to pair with all MHC class I heavy chains. In this report we describe the design and expression in a T cell hybridoma of two modalities of beta(2) microglobulin polypeptides, fused with the transmembrane and intracellular portion of CD3zeta chain. In the absence of a particular antigenic peptide, the chimeric product associates with different endogenous MHC class I heavy chains and triggers T cell activation upon heavy chain cross-linking. When an antigenic peptide is covalently attached to the N-terminus of the chimeric polypeptide, transfectants express high level of surface peptide-class I complexes and respond to antibodies and target T cells in a peptide-specific manner. Our results provide the basis for a universal genetic approach aimed at antigen-specific immunotargeting of pathogenic CD8(+) T cells.
Adaptive Kalman filter approach for road geometry estimation (2004)

This paper describes an adaptive Kalman filter based method for accurate estimation of forward path geometry of an automobile. The forward geometry is modeled as two contiguous clothoid segments with different geometries and continuous curvature across the transition between them. This results in a closed-form parametric expression of the same polynomial order as previous models. Instead of using a conventional Kalman filter with fixed process model parameters based on a compromise between noise and filter lag, we adaptively tune the process model parameters. This results in the better filter performance with stable estimates during constant geometry scenarios and faster response during abrupt geometry transitions. Performance evaluation of the proposed method on various simulated road geometries and comparing with previous approaches demonstrate the feasibility and higher accuracy of the proposed method. The high accuracy estimation of forward path or road geometry is directly useful in applications that rely on detecting targets in the forward path of the host vehicle, e.g., adaptive cruise control and automotive collision warning.
Hierarchical image segmentation by polygon grouping (2008)

We present a simple cascading algorithm for rapid hierarchical image segmentation based on perceptually driven contour completion and scene statistics. We start with an initial fine-scale segmentation of an image obtained by perceptual completion of partial contours into polygonal regions using region-contour correspondences established by Delaunay triangulation of edge pixels. The resulting polygon size distribution is analyzed for a dominant mode of granularity of the image. Polygons whose sizes are less than or equal to this granularity are merged with their spectrally closest neighbors to obtain the next level of polygonal segments in the hierarchy. The iterative application of this process precipitates textured regions as polygons with highly convolved boundaries and helps distinguish them from objects which typically have more regular boundaries.
Initial pulse-echo imaging results with one-dimensional capacitive micromachined ultrasonic transducer arrays (2000)

In this paper, the first experimental results of pulse-echo imaging employing a 1-D capacitive micromachined ultrasonic transducer array are presented. A 1-D array consisting of 16 elements is used in the experiment. A wire phantom consisting of seven steel wires immersed in vegetable oil is used as the imaging target. A B-scan image with a sector angle of 90 degrees and an image depth of 150 mm is reconstructed by employing RF beamforming and synthetic phase array approaches. The reconstructed image is displayed at different display dynamic ranges. The measured near and far side lobe levels are around /spl sim/25 dB and /spl sim/35 dB, respectively. The noise floor of the image is below /spl sim/50 dB.