gebhart/patrepeval huggingface dataset:
Potential role for phosphatidic acid in mediating the inflammatory responses to TNF alpha and IL-1 beta. (1994)

Tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and endotoxin (LPS) are potent pro-inflammatory mediators which induce multiple and diverse biological responses in a wide variety of cell types. However, these pro-inflammatory mediators also have significant overlap and redundancy in their biological effects. This suggests that there is significant diversity in second messenger signal transduction systems induced by these stimuli to explain the diversity in biological responses, as well as significant redundancy. Here we show that one such second messenger common to several proinflammatory stimuli may be phosphatidic acid (PA). Intracellular PA species, which may have intracellular signaling functions, are rapidly induced in P388 monocytic leukemia cells by TNF alpha, IL-1 beta, or LPS. These PA species vary according to the bond type (i.e., sn-1 ester vs. ether vs. vinyl ether), acyl chain length, and the degree of saturation in the sn-1 and sn-2 positions. Although PA itself may have direct second messenger activities, many of the PA species induced are converted to diacylglycerol species (DG), which are structurally distinct from the DGs generated by phosphatidylcholine-specific phospholipase C (PC-PLC). Lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine; LSF] selectively inhibits generation of selected species of PA in P388 cells induced by TNF alpha, IL-1 beta or LPS. TNF alpha-induced sphingomyelin hydrolysis, PLC-mediated PC hydrolysis, and DG kinase-mediated PA formation or TNF alpha-induced NF-kappa B activation and apoptosis are not inhibited by LSF. LSF has a marked protective effect in a variety of acute inflammatory animal models that may be due to inhibition of this shared second messenger pathway involving PA.
A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases (2014)

A novel fragment-based drug discovery approach is reported which irreversibly tethers drug-like fragments to catalytic cysteines. We attached an electrophile to 100 fragments without significant alterations in the reactivity of the electrophile. A mass spectrometry assay discovered three nonpeptidic inhibitors of the cysteine protease papain. The identified compounds display the characteristics of irreversible inhibitors. The irreversible tethering system also displays specificity: the three identified papain inhibitors did not covalently react with UbcH7, USP08, or GST-tagged human rhinovirus 3C protease.
Addition of growth hormone secretion signal to basic fibroblast growth factor results in cell transformation and secretion of aberrant forms of the protein. (1988)

Basic fibroblast growth factor (bFGF) is a potent mitogen for a wide variety of cell types. Unlike most growth factors, the primary translation product for bFGF appears to lack a secretory signal peptide. To explore the normal mode of bFGF release, as well as to investigate the growth factor's oncogenic potential, expression vectors were created for a bFGF cDNA and for a chimeric molecule in which the bFGF coding sequence was linked to the human growth hormone signal peptide sequence. Transfection of NIH3T3 cells with the bFGF cDNA vectors caused the synthesis of high levels of biologically active, cell-associated bFGF, but no evidence of transformation was detected. In contrast, the chimeric bFGF-signal peptide expression vector induced foci of transformation at a very high frequency. The transformed cells grew in soft agar and were tumorigenic in nude mice. The majority of the immunoreactive bFGF species made by the transformed cells was found in the conditioned medium and appeared to be posttranslationally modified, indicating that the chimeric bFGF-signal peptide molecule was processed through the secretory pathway. The secreted bFGF exhibited little mitogenic activity, suggesting that interaction of bFGF with its receptor likely occurs while the fusion protein is being processed along the secretory pathway.
Novel Synthetic Route to 2,5-Disubstituted Furan Derivatives through Surface Active Agent-Catalysed Dehydration of D(-)-Fructose. (2001)

5-Chloromethyl-2-furfural, generated in situ by surface active agent-catalysed dehydration of D(-)-fructose, was conducted to obtain 5-methyl-2-furfural,2,5-dimethyl furan,2,5-hexanedione and 2,5-dimethyl-1-thioureidopyrrole.
Specificity of Signal Peptide Recognition in Tat-Dependent Bacterial Protein Translocation (2001)

The bacterial twin arginine translocation (Tat) pathway translocates across the cytoplasmic membrane folded proteins which, in most cases, contain a tightly bound cofactor. Specific amino-terminal signal peptides that exhibit a conserved amino acid consensus motif, S/T-R-R-X-F-L-K, direct these proteins to the Tat translocon. The glucose-fructose oxidoreductase (GFOR) of Zymomonas mobilis is a periplasmic enzyme with tightly bound NADP as a cofactor. It is synthesized as a cytoplasmic precursor with an amino-terminal signal peptide that shows all of the characteristics of a typical twin arginine signal peptide. However, GFOR is not exported to the periplasm when expressed in the heterologous host Escherichia coli, and enzymatically active pre-GFOR is found in the cytoplasm. A precise replacement of the pre-GFOR signal peptide by an authentic E. coli Tat signal peptide, which is derived from pre-trimethylamine N-oxide (TMAO) reductase (TorA), allowed export of GFOR, together with its bound cofactor, to the E. coli periplasm. This export was inhibited by carbonyl cyanide m-chlorophenylhydrazone, but not by sodium azide, and was blocked in E. coli tatC and tatAE mutant strains, showing that membrane translocation of the TorA-GFOR fusion protein occurred via the Tat pathway and not via the Sec pathway. Furthermore, tight cofactor binding (and therefore correct folding) was found to be a prerequisite for proper translocation of the fusion protein. These results strongly suggest that Tat signal peptides are not universally recognized by different Tat translocases, implying that the signal peptides of Tat-dependent precursor proteins are optimally adapted only to their cognate export apparatus. Such a situation is in marked contrast to the situation that is known to exist for Sec-dependent protein translocation.
A ras- Mutated Peptide Targeted by CTL Infiltrating a Human Melanoma Lesion (2002)

Ags derived from commonly mutated oncogenic proteins seem ideally suited as targets for tumor immunotherapy. Nonetheless, only a few mutated epitopes efficiently presented by human tumors have thus far been identified. We describe here an approach to identify such epitopes. This approach involves: 1) identifying tumors expressing a ras mutation and isolating the tumor-infiltrating lymphocytes (TIL); 2) transfecting COS cells to induce expression of unknown mutated peptides in the context of a patient's HLA class I molecules; and 3) screening epitope recognition by using TIL from the tumors expressing a ras mutation. By using this approach, there appeared to be a N-ras mutation (a glutamine-to-arginine exchange at residue 61 (Q61R)), detected in a melanoma lesion, which was recognized specifically by the autologous TIL in the HLA-A*0101 context. The ras peptide 55-64(Q61R) was the epitope of these TIL and was regularly presented by Q61R-mutated HLA-A*0101(+) melanoma cell lines. This peptide and its wild-type homolog (55-64(wt)) bound to HLA-A*0101 with similar affinities. However, only the mutated peptide could induce specific CTL expansion from PBL. All the CTL clones specific to the mutated peptide, failed to recognize the wild-type sequence on both COS and melanoma cells. These data thus show that oncogenic protein mutations can create shared tumor-specific CTL epitopes, efficiently presented by tumor cells, and that screening for oncogene-transfected COS cell recognition by TIL (from tumors containing mutations) is a powerful approach for the identification of these epitopes.
Plant hormone perception and action: a role for G–protein signal transduction? (1998)

Plants perceive and respond to a profusion of environmental and endogenous signals that influence their growth and development. The G-protein signalling pathway is a mechanism for transducing extracellular signals that is highly conserved in a range of eukaryotes and prokaryotes. Evidence for the existence of G-protein signalling pathways in higher plants is reviewed, and their potential involvement in plant hormone signal transduction evaluated. A range of biochemical and molecular studies have identified potential components of G-protein signalling in plants, most notably a homologue of the G-protein coupled receptor superfamily (GCR1) and the G alpha and G beta subunits of heterotrimeric G-proteins. G-protein agonists and antagonists are known to influence a variety of signalling events in plants and have been used to implicate heterotrimeric G-proteins in gibberellin and possibly auxin signalling. Antisense suppression of GCR1 in Arabidopsis leads to a phenotype which supports a role for this receptor in cytokinin signalling. These observations suggest that higher plants have at least some of the components of G-protein signalling pathways and that these might be involved in the action of certain plant hormones.
The Growth in Vitro of Single Isolated Tissue Cells (1948)

The Growth in Vitro of Single Isolated Tissue Cells Get access Katherine K. Sanford, Katherine K. Sanford Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle, Wilton R. Earle Search for other works by this author on: Oxford Academic PubMed Google Scholar Gwendolyn D. Likely Gwendolyn D. Likely National Cancer Institute, National Institutes of Health, Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 3, December 1948, Pages 229–246, https://doi.org/10.1093/jnci/9.3.229 Published: 01 December 1948 Article history Received: 16 August 1948 Published: 01 December 1948
Enzymatic conversion of lignocellulose into fermentable sugars: challenges and opportunities (2007)

Abstract The economic dependency on fossil fuels and the resulting effects on climate and environment have put tremendous focus on utilizing fermentable sugars from lignocellulose, the largest known renewable carbohydrate source. The fermentable sugars in lignocellulose are derived from cellulose and hemicelluloses but these are not readily accessible to enzymatic hydrolysis and require a pretreatment, which causes an extensive modification of the lignocellulosic structure. A number of pretreatment technologies are under development and being tested in pilot scale. Hydrolysis of lignocellulose carbohydrates into fermentable sugars requires a number of different cellulases and hemicellulases. The hydrolysis of cellulose is a sequential breakdown of the linear glucose chains, whereas hemicellulases must be capable of hydrolysing branched chains containing different sugars and functional groups. The technology for pretreatment and hydrolysis has been developed to an extent that is close to a commercially viable level. It has become possible to process lignocellulose at high substrate levels and the enzyme performance has been improved. Also the cost of enzymes has been reduced. Still a number of technical and scientific issues within pretreatment and hydrolysis remain to be solved. However, significant improvements in yield and cost reductions are expected, thus making large‐scale fermentation of lignocellulosic substrates possible. © 2007 Society of Chemical Industry and John Wiley &amp; Sons, Ltd
Methane Oxidation in Termite Hindguts: Absence of Evidence and Evidence of Absence (2007)

A steep oxygen gradient and the presence of methane render the hindgut internal periphery of termites a potential habitat for aerobic methane-oxidizing bacteria. However, methane emissions of various termites increased, if at all, only slightly when termites were exposed to an anoxic (nitrogen) atmosphere, and (14)CH(4) added to the air headspace over live termites was not converted to (14)CO(2). Evidence for the absence of methane oxidation in living termites was corroborated by the failure to detect pmoA, the marker gene for particulate methane monooxygenase, in hindgut DNA extracts of all termites investigated. This adds robustness to our concept of the degradation network in the termite hindgut and eliminates the gut itself as a potential sink of this important greenhouse gas.
Abdominal Obesity in Older Women: Potential Role for Disrupted Fatty Acid Reesterification in Insulin Resistance (2008)

These findings support the premise of dysregulated fatty acid reesterification with abdominal obesity as a pathophysiological link to perturbed glucose metabolism across multiple tissues in aging.
Singlemode optical switches based on SOI waveguideswith large cross-section (1994)

The realisation of a thermo-optical Mach-Zehnder interferometer switch based on SOI (silicon-on-insulator) material is reported. At a wavelength of 1.3 µm, on-off ratios of 13 dB (TE) aud 9 dB (TM) are achieved with a switching power of 150 mW. The measured rise time is 5 µs.
Vertical Cavity Surface Emitting Lasers (1995)

Vertical cavity surface emitting laser (VCSEL) structures have been grown by&#13;\nboth metal-organic chemical vapour deposition (MOCVD) and molecular beam&#13;\nepitaxy (MBE). These incorporate 3 strained InGaAs / GaAs quantum wells placed&#13;\nresonantly in a two wavelength long optical cavity, formed between AlAs / GaAs&#13;\nquarter wave dielectric reflector stacks through which current is injected.&#13;\nThe reflection spectra of these stacks is studied in detail; the effects on the&#13;\nlaser threshold gain of absorption due to impurities and of errors in growth are&#13;\ninvestigated. Methods of disruption of the AlAs / GaAs heterointerfaces have been&#13;\nused to reduce the operating voltage. The completed designs use 200A intermediate&#13;\nlayers containing 30 or 50% aluminium or a superlattice graded region simpler than&#13;\nthat used in previous designs. The effectiveness acceptor dopants; Be in MBE, C and&#13;\nZn in MOCVD; is studied also. Modulation doping was employed to reduce the&#13;\neffects of optical absorption.&#13;\nDevices were fabricated into mesas by SiC14 reactive ion etching or defined&#13;\nby proton implant isolation. MBE grown devices were resonant at wavelengths in the&#13;\nrange 950 to 1059mn with essentially constant (at —1020nm) eihhi transition&#13;\nenergies in the wells. A detailed study of the wavelength variation of threshold&#13;\ncurrent density &#13;\nJth (X)was made. A minimum of 366A.cnr2 was measured at&#13;\n1018nm in mesa devices. A similar relation is found for ion-implanted devices but the&#13;\nminimum is increased to 535A.cm-2 by incomplete isolation. Gain calculations,&#13;\nincluding strain effects, are used to explain the Jth(X) variation.&#13;\nImplanted devices offer superior c.w. performance due to reduced thermal and&#13;\nohmic resistances. The relative offset between the gain spectrum and cavity resonance&#13;\nwas examined for c.w. operation. It was found that carrier thermal effects limit the&#13;\noutput power rather than shifts in the offset.&#13;\nThe bias voltage of MOCVD grown devices is as low as 1.7V and the&#13;\nthreshold current is as low as 764A.cm-2. This is higher than for MBE grown devices&#13;\nbecause of growth thickness errors and non-optimal alignment of the gain spectrum&#13;\nand cavity mode. The uniformity in emission wavelength is ±1% over 80% of a 2 inch&#13;\ndiameter wafer, offering suitability for very large uniform arrays.
Synthesized Light Transients (2011)

Manipulation of electron dynamics calls for electromagnetic forces that can be confined to and controlled over sub-femtosecond time intervals. Tailored transients of light fields can provide these forces. We report on the generation of subcycle field transients spanning the infrared, visible, and ultraviolet frequency regimes with a 1.5-octave three-channel optical field synthesizer and their attosecond sampling. To demonstrate applicability, we field-ionized krypton atoms within a single wave crest and launched a valence-shell electron wavepacket with a well-defined initial phase. Half-cycle field excitation and attosecond probing revealed fine details of atomic-scale electron motion, such as the instantaneous rate of tunneling, the initial charge distribution of a valence-shell wavepacket, the attosecond dynamic shift (instantaneous ac Stark shift) of its energy levels, and its few-femtosecond coherent oscillations.
Percutaneous transrenal endoureteral radio-frequency electrocautery for occlusion: case report. (1989)

In a patient with advanced cervical carcinoma who had a large vesicovaginal fistula, the authors applied radio-frequency (RF) current endoluminally to the ureter via a percutaneous nephrostomy tract to occlude the ureter. Perineal drainage was initially reduced and then stopped entirely. The procedure was relatively easy to perform and was successful in achieving occlusion until the patient's death 2 1/2 months later.
Regenerative Therapies for Diabetic Microangiopathy (2012)

Hyperglycaemia occurring in diabetes is responsible for accelerated arterial remodeling and atherosclerosis, affecting the macro- and the microcirculatory system. Vessel injury is mainly related to deregulation of glucose homeostasis and insulin/insulin-precursors production, generation of advanced glycation end-products, reduction in nitric oxide synthesis, and oxidative and reductive stress. It occurs both at extracellular level with increased calcium and matrix proteins deposition and at intracellular level, with abnormalities of intracellular pathways and increased cell death. Peripheral arterial disease, coronary heart disease, and ischemic stroke are the main causes of morbidity/mortality in diabetic patients representing a major clinical and economic issue. Pharmacological therapies, administration of growth factors, and stem cellular strategies are the most effective approaches and will be discussed in depth in this comprehensive review covering the regenerative therapies of diabetic microangiopathy.
Combining Local Immunotoxins Targeting Mesothelin with CTLA-4 Blockade Synergistically Eradicates Murine Cancer by Promoting Anticancer Immunity (2017)

Immune checkpoint blockade using antibodies to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) benefits a limited number of cancer patients. SS1P and LMB-100 are immunotoxins that target mesothelin. We observed delayed responses to SS1P in patients with mesothelioma suggesting that antitumor immunity was induced. Our goal was to stimulate antitumor immunity by combining SS1P or LMB-100 with anti-CTLA-4. We constructed a BALB/c breast cancer cell line expressing human mesothelin (66C14-M), which was implanted in one or two locations. SS1P or LMB-100 was injected directly into established tumors and anti-CTLA-4 administered i.p. In mice with two tumors, one tumor was injected with immunotoxin and the other was not. The complete regression rate was 86% for the injected tumors and 53% for the uninjetced tumors. No complete regressions occurred when drugs were given separately. In regressing tumors, dying and dead tumor cells were intermingled with PMNs and surrounded by a collar of admixed eosinophils and mononuclear cells. Tumor regression was associated with increased numbers of tumor-infiltrating CD8<sup>+</sup> cells and blocked by administration of antibodies to CD8. Surviving mice were protected from tumor rechallenge by 66C14 cells not expressing mesothelin, indicating the development of antitumor immunity. The antitumor effect was abolished when a mutant noncytotoxic variant was used instead of LMB-100, showing that the antitumor response is not mediated by recognition of a foreign bacterial protein. Our findings support developing a therapy composed of immunotoxins and checkpoint inhibitors for patients. <i>Cancer Immunol Res; 5(8); 685-94. ©2017 AACR</i>.
Antibody Binding Regions on Human Nerve Growth Factor Identified by Homolog- and Alanine-Scanning Mutagenesis (2000)

The binding specificities of a panel of mouse monoclonal antibodies (MAbs) to human nerve growth factor (hNGF) were determined by epitope mapping using chimeric and point mutants of NGF. Subsequently, the MAbs were used to probe NGF structure-function relationships. Six MAbs, which recognize distinct or partially overlapping regions of hNGF, were evaluated for their ability to block the binding of hNGF to the TrkA and p75 NGF receptors in various in vitro assays, which included blocking of TrkA autophosphorylation and blocking of NGF-dependent survival of dorsal root ganglion sensory neurons. Three MAbs (911,912,938) were potent blockers of all activities. Potent blocking of p75 binding occurs only with MAb 909, which recognizes an NGF region identified by mutagenesis as important for NGF-p75 binding. These results are consistent with recently proposed models of binding regions involved in NGF-TrkA and NGF-p75 interactions generated through mutagenic analysis and structure determination of the NGF-TrkA complex. These studies provide insight to the epitope specificities and potency of MAbs that would be useful for physiological NGF blocking studies.
Copper‐Catalyzed Three‐Component Oxytrifluoromethylation of Alkenes with Sodium Trifluoromethanesulfinate and Hydroxamic Acid (2013)

Radical paths: The title reaction of olefins with NaSO2CF3 and N-hydroxy-N-phenylacetamide at room temperature is described for the first time (see scheme). This reaction provides a practical and convenient route to a series of trifluoromethylated alcohols bearing a wide range of functional groups. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Zipping, entanglement, and the elastic modulus of aligned single-walled carbon nanotube films (2013)

Reliably routing heat to and from conversion materials is a daunting challenge for a variety of innovative energy technologies--from thermal solar to automotive waste heat recovery systems--whose efficiencies degrade due to massive thermomechanical stresses at interfaces. This problem may soon be addressed by adhesives based on vertically aligned carbon nanotubes, which promise the revolutionary combination of high through-plane thermal conductivity and vanishing in-plane mechanical stiffness. Here, we report the data for the in-plane modulus of aligned single-walled carbon nanotube films using a microfabricated resonator method. Molecular simulations and electron microscopy identify the nanoscale mechanisms responsible for this property. The zipping and unzipping of adjacent nanotubes and the degree of alignment and entanglement are shown to govern the spatially varying local modulus, thereby providing the route to engineered materials with outstanding combinations of mechanical and thermal properties.
Privacy enhancement for Internet electronic mail: Part III - algorithms, modes, and identifiers (1989)

This RFC provides definitions, references, and citations for
algorithms, usage modes, and associated identifiers used in RFC-1113
and RFC-1114 in support of privacy-enhanced electronic mail.
[STANDARDS-TRACK]