gebhart/patrepeval huggingface dataset:
ICI D1694, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo: a new agent for clinical study. (1991)

N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2-thenoyl)-L-glutamic acid (ICI D1694) is a water-soluble, folate-based thymidylate synthase (TS) inhibitor designed to be a less toxic and more potent analogue of the clinically tested N10-propargyl-5,8-dideazafolic acid. Inhibition of isolated L1210 TS by ICI D1694 is mixed noncompetitive (although tending toward competitive), with a Ki of 62 nM (Kies = 960 nM). The synthetic gamma-polyglutamates are up to 2 orders of magnitude more potent as inhibitors of TS; e.g., the tetraglutamate (glu4) has a Ki of 1.0 nM (Kies = 15 nM). Although inhibitory activity of ICI D1694 toward rat liver dihydrofolate reductase was similar to that of TS (Ki = 92 nM; competitive inhibition) the polyglutamate derivatives did not show enhanced activity. ICI D1694 was also a very potent inhibitor of L1210 cell growth (50% inhibitory activity = 8 nM). L1210 growth inhibition was not observed in the presence of thymidine, consistent with TS being the locus of action. Folinic acid antagonized L1210 growth inhibition in a competitive fashion such that the highest folinic acid concentration used (25 microM) increased the 50% inhibitory activity 6000-fold. When given as a 4-h delayed "rescue", folinic acid was much less effective in antagonizing growth inhibition. These observations are consistent with folinic acid competing with ICI D1694 for uptake into the cell and/or intracellular polyglutamation. The L1210:1565 cell line, which has greatly impaired reduced-folate/methotrexate transport and thus is resistant to methotrexate, was significantly cross-resistant to ICI D1694 (121-fold), suggesting that ICI D1694 is dependent on this uptake mechanism for good cytotoxic potency in L1210 cells. L1210 cells that were incubated for 4 h with 0.1 microM 3H-ICI D1694 accumulated approximately 1.5 microM intracellular 3H, and the high performance liquid chromatography analysis of the cell extracts demonstrated that 96% of the 3H was associated with the ICI D1694 polyglutamate fractions (principally glu4). Upon resuspension in drug-free medium for 24 h, approximately 75% of the cellular 3H was retained, this being the higher polyglutamate pool (glu4-6). In mice, after a single bolus injection of 10 mg/kg of ICI D1694, TS was inhibited greater than 80% for 24 h in ascitic L1210:NCI cells (as measured by the rate of 3H release from [5-3H]deoxyuridine). ICI D1694 cured the L1210:ICR ascitic tumor in mice at 0.4 mg/kg daily for 5 days (maximum tolerated dose, approximately 50 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS)
A Process to Produce Microcellular PVC (1993)

Abstract A novel process to produce microcellular PVC foams with a very homogeneous cell distribution and cell densities ranging from 10 7 to 10 9 cells/cm 3 is described. Microcellular PVC foams with relative densities (density of foam divided by the density of unfoamed polymer) ranging from 0.15 to 0.94 have been produced. In this paper, experimental results on bubble nucleation and growth are presented. It was found that the bubble nucleation density increases with foaming temperature and eventually reaches a limiting value, while the average bubble diameter is relatively independent of the foaming temperature. A majority of the cell growth was found to occur in the early stages of foaming.
A Rapid Bootstrap Algorithm for the RAxML Web Servers (2008)

Despite recent advances achieved by application of high-performance computing methods and novel algorithmic techniques to maximum likelihood (ML)-based inference programs, the major computational bottleneck still consists in the computation of bootstrap support values. Conducting a probably insufficient number of 100 bootstrap (BS) analyses with current ML programs on large datasets-either with respect to the number of taxa or base pairs-can easily require a month of run time. Therefore, we have developed, implemented, and thoroughly tested rapid bootstrap heuristics in RAxML (Randomized Axelerated Maximum Likelihood) that are more than an order of magnitude faster than current algorithms. These new heuristics can contribute to resolving the computational bottleneck and improve current methodology in phylogenetic analyses. Computational experiments to assess the performance and relative accuracy of these heuristics were conducted on 22 diverse DNA and AA (amino acid), single gene as well as multigene, real-world alignments containing 125 up to 7764 sequences. The standard BS (SBS) and rapid BS (RBS) values drawn on the best-scoring ML tree are highly correlated and show almost identical average support values. The weighted RF (Robinson-Foulds) distance between SBS- and RBS-based consensus trees was smaller than 6% in all cases (average 4%). More importantly, RBS inferences are between 8 and 20 times faster (average 14.73) than SBS analyses with RAxML and between 18 and 495 times faster than BS analyses with competing programs, such as PHYML or GARLI. Moreover, this performance improvement increases with alignment size. Finally, we have set up two freely accessible Web servers for this significantly improved version of RAxML that provide access to the 200-CPU cluster of the Vital-IT unit at the Swiss Institute of Bioinformatics and the 128-CPU cluster of the CIPRES project at the San Diego Supercomputer Center. These Web servers offer the possibility to conduct large-scale phylogenetic inferences to a large part of the community that does not have access to, or the expertise to use, high-performance computing resources.
Surface Plasmon Resonance of Silver Nanoparticles on Vanadium Dioxide (2006)

The localized surface plasmon resonance (SPR) spectrum of silver nanoparticles fabricated on a thermochromatic film, vanadium dioxide (VO2), is studied in this paper. Owing to the temperature-dependent dielectric function of VO2, the SPR band dramatically exhibits temperature dependence in the range of 30-80 degrees C. The peak extinction wavelength, lambda(SPR), blueshifts as temperature increases and reversibly redshifts as temperature decreases. The shift magnitude (DeltalambdaSPR) is strongly dependent on the silver mass thickness, dm; a value of 50 nm of DeltalambdaSPR is achieved for particles (mean diameter 51 nm) with dm=2 nm while a value of 250 nm is achieved for particles (mean diameter 133 nm) with dm=10 nm. Beyond the SPR band, it is interesting to find that the spectral line shape of silver particles is dominated by the imaginary part of the dielectric function of VO2. These results can be interpreted based on dynamical Maxwell-Garnett theory.
Cationic Liposome-Mediated GDNF Gene Transfer after Spinal Cord Injury (2002)

Glial cell line-derived neurotrophic factor (GDNF) has been shown to protect cranial and spinal motoneurons, which suggests potential uses of GDNF in the treatment of spinal cord injury (SCI) and motor neuron disease. We examined neuroprotective effect of cationic liposome-mediated GDNF gene transfer in vivo on axonal regeneration and locomotor function recovery after SCI in adult rats. The mixture of DC-Chol liposomes and recombinant plasmid pEGFP-GDNF cDNA was injected after SCI. RT-PCR confirmed the increased expression of GDNF mRNA in the injected areas at 7 days after injection. The expression of EGFP-GDNF was observed in the cells around the injection locus by fluorescence microscope at least 4 weeks after injection. Four weeks after GDNF gene transfer, regeneration of the corticospinal tracts was assessed using anterograde tract tracing. There are more HRP labeling of corticospinal tract axons across the lesion in GDNF group compared with control group. In GDNF group, the maximum distance these labeled axons extended varied in different animals and ranged from 5 mm to approximately 9 mm from the lesion. In control group, no HRP labeled axons extended caudal to the lesion. The locomotion function of hindlimbs of rats was evaluated using inclined plane test and BBB locomotor scores. The locomotion functional scores in GDNF group were higher than that in control group within 1-4 weeks after SCI (p < 0.05). These data demonstrate that in vivo transfer of GDNF cDNA can promote axonal regeneration and enhance locomotion functional recovery, suggesting that cationic liposome-mediated delivery of GDNF cDNA may be a practical gene transfer method for traumatic SCI treatment.
The Rep52 Gene Product of Adeno-Associated Virus Is a DNA Helicase with 3′-to-5′ Polarity (1998)

The rep gene of adeno-associated virus type 2 encodes four overlapping proteins from two separate promoters, termed P5 and P19. The P5-promoted Rep proteins, Rep78 and Rep68, are essential for viral DNA replication, and a wealth of data concerning the biochemical activities of these proteins has been reported. In contrast, data concerning the biochemical functions of the P19-promoted Rep proteins, Rep52 and Rep40, are lacking. Here, we describe enzymatic activities associated with a bacterially expressed maltose-binding protein (MBP)-Rep52 fusion protein. Purified MBP-Rep52 possesses 3'-to-5' DNA helicase activity that is strictly dependent upon the presence of nucleoside triphosphate and divalent cation cofactors. In addition, MBP-Rep52 demonstrates a constitutive ATPase activity that is active in the absence of DNA effector molecules. An MBP-Rep52 chimera bearing a lysine-to-histidine substitution at position 116 (K116H) within a consensus helicase- and ATPase-associated motif (motif I or Walker A site) was deficient for both DNA helicase and ATPase activities. In contrast to a Rep78 A-site mutant protein bearing a corresponding amino acid substitution at position 340 (K340H), the MBP-Rep52 A-site mutant protein failed to exhibit a trans-dominant negative effect when it was mixed with wild-type MBP-Rep52 or MBP-Rep78 in vitro. This lack of trans dominance, coupled with the results of coimmunoprecipitation and gel filtration chromatography experiments reported here, suggests that the ability of Rep52 to engage in multimeric interactions may differ from that of Rep78 or -68.
Study of matrix metalloproteinases and their inhibitors in breast cancer (2007)

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.
The User Interface and Implementation of an IC Layout Editor (1984)

This paper describes several novel aspects of Caesar, a layout editor for Manhattan-style integrated circuits. The program's user interface is similar to painting. By hiding many irrelevant details, the painting mechanism provides a powerful yet simple user interface. Its implementation using horizontal strips is efficient in both time and space. To handle large circuits efficiently, Caesar represents them hierarchically and capitalizes on their hierarchical structure to avoid excess computation and I/O. Mask information is rendered on color displays with a novel combination of transparent and opaque layers that clarifies layer interactions even in the presence of a large number of mask layers.
Treatment of acne vulgaris (2006)

This article covers the assessment and diagnosis of acne vulgaris. It explores the strategies for treating mild, moderate and severe acne and recommends appropriate nursing interventions.
Achievement of well conducting wide band-gap semiconductors: Role of solubility and of nonequilibrium impurity incorporation (1989)

A long-standing problem for wide band-gap semiconductors is that of achieving good bipolar conductivity. I here show that this difficulty can be understood via solubility considerations of dopant incorporation. Reports of good conductivity in such materials are likely due to nonequilibrium impurity incorporation, and prior literature is reinterpreted to provide examples of this view.
Broad requirement for terminal sialic acid residues and FcγRIIB for the preventive and therapeutic activity of intravenous immunoglobulins in vivo (2014)

Intravenous immunoglobulin (IVIg) therapy is widely used to treat a variety of autoimmune diseases including immunothrombocytopenia, chronic inflammatory demyelinating polyneuropathy, and more recently autoimmune skin blistering diseases. Despite this well-documented clinical success, the precise molecular and cellular mechanisms underlying this immunomodulatory activity are discussed controversially. In particular, the clinically relevant therapeutic pathway of IVIg-mediated immune modulation has not been studied in detail. In the present study, we use four independent in vivo model systems of auto-Ab-mediated autoimmune disease to identify a common pathway explaining IVIg activity under therapeutic conditions in vivo. We show that irrespective of the in vivo model system, IVIg activity is strictly dependent on the presence of terminal sialic acid residues and the inhibitory FcγRIIB under preventive as well as therapeutic treatment conditions. In contrast, specific ICAM3 grabbing nonintegrin related 1, previously demonstrated to be essential under preventative treatment conditions, showed a disease-specific impact on IVIg-mediated resolution of established autoimmune disease.
Petrophysical Considerations in Evaluating and Producing Shale Gas Resources (2010)

Abstract We present a practical assessment of petrophysical properties of shales and their measurement in the lab and via logs. Gasbearing shale present unique measurement challenges due to their ultra-low permeability and complicated pore volume connectivity. The combination of low intrinsic permeability and gas sorption effects renders these reservoirs "unconventional". Advances in horizontal drilling and hydraulic stimulation have transformed gas-shale resources into economic reserves. Given their economic significance, there is a strong drive to understand gas shale petrophysical property measurements, both in the laboratory and in the subsurface. We note that various core analysis protocols are used in different laboratories leading to physical property measurements that are inconsistent, even when measured on identical sample sets. In addition, log analysis of kerogen-rich shale is ‘unconventional’ compared to classical techniques used in tight gas sands. As shale gas evaluation is becoming widely practiced among service companies and operators, we will focus on three reservoir assessment categories: storage capacity (gas-in-place), flow capacity (gas deliverability) and mechanical properties impacting hydraulic stimulation. Within each of these categories we have identified influential petrophysical properties such as rock composition, total organic carbon (TOC) content, porosity, saturation, permeability and mechanical properties. Specifically, we demonstrate the importance of estimating accurate mineral and kerogen content as these properties directly impact rock quality, hydraulic fracturing protocols, and gas-in-place estimations. In reviewing these practices, we also will show the need and possible direction of new technologies that will be required for making evaluations more accurate and quantitative in the future.
Vascular Outcome in Patients With Homocystinuria due to Cystathionine β-Synthase Deficiency Treated Chronically (2001)

An inborn error of metabolism, homocystinuria due to cystathionine beta-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess the effectiveness of long-term homocysteine-lowering treatment in reducing vascular risk in 158 patients. Vascular outcomes were analyzed and effectiveness of treatment in reducing vascular risk was evaluated by comparison of actual to predicted number of vascular events, with the use of historical controls from a landmark study of 629 untreated patients with cystathionine beta-synthase deficiency. The 158 patients had a mean (range) age of 29.4 (4.5 to 70) years; 57 (36%) were more than 30 years old, and 10 (6%) were older than 50 years. There were 2822 patient-years of treatment, with an average of 17.9 years per patient. Plasma homocysteine levels were markedly reduced from pretreatment levels but usually remained moderately elevated. There were 17 vascular events in 12 patients at a mean (range) age of 42.5 (18 to 67) years: pulmonary embolism (n=3), myocardial infarction (n=2), deep venous thrombosis (n=5), cerebrovascular accident (n=3), transient ischemic attack (n=1), sagittal sinus thrombosis (n=1), and abdominal aortic aneurysm (n=2). Without treatment, 112 vascular events would have been expected, for a relative risk of 0.09 (95% CI 0.036 to 0.228; P<0.0001). Treatment regimens designed to lower plasma homocysteine significantly reduce cardiovascular risk in cystathionine beta-synthase deficiency despite imperfect biochemical control. These findings may be relevant to the significance of mild hyperhomocysteinemia that is commonly found in patients with vascular disease.
Charge carriers in rechargeable batteries: Na ions vs. Li ions (2013)

We discuss the similarities and dissimilarities of sodium- and lithium-ion batteries in terms of negative and positive electrodes. Compared to the comprehensive body of work on lithium-ion batteries, research on sodium-ion batteries is still at the germination stage. Since both sodium and lithium are alkali metals, they share similar chemical properties including ionicity, electronegativity and electrochemical reactivity. They accordingly have comparable synthetic protocols and electrochemical performances, which indicates that sodium-ion batteries can be successfully developed based on previously applied approaches or methods in the lithium counterpart. The electrode materials in Li-ion batteries provide the best library for research on Na-ion batteries because many Na-ion insertion hosts have their roots in Li-ion insertion hosts. However, the larger size and different bonding characteristics of sodium ions influence the thermodynamic and/or kinetic properties of sodium-ion batteries, which leads to unexpected behaviour in electrochemical performance and reaction mechanism, compared to lithium-ion batteries. This perspective provides a comparative overview of the major developments in the area of positive and negative electrode materials in both Li-ion and Na-ion batteries in the past decade. Highlighted are concepts in solid state chemistry and electrochemistry that have provided new opportunities for tailored design that can be extended to many different electrode materials for sodium-ion batteries.
Citrus Greening Disease (1991)

Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for ...Read More
Direct Electrospray Ionization Mass Spectrometric Profiling of Real-World Samples via a Solid Sampling Probe (2013)

This study presents a novel direct analysis strategy for rapid mass spectrometric profiling of biochemicals in real-world samples via a direct sampling probe (DSP) without sample pretreatments. Chemical modification is applied to a disposable stainless steel acupuncture needle to enhance its surface area and hydrophilicity. After insertion into real-world samples, biofluid can be attached on the DSP surface. With the presence of a high DC voltage and solvent vapor condensing on the tip of the DSP, analyte can be dissolved and electrosprayed. The simplicity in design, versatility in application aspects, and other advantages such as low cost and disposability make this new method a competitive tool for direct analysis of real-world samples.
Cysteine Cathepsins and the Cutting Edge of Cancer Invasion (2007)

Cysteine cathepsins are a family of lysosomal proteases that are often upregulated in various human cancers, and have been implicated in distinct tumorigenic processes such as angiogenesis, proliferation, apoptosis and invasion. During cancer progression, cathepsins are often translocated to the cell surface of tumor cells or are secreted into the extracellular milieu, where they can promote tumor invasion through several possible mechanisms. First, they can directly cleave components of the extracellular matrix and basement membrane, essentially clearing a path for the migration of tumor cells away from the primary tumor mass. Second, at the cell membrane, cathepsins can direct a proteolytic cascade in which they activate other proteases such as matrix metalloproteinases and urokinase plasminogen activator, which in turn promote invasion. Finally, cleavage of the cell adhesion protein, E-cadherin, at the cell surface can disrupt adherens junctions and thus facilitate cancer cell migration and invasion. Therefore, cathepsins are now emerging as major players in tumor progression, making them potential drug targets for a wide range of human cancers.
Site-Occupation-Tuned Superionic LiₓScCl₃₊ₓHalide Solid Electrolytes for All-Solid-State Batteries (2020)

The enabling of high energy density of all-solid-state lithium batteries (ASSLBs) requires the development of highly Li⁺-conductive solid-state electrolytes (SSEs) with good chemical and electrochemical stability. Recently, halide SSEs based on different material design principles have opened new opportunities for ASSLBs. Here, we discovered a series of LiₓScCl₃₊ₓ SSEs (x = 2.5, 3, 3.5, and 4) based on the cubic close-packed anion sublattice with room-temperature ionic conductivities up to 3 × 10–³ S cm–¹. Owing to the low eutectic temperature between LiCl and ScCl₃, LiₓScCl₃₊ₓ SSEs can be synthesized by a simple co-melting strategy. Preferred orientation is observed for all the samples. The influence of the value of x in LiₓScCl₃₊ₓ on the structure and Li⁺ diffusivity were systematically explored. With increasing x value, higher Li⁺, lower vacancy concentration, and less blocking effects from Sc ions are achieved, enabling the ability to tune the Li⁺ migration. The electrochemical performance shows that Li₃ScCl₆ possesses a wide electrochemical window of 0.9–4.3 V vs Li⁺/Li, stable electrochemical plating/stripping of Li for over 2500 h, as well as good compatibility with LiCoO₂. LiCoO₂/Li₃ScCl₆/In ASSLB exhibits a reversible capacity of 104.5 mAh g–¹ with good cycle life retention for 160 cycles. The observed changes in the ionic conductivity and tuning of the site occupations provide an additional approach toward the design of better SSEs.