gebhart/patrepeval huggingface dataset:
Abstract P216: Nicotinamide Nucleotide Transhydrogenase Regulates Mitochondrial Redox Balance and Endothelial Function in Response to Angiotensin II (2017)

Hypertension (HTN) involves increased peripheral resistance to blood flow mediated by changes in vascular tone. Endothelial dysfunction is an initiating step in HTN and mitochondrial reactive oxygen species (ROS) contribute to endothelial dysfunction. Nicotinamide nucleotide transhydrogenase (NNT) is a critical enzyme in the regulation of mitochondrial NADPH levels and can impact mitochondrial redox status. We have demonstrated that the loss of NNT in C57Bl/6J mice is associated with a more severe hypertensive phenotype in response to Ang II characterized by mitochondrial and vascular dysfunction driven by vascular ROS production in vivo and in vitro . Little is known regarding the role of NNT human endothelial cells, but based on previous studies we hypothesize that the loss of NNT promotes mitochondrial and cellular ROS production and disrupts normal endothelial • NO function. In human aortic endothelial cells (HAEC) treatment with 500nM Ang II for two hours significantly increased NNT expression (225 + 1 3%) and glutathione peroxidase 2 (Gpx2) activity (17.81 + 0 .75 vs 29.06 + 2 .53 nmol/min/ug protein) consistent with NNT’s role in driving the mitochondrial antioxidant systems. Conversely, siRNA knockdown of NNT inhibited Gpx2 activity (18.32 + 1.17 vs 13.16 + 0 .7 nmol/min/ug protein) and increased mitochondrial superoxide production (0.12 + 0 .01 vs 0.17 + 0 .01 nmol/mg protein) in response to Ang II. These changes in the redox balance of the mitochondria contribute to mitochondrial dysfunction where the loss of NNT led to a marked decrease in the respiratory control ratio (RCR) of the mitochondria (6.42 + 0 .17 vs 3.83 + 0 .1) of Ang II treated cells. Ultimately, this shift to a pro-oxidative mitochondrial redox phenotype in these cells conspired to inhibit Ang II-induced • NO production (35.60 + 1 .28 vs 30.10 + 1 .24 pmol/mg protein). Our data indicate that the absence of NNT expression increases the steady state levels of mitochondrial ROS through increased ROS production and decreased antioxidant activity, which is contributes to reduced • NO production and endothelial dysfunction. These studies highlight NNT as a novel regulator of mitochondrial redox tone that may critically impact the ability of vascular ROS to contribute to the development of HTN.
Transmural activations and stimulus potentials in three-dimensional anisotropic canine myocardium. (1988)

Epicardial and endocardial pacing are widely used, yet little is known about the three-dimensional distribution of potentials generated by the pacing stimulus or the spread of activation from these pacing sites. In six open-chest dogs, simultaneous recordings were made from 120 transmural electrodes in 40 plunge electrodes within a 35 X 20 X 5-mm portion of the right ventricular outflow tract during epicardial and endocardial pacing at a strength of twice diastolic threshold and at 1 mA. The magnitude of extracellular potentials generated by the stimulus and the activation times were compared in regions proximal (less than 10-12 mm) and distal to the pacing site. Local fiber orientation was histologically determined at each recording electrode. For endocardial pacing, endocardial potentials were larger than epicardial potentials only in the proximal region (p less than 0.001); while in the distal region, epicardial potentials were larger (p less than 0.001), and endocardial activation occurred earlier than epicardial activation for both regions (p less than 0.001). For epicardial pacing, epicardial potentials were larger than endocardial potentials in both regions (p less than 0.001), and epicardial activation occurred earlier only in the proximal region (p less than 0.02), while endocardial activation occurred before epicardial activation in the distal region (p less than 0.01). In planes of recording electrodes parallel to the epicardium and endocardium, the initial isochrones were elliptical with the major axes of the ellipses along the mean fiber orientation between the pacing site and recording plane rather than along the local fiber orientation in the recording plane. Thus, the ellipses in each plane rotated with respect to each other so that in three dimensions the activation front was helicoid, yet the twist of the helix was less than that of the corresponding transmural rotation of fibers. For pacing from the right ventricular outflow tract, we conclude that beyond 10-12 mm from endocardial and epicardial pacing sites epicardial stimulus potentials in both cases are larger than endocardial potentials because of resistivity differences inside and outside the heart wall and activation in both cases is primarily endocardial to epicardial because of rapid endocardial conduction, and we conclude that the initial spread of activation is helicoid and determined by transmural fiber direction.
Remote Attestation for HDD Files Using Kernel Protection Mechanism (2010)

A remote attestation that measures files on a hard disk drive (HDD) is important for intrusion detection on a data center server. When the server is infected by a rootkit or when a file measurement application is manipulated, the response of the kernel or the measurement application is not reliable. A trusted platform module (TPM) that achieves a chain of trust from BIOS to kernel upon booting is proposed to provide the remote attestation. However, as the data center server is rarely rebooted, the TPM is ill suited for file measurements of the running server. In this paper, we propose an on-demand remote attestation scheme for HDD files of the server. We designed and implemented a trust chain from the BIOS via the kernel and the file measurement application to the HDD files on a running server for secure integrity measurement. A memory virtualization technique is applied to guarantee the integrity of the running kernel, and the file measurement application is verified using a code signature. Also, we implement a mechanism that attaches the server's signature to a measurement result in a trusted kernel. Finally, our proposed scheme achieves a result whereby the remote verifier can measure the integrity of the server files securely at any time.
Cross‐presentation of a CMV pp65 epitope by human dendritic cells using bee venom PLA2 as a membrane‐binding vector (2005)

We have used bee venom phospholipase A2 as a vector to load human dendritic cells ex vivo with a major histocompatibility complex (MHC) class I-restricted epitope fused to its C-terminus. The fusion protein bound to human monocyte-derived dendritic cells and was internalized into early endosomes. In vitro immunization experiments showed that these dendritic cells were able to generate specific CD8 T cell lines against the epitope carried by the fusion protein. Cross-presentation did not require proteasome, transporter associated with antigen processing, or endosome proteases, but required newly synthesized MHC molecules. Comparison of the antigen presentation pathway observed in this study to that followed by other toxins used as vectors is discussed.
TRS-based PCR as a potential tool for inter-serovar discrimination of Salmonella Enteritidis, S. Typhimurium, S. Infantis, S. Virchow, S. Hadar, S. Newport and S. Anatum (2014)

Salmonella enterica subsp. enterica comprises a number of serovars, many of which pose an epidemiological threat to humans and are a worldwide cause of morbidity and mortality. Most reported food infection outbreaks involve the serovars Salmonella Enteritidis and Salmonella Typhimurium. Rapid identification to determine the primary sources of the bacterial contamination is important to the improvement of public health. In recent years, many DNA-based techniques have been applied to genotype Salmonella. Herein, we report the use of a manual TRS-PCR approach for the differentiation of the Salmonella enterica subspecies enterica serovars in a single-tube assay. One hundred seventy Salmonella strains were examined in this work. These consisted of serovars S. Enteritidis, S. Typhimurium, S. Infantis, S. Virchow, S. Hadar, S. Newport and S. Anatum. Five of the TRS-primers, N6(GTG)4, N6(CAC)4, N6(CGG)4, N6(CCG)4 and N6(CTG)4, perfectly distinguished the S. Enteritidis and S. Typhimurium serovars, and the N6(GTG)4 primer additionally grouped the other five frequently isolated serovars. In our opinion, the TRS-PCR methodology could be recommended for a quick and simple DNA-based test for inter-serovar discrimination of Salmonella strains.
Improving image quality and acoustic transparency in MRgFUS at 3T using a low-profile, flexible receive coil array (2023)

Transcranial MRgFUS has been successfully used to treat a variety of neurodegenerative diseases. However, body coil brain image quality is poor, and a low-signal band artifact may occur in some regions due to RF wave reflections. Further, acoustic coil transparency has not been addressed extensively to date. In this work, we simulate a 10-channel coil design that can significantly increase the SNR by a factor of 20 over the body coil and thus indirectly improve the signal at the region of interests. Acoustic simulations/experiments exhibit transparency of the FUS-Flex coil as high as 97% at 650 kHz.
Synthesis and Swelling Behavior of Highly Porous Epoxy Polymers (2020)

Many advantageous properties of cross-linked polymers relate to their network structures. In this study, network structures of three DGEBA-based epoxy systems at various DGEBA monomer sizes were investigated via equilibrium swelling and glass transition behavior. Each system was cured with a tetra-functional diamine, 4,4'-methylenebiscyclohexanamine, in the presence of a nonreactive solvent, i.e., THF at a solvent-to-monomer volume fraction ranging from 0 to 92%. Experimental results revealed that the conventional swelling model (the Dušek model) accurately calculates <i>M</i> <sub>c</sub> values of the cured gels prepared in moderate dilute environments, up to approximately 60% by volume of THF. For gels cured in extreme dilute environments, i.e., in the presence of above 60% by volume of THF, the calculated <i>M</i> <sub>c</sub> values using the Dušek model were found to increase sharply as a function of the initial solvent content. The observed dramatic increase in <i>M</i> <sub>c</sub> values was not supported by the dry <i>T</i> <sub>g</sub> of the identical polymer systems. In fact, the dry <i>T</i> <sub>g</sub> values of the polymer systems were found to be relatively insensitive to the initial solvent content. A modification was proposed to the Dušek model that incorporates an additional term, which accounts for the probability of finding elastic chains in a polymer network. Using the modified equation, <i>M</i> <sub>c</sub> values were varied as expected with the molecular weight of DGEBA and insensitive to the amount of the solvent initially used during cure. Furthermore, the modified <i>M</i> <sub>c</sub> values were shown to be consistent with the dry <i>T</i> <sub>g</sub> values in view of the Fox and Loshaek model.
Dynamic small-signal chirp characteristics of external and integrated modulators (2015)

We demonstrate that our recently proposed chirp measurement technique can be applied to the measurement and visualization of the small-signal dynamic chirp characteristics of modulators in vector space for the first time. Both discrete modulators and those integrated in externally modulated laser modules can be characterized by this method. The results agree with existing method to the first order approximation, whilst dynamic chirp change can also be measured during amplitude transition.
Homogenized halides and alkali cation segregation in alloyed organic-inorganic perovskites (2019)

The role of the alkali metal cations in halide perovskite solar cells is not well understood. Using synchrotron-based nano-x-ray fluorescence and complementary measurements, we found that the halide distribution becomes homogenized upon addition of cesium iodide, either alone or with rubidium iodide, for substoichiometric, stoichiometric, and overstoichiometric preparations, where the lead halide is varied with respect to organic halide precursors. Halide homogenization coincides with long-lived charge carrier decays, spatially homogeneous carrier dynamics (as visualized by ultrafast microscopy), and improved photovoltaic device performance. We found that rubidium and potassium phase-segregate in highly concentrated clusters. Alkali metals are beneficial at low concentrations, where they homogenize the halide distribution, but at higher concentrations, they form recombination-active second-phase clusters.
FashionVLP: Vision Language Transformer for Fashion Retrieval with Feedback (2022)

Fashion image retrieval based on a query pair of reference image and natural language feedback is a challenging task that requires models to assess fashion related information from visual and textual modalities simultaneously. We propose a new vision-language transformer based model, FashionVLP, that brings the prior knowledge contained in large image-text corpora to the domain of fashion image retrieval, and combines visual information from multiple levels of context to effectively capture fashion-related information. While queries are encoded through the transformer layers, our asymmetric design adopts a novel attention-based approach for fusing target image features without involving text or transformer layers in the process. Extensive results show that FashionVLP achieves the state-of-the-art performance on benchmark datasets, with a large 23% relative improvement on the challenging FashionIQ dataset, which contains complex natural language feedback.
Die Wichtigkeit der Dosierung anti-glycolytischer Therapie: im Gegensatz zu einer niedrigen Dosis, führt eine hohe Dosierung eines PFKFB3-blockers nicht zu Tumor-Gefäßnormalisierung, sondern verursacht Gefäß-Desintegration (2017)

Tumorgefäße sind strukturell und funktionell abnormal, wodurch die Perfusion, Oxygenierung und Chemotherapieeffektivität beeinträchtigt wird, während gleichzeitig die Krebszellinvasion und Metastasierung gefördert werden. Das Konzept der Tumor-Gefäßnormalisierung erhält zunehmend Aufmerksamkeit, um diesen Effekten entgegenzuwirken. Wir zeigten kürzlich, dass die Behandlung von Tumor-tragenden Mäusen mit 3PO, einem pharmakologischen Blocker des glykolytischen Aktivators PFKFB3, in einer niedrigen Dosis (25 mg/kg), die die Krebszellen nicht beeinflusst, eine Tumor-Gefäßnormalisierung induzierte, die Metastasierung reduzierte und die Wirksamkeit von Chemotherapie verbesserte. Allerdings war diese Dosis fast 3-fach niedriger als die Dosis, die eingesetzt wurde, um das Tumorwachstum zu hemmen. Das Ziel dieser Untersuchung war es nun, die Effekte von solch einer maximal tolerablen Dosis auf die Tumor-Blutgefäße zu untersuchen.
Gas Vesicles across Kingdoms: A Comparative Solid-State Nuclear Magnetic Resonance Study (2013)

The buoyancy organelles of aquatic microorganisms have to meet stringent specifications: allowing gases to equilibrate freely across the proteinaceous shell, preventing the condensation of water vapor inside the hollow cavity and resisting collapse under hydrostatic pressures that vary with column depth. These properties are provided by the 7- to 8-kDa gas vesicle protein A (GvpA), repeats of which form all but small, specialized portions of the shell. Magic angle spinning nuclear magnetic resonance is uniquely capable of providing high-resolution information on the fold and assembly of GvpA. Here we compare results for the gas vesicles of the haloarchaea Halobacterium salinarum with those obtained previously for the cyanobacterium Anabaena flos-aquae. The data suggest that the two organisms follow similar strategies for avoiding water condensation. On the other hand, in its relatively shallow habitat, H. salinarum is able to avoid collapse with a less costly GvpA fold than is adopted by A. flos-aquae.
Self-assemblies of nucleolipid supramolecular synthons show unique self-sorting and cooperative assembling process (2019)

The inherent control of the self-sorting and co-assembling process that has evolved in multi-component biological systems is not easy to emulate in vitro using synthetic supramolecular synthons. Here, using the basic component of nucleic acids and lipids, we describe a simple platform to build hierarchical assemblies of two component systems, which show an interesting self-sorting and co-assembling behavior. The assembling systems are made of a combination of amphiphilic purine and pyrimidine ribonucleoside-fatty acid conjugates (nucleolipids), which were prepared by coupling fatty acid acyl chains of different lengths at the 2'-O- and 3'-O-positions of the ribose sugar. Individually, the purine and pyrimidine nucleolipids adopt a distinct morphology, which either supports or does not support the gelation process. Interestingly, due to the subtle difference in the order of formation and stability of individual assemblies, different mixtures of supramolecular synthons and complementary ribonucleosides exhibit a cooperative and disruptive self-sorting and co-assembling behavior. A systematic morphological analysis combined with single crystal X-ray crystallography, powder X-ray diffraction (PXRD), NMR, CD, rheological and 3D X-ray microtomography studies provided insights into the mechanism of the self-sorting and co-assembling process. Taken together, this approach has enabled the construction of assemblies with unique higher ordered architectures and gels with remarkably enhanced mechanical strength that cannot be derived from the respective single component systems.
Evolution of Multiple Domains of the HIV-1 Envelope Glycoprotein during Coreceptor Switch with CCR5 Antagonist Therapy (2022)

HIV-1 uses CD4 as a receptor and chemokine receptors CCR5 and/or CXCR4 as coreceptors. CCR5 antagonists are a class of antiretrovirals used to inhibit viral entry. Phenotypic prediction algorithms such as Geno2Pheno are used to assess CCR5 antagonist eligibility, for which the V3 region is screened. However, there exist scenarios where the algorithm cannot give an accurate prediction of tropism. The current study examined coreceptor shift of HIV-1 from CCR5-tropic strains to CXCR4-tropic or dual-tropic strains among five subjects in a clinical trial of the CCR5 antagonist vicriviroc. Envelope gene amplicon libraries were constructed and subjected to next-generation sequencing, as well as single-clone sequencing and functional analyses. Approximately half of the amplified full-length single envelope-encoding clones had no significant activity for infection of cells expressing high levels of CD4 and CCR5 or CXCR4. Functional analysis of 9 to 21 individual infectious clones at baseline and at the time of VF were used to construct phylogenetic trees and sequence alignments. These studies confirmed that specific residues and the overall charge of the V3 loop were the major determinants of coreceptor use, in addition to specific residues in other domains of the envelope protein in V1/V2, V4, C3, and C4 domains that may be important for coreceptor shift. These results provide greater insight into the viral genetic determinants of coreceptor shift. <b>IMPORTANCE</b> This study is novel in combining single-genome sequence analysis and next-generation sequencing to characterize HIV-1 quasispecies. The work highlights the importance of mutants present at frequencies of 1% or less in development of drug resistance. This study highlights a critical role of specific amino acid substitutions outside V3 that contribute to coreceptor shift as well as important roles of the V1/V2, V4, C3, and C4 domain residues.
The Immunomodulatory Effect of the Antidepressant Sertraline in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis (2010)

We suggest that sertraline might be an add-on option for multiple sclerosis treatment.
Cost‐effectiveness of the highly effective direct‐acting antivirals in the treatment of chronic hepatitis C in Hong Kong (2016)

The most desirable costs of the Highly Effective DAAs would be below US$43,553 if Sofosbuvir-PR rescue therapy is used and below US$56,985 if Boceprevir-PR therapy is used.
Multi-Cell Systems (2016)

We now extend the single-cell performance analysis of Chapter 3 to the multi-cell setting as modeled in Section 2.2.2. The activities in the various cells occur synchronously, but otherwise there is no cell-to-cell cooperation, with the exception of pilot assignment and possibly power control. Each base station serves its own terminals. Data transmission activities are identical to their single-cell counterparts. The channel estimation, however, has to account for reuse of pilots in other cells.
Myocardial Tissue Characterization Using Magnetic Resonance Noncontrast T1 Mapping in Hypertrophic and Dilated Cardiomyopathy (2012)

In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.
Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features (2020)

Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants.
ESCRT-dependent STING degradation inhibits steady-state and cGAMP-induced signalling (2023)

Stimulator of interferon genes (STING) is an intracellular sensor of cyclic di-nucleotides involved in the innate immune response against pathogen- or self-derived DNA. STING trafficking is tightly linked to its function, and its dysregulation can lead to disease. Here, we systematically characterize genes regulating STING trafficking and examine their impact on STING-mediated responses. Using proximity-ligation proteomics and genetic screens, we demonstrate that an endosomal sorting complex required for transport (ESCRT) complex containing HGS, VPS37A and UBAP1 promotes STING degradation, thereby terminating STING-mediated signaling. Mechanistically, STING oligomerization increases its ubiquitination by UBE2N, forming a platform for ESCRT recruitment at the endosome that terminates STING signaling via sorting in the lysosome. Finally, we show that expression of a UBAP1 mutant identified in patients with hereditary spastic paraplegia and associated with disrupted ESCRT function, increases steady-state STING-dependent type I IFN responses in healthy primary monocyte-derived dendritic cells and fibroblasts. Based on these findings, we propose that STING is subject to a tonic degradative flux and that the ESCRT complex acts as a homeostatic regulator of STING signaling.