gebhart/patrepeval huggingface dataset:
Development and validation of warning system of ventricular tachyarrhythmia in patients with heart failure with heart rate variability data (2018)

Implantable-cardioverter defibrillators (ICD) detect and terminate life-threatening ventricular tachyarrhythmia with electric shocks after they occur. This puts patients at risk if they are driving or in a situation where they can fall. ICD's shocks are also very painful and affect a patient's quality of life. It would be ideal if ICDs can accurately predict the occurrence of ventricular tachyarrhythmia and then issue a warning or provide preventive therapy. Our study explores the use of ICD data to automatically predict ventricular arrhythmia using heart rate variability (HRV). A 5 minute and a 10 second warning system are both developed and compared. The participants for this study consist of 788 patients who were enrolled in the ICD arm of the Sudden Cardiac Death-Heart Failure Trial (SCD-HeFT). Two groups of patient rhythms, regular heart rhythms and pre-ventricular-tachyarrhythmic rhythms, are analyzed and different HRV features are extracted. Machine learning algorithms, including random forests (RF) and support vector machines (SVM), are trained on these features to classify the two groups of rhythms in a subset of the data comprising the training set. These algorithms are then used to classify rhythms in a separate test set. This performance is quantified by the area under the curve (AUC) of the ROC curve. Both RF and SVM methods achieve a mean AUC of 0.81 for 5-minute prediction and mean AUC of 0.87-0.88 for 10-second prediction; an AUC over 0.8 typically warrants further clinical investigation. Our work shows that moderate classification accuracy can be achieved to predict ventricular tachyarrhythmia with machine learning algorithms using HRV features from ICD data. These results provide a realistic view of the practical challenges facing implementation of machine learning algorithms to predict ventricular tachyarrhythmia using HRV data, motivating continued research on improved algorithms and additional features with higher predictive power.
A 1 V 0.9 mW at 100 MHz 2 k×16 b SRAM utilizing a half-swing pulsed-decoder and write-bus architecture in 0.25 μm dual-Vt CMOS (2002)

The main limitation resulting from reducing signal swings is reduction in gate overdrive at the receiving transistor leading to delay penalty. This design overcomes this using positive and negative half-swing signals on high-capacitance predecode lines so active decode circuits see a full gate-overdrive, while reducing decoder power. The half-Vdd supply is generated internally with high efficiency using charge-recycling between positive and negative half-swing signals. SRAM architecture and decoder organization are described.
Scalable and Efficient Data Authentication for Decentralized Systems. (2019)

Public blockchains like Ethereum use Merkle trees to verify transactions
received from untrusted servers before applying them to the blockchain. We
empirically show that the low throughput of such blockchains is due to the I/O
bottleneck associated with using Merkle trees for processing transactions. We
present RAINBLOCK, a new architecture for public blockchains that increases
throughput without affecting security. \sysname achieves this by tackling the
I/O bottleneck on two fronts: first, decoupling transaction processing from
I/O, and removing I/O from the critical path; second, reducing I/O
amplification by customizing storage for blockchains. RAINBLOCK uses a novel
variant of the Merkle tree, the Distributed Sharded Merkle tree (DSM-TREE) to
store system state. We evaluate RAINBLOCK using workloads based on public
Ethereum traces (including smart contracts) and show that \sysname processes
20K transactions per second in a geo-distributed setting with four regions
spread across three continents.
Bimodal distribution of BaI vibrational states from the reaction Ba+CF3I (1977)

Unrelaxed vibrational state distributions of BaI product are reported for the reaction Ba+CF3I→BaI+CF3, using laser-induced fluorescence. Product state distributions were measured using a beam–gas arrangement and a primitive angular distribution was also determined using a crossed-beam configuration. The BaI vibrational distribution is bimodal with a low vibrational component peaking at v∼27 and a high vibrational component peaking at v∼47. At least 75% of the BaI is produced in the high vibrational levels. The angular distribution indicates that the BaI formed in the high vibrational states is scattered in a forward direction with respect to the Ba beam, but the low vibrational component is not sharply forward scattered. The Ba+CF3I reaction is thought to proceed by two mechanisms: (1) attack in the direction of I–CF3, leading to BaI product formation with low vibrational energy; and (2) attack in the direction of CF3–I, either by initial attack of the CF3 end followed by migration or by attack of the I end at large impact parameters, leading to BaI product formation with high vibrational energy.
Paper 233: Isolation and Characterization of Human Meniscus‐Derived Vascular Stem Cells (2012)

The sources of various adult-derived stem cells, including muscle-derived stem cells, have been recently reported to be associated with vascular-derived cells. Since meniscus tears in the peripheral vascularized region can be successfully repaired, we believe that the repair is mediated by similar vascular-derived cells. Given the advantages for self-repair inherent in the vascularized region of the meniscus, we hypothesized that this region might possess a richer supply of vascular-derived stem cells when compared to the avascular region.
Effect of alpha-fluorination of valproic acid on valproyl-S-acyl-CoA formation in vivo in rats. (2001)

Studies designed to compare valproic acid (VPA) with its alpha-fluorinated derivative (F-VPA) for their abilities to form acyl-CoA thioester derivatives in vivo are described. Recent studies have shown that alpha-fluorination of a hepatotoxic metabolite of VPA (Delta(4)-VPA) resulted in a nonhepatotoxic derivative. We hypothesize that the decrease in hepatotoxicity may be related to a lack of formation of the intermediary acyl-CoA thioester. To determine the effect of alpha-fluoro substitution on acyl-CoA formation, we synthesized F-VPA and compared it with VPA for its ability to form the acyl-CoA thioester derivative in vivo in rat liver. Thus, after dosing rats with VPA or F-VPA, animals were sacrificed (0.05-, 0.5-, 1-, 2-, and 5-h postadministration) for the analysis of liver tissue. High-performance liquid chromatography (HPLC) and electrospray ionization/tandem mass spectrometry analysis of liver extracts from VPA-dosed rats showed the presence of VPA-CoA that was maximal after 0.5 h (185 nmol/g of liver) and was still measurable 5-h postadministration (90 nmol/g of liver). In agreement with our hypothesis, F-VPA did not form the corresponding acyl-CoA derivative as determined by the absence of F-VPA-CoA upon HPLC analysis of liver extracts from F-VPA-dosed rats. Further examination of liver tissue for the presence of free acids revealed that the differences in acyl-CoA formation cannot be explained by differences in VPA and F-VPA free acid concentrations. From these observations and related studies showing the lack of toxicity due to alpha-fluoro substitution, we propose that metabolism of VPA by acyl-CoA formation may mediate the hepatotoxicity of the drug.
Electroconvulsive therapy and psychiatric readmission in major depressive disorder – A population‐based register study (2021)

This study suggests that ECT reduces the risk of psychiatric readmission in certain subgroups of patients with MDD. Since patients receiving ECT tend to be more difficult to treat, there is a risk of residual confounding.
Recovery of Minerales Monclova Minas V (1999)

Methane issuing from a roof-bolt hole ignited when the hot bit was withdrawn. Similar ignitions have occurred in other mines. This one differed in that flames spread quickly, coal was ignited, and, after three futile hours of applying inadequate water and extinguishing agents, the mine was sealed. Fires are fuel and ventilation controlled. In this mine there was an abundance of methane, coal, and wood lagging. Recovery of the mine, therefore, depended on successful control of its ventilation. The recovery was done without anyone suffering a scratch; a remarkable feat considering the abnormal methane outflows and concentrations, the continuing evidence of on-going thermal reactions, and what once were inexperienced but now amongst the best mine rescue men.
Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer (2022)

Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer mortality worldwide, highlighting an urgent need for new therapeutic options and combination strategies for patients. The orchestration of potent T cell responses against human cancers is necessary for effective antitumour immunity. However, regression of a limited number of cancers has been induced by immune checkpoint inhibitors, T cell engagers (TCEs) and/or oncolytic viruses. Although one TCE has been FDA-approved for the treatment of hematological malignancies, many challenges exist for the treatment of solid cancers. Here, we show that TCEs targeting CEACAM5 and CD3 stimulate robust activation of CD4 and CD8-positive T cells in <i>in vitro</i> co-culture models with colorectal cancer cells, but <i>in vivo</i> efficacy is hindered by a lack of TCE retention in the tumour microenvironment and short TCE half-life, as demonstrated by HiBiT bioluminescent TCE-tagging technology. To overcome these limitations, we engineered Bispecific Engager Viruses, or BEVirs, a novel tumour-targeted vaccinia virus platform for intra-tumour delivery of these immunomodulatory molecules. We characterized virus-mediated TCE-secretion, TCE specificity and functionality from infected colorectal cancer cells and patient tumour samples, as well as TCE cytotoxicity in spheroid models, in the presence and absence of T cells. Importantly, we show regression of colorectal tumours in both syngeneic and xenograft mouse models. Our data suggest that a different profile of cytokines may contribute to the pro-inflammatory and immune effects driven by T cells in the tumour microenvironment to provide long-lasting immunity and abscopal effects. We establish combination regimens with immune checkpoint inhibitors for aggressive colorectal peritoneal metastases. We also observe a significant reduction in lung metastases of colorectal tumours through intravenous delivery of our oncolytic virus driven T-cell based combination immunotherapy to target colorectal tumours and FAP-positive stromal cells or CTLA4-positive T<sub>reg</sub> cells in the tumour microenvironment. In summary, we devised a novel combination strategy for the treatment of colorectal cancers using oncolytic vaccinia virus to enhance immune-payload delivery and boost T cell responses within tumours.
Activation of Molecules in Confined Spaces:  An Approach to Zeolite−Guest Supramolecular Systems (1997)

Ab initio calculations showing frontier molecular orbital energy modifications of a guest molecule when located inside a microporous zeolitic cavity are presented. Micropores of zeolites Beta, ZSM-12, and ZSM-5 have been modeled using all silica clusters from which it is found that the highest occupied molecular orbital (HOMO) energy of toluene increases when going from the gas phase state to restricted microporous environments. The influence of the zeolite cavity size and its chemical composition on the toluene HOMO energy are discussed. Regarding the size of the confining environment, it is found that the smaller the zeolite cavity the higher is the rise in toluene HOMO energy. The effect of the chemical composition on the toluene HOMO energy was tested in the ZSM-5 zeolite by varying the Al content. The results obtained showed that the frontier orbital energy increases upon decreasing the Al content of the cluster. As a consequence of the confinement effect, toluene reactivity in zeolite catalyzed reactions is expected to change toward a more covalent behavior in which electronic transference from the toluene molecule to an electronic acceptor will be more favored than in gas phase reactions.
Antigenic variation of influenza A virus nucleoprotein detected with monoclonal antibodies (1980)

Monoclonal antibodies were used to study antigenic variation in the nucleoprotein of influenza A viruses. We found that the nucleoprotein molecule of the WSN/33 strain possesses at least five different determinants. Viruses of other influenza A virus subtypes showed antigenic variation in these nucleoprotein determinants, although changes in only one determinant were detected in H0N1 and animal strains. The nucleoprotein of human strains isolated from 1933 through 1979 could be divided into six groups, based on their reactivities with monoclonal antibodies; these groups did not correlate with any particular hemagglutinin or neuraminidase subtype. Our results indicate that antigenic variation in the nucleoproteins of influenza A viruses proceeds independently of changes in the viral surface antigens and suggest that point mutations and genetic reassortment may account for nucleoprotein variability.
Evaluation of Disulfide Bond Position to Enhance the Thermal Stability of a Highly Stable Single Domain Antibody (2014)

Single domain antibodies are the small recombinant variable domains derived from camelid heavy-chain-only antibodies. They are renowned for their stability, in large part due to their ability to refold following thermal or chemical denaturation. In addition to refolding after heat denaturation, A3, a high affinity anti-Staphylococcal Enterotoxin B single domain antibody, possesses a melting temperature of ∼84°C, among the highest reported for a single domain antibody. In this work we utilized the recently described crystal structure of A3 to select locations for the insertion of a second disulfide bond and evaluated the impact that the addition of this second bond had on the melting temperature. Four double-disulfide versions of A3 were constructed and each was found to improve the melting temperature relative to the native structure without reducing affinity. Placement of the disulfide bond at a previously published position between framework regions 2 and 3 yielded the largest improvement (>6°C), suggesting this location is optimal, and seemingly provides a universal route to raise the melting temperature of single domain antibodies. This study further demonstrates that even single domain antibodies with extremely high melting points can be further stabilized by addition of disulfide bonds.
Blast crisis in a murine model of chronic myelogenous leukemia. (1991)

The P210bcr/abl protein is produced in cells from patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Retroviral transfer of the gene encoding P210bcr/abl into murine bone marrow induces a granulocytic leukemia that models the chronic phase of human CML. We have transferred the leukemic clone to syngeneic animals, albeit with surprising inefficiency, and have observed CML and clonally related acute leukemias of lymphoid or myeloid phenotype in some transplant recipients. These data show that murine CML can result from retroviral transfer of the bcr/abl gene into pluripotent hematopoietic stem cells, that infected clones repopulate poorly after adoptive transfer, and that these clones can give rise to acute leukemia, reflecting evolution to a phase resembling blast crisis in the human disease.
Cell signaling pathways elicited by asbestos. (1997)

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.
Purification of Recombinant Acyl-Coenzyme A:Cholesterol Acyltransferase 1 (ACAT1) from H293 Cells and Binding Studies between the Enzyme and Substrates Using Difference Intrinsic Fluorescence Spectroscopy (2010)

Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) is a membrane-bound enzyme utilizing long-chain fatty acyl-coenzyme A and cholesterol to form cholesteryl esters and coenzyme A. Previously, we had expressed tagged human ACAT1 (hACAT1) in CHO cells and purified it to homogeneity; however, only a sparse amount of purified protein could be obtained. Here we report that the hACAT1 expression level in H293 cells is 18-fold higher than that in CHO cells. We have developed a milder purification procedure to purify the enzyme to homogeneity. The abundance of the purified protein enabled us to conduct difference intrinsic fluorescence spectroscopy to study the binding between the enzyme and its substrates in CHAPS/phospholipid mixed micelles. The results show that oleoyl-CoA binds to ACAT1 with K(d) = 1.9 μM and elicits significant structural changes of the protein as manifested by the significantly positive changes in its fluorescence spectrum; stearoyl-CoA elicits a similar spectrum change but much lower in magnitude. Previously, kinetic studies had shown that cholesterol is an efficient substrate and an allosteric activator of ACAT1, while its diastereomer epicholesterol is neither a substrate nor an activator. Here we show that both cholesterol and epicholesterol induce positive changes in the ACAT1 fluorescence spectrum; however, the magnitude of spectrum changes induced by cholesterol is much larger than epicholesterol. These results show that stereospecificity, governed by the 3β-OH moiety in steroid ring A, plays an important role in the binding of cholesterol to ACAT1.
Episomal expression of wild-type CFTR corrects cAMP-dependent chloride transport in respiratory epithelial cells. (1996)

The isolation of the gene responsible for the Cl- ion transport defect in cystic fibrosis (CF) has provided important information about the relationship between the disease pathology and the underlying genetic and biochemical mechanisms. In addition, new areas of investigation and therapy are now possible. Most notably, the isolation of the CF gene, the cystic fibrosis transmembrane conductance regulator (CFTR) has been led to the development of different gene therapy strategies. To circumvent possible complications due to insertional mutagenesis and virally induced immune responses, we have employed Epstein-Barr virus (EBV)-based expression vectors for correction of the cAMP-dependent Cl- transport defect associated with CF. A CFTR-containing expression construct under the regulation of the Rous sarcoma virus (RSV) long terminal repeat (LTR) (pREP5/CFTR) was introduced into transformed human airway epithelial cells defective in cAMP-dependent Cl-transport. Transfected cells were assayed for Cl- ion transport by (36)Cl- efflux, SPQ, and patch clamp and showed restoration of intact cAMP-dependent transport. CFTR transcription from pREP5/CFTR was detected by Northern hybridization. The level of response to agonists appeared to be dependent on the level of CFTR expression. When cells were tested for functional expression of CFTR after removal of selection pressure, they showed a continuous decrease in responsiveness to forskolin as a function of time after removal of selection. This decrease correlated with a loss of CFTR mRNA in the loss of the PREP5/CFTR. After 12 to 15 weeks growth without selection both cAMP-dependent Cl- transport and plasmid-derived CFTR mRNA were not detectable. However, it was still possible to rescue cAMP-dependent Cl- transport in these transfected cells by reselection suggesting the presence of the CFTR containing plasmid in a portion of the cells. Analysis of DNA indicated that the pREP5/CFTR vector copy number was reduced from 30 copies per cell with continuous selection, to approximately 0.3 copies per cell after 20 weeks without hygromycin B.
The CD8 + Memory Stem T Cell (T SCM ) Subset Is Associated with Improved Prognosis in Chronic HIV-1 Infection (2014)

HIV-1 infection leads to profound impairment of the immune system. T(SCM) constitute a recently identified lymphocyte subset with stem cell-like qualities, including the ability to generate other memory T cell subtypes, and are therefore likely to play an important role in controlling viral infection. We investigated the relationship between the size of the CD8(+) T(SCM) compartment and HIV-1 disease progression in a cohort of chronically infected individuals. Our results suggest that HAART restores a normal frequency of CD8(+) T(SCM) and that the natural preservation of this subset in the setting of untreated HIV-1 infection is associated with improved viral control and immunity. Therefore, the CD8(+) T(SCM) population may represent a correlate of protection in chronic HIV-1 infection that is directly relevant to the design of T cell-based vaccines, adoptive immunotherapy approaches, or the pharmacologic induction of T(SCM).
Advances in Light Emission from Group-IV Alloys via Lattice Engineering and n-Type Doping Based on Custom-Designed Chemistries (2014)

Intrinsic and n-type Ge1–ySny alloys with y = 0.003–0.11 have been grown on Ge-buffered Si via reactions of Ge3H8 and SnD4 hydrides using UHV-CVD techniques. The films exhibit large thicknesses (t > 600 nm), low dislocation densities (107/cm2), planar surfaces (AFM RMS ≈ 2 for intrinsic films) and mostly relaxed microstructures, making them suitable for subsequent characterization of the emission properties using photoluminescence (PL) spectroscopy. The PL spectra are acquired at room temperature and show tunable and distinct direct and indirect gap emission peaks versus composition. The peak intensity in a given sample is found to increase by exposing the layers to hydrogen plasma, indicating that surface passivation plays an important role in eliminating carrier recombination traps. The PL intensity is further increased by n-type doping with P/As atoms at levels 0.8–7 × 1019 cm–3using P(GeH3)3, P(SiH3)3, and As(SiH3)3 precursors, indicating that desirable direct gap conditions can be approached even at relatively modest 6–8% Sn contents. The indirect and direct gap energies of the samples are then used to determine the direct gap cross over point at ∼9% Sn. Collectively the results in this paper show that strong light emission can be generated in this class of narrow gap alloys by adjusting the Sn content, subjecting the samples to post growth passivation treatments or doping the system n-type. The influence of precursor chemistry on the activation properties and optical behavior of the materials is explored with the objective to optimize the PL response near the indirect–direct gap threshold. New methods embodying environmentally safe conditions are designed to produce the dopant compounds in high purity for application in future generation working devices requiring enhanced IR optical performance.