gebhart/patrepeval huggingface dataset:
Oxysterol‐induced osteogenic differentiation of marrow stromal cells is regulated by Dkk‐1 inhibitable and PI3‐kinase mediated signaling (2008)

Osteoporosis and its complications cause morbidity and mortality in the aging population, and result from increased bone resorption by osteoclasts in parallel with decreased bone formation by osteoblasts. A widely accepted strategy for improving bone health is targeting osteoprogenitor cells in order to stimulate their osteogenic differentiation and bone forming properties through the use of osteoinductive/anabolic factors. We previously reported that specific naturally occurring oxysterols have potent osteoinductive properties, mediated in part through activation of hedgehog signaling in osteoprogenitor cells. In the present report, we further demonstrate the molecular mechanism(s) by which oxysterols induce osteogenesis. In addition to activating the hedgehog signaling pathway, oxysterol-induced osteogenic differentiation is mediated through a Wnt signaling-related, Dkk-1-inhibitable mechanism. Bone marrow stromal cells (MSC) treated with oxysterols demonstrated increased expression of osteogenic differentiation markers, along with selective induced expression of Wnt target genes. These oxysterol effects, which occurred in the absence of beta-catenin accumulation or TCF/Lef activation, were inhibited by the hedgehog pathway inhibitor, cyclopamine, and/or by the Wnt pathway inhibitor, Dkk-1. Furthermore, the inhibitors of PI3-Kinase signaling, LY 294002 and wortmanin, inhibited oxysterol-induced osteogenic differentiation and induction of Wnt signaling target genes. Finally, activators of canonical Wnt signaling, Wnt3a and Wnt1, inhibited spontaneous, oxysterol-, and Shh-induced osteogenic differentiation of bone marrow stromal cells, suggesting the involvement of a non-canonical Wnt pathway in pro-osteogenic differentiation events. Osteogenic oxysterols are, therefore, important small molecule modulators of critical signaling pathways in pluripotent mesenchymal cells that regulate numerous developmental and post-developmental processes.
Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management (2018)

Despite the important role of high-intensity statins in reducing atherosclerotic cardiovascular disease events in secondary and primary prevention, substantial residual risk persists, particularly among high-risk patients with type 2 diabetes mellitus, metabolic syndrome, and obesity. Considerable attention is currently directed to the role that elevated triglycerides (TGs) and non-high-density lipoprotein cholesterol levels play as important mediators of residual atherosclerotic cardiovascular disease risk, which is further strongly supported by genetic linkage studies. Previous trials with fibrates, niacin, and most cholesterol ester transfer protein inhibitors that targeted high-density lipoprotein cholesterol raising, and/or TG lowering, have failed to show conclusive evidence of incremental event reduction after low-density lipoprotein cholesterol levels were "optimally controlled" with statins. Although omega-3 fatty acids are efficacious in lowering TG levels and may have pleiotropic effects such as reducing plaque instability and proinflammatory mediators of atherogenesis, clinical outcomes data are currently lacking. Several ongoing randomized controlled trials of TG-lowering strategies with an optimal dosage of omega-3 fatty acids are nearing completion.
Constitutive synthesis of a transport function encoded by the Thiobacillus ferrooxidans merC gene cloned in Escherichia coli (1990)

Mercuric reductase activity determined by the Thiobacillus ferrooxidans merA gene (cloned and expressed constitutively in Escherichia coli) was measured by volatilization of 203Hg2+. (The absence of a merR regulatory gene in the cloned Thiobacillus mer determinant provides a basis for the constitutive synthesis of this system.) In the absence of the Thiobacillus merC transport gene, the mercury volatilization activity was cryptic and was not seen with whole cells but only with sonication-disrupted cells. The Thiobacillus merC transport function was compared with transport via the merT-merP system of plasmid pDU1358. Both systems, cloned and expressed in E. coli, governed enhanced uptake of 203Hg2+ in a temperature- and concentration-dependent fashion. Uptake via MerT-MerP was greater and conferred greater hypersensitivity to Hg2+ than did uptake with MerC. Mercury uptake was inhibited by N-ethylmaleimide but not by EDTA. Ag+ salts inhibited mercury uptake by the MerT-MerP system but did not inhibit uptake via MerC. Radioactive mercury accumulated by the MerT-MerP and by the MerC systems was exchangeable with nonradioactive Hg2+.
Metabonomic Applications in Toxicity Screening and Disease Diagnosis (2002)

Biofluid NMR spectroscopy is a powerful tool providing a comprehensive metabolic profile of the low molecular weight components in biofluids that reflect concentrations and fluxes of endogenous metabolites involved in key intermediary cellular pathways, thereby giving an indication of an organisms physiological or pathophysiological status [1]. The interaction of pharmacological agents with cells and tissues can also be monitored using recently developed high resolution magic-angle spinning (HRMAS) NMR spectroscopic technology for biological matrices [1]. However, recent developments in both spectrometer and software technology has resulted in improved capacity for sample handling, leading to a rapid growth in the size of toxicological spectral databases, and increased the complexity of the biological spectral data generated. Thus more emphasis has been placed on the need to develop improved automated procedures for data processing and interpretation. By harnessing chemometric tools for analysis of complex spectral data, the toxicological consequences of xenobiotic exposure can be evaluated efficiently on line. Automation of spectral processing procedures and the construction of mathematically based 'expert systems' for the prediction of drug-induced toxicity founded on IH NMR spectral profiles have now been achieved. Chemometric analysis of biological NMR spectra has provided the main analytical platform for metabonomic analysis, providing a systems approach to evaluating pathophysiological or genetic influences on the metabolic status of an organism [1]. This technology is currently being given high-priority in the pharmaceutical industry with respect to development of efficient high throughput toxicity screening systems for lead candidate selection. In this article, we review the recent developments in metabonomics and consider their application in toxicological screening, disease diagnosis and functional genomics.
Deconstructing Human-assisted Video Transcription and Annotation for Legislative Proceedings (2020)

Legislative proceedings present a rich source of multidimensional information that is crucial to citizens and journalists in a democratic system. At present, no fully automated solution exists that is capable of capturing all the necessary information during such proceedings. Even if professional-quality automated transcriptions existed, other tasks such as speaker or rhetorical position identifications are not fully automatable. This work focuses on improving and evaluating the transcription software used by the Digital Democracy initiative, named Transcription Tool. Human transcribers work to up-level state legislative proceedings using this tool. Five phases of tool improvements are introduced and for each phase, the resulting change in efficiency is measured. We investigate over 12,000 individual transcription sessions (2,300 hours of video), where each session is the record of one bill discussion. A set of about 3,200 sessions belonging to a single cohort of 20 transcribers is further evaluated. Through introduction of new tool features, human-assisted transcription efficiency can be improved by 19.4% over five phases. Furthermore, investigation into transcriber usage patterns reveals that transcription time is composed of passive time, speaker identification, text correction, tool startup, as well as splitting and merging utterances. We analyze and rank these as a contribution.
Combined Optical and X-ray Tomosynthesis Breast Imaging (2010)

The optical and DBT images were structurally consistent. The malignant tumors and benign lesions demonstrated different Hb(T) and scattering contrasts, which can potentially be exploited to reduce the false-positive rate of conventional mammography and unnecessary biopsies.
High-Pressure Structural Stability and Elasticity of Supercrystals Self-Assembled from Nanocrystals (2010)

We report here combined quasi-hydrostatic high-pressure small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD) studies on faceted 3D supercrystals (SCs) self-assembled from colloidal 7.0 nm spherical PbS nanocrystals (NCs). Diamond anvil cell (DAC) SAXS experiments in the pressure range from ambient to 12.5 GPa revealed nearly perfect structural stability of the SCs, with face-centered cubic organization of the NCs. Pressure-induced ordering (annealing effect) of the superstructure was observed. The ambient pressure bulk modulus of the SCs was calculated to be ∼5 GPa for compression and ∼14.5 GPa for decompression from fitting of Vinet and Birch-Murnaghan equations of state. XRD measurements revealed strong preferential crystallographic orientation of the NCs through all phase transformations to as high as 55 GPa without any indication of NC sintering. The first phase transition pressure of the NCs was found between 8.1 and 9.2 GPa and proceeds through homogeneous nucleation. Bulk modulus of PbS NCs was calculated to be ∼51 GPa based on fitting to the equations of state (K(PbS,bulk) ∼ 51-57 GPa). Closest surface-to-surface distance between the NCs in the SCs was calculated based on combined XRD and SAXS data, to reversibly tune from ∼1.56 nm to ∼0.9-0.92 nm and back to ∼1.36 nm in the ambient-12.5 GPa-ambient pressure cycle. The bulk modulus of the ligand matrix was extrapolated to be ∼2.2-2.95 GPa. These results show a general method of tuning NC interactions in packed nanoparticle solids.
Immune reactions against hepatitis B viral antigens lead to the rejection of hepatocellular carcinoma in BALB/c mice. (1993)

Human hepatitis B virus (HBV) is closely associated with hepatocellular carcinoma. However, the mechanism of carcinogenesis and the immune responses to HBV infection and hepatocellular carcinoma are not clearly understood. Recently, we established BALB/c mouse liver (ML) cell lines and demonstrated that transfection of ML cell lines with HBV dimer DNA resulted in the expression of HBV antigens (1). The HBV-transfected ML cells and the parental ML cells showed similar tumorigenicity in nude mice. However, the HBV-transfected cells had much lower tumorigenicity in BALB/c mice. Similar results were also obtained in two cloned ML cell lines, ML-1.1 and ML-1.2, transfected with plasmid DNA containing HBs, HBc, or HBx gene. Furthermore, adoptive transfer of spleen cells from BALB/c mice immunized with HBsAg- or HBcAg-expressing ML-1.1 cells caused regression of tumor cells expressing the corresponding antigens in nude mice. In addition, transfer of spleen cells from BALB/c mice immunized with purified HBsAg or HBcAg also caused tumor regression. These results demonstrate that HBsAg and HBcAg can induce immunity which leads to the rejection of hepatocellular carcinoma in vivo.
Diagnosis of Bovine Viral Diarrhea Virus Infection using Monoclonal Antibodies (1990)

The monoclonal antibody (MAb) D89 against bovine viral diarrhea virus (BVDV) was used in conjunction with fluorescein-conjugated anti-mouse immunoglobulin in an indirect fluorescent antibody (IFA) procedure on frozen tissue sections and cell culture. During the 2-year study, BVDV was isolated from specimens submitted in 460 cases. The D89 Mab detected all but 2 BVDV isolates, both cytopathic. In 316 of the cases in which BVD virus was detected by IFA, specimens were inoculated on bovine turbinate cells and examined for BVDV antigens at 3-5, 10, and 20 days postinoculation. The BVDV was detected in 238/316 cases (75%) after 3-5 days incubation. The remainder were not detected until 10 or 20 days postinoculation. Virus isolation was enhanced in the early test if plates were centrifuged at the time of inoculation. Results suggest that D89 monoclonal antibody is a suitable diagnostic reagent for the detection of BVDV isolated from diagnostic specimens. The D89 MAb can be used for the detection of BVDV in both cell culture and tissues. Combination of D89 with another BVDV MAb (C17) did not improve the ability to detect BVDV in tissues compared to using D89 only, and the combined Mab's resulted in an increase in nonspecific fluorescence when used on tissues. Although pooling of different BVDV monoclonal antibodies may be necessary to detect all strains of BVDV in cell culture, pooling should be used with caution on tissues. Early detection of BVDV in cell culture by this IFA procedure permits faster confirmation of BVDV diagnosis when compared to the usual routine testing for noncytopathic BVDV at termination of first passage in cell culture.
Microfluidic-photonic-delectrophoretic integrated circuits for biophotonic sensing (2004)

This work demonstrates microfluidic-photonic-dielectrophoretic integrated circuits fabricated using a novel technology involving micromolding, polymer bonding, and channel waveguides with capillary filling. This represents a new class of circuits particularly attractive to lab-on-a-chip and biomedical applications.
Induction of Autophagic Cell Death Circumvents Azacitidine-Resistance In Myelodysplastic Syndrome-Derived Cell Lines (2010)

Abstract Abstract 1817 Azacitidine (AZA) is the first line treatment for IPSS (index prognostic scoring system) high-risk myelodysplastic syndrome (HR-MDS). To date, only Khan et al. (Exp Hematol. 2008) and Hollenbach et al. (PLoS One. 2009) have reported apoptosis as a mechanism of AZA effect on MDS cell lines. Nevertheless, approximately 40% of patients treated with AZA are refractory to this molecule. To investigate the possible mechanisms of AZA resistance in MDS cells, we developped AZA-resistant cell clones (AZA-R) from the well-characterized MDS cell line SKM1. The bulk resistant SKM1 cell line (AZA-R) was obtained following long time exposure of cells to iterative and increasing doses of AZA ranging from 0.1 to 8mM. We first showed that AZA triggered loss of cell metabolism in SKM1 parental cells but not in their AZA-resistant counterpart at a maximally effective dose of 1mM. AZA-mediated loss of cell metabolism accounted mainly for induction of apoptosis as judged by both an increase in caspase 9 and 3 activities triggered by this compound and by a significant protection in the presence of the pan-caspase inhibitor Z-VAD-fmk in SKM1 parental cells. Conversely, no or very few activation of caspases and apoptosis were detected in AZA-R cells strongly suggesting that apoptosis is impaired in AZA-R SKM1 cells. Finally, unlike in SKM1 cells, AZA failed to induce mitochondrial membrane permeabilization in AZA-R SKM1 cells. Importantly, basal autophagy was increased in AZA-R versus AZA-S cells as shown by LC3-I cleavage into LC3-II, p62/SQSTM1 protein expression, cathepsin B activation, mTOR and S6 ribosomal protein dephosphorylation and finally electronic microscopy experiments. In addition, Acadesine, an adenosine derivative and AMPK agonist which targets autophagy was capable to circumvent AZA resistance in both AZA-R SKM1 cells and in medullary cells from five MDS patients resistant to AZA after 6 cycles of Azacitidine. In conclusion, targeting autophagy appears as an attractive therapeutical strategy to circumvent AZA resistance in both established MDS cell lines and cells from MDS patients. Therefore, drugs capable of inducing autophagy or autophagic cell death, such as Acadesine (Robert et al., PLoS One. 2009) which is currently in phase II clinical trials for the treatment of Chronic Lymphoblastic Leukemia could be also beneficial for HR-MDS patients resistant to AZA. Disclosures: Cluzeau: Celgene: Consultancy. Raynaud:Celgene: Consultancy.
ChemInform Abstract: AN ASYMMETRIC REDUCTION OF PROCHIRAL KETONES WITH A CHIRAL HYDRIDE REAGENT PREPARED FROM LITHIUM ALUMINUM HYDRIDE AND (S)‐2‐(2,6‐XYLIDINOMETHYL)PYRROLIDINE (1979)

Abstract Ausgehend vom (S)‐Prolin (I) wird auf dem im Formelschema skizzierten Weg das Reduktions‐Reagens (IX) hergestellt.
Separation and Detection of Smokeless Powder Additives by Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (<scp>UPLC</scp>/<scp>MS</scp>/<scp>MS</scp>)<sup>,</sup> (2013)

A reversed phase gradient ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) method has been developed for the analysis of smokeless powders. A total of 20 different components were separated by UPLC and detected by MS/MS in multiple reaction monitoring (MRM) mode. These compounds included diphenylamines, centralites, nitrotoluenes, nitroglycerin, and various phthalates. Simultaneous positive and negative electrospray ionization (ESI) was used along with negative atmospheric pressure chemical ionization (APCI) to detect all compounds in a single analysis. Analysis times were under 8 min with a gradient of 10-73% organic at a flow rate of 0.500 mL/min. With this method, ultraviolet and MRM limits of detection ranging from 0.08 to 2.6 ng and 0.4-64 ng injected were achieved. Commercially available smokeless powders were also extracted with methylene chloride and characterized using the developed UPLC/MS/MS method. The procedure permits the determination of compositional differences between different brands as well as lot-to-lot variations.
STEP: Sequentiality and Thrashing Detection Based Prefetching to Improve Performance of Networked Storage Servers (2007)

State-of-the-art networked storage servers are equipped with increasingly powerful computing capability and large DRAM memory as storage caches. However, their contribution to the performance improvement of networked storage system has become increasingly limited. This is because the client-side memory sizes are also increasing, which reduces capacity misses in the client buffer caches as well as access locality in the storage servers, thus weakening the caching effectiveness of server storage caches. Proactive caching in storage servers is highly desirable to reduce cold misses in clients. We propose an effective way to improve the utilization of storage server resources through prefetching in storage servers for clients. In particular, our design well utilizes two unique strengths of networked storage servers which are not leveraged in existing storage server prefetching schemes. First, powerful storage servers have idle CPU cycles, under-utilized disk bandwidth, and abundant memory space, providing many opportunities for aggressive disk data prefetching. Second, the servers have the knowledge about high-latency operations in storage devices, such as disk head positioning, which enables efficient disk data prefetching based on an accurate cost-benefit analysis of prefetch operations. We present STEP - a Sequentiality and Thrashing dEtec- tion based Prefetching scheme, and its implementation with Linux Kernel 2.6.16. Our performance evaluation by replaying storage performance council (SPC) 's OLTP traces shows that server performance improvements are up to 94% with an average of 25%. Improvements with frequently used Unix applications are up to 53% with an average of 12%. Our experiments also show that STEP has little effect on workloads with random access patterns, such as SPC Web-search traces.
Cross-application data provenance and policy enforcement (2011)

We present a new technique that can trace data provenance and enforce data access policies across multiple applications and machines. We have developed Garm, a tool that uses binary rewriting to implement this technique on arbitrary binaries. Users can use Garm to attach access policies to data and Garm enforces the policy on all accesses to the data (and any derived data) across all applications and executions. Garm uses static analysis to generate optimized instrumentation that traces the provenance of an application's state and the policies that apply to this state. Garm monitors the interactions of the application with the underlying operating system to enforce policies. Conceptually, Garm combines trusted computing support from the underlying operating system with a stream cipher to ensure that data protected by an access policy cannot be accessed outside of Garm's policy enforcement mechanisms. We have evaluated Garm with several common Linux applications. We found that Garm can successfully trace the provenance of data across executions of multiple applications and enforce data access policies on the application's executions.
A transconductive graphene pressure sensor (2013)

We present a graphene pressure transducer consisting of an array of suspended circular graphene membranes over 3μm diameter holes in silicon dioxide on degenerately doped silicon. The transconductive nature of graphene allows the change in pressure to be translated into a change in resistance across the suspended graphene membranes. The pressure-induced deflections of the membrane vary the distance between the DC biased silicon back-gate and graphene membrane, changing the effective electric field which results in variations in the resistance of the suspended graphene. Our results demonstrate that pressure sensors constructed with graphene possess potential advantages over conventional pressure sensors such as higher sensitivity with diaphragm dimensions over 200X smaller than that of typical pressure transducers.
Dynamical Signature of the Mott-Hubbard Transition in Ni(S,Se) <sub>2</sub> (1996)

The transition metal chalcogenide Ni(S,Se)2 is one of the few highly correlated, Mott-Hubbard systems without a strong first-order structural distortion that normally cuts off the critical behavior at the metal-insulator transition. The zero-temperature (T) transition was tuned with pressure, and significant deviations were found near the quantum critical point from the usual T1/2 behavior of the conductivity characteristic of electron-electron interactions in the presence of disorder. The transport data for pressure and temperature below 1 kelvin could be collapsed onto a universal scaling curve.
Automated system for screening hearing using the auditory brainstem response (1988)

Routine screening of hearing using the auditory brainstem response (ABR) in infants, such as neonates in the special care baby unit, requires a system which is quick, user-friendly and gives a simple outcome. A system which consists of a stimulator/amplifier unit for recording the ABR controlled by a standard Master Series BBC Microcomputer is described which fulfils these requirements. The test procedure is highly automated, and a pass or refer decision for the screen on each ear is given by a machine-scoring algorithm which detects the ABR waveform.
Thin film transparent thermocouples (2002)

Transparent thin-film electrical conductors have been sputter-deposited to form transparent thermocouples. Indium tin oxide (ITO) and antimony tin oxide (ATO) have demonstrated Seebeck coefficients of 12-80 mu V/ degrees C depending on their conductivity and fabrication parameters. A direct relationship between resistivity and thermoelectric coefficient was indicated with films ranging from 0.001 to 0.1 Omega -cm and outputs of 12-80 mu V/ degrees C. In addition, thermoelectric measurements are reported on commercial ATO and ITO transparent films. It is noted that the control of fabrication parameters such as substrate temperature, sputtering atmosphere and rates, uniformity of deposition over substrate, and thermal treatments is important for controlling resistivity and thermoelectric output. Commercially available transparent electrically conductive films could be patterned to obtain transparent thermocouples and arrays.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>