gebhart/patrepeval huggingface dataset:
Trial Watch (2013)

Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of <i>Mycobacterium bovis</i> that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of <i>Salmonella minnesota</i> that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of <i>OncoImmunology</i>, we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.
Proteolytic Activity of Human Osteoclast Cathepsin K (1996)

Human cathepsin K is a recently identified protein with high primary sequence homology to members of the papain cysteine protease superfamily including cathepsins S, L, and B and is selectively expressed in osteoclasts (Drake, F.H., Dodds, R., James I., Connor J., Debouck, C., Richardson, S., Lee, E., Rieman, D., Barthlow, R., Hastings, G., and Gowen, M. (1996) J. Biol., Chem. 271, 12511-12516). To characterize its catalytic properties, cathepsin K has been expressed in baculovirus-infected SF21 cells and the soluble recombinant protein isolated from growth media was purified. Purified protein includes an inhibitory pro-leader sequence common to this family of protease. Conditions for enzyme activation upon removal of the pro-sequence have been identified. Fluorogenic peptides have been identified as substrates for mature cathepsin K. In addition, two protein components of bone matrix, collagen and osteonectin, have been shown to be substrates of the activated protease. Cathepsin K is inhibited by E-64 and leupeptin, but not for by pepstatin, EDTA, phenylmethylsulfonyl fluoride, or phenanthroline, consistent with its classification within the cysteine protease class. Leupeptin has been characterized as a slow binding inhibitor of cathepsin K (kobs/[I] = 273,000 m(-1).s(-1)). Cathepsin K may represent the elusive protease implicated in degradation of protein matrix during bone resorption and represents a novel molecular target in treatment of disease states associated with excessive bone loss such as osteoporosis.
Human natural killer cells (2008)

Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells "see," lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.
Effect of Simultaneous Substitution of Y and Ta on the Stabilization of Cubic Phase, Microstructure, and Li+ Conductivity of Li7La3Zr2O12 Lithium Garnet (2014)

Garnet-type lithium stuffed oxide Li7La3Zr2O12 (LLZ) in the cubic phase has received significant attention because of its high Li(+) conductivity at room temperature and excellent stability against lithium metal anodes. In addition to the high Li(+) conductivity, the dense microstructure is also a critical issue for the successful application of LLZ as a solid electrolyte membrane in all-solid-state lithium and lithium-air batteries. The stabilization of LLZ in the cubic phase with dopants indicated a reduction in sintering temperature with La(3+) site doping and improved conductivity by doping the Zr(4+) site. However, there are only a few reports regarding the simultaneous substitution on the La(3+) and on the Zr(4+) site in LLZ. In the present study, systematic investigations have been carried out on Li7-xLa3-yYyZr2-xTaxO12 (x = 0.4, y = 0, 0.125, 0.25, and 0.5) to understand the effect of simultaneous substitution of Y(3+) for La(3+) and Ta(5+) for Zr(4+) in LLZ on the stabilization of the high conductive cubic phase, microstructure, and Li(+) conduction behavior. Powder X-ray diffraction (PXRD) revealed the stabilization of a cubic-like garnet structure for the entire selected compositional range of Li7-xLa3-yYyZr2-xTaxO12 (x = 0.4, y = 0, 0.125, 0.25, and 0.5) samples sintered at 750 °C. However, the Raman spectra revealed that the cubic phase stabilized at around 750 °C for the Li7-xLa3-yYyZr2-xTaxO12 (x = 0.4, y = 0, 0.125, 0.25, and 0.5) samples is different from the high Li(+) conductive cubic phase (Ia3̅d), and the transformation to the high Li(+) conductive cubic phase with a distorted lithium sublattice (Ia3̅d) is observed only for the samples sintered at elevated temperature. Preliminary thermogravimetric (TG), Raman, and Fourier transform infrared (FTIR) studies indicated that the observed low temperature cubic phase of the investigated samples sintered at 750 °C might result from insertion of water vapor from the humid atmosphere into the crystal lattice and subsequent replacement of the lithium ions by protons to form O-H bonds. The AC impedance analysis indicated that the optimal Y substitution in Li7-xLa3-yYyZr2-xTaxO12 (x = 0.4, y = 0.125 and 0.25) helps to reduce the grain boundary resistance in a major way and also helps to reduce the bulk resistance slightly. Among the investigated compositions, Li6.6La2.75Y0.25Zr1.6Ta0.4O12 sintered at 1200 °C exhibits a maximized room temperature total (bulk + grain boundary) Li(+) conductivity of 4.36 × 10(-4) S cm(-1) along with the improved ceramic density.
Towards a new approach to reveal dynamical organization of the brain using topological data analysis (2018)

Little is known about how our brains dynamically adapt for efficient functioning. Most previous work has focused on analyzing changes in co-fluctuations between a set of brain regions over several temporal segments of the data. We argue that by collapsing data in space or time, we stand to lose useful information about the brain's dynamical organization. Here we use Topological Data Analysis to reveal the overall organization of whole-brain activity maps at a single-participant level-as an interactive representation-without arbitrarily collapsing data in space or time. Using existing multitask fMRI datasets, with the known ground truth about the timing of transitions from one task-block to next, our approach tracks both within- and between-task transitions at a much faster time scale (~4-9 s) than before. The individual differences in the revealed dynamical organization predict task performance. In summary, our approach distills complex brain dynamics into interactive and behaviorally relevant representations.
“Chemical Mutation” by Amino Acid Exchange in the Reactive Site of a Proteinase Inhibitor and Alteration or Its Inhibitor Specifity (1981)

By chemical intervention in the reactive center of an enzyme-inhibitor it has been possible to replace lysine by valine, i.e. by a non-basic amino acid. Hitherto, this was possible via an enzymatic pathway only in exceptional cases. The native Kunitz inhibitor (1) from bovine organs inhibits trypsin very strongly, but hardly inhibits leukolytic elastase at all; the chemically modified product (2) is a very good inhibitor for elastase from human leukocytes. The method is capable of generalization.
Three overlapping lct genes involved in L-lactate utilization by Escherichia coli (1993)

In Escherichia coli, the lct locus at min 80 on the chromosome map is associated with ability to grow on L-lactate and to synthesize a substrate-inducible flavin-linked dehydrogenase. Similar to that of the glpD-encoded aerobic glycerol-3-phosphate dehydrogenase, the level of induced enzyme activity is elevated by aerobiosis. Both of these controls are mediated by the two-component signal transduction system ArcB/ArcA, although sensitivity to the control is much more striking for L-lactate dehydrogenase. This study disclosed that the lct locus contained three overlapping genes in the clockwise order of lctD (encoding a flavin mononucleotide-dependent dehydrogenase), lctR (encoding a putative regulator), and lctP (encoding a permease) on the chromosomal map. These genes, however, are transcribed in the counterclockwise direction. No homology in amino acid sequence was found between aerobic glycerol-3-phosphate dehydrogenase and L-lactate dehydrogenase. A phi (lctD-lac) mutant was inducible by L-lactate but not D-lactate. Although the mutant lost the ability to grow on L-lactate, growth on D-lactate, known to depend on a different enzyme, remained normal.
Botulinum Toxin in the Management of Lower Urinary Tract Dysfunction: Contemporary Update (2005)

No AccessJournal of UrologyUrological Survey: Voiding Function and Dysfunction, Bladder Physiology and Pharmacology, and Female Urology1 Aug 2005Botulinum Toxin in the Management of Lower Urinary Tract Dysfunction: Contemporary Update Alan J. WeinM.D. Alan J. WeinAlan J. Wein More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)68335-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Botulinum Toxin in the Management of Lower Urinary Tract Dysfunction: Contemporary Update." The Journal of Urology, 174(2), pp. 611–612 © 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 174Issue 2August 2005Page: 611-612 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information Alan J. Wein More articles by this author Expand All Advertisement PDF downloadLoading ...
Simple networks for pixel plane median filtering (1993)

The authors present networks that estimate the median of an odd number of inputs. The simplicity of these circuits rivals that of resistive grids, allowing their use in pixel plane processing systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The pervasive chemistry of metal–organic frameworks (2009)

A graphical abstract is available for this content
Effect of physical environment on the conformation of ricin Influence of low pH (1986)

The molecular properties of ricin (the toxic lectin from Ricinus communis seeds, RCA II or RCA 60) were evaluated by analytical ultracentrifugation, viscosimetry, c.d., fluorescence and equilibrium dialysis. Measurements of sedimentation (S0(20,W) = 4.60 S) and viscosity (eta = 2.96 X 10(-2) dl/g) indicated that, at neutral pH, the ricin molecule is very compact. Various transitions were explored, and a pH-triggered change in the ricin conformation was observed between pH 7 and 4. In this range, the sedimentation coefficient, far-u.v. c.d. and fluorescence altered simultaneously without unfolding. Below pH 7 the change in the ricin conformation was accompanied by a decrease in the affinity of ricin for galactosides, and at pH 4.0 by an alteration in its binding capacity. These effects of low pH are discussed in relation to the physical conditions encountered by ricin molecules during their entry into living cells.
Indirect Spectrophotometric Determination of Trace Quantities of Hydrazine (2004)

An indirect, sensitive and accurate method for the determination of trace amounts of hydrazine is described. The method is based on the oxidation of hydrazine by a known excess of iodate in the presence of hydrochloric acid. The unreacted iodate is used in the oxidation of hydroxylamine to nitrite. Sulfanilic acid is diazotized by the nitrite formed. The resulting diazonium ion is coupled with N-(1-naphthyl)ethylenediamine to form a stable azo dye, which shows an absorption maximum at 540 nm. Hydrazine can be determined in the range of 20-400 ng <TEX>$mL^{-1}$</TEX> with a detection limit of 3.1 ng <TEX>$mL^{-1}$</TEX>. The relative standard deviation for 50, 200 and 400 ng <TEX>$mL^{-1}$</TEX> of hydrazine is 2, 1.5 and 1.3%, respectively (n = 10). The method was applied to the determination of hydrazine in water samples.
GENETIC VARIATION IN REACTION TO SCLEROTINIA STEM ROT IN Brassica SPECIES (1989)

Twenty-five cultivars and strains representing five Brassica species were tested under controlled conditions for their reaction to infection by Sclerotinia sclerotiorum, the causal agent of sclerotinia stem rot. Using the rate of stem lesion expansion as an indicator of the resistance of stem tissue to the pathogen, significant differences were present between species and among cultivars/strains within species. Although S 0 parent-S 1 progeny heritability of stem lesion expansion was low, S 0 plants of Brassica campestris and B. juncea with increased sclerotinia stem rot resistance could be selected.Key words: Brassica, Sclerotinia sclerotiorum, stem rot resistance, selection technique
Caspase-9/-3 Activation and Apoptosis Are Induced in Mouse Macrophages upon Ingestion and Digestion of Escherichia coli Bacteria (2002)

A number of highly virulent, intracellular bacteria are known to induce cell death by apoptosis in infected host cells. In this work we demonstrate that phagocytosis of bacteria from the Escherichia coli laboratory strain K12 DH5alpha is a potent cell death stimulus for mouse macrophages. RAW264.7 mouse macrophages took up bacteria and digested them within 2-4 h as investigated with green fluorescent protein-expressing bacteria. No evidence of apoptosis was seen at 8 h postexposure, but at 24 h approximately 70% of macrophages displayed an apoptotic phenotype by a series of parameters. Apoptosis was blocked by inhibition of caspases or by forced expression of the apoptosis-inhibiting protein Bcl-2. Processing of caspase-3 and caspase-9 but not caspase-8 was seen suggesting that the mitochondrial branch of the apoptotic pathway was activated. Active effector caspases could be detected in two different assays. Because the adapter molecule myeloid differentiation factor 88 (MyD88) has been implicated in apoptosis, involvement of the Toll-like receptor pathway was investigated. In RAW264.7 cells, heat-treated bacteria were taken up poorly and failed to induce significant apoptosis. However, cell activation was almost identical between live and heat-inactivated bacteria as measured by extracellular signal-regulated kinase activation, generation of free radicals, and TNF secretion. Furthermore, primary bone marrow-derived macrophages from wild-type as well as from MyD88-deficient mice underwent apoptosis upon phagocytosis of bacteria. These results show that uptake and digestion of bacteria leads to MyD88-independent apoptosis in mouse macrophages. This form of cell death might have implications for the generation of the immune response.
Editorial: The Physiology and Pharmacology of Leucine-rich Repeat GPCRs (2016)

EDITORIAL article Front. Endocrinol., 17 June 2016Sec. Molecular and Structural Endocrinology Volume 7 - 2016 | https://doi.org/10.3389/fendo.2016.00056
Fabrication of micron size Nb/Al-Al/sub 2/O/sub 3//Nb junctions with a trilevel resist liftoff process (1991)

A trilevel resist, consisting of polyimide planarization, SiO/sub 2/ barrier, and photoresist, was used to pattern junction areas in Nb/Al-Al/sub 2/O/sub 3//Nb trilayer films. After reactive ion etching to define the junction areas, the perimeter of the junction was revealed, and excellent liftoff structures were defined with an oxygen plasma shrink of the exposed polyimide sidewalls. A subsequently deposited insulation layer seals the sides and the top surface along the perimeter of the Nb counter electrode button. High-quality superconductor-insulator-superconductor (SIS) junctions with diameters as small as 1.2 mu m and V/sub m/ as large as 1500 mV at 2.0 K have been fabricated. An SIS receiver using these junctions with integrated tuning elements has a DSB noise temperature of 58 K at 230 GHz. This is believed to be the lowest receiver noise temperature ever reported at this frequency.
Oases:robustde novoRNA-seq assembly across the dynamic range of expression levels (2012)

Oases is freely available under the GPL license at www.ebi.ac.uk/~zerbino/oases/.
Microcomputer Based Feeder Protection and Monitoring System - Utility Experience (1987)

This paper describes the experience of Houston Lighting & Power Company with the field operation of the Feeder Protection and Monitoring System developed by Texas A&M University. The Feeder Protection and Monitoring System (FPMS) is fully described from a functional perspective. The paper describes the design objectives of the project. The field testing of the device and its subsequent use as a monitoring and diagnostic tool are reviewed in detail. The potential value of the system to utilities and the need for modifications and further research are included. The perspective of HL&P on integrated substation control and protection is given.
A Systematic Analysis of Peptide Linker Length and Liposomal Polyethylene Glycol Coating on Cellular Uptake of Peptide-Targeted Liposomes (2013)

PEGylated liposomes are attractive pharmaceutical nanocarriers; however, literature reports of ligand-targeted nanoparticles have not consistently shown successful results. Here, we employed a multifaceted synthetic strategy to prepare peptide-targeted liposomal nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities to evaluate the role of liposomal PEG coating, peptide EG-linker length, and peptide valency on cellular uptake in a systematic manner. We analyzed these parameters in two distinct disease models where the liposomes were functionalized with either HER2- or VLA-4-antagonistic peptides to target HER2-overexpressing breast cancer cells or VLA-4-overexpressing myeloma cells, respectively. When targeting peptides were tethered to nanoparticles with an EG45 (∼PEG2000) linker in a manner similar to a more traditional formulation, their cellular uptake was not enhanced compared to non-targeted versions regardless of the liposomal PEG coating used. Conversely, reduction of the liposomal PEG to PEG350 and the peptide linker to EG12 dramatically enhanced cellular uptake by ∼9 fold and ∼100 fold in the breast cancer and multiple myeloma cells, respectively. Uptake efficiency reached a maximum and a plateau with ∼2% peptide density in both disease models. Taken together, these results demonstrate the significance of using the right design elements such as the appropriate peptide EG-linker length in coordination with the appropriate liposomal PEG coating and optimal ligand density in efficient cellular uptake of liposomal nanoparticles.
Low CD4/CD8 T-Cell Ratio Associated with Inflammatory Arthropathy in Human T-Cell Leukemia Virus Type I Tax Transgenic Mice (2011)

Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients.
γ-Secretase Inhibitors Abrogate Oxaliplatin-Induced Activation of the Notch-1 Signaling Pathway in Colon Cancer Cells Resulting in Enhanced Chemosensitivity (2009)

Because Notch signaling is implicated in colon cancer tumorigenesis and protects cells from apoptosis by inducing prosurvival targets, it was hypothesized that inhibition of Notch signaling with gamma-secretase inhibitors (GSI) may enhance the chemosensitivity of colon cancer cells. We first show that the Notch-1 receptor, as well as its downstream target Hes-1, is up-regulated with colon cancer progression, similar to other genes involved in chemoresistance. We then report that chemotherapy induces Notch-1, as oxaliplatin, 5-fluorouracil (5-FU), or SN-38 (the active metabolite of irinotecan) induced Notch-1 intracellular domain (NICD) protein and activated Hes-1. Induction of NICD by oxaliplatin was caused by an increase in the activity and expression of gamma-secretase complex, as suppression of the protein subunit nicastrin with small interfering RNA (siRNA) prevented NICD induction after oxaliplatin. Subsequent inhibition of Notch-1 signaling with a sulfonamide GSI (GSI34) prevented the induction of NICD by chemotherapy and blunted Hes-1 activation. Blocking the activation of Notch signaling with GSI34 sensitized cells to chemotherapy and was synergistic with oxaliplatin, 5-FU, and SN-38. This chemosensitization was mediated by Notch-1, as inhibition of Notch-1 with siRNA enhanced chemosensitivity whereas overexpression of NICD increased chemoresistance. Down-regulation of Notch signaling also prevented the induction of prosurvival pathways, most notably phosphoinositide kinase-3/Akt, after oxaliplatin. In summary, colon cancer cells may up-regulate Notch-1 as a protective mechanism in response to chemotherapy. Therefore, combining GSIs with chemotherapy may represent a novel approach for treating metastatic colon cancers by mitigating the development of chemoresistance.
The Gastric Mucosal Barrier (1970)

Skillman, John J. M.D.; Gould, Sharon A. M.D.; Chung, Raphael S. K. M.B.; Silen, William M.D. Author Information
Effects of Driekoppies Dam on the distribution of trees and carbon uptake at Timphisini area, in Swaziland (2004)

The purpose of this study was to investigate the effect of dam construction on the distribution of trees and carbon uptake at Timphisini area. In carrying out this study, a field survey was undertaken in 16 quadrants along the Lomati River, with eight quadrants demarcated on each side of the river. In each quadrant the types and number of species were counted and soil samples taken at 15 cm, 30cm and 45 cm depths. To analyze the data two statistical techniques were used. First, the Student’s test was used to test the significance of the difference between the affected and control site. This is a parametric test of the difference between two samples. The research also used canonical discriminant functions to test the significance of the soil properties namely, organic matter, moisture content and soil pH and location of quadrant in the distribution of species and species diversity within the study area. This technique considers several variables simultaneously at the same time to determine linear combinations for separating groups. The findings indicate that the dam has resulted in some species being endangered. Furthermore, the results indicated that there is a clear difference between the affected and control site on the basis of the number of species and species richness. Finally, the findings depict that soil properties act collectively influencing the distribution of trees and species diversity. As a result of the change in the distribution of trees, there has been a decline in carbon uptake within the study area, Timphisini. 1 Department of Geography, Environmental Science and Planning, Faculty of Science, university of Swaziland, P/B 4, Kwaluseni, Swaziland