gebhart/patrepeval huggingface dataset:
Passive Immunization with Phospho-Tau Antibodies Reduces Tau Pathology and Functional Deficits in Two Distinct Mouse Tauopathy Models (2015)

In Alzheimer's disease (AD), an extensive accumulation of extracellular amyloid plaques and intraneuronal tau tangles, along with neuronal loss, is evident in distinct brain regions. Staging of tau pathology by postmortem analysis of AD subjects suggests a sequence of initiation and subsequent spread of neurofibrillary tau tangles along defined brain anatomical pathways. Further, the severity of cognitive deficits correlates with the degree and extent of tau pathology. In this study, we demonstrate that phospho-tau (p-tau) antibodies, PHF6 and PHF13, can prevent the induction of tau pathology in primary neuron cultures. The impact of passive immunotherapy on the formation and spread of tau pathology, as well as functional deficits, was subsequently evaluated with these antibodies in two distinct transgenic mouse tauopathy models. The rTg4510 transgenic mouse is characterized by inducible over-expression of P301L mutant tau, and exhibits robust age-dependent brain tau pathology. Systemic treatment with PHF6 and PHF13 from 3 to 6 months of age led to a significant decline in brain and CSF p-tau levels. In a second model, injection of preformed tau fibrils (PFFs) comprised of recombinant tau protein encompassing the microtubule-repeat domains into the cortex and hippocampus of young P301S mutant tau over-expressing mice (PS19) led to robust tau pathology on the ipsilateral side with evidence of spread to distant sites, including the contralateral hippocampus and bilateral entorhinal cortex 4 weeks post-injection. Systemic treatment with PHF13 led to a significant decline in the spread of tau pathology in this model. The reduction in tau species after p-tau antibody treatment was associated with an improvement in novel-object recognition memory test in both models. These studies provide evidence supporting the use of tau immunotherapy as a potential treatment option for AD and other tauopathies.
Status of bcr-abl tyrosine kinase inhibitors in chronic myelogenous leukemia (2000)

The bcr-abl fusion protein is present in the vast majority of cases of chronic myelogenous leukemia, and the deregulated tyrosine kinase activity of this protein is essential for leukemic transformation. Thus, bcr-abl is an ideal target for pharmacologic inhibition. In preclinical studies, ST1571 (formerly CGP57148B), an abl-specific, tyrosine kinase inhibitor, selectively killed bcr-abl-expressing cells both in vitro and in vivo. In early clinical trials of ST1571, encouraging results have been obtained, and there is already a suggestion that ST1571 may soon need to be incorporated into treatment algorithms for chronic myelogenous leukemia.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotides (1993)

We report the analysis and characterization of natural and modified oligonucleotides by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The present technology was highly improved for this class of compounds by using a new matrix, 2,4,6-trihydroxy acetophenone, together with di- and triammonium salts of organic or inorganic acids to suppress peak broadening due to multiple ion adducts. This methodology can be used in combination with time dependent degradation of oligonucleotides by exonucleases as powerful tool to determine sequence compositions.
Extended scheduler for efficient frequency scaling in virtualized systems (2012)

Nowadays, virtualization is present in almost all computing infrastructures. Thanks to server consolidation and VM migration, virtualization helps in power reduction. However, modern powerful computers with higher processor frequency, multiple cores and multiple CPUs constitute the main factor contributing to the continuous increase of energy consumption. In this context, energy management takes a critical importance. A hardware technology, called Dynamic Voltage and Frequency Scaling (DVFS), serves to dynamically modify the processor frequency (according to the CPU needs) in order to achieve less energy consumption. However, lowering frequency also generates poor virtual machine (VM) performance. In this paper, we propose a solution consisting of an extended VM scheduler and DVFS, and report some experiments based on this proposal. This enhanced scheduler, according to VM CPU load, dynamically scales processor frequency in order to save energy. The idea is to adapt the current VM scheduler to analyze CPU load, and modify the current processor frequency to the lowest possible, but still support the guaranteed VM performance. The algorithm is designed and simulated on a web server as the sample application and Xen as the virtualization platform. Test results and performance evaluations prove our design and implementation.
Plant and Fungal Protein and Glycoprotein Toxins Inhibiting Eukaryote Protein Synthesis (1985)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Oxidation of Amino Acids. IV. Reaction of Dibenzoyl Peroxide With ω-Amino Acid Esters (1987)

N-Acetyl N-benzoyloxy ?-amino acid esters were obtained by the oxidation of the ester amine group with dibenzoyl peroxide and subsequent acetylation. The yield of the desired product increased with the length of the carbon chain.
Spectral measurement in reflection on steeply aspheric surfaces (2008)

The controls by optical mean of coatings deposited on optical components are generally made with flat witnesses. When the components are spherical or aspherical, like lenses or mirrors, the spectral response may vary because of the nonuniformity of thickness that is really linked to the deposition process. For large radius of curvature, control can be achieved even with classical spectrophotometers. However, control becomes more and more difficult when the radius of curvature decreases or when the optical device has a complex shape. Thus special devices are needed to perform this kind of measurement. ZEISS and CEA Le Ripault use spectral reflection as a mean of measurement, which enables to investigate optical coatings on curved parts. Two different devices have been implemented and used to measure the same antireflective coating deposited on an aspheric lens. In this work, we show the obtained results and we compare these results to theoretical simulation.
The Wnt connection to tumorigenesis (2004)

Wnt signaling has been identified as one of the key signaling pathways in cancer, regulating cell growth, motility and differentiation. Because of its widespread activation in diverse human tumor diseases, the Wnt pathway has gained considerable and growing interest in tumor research over recent years. Evidence that altered Wnt signaling is important for human tumor development came from three major findings: (i) the tumor suppressor adenomatous polyposis coli (APC) binds to the Wnt pathway component beta-catenin and is involved in its degradation, (ii) mutations of APC in colon tumors lead to stabilization of the beta-catenin protein and (iii) tumor-associated mutations of beta-catenin in colorectal cancer as well as in other tumor types lead to its stabilisation, qualifying beta-catenin as a proto-oncogene. Here we will describe the biochemical interactions which shape the Wnt pathway and focus on its role in tumorigenesis.
Engineering salt-tolerantBrassicaplants: Characterization of yield and seed oil quality in transgenic plants with increased vacuolar sodium accumulation (2001)

Transgenic Brassica napus plants overexpressing AtNHX1, a vacuolar Na(+)/H(+) antiport from Arabidopsis thaliana, were able to grow, flower, and produce seeds in the presence of 200 mM sodium chloride. Although the transgenic plants grown in high salinity accumulated sodium up to 6% of their dry weight, growth of the these plants was only marginally affected by the high salt concentration. Moreover, seed yields and the seed oil quality were not affected by the high salinity of the soil. Our results demonstrate the potential use of these transgenic plants for agricultural use in saline soils. Our findings, showing that the modification of a single trait significantly improved the salinity tolerance of this crop plant, suggest that with a combination of breeding and transgenic plants it could be possible to produce salt-tolerant crops with far fewer target traits than had been anticipated.
Human Multiple Myeloma Cells Are Sensitized to Topoisomerase II Inhibitors by CRM1 Inhibition (2009)

Topoisomerase IIalpha (topo IIalpha) is exported from the nucleus of human myeloma cells by a CRM1-dependent mechanism at cellular densities similar to those found in patient bone marrow. When topo IIalpha is trafficked to the cytoplasm, it is not in contact with the DNA; thus, topo IIalpha inhibitors are unable to induce DNA-cleavable complexes and cell death. Using a CRM1 inhibitor or a CRM1-specific small interfering RNA (siRNA), we were able to block nuclear export of topo IIalpha as shown by immunofluorescence microscopy. Human myeloma cell lines and patient myeloma cells isolated from bone marrow were treated with a CRM1 inhibitor or CRM1-specific siRNA and exposed to doxorubicin or etoposide at high cell densities. CRM1-treated cell lines or myeloma patient cells were 4-fold more sensitive to topo II poisons as determined by an activated caspase assay. Normal cells were not significantly affected by CRM1-topo II inhibitor combination treatment. Cell death was correlated with increased DNA double-strand breaks as shown by the comet assay. Band depletion assays of CRM1 inhibitor-exposed myeloma cells showed increased topo IIalpha covalently bound to DNA. Topo IIalpha knockdown by a topo IIalpha-specific siRNA abrogated the CRM1-topo II therapy synergistic effect. These results suggest that blocking topo IIalpha nuclear export sensitizes myeloma cells to topo II inhibitors. This method of sensitizing myeloma cells suggests a new therapeutic approach to multiple myeloma.
Identification and Characterization of Novel Antimicrobial Decapeptides Generated by Combinatorial Chemistry (1998)

Novel combinatorial libraries consisting of simplified amino acid sequences were designed to screen for peptides active against the Candida albicans membrane. A novel decapeptide, KKVVFKVKFK, that had a unique primary amino acid sequence was identified in this work. This peptide irreversibly inhibited the growth of C. albicans and showed a broad range of antibacterial activity but no hemolytic activity. Circular dichroism spectra revealed that the predominant secondary structure of this peptide strongly depended on the membrane-mimetic environments; the peptide preferred to form an amphipathic alpha-helical structure in the presence of 50% trifluoroethanol, while it preferred to adopt a distorted alpha-helical structure in the presence of sodium dodecyl sulfate micelles. Experiments in which dye was released from vesicles indicated that this novel antimicrobial peptide killed microorganisms through the action on the membrane as its primary target. Replacement of amino acids in this active decapeptide on the basis of information from the libraries could provide unique information about factors affecting its antimicrobial activity such as its secondary structure, net positive charge, and hydrophobicity.
Malignant Hyperthermia (1980)

In MH, skeletal muscle acutely and unexpectedly increases its oxygen consumption and lactate production, resulting in greater heat production, respiratory and metabolic acidosis, muscle ridigity, sympathetic stimulation, and increased cellular permeability. The best-accepted theory is that MH is due to an inability to control calcium concentrations within the muscle fiber, and may involve a generalized alteration in cellular or subcellular membrane permeability. Episodes are predictably initiated in susceptible people and swine by potent volative anethetic agents or succinylcholine. In addition, in swine, MH is consistently triggered by excitement, apprehension, exercise, or environmental stress such as heat or hypoxia. Several genetic factors probably control the human and porcine inheritance of MH. Sympathetic involvement in MH, while controversial, is probably a response to stress that affects blood flow, heat loss, and myocardial function, rather than a direct sympathetic activation of susceptible muscle. Diagnosis is based upon extraordinary temperature and acid-base and muscle aberrations. Specific treatment is the action of dantrolene upon muscle calcium movements; sympatomatic treatment is by reversal of acid-base and temperature changes. Evaluation of affected families is guided by measurements of circulating creatine phosphokinase and by analysis of drug-induced contractures in muscle biopsy specimens. Anesthesia for susceptible patients includes thiopental, opiates, droperidol, pancuronium, nitrous oxide, and preoperative oral doses of dantrolene.
Rate 3/4 Convolutional Coding of 16-PSK: Code Design and Performance Study (1984)

Convolutional coding coupled with 16-PSK modulation is investigated for bandwidth efficient transmission. Rate 3/4, small memory codes are found which are optimized in the free-distance sense on the Gaussian channel. These codes provide up to 4.8 dB of coding gain with 32 states over uncoded 8-PSK, a scheme having the same spectral efficiency as the codes described. The performance is compared with earlier findings of Ungerboeck and some recent results on <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R = 2/3</tex> coded 8-PSK. In addition, we present results of a channel transmission study to assess the performance of the four-state code on the band-limited nonlinear channel, and find that performance of the coded scheme degrades comparably with uncoded 8-PSK, i.e., coding gain is roughly preserved.
Living Free-Radical Dispersion Polymerization of Styrene (1998)

Polystyrene latexes were synthesized via living free-radical chemistry with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) in both alcoholic and aqueous alcoholic media using poly(N-vinylpyrrolidone) (PVP) as a steric stabilizer at 112−130 °C. Genuine dispersion polymerization was only achieved in ethylene glycol or ethylene glycol−water mixtures. In the absence of TEMPO, near-quantitative monomer conversions, high molecular weights, broad molecular weight distributions, and submicrometer-sized latexes were obtained. The addition of TEMPO had a profound effect on the polymerization chemistry: only moderate monomer conversions (as low as 20%, with a maximum conversion of 60% obtained after 71 h) and larger, typically micrometer-sized, latexes were obtained with TEMPO-mediated syntheses. Polydispersities (Mw/Mn's) as low as 1.11 were achieved in the presence of TEMPO, but only relatively low molecular weight polystyrene chains were obtained. All TEMPO-synthesized latexes had spherical particle morphologies and very broad size distributions, as evidenced by scanning electron microscopy (SEM) and disk centrifuge photosedimentometry (DCP), respectively. Surprisingly, high Γ values were calculated for the adsorbed PVP stabilizer, which suggests that it is not located exclusively on the outside of the polystyrene latex particles.
High Power Lasers and Laser Machining Technology (1989)

This book reports on research taking place in Europe, the Soviet Union, Japan, and the U.S. that continues the development of efficient laser devices operating on an increasing number of wavelengths. Sessions on laser machining technology describe applications in welding, melting, vaporization, and surface treatment of materials, and these papers detail some of the latest techniques being employed in a variety of situations.
Role of the Endothelium and Cyclic GMP in Renal Vasodilator Responses to Cryptolepine in Rats (1994)

Isolated perfused rat kidney was used to examine the possible mechanisms involved in the hypotensive/vasodilator actions of cryptolepine. In kidneys preconstricted by phenylephrine (PE 5-7.5 x 10(-7) M), cryptolepine at bolus doses of 2.5, 5, and 10 micrograms elicited dose-dependent reductions in perfusion pressure by 29.8 +/- 4.1, 43.3 +/- 3.9, and 54.3 +/- 4.9 mm Hg, respectively. In the presence of indomethacin, cryptolepine-induced reduction in perfusion pressure was not significantly changed, suggesting a lack of a cyclooxygenase-mediated component in its renal vasodilator response. Removal of the endothelium with p-bromophenacyl bromide (p-BPB 10 microM) inhibited the vasodilator response to cryptolepine 2.5, 5, and 10 micrograms to 10.2 +/- 1.8, 15.9 +/- 1.5, and 20.2 +/- 2.0 mm Hg, respectively (p < 0.01). The vasodilator response to acetylcholine (ACh 50 ng) was also reduced from a control value of 56.7 +/- 4.5 to 15.3 +/- 1.9 mm Hg (p < 0.01); responses to sodium nitroprusside (SNP 5 micrograms) and isoprenaline (1 microgram) were not affected. In kidneys treated with hydroquinone (10(-5) and 10(-4) M), a specific inhibitor of endothelium-dependent vasodilation, cryptolepine- and ACh-induced vasodilation were inhibited dose dependently (p < 0.01). N omega-nitro-L-arginine (L-NNA 10(-5)-10(-4) M), a specific inhibitor of the synthesis/release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO), attenuated the vasodilator response to cryptolepine and ACh (50 ng) dose dependently. At 10(-4) M L-NNA, cryptolepine-induced vasodilation was reduced to 6.6 +/- 2.2 (2.5 micrograms), 10.9 +/- 2.2 (5 micrograms), and 13.3 +/- 1.4 mm Hg (10 micrograms). L-Arginine (10(-4) and 3 x 10(-4) M) but not D-arginine (10(-4) M) inhibited the effects of L-NNA, with vasodilatory effects of cryptolepine returning to control values, suggesting that the vasodilator material released by cryptolepine is EDRF, possibly NO. Methylene blue (MB 10(-4) M), the inhibitor of soluble guanylate cyclase which inhibited 50 ng ACh and 5 micrograms SNP-induced vasodilation also reduced the vasodilatory responses to cryptolepine to 0.8 +/- 0.8 (2.5 micrograms), 4.2 +/- 4.2 (5 micrograms), and 10.8 +/- 6.2 mm Hg (10 micrograms) suggesting that the effector pathway for cryptolepine-induced vasodilation is soluble guanylate cyclase-linked increase in cyclic GMP of vascular smooth muscle.
Glioma-Associated Cancer-Initiating Cells Induce Immunosuppression (2010)

Cancer-initiating cells contribute to tumor evasion of the immunosurveillance and approaches that alter the differentiation state may have immunotherapeutic potential.
Predicting drug susceptibility of non–small cell lung cancers based on genetic lesions (2009)

Somatic genetic alterations in cancers have been linked with response to targeted therapeutics by creation of specific dependency on activated oncogenic signaling pathways. However, no tools currently exist to systematically connect such genetic lesions to therapeutic vulnerability. We have therefore developed a genomics approach to identify lesions associated with therapeutically relevant oncogene dependency. Using integrated genomic profiling, we have demonstrated that the genomes of a large panel of human non-small cell lung cancer (NSCLC) cell lines are highly representative of those of primary NSCLC tumors. Using cell-based compound screening coupled with diverse computational approaches to integrate orthogonal genomic and biochemical data sets, we identified molecular and genomic predictors of therapeutic response to clinically relevant compounds. Using this approach, we showed that v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations confer enhanced Hsp90 dependency and validated this finding in mice with KRASdriven lung adenocarcinoma, as these mice exhibited dramatic tumor regression when treated with an Hsp90 inhibitor. In addition, we found that cells with copy number enhancement of v-abl Abelson murine leukemia viral oncogene homolog 2 (ABL2) and ephrin receptor kinase and v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) (SRC) kinase family genes were exquisitely sensitive to treatment with the SRC/ABL inhibitor dasatinib, both in vitro and when it xenografted into mice. Thus, genomically annotated cell-line collections may help translate cancer genomics information into clinical practice by defining critical pathway dependencies amenable to therapeutic inhibition.
The Crystal Structure, Mutagenesis, and Activity Studies Reveal that Patatin Is a Lipid Acyl Hydrolase with a Ser-Asp Catalytic Dyad (2003)

Patatin is a nonspecific lipid acyl hydrolase that accounts for approximately 40% of the total soluble protein in mature potato tubers, and it has potent insecticidal activity against the corn rootworm. We determined the X-ray crystal structure of a His-tagged variant of an isozyme of patatin, Pat17, to 2.2 A resolution, employing SeMet multiwavelength anomalous dispersion (MAD) phasing methods. The patatin crystal structure has three molecules in the asymmetric unit, an R-factor of 22.0%, and an R(free) of 27.2% (for 10% of the data not included in the refinement) and includes 498 water molecules. The structure notably revealed that patatin has a Ser-Asp catalytic dyad and an active site like that of human cytosolic phospholipase A(2) (cPLA(2)) [Dessen, A., et al. (1999) Cell 97, 349-360]. In addition, patatin has a folding topology related to that of the catalytic domain of cPLA(2) and unlike the canonical alpha/beta-hydrolase fold. The structure confirms our site-directed mutagenesis and bioactivity data that initially suggested patatin possessed a Ser-Asp catalytic dyad. Alanine-scanning mutagenesis revealed that Ser77 and Asp215 were critical for both esterase and bioactivity, consistent with prior work implicating a Ser residue [Strickland, J. H., et al. (1995) Plant Physiol. 109, 667-674] and a Ser-Asp dyad [Hirschberg, H. J. H. B., et al. (2001) Eur. J. Biochem. 268, 5037-5044] in patatin's catalytic activity. The crystal structure aids the understanding of other structure-function relationships in patatin. Patatin does not display interfacial activation, a hallmark feature of lipases, and this is likely due to the fact that it lacks a flexible lid that can shield the active site.
Fracturing Design Aimed at Enhancing Fracture Complexity (2010)

Abstract The potential for shale formations as a source of gas production has been recognized. However, shale permeability in a nano-Darcy scale represents a significant technological challenge to recover trapped hydrocarbon effectively. The fracturing of wells has been widely used to enhance the economic aspects of the reservoir. Connecting the created hydraulic fractures to the natural fractures or induced-stress fractures would further improve the productivity of the wells. Fracturing heterogeneous (naturally fractured) formation involves unique aspects in the fracturing processes, rock mechanics, and fluid-flow aspects. In some cases, the natural fractures might not be sufficiently conductive or could be held closed during fracturing operations as a result of the existing in-situ stresses. In this paper, hydraulic fracturing-design techniques to neutralize the stress anisotropy in the formation to allow the opening of the natural fractures during the hydraulic-fracture propagation are presented. Overcoming anisotropy effects would allow the operator to inject moderate amounts of proppant into the natural fractures and maximize the contact area within the reservoir. Geomechanics development behind these techniques is presented in this paper. The presented technology would allow operators to optimize placement of fractures across the horizontal well based on the geomechanics properties of the formation. The fluid-flow aspects of these enhanced completion processes are also discussed.