gebhart/patrepeval huggingface dataset:
Treatment of Gram-Negative Bacteremia and Shock with Human Antiserum to a MutantEscherichia coli (1982)

In an effort to decrease deaths from gram-negative bacteremia and endotoxin shock, we treated bacteremic patients with human antiserum to endotoxin (lipopolysaccharide) core. Antiserum was prepared by vaccinating healthy men with heat-killed Escherichia coli J5; this mutant lacks lipopolysaccharide oligosaccharide side chains, so that the core, which is nearly identical to that of most other gram-negative bacteria, is exposed for antibody formation. In a randomized controlled trial, patients were given either J5 antiserum or preimmune control serum intravenously, near the onset of illness. The number of deaths in the bacteremic patients was 42 of 109 (39 per cent) in controls and 23 of 103 (22 per cent) in recipients of J5 antiserum (P = 0.011). In those with profound shock, mortality was 30 of 39 (77 per cent) in controls and 18 of 41 (44 per cent) in recipients of J5 antiserum (P = 0.003). We conclude that human antiserum to the lipopolysaccharide core can substantially reduce deaths from gram-negative bacteremia.
Selected Combination Therapy with Sorafenib: A Review of Clinical Data and Perspectives in Advanced Solid Tumors (2008)

The development of targeted therapies has provided new options for the management of patients with advanced solid tumors. There has been particular interest in agents that target the mitogen-activated protein kinase pathway, which controls tumor growth and survival and promotes angiogenesis. Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in renal cell carcinoma, and there is a strong rationale for investigating its use in combination with other agents. In particular, targeting multiple Raf isoforms with sorafenib may help to overcome resistance to other agents, while the ability of sorafenib to induce apoptosis may increase the cytotoxicity of chemotherapeutic agents. Based on positive results in preclinical studies, further investigation in phase I and II studies has shown potential antitumor activity when sorafenib is combined with cytotoxic agents in different solid tumors, including hepatocellular carcinoma and melanoma. Promising results have been reported in phase I and II studies of sorafenib combined with paclitaxel and carboplatin, with oxaliplatin in gastric and colorectal cancer, with docetaxel in breast cancer, with gemcitabine in ovarian cancer, and with capecitabine in different solid tumors. Phase II and III studies are currently investigating the use of sorafenib in combination with different agents in a variety of solid tumors. The primary objective of this review is to summarize the early clinical studies of sorafenib with cytotoxic agents and discuss future perspectives of these combinations in different tumor types.
Brain-to-brain entrainment: EEG interbrain synchronization while speaking and listening (2017)

Electroencephalographic hyperscanning was used to investigate interbrain synchronization patterns in dyads of participants interacting through speech. Results show that brain oscillations are synchronized between listener and speaker during oral narratives. This interpersonal synchronization is mediated in part by a lower-level sensory mechanism of speech-to-brain synchronization, but also by the interactive process that takes place in the situation per se. These results demonstrate the existence of brain-to-brain entrainment which is not merely an epiphenomenon of auditory processing, during listening to one speaker. The study highlights the validity of the two-person neuroscience framework for understanding induced brain activity, and suggests that verbal information exchange cannot be fully understood by examining the listener's or speaker's brain activity in isolation.
Additive CAD/CAM Process for Dental Prostheses (2010)

This article describes the evolution of a computer-aided design/computer-aided manufacturing (CAD/CAM) process where ceramic paste is deposited in a layer-by-layer sequence using a computer numerical control machine to build up core and fixed partial denture (FPD) structures (robocasting). Al(2)O(3) (alumina) or ZrO(2) (Y-TZP) are blended into a 0.8% aqueous solution of ammonium polyacrylate in a ratio of approximately 1:1 solid:liquid. A viscosifying agent, hydroxypropyl methylcellulose, is added to a concentration of 1% in the liquid phase, and then a counter polyelectrolyte is added to gel the slurry. There are two methods for robocasting crown structures (cores or FPD framework). One is for the core to be printed using zirconia ink without support materials, in which the stereolithography (STL) file is inverted (occlusal surface resting on a flat substrate) and built. The second method uses a fugitive material composed of carbon black codeposited with the ceramic material. During the sintering process, the carbon black is removed. There are two key challenges to successful printing of ceramic crowns by the robocasting technique. First is the development of suitable materials for printing, and second is the design of printing patterns for assembly of the complex geometry required for a dental restoration. Robocasting has room for improvement. Current development involves enhancing the automation of nozzle alignment for accurate support material deposition and better fidelity of the occlusal surface. An accompanying effort involves calculation of optimal support structures to yield the best geometric results and minimal material usage.
Transcutaneous fiber optic Raman spectroscopy of bone using annular illumination and a circular array of collection fibers (2006)

Transcutaneous bone Raman spectroscopy with an exciting annulus of 785-nm laser light surrounding the field of view of a circular array of collection fibers is demonstrated. The configuration provides distributed laser light. The annulus is located 2 to 3 mm beyond the edge of the field of view of the collection fibers to reject contributions from skin and other overlying tissues. Data are presented for rat and chicken tissue. For rat tibia, the carbonate/phosphate ratio measured at a depth of 1 mm below the skin is in error by 2.3% at an integration time of 120 s and within 10% at a 30-s integration time. For chicken tibia 4 mm below the skin surface, the error is less than 8% with a 120-s integration time.
Zintl phases for thermoelectric devices (2007)

By converting waste heat into electricity and improving the efficiency of refrigeration systems, thermoelectric devices could play a significant role in solving today's energy problems. Increasing the thermoelectric efficiency (as measured by the thermoelectric material's figure-of-merit, zT) is critical to the development of this technology. Complex Zintl phases, in particular, make ideal candidates for thermoelectric materials because the necessary "electron-crystal, phonon-glass" properties can be engineered with an understanding of the Zintl chemistry. A recent example is the discovery that Yb(14)MnSb(11), a transition metal Zintl compound, has twice the zT as the material currently in use at NASA. This perspective outlines a strategy to discover new high zT materials in Zintl phases, and presents results pointing towards the success of this approach.
Characterizing Voltage Losses in an SO2Depolarized Electrolyzer Using Sulfonated Polybenzimidazole Membranes (2017)

The hybrid sulfur cycle has been investigated as a means to produce CO2-free hydrogen efficiently on a large scale through the decomposition of H2SO4 to SO2, O2, and H2O, and then electrochemically oxidizing SO2 back to H2SO4 with the cogeneration of H2. The net effect is the production of hydrogen and oxygen from water. Recently, sulfonated polybenzimidazoles (s-PBI) have been investigated as a replacement for Nafion due to the ability to offer increased process efficiency through the generation of higher acid concentrations at lower potentials. Here, we measure the acid concentrations and individual potential contributions toward the overall operating voltage seen in the SO2-depolarized-electrolyzer. We then determine model parameters necessary to predict voltage losses in a cell over a wide range of operating temperatures, pressures, currents and reactant flow rates.
Molecular basis for insulin fibril assembly (2009)

In the rare medical condition termed injection amyloidosis, extracellular fibrils of insulin are observed. We found that the segment of the insulin B-chain with sequence LVEALYL is the smallest segment that both nucleates and inhibits the fibrillation of full-length insulin in a molar ratio-dependent manner, suggesting that this segment is central to the cross-beta spine of the insulin fibril. In isolation from the rest of the protein, LVEALYL forms microcrystalline aggregates with fibrillar morphology, the structure of which we determined to 1 A resolution. The LVEALYL segments are stacked into pairs of tightly interdigitated beta-sheets, each pair displaying the dry steric zipper interface typical of amyloid-like fibrils. This structure leads to a model for fibrils of human insulin consistent with electron microscopic, x-ray fiber diffraction, and biochemical studies.
Posttranscriptional Control of the Expression and Function of Diacylglycerol Acyltransferase-1 in Mouse Adipocytes (2002)

Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) catalyzes the final step of triglyceride synthesis in mammalian cells. Data obtained from DGAT1-knockout mice have indicated that this enzyme plays an important role in energy homeostasis. We investigated the regulation of the expression and function of DGAT1 in mouse 3T3-L1 cell as a model for mammalian adipocytes. We demonstrated that the DGAT1 protein level increased by approximately 90-fold following differentiation of 3T3-L1 into mature adipocytes, a change that was accompanied by approximately 7-fold increase in DGAT1 mRNA. On the other hand, forced overexpression of DGAT1 mRNA by >20-fold via a recombinant adenovirus only resulted in approximately 2-fold increase in DGAT1 protein in mature adipocytes and little increase in preadipocytes. These results indicated that gene expression of DGAT1 in adipocytes is subjected to rigorous posttranscriptional regulation, which is modulated significantly by the differentiation status of 3T3-L1 cells. Protein stability is not a significant factor in the control of DGAT1 expression. The steady-state levels of DGAT1 were unaffected by blockage of proteolytic pathways by ALLN. However, translational control was suggested by sequence analysis of the 5'-untranslated region of human DGAT1 (hDGAT1) mRNA. We found that the level of DGAT1 activity was predominantly a function of the steady-state level of DGAT1 protein. No significant functional changes were observed when the conserved tyrosine phosphorylation site in hDGAT1 was mutated by a single base pair substitution. Despite only a approximately 2-fold increase in DGAT1 protein caused by recombinant viral transduction, a proportionate increase in cellular triglyceride synthesis resulted without affecting the triglyceride lipolysis rate, leading to >2-fold increase in intracellular triglyceride accumulation. No change in adipocyte morphology or in the expression levels of lipoprotein lipase, proxisomal proliferation-activating receptor-gamma, and aP2 was evident secondary to DGAT1 overexpression at different stages in 3T3-L1 differentiation. These data suggest that dysregulation of DGAT1 may play a role in the development of obesity, and manipulation of the steady-state level of DGAT1 protein may offer a potential means to treat or prevent obesity.
Synthesis of Polyethylene Glycol (PEG) Derivatives and PEGylated−Peptide Biopolymer Conjugates (2003)

We synthesized a library of 50 poly(ethylene glycol) (PEG) derivatives to expand the extent of conjugation with biologically active molecules (biopolymers, peptides, drugs, etc.) and biomaterial substrates. The formation of PEG derivatives was confirmed with HPLC, (1)H and (13)C NMR. PEG derivatives were polymerized into networks in order to study the role of PEG and terminal functional groups in modulating the hydrophilicity of biomaterials and cell-biomaterial interaction. The resulting surface hydrophilicity and the number of adhered fibroblasts were primarily dependent on the PEG concentration with the molecular weight and the terminal functional group of PEG derivatives being less important. One of PEG derivatives, PEG-bis-glutarate, was utilized to link peptide sequences to gelatin backbone in the formation of novel biomedical hydrogels. PEG-peptide conjugates were characterized by mass spectroscopy. PEG-peptide modified gelatins were characterized by gel permeation chromatography.
Treatment of Inborn Errors of Urea Synthesis (1982)

Children with inborn errors of urea synthesis accumulate ammonium and other nitrogenous precursors of urea, leading to episodic coma and a high mortality rate. We used alternative pathways for the excretion of waste nitrogen as substitutes for the defective ureagenic pathways in 26 infants. These pathways involve synthesis and excretion of hippurate after sodium benzoate administration, and of citrulline and argininosuccinate after arginine supplementation. The children were treated for seven to 62 months; 22 survived. The mean plasma level of ammonium ( +/- S.E.) was 36 +/- 2 mumol per liter, and that of benzoate was 1.5 +/- 1.0 mg per deciliter. Alternative pathways accounted for between 28 and 59 per cent of the total "effective" excretion of waste nitrogen. Nineteen infants had normal height, weight, and head circumference, and 13 had normal intellectual development. Activation of alternative pathways of waste nitrogen excretion can prolong survival and improve clinical outcome in children with inborn errors of urea synthesis.
Mutational Analysis of STE5 in the Yeast Saccharomyces cerevisiae: Application of a Differential Interaction Trap Assay for Examining Protein-Protein Interactions (1997)

Ste5 is essential for the yeast mating pheromone response pathway and is thought to function as a scaffold that organizes the components of the mitogen-activated protein kinase (MAPK) cascade. A new method was developed to isolate missense mutations in Ste5 that differentially affect the ability of Ste5 to interact with either of two MAPK cascade constituents, the MEKK (Ste11) and the MEK (Ste7). Mutations that affect association with Ste7 or with Ste11 delineate discrete regions of Ste5 that are critical for each interaction. Co-immunoprecipitation analysis, examining the binding in vitro of Ste5 to Ste11, Ste7, Ste4 (G protein beta subunit), and Fus3 (MAPK), confirmed that each mutation specifically affects the interaction of Ste5 with only one protein. When expressed in a ste5 delta cell, mutant Ste5 proteins that are defective in their ability to interact with either Ste11 or Ste7 result in a markedly reduced mating proficiency. One mutation that clearly weakened (but did not eliminate) interaction of Ste5 with Ste7 permitted mating at wild-type efficiency, indicating that an efficacious signal is generated even when Ste5 associates with only a small fraction of (or only transiently with) Ste7. Ste5 mutants defective in association with Ste11 or Ste7 showed strong interallelic complementation when co-expressed, suggesting that the functional form of Ste5 in vivo is an oligomer.
[P3–164]: FUNCTIONAL CHARACTERIZATION OF A RARE GENETIC VARIANT IN PHOSPHOLIPASE Cγ2 WHICH IS ASSOCIATED WITH A BENEFICIAL EFFECT ON THE PROGRESSION OF ALZHEIMER's DISEASE (2017)

PLCG2 is an important modulator of T- and B –lymphocyte mediated immune response and plays a crucial role in signal transmission by cleavage of 1-phosphatidylinositol-4,5-bisphosphate to diacylglycerol and inositol-3 phosphate, which further activates various PKC mediated signaling cascades. Receptor mediated activation of PLCG2 is controlled by receptor tyrosine kinases like BTK, LYN, GAB2, and TREM2, which makes of PLCG2 a good downstream modulator of signal cascades related to Alzheimer's disease (AD). Here, we functionally characterize a mutPLCG2 variant by cell biological and biochemical approaches. We also explore the effect of this variant on AD-relevant cerebrospinal fluid (CSF) biomarkers. Effect of mutPLCG2 construct was explored in transient transfected COS cell. Activation of PLCG2 variants were analyzed by both transfections with Btk or Rac2-G12V, or treatment with recombinant epidermal growth factor and a subsequent measurement of inositol phosphate level. In order to reduce clonal artefacts and ensure equal expression levels, stably PLCG2 WT and Mut expressing Hek FlpIn cells were generated for cell biological and biochemical experiments. Variant on PLCG2 was genotyped in a cohort of 1000 individuals with values for amyloid-beta 42, Tau and pTau levels on CSF. COS cells expressing transiently either PLCG2 WT or mutPLCG2 showed significant differences in inositol phosphate formation when transfected with bruton's tyrosine kinase or the constitutively active Rho GTPase, Rac2-G12V. Similar results were observed when PLCG2 activation was induced by EGF. Following experiments in stable HEK FlpIn cells showed no difference in protein expression level or migration between WT and mutPLCG2under control conditions. Further analysis of the PKCθ/NFκB pathway showed also no effects under control conditions. Next, we analyses the effect of this genetic variant on CSF levels of different biomarkers relevant for AD. We observed that carriers of the rare variant showed lower levels of pTau compared to non-carriers. Interestingly, this difference in pTau was stronger in mild cognitive impartments than in AD patients. Here we functionally characterized a rare variant in PLCG2 providing a potential link to the protective effect seen in AD. Additional experiments are currently underway and will be presented at the AAIC in London.
Molecular Correlates of Primate Nuclear Transfer Failures (2003)

Somatic cell nuclear transfer (SCNT) ([1][1]) in nonhuman primates could accelerate medical research by contributing identical animals for research and clarifying embryonic stem cell potentials ([2][2]). Although rhesus embryos begin development after embryonic cell nuclear transfer (ECNT) ([3–5][
Out‐and‐in spiral spectroscopic imaging in rat brain at 7 T (2003)

With standard spectroscopic imaging, high spatial resolution is achieved at the price of a large number of phase-encoding steps, leading to long acquisition times. Fast spatial encoding methods reduce the minimum total acquisition time. In this article, a k-space scanning scheme using a continuous series of growing and shrinking, or "out-and-in," spiral trajectories is implemented and the feasibility of spiral spectroscopic imaging for animal models at high B(0) field is demonstrated. This method was applied to rat brain at 7 T. With a voxel size of about 8.7 microl (as calculated from the point-spread function), a 30 x 30 matrix, and a spectral bandwidth of 11 kHz, the minimum scan time was 9 min 20 sec for a signal-to-noise ratio of 7.1 measured on the N-acetylaspartate peak.
Updating semantic information to support coordination in distributed software development environments (2002)

The authors address the coordination problem that arises when a group of people develop software products cooperatively under distributed environments. They present a framework for applying attribute grammars to construct distributed software environments. In the framework, a class of software products and their semantic information are specified in a rule-based and functional way. A software product instance and its associated information are represented as a set of attributed subtrees which are distributed across workstations. A data structure called internal compressed dependency graph and a distributed attribute evaluation algorithm are introduced for realizing efficient and fault-tolerant information updating. Since the framework tolerates network failures, the cooperative development can be carried out even when the connecting network is unreliable.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Potassium Channel-blockers as Therapeutic Agents to Interfere with Bone Resorption of Periodontal Disease (2005)

AICD, activation-induced cell death; APC, antigen-presenting cells; B(K), large conductance; CRAC, calcium release-activated calcium channels; DC, dendritic cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IFN-gamma, interferon-gamma; IP(3), inositol (1,4,5)-triphosphate; (K)ir, inward rectifier; JNK, c-Jun N-terminal kinase; I(K), intermediate conductance; LPS, lipopolysaccharide; L, ligand; MCSF, macrophage colony-stimulating factor; MHC, major histocompatibility complex; NFAT, nuclear factor of activated T-cells; RANK, receptor activator of nuclear factor-kappaB; T(CM), central memory T-cells; T(EM), effector memory T-cells; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; OPG, osteoprotegerin; Omp29, 29-kDa outer membrane protein; PKC, protein kinase C; PLC, phospholipase C; RT-PCR, reverse-transcriptase polymerase chain-reaction; S(K), small conductance; TCR, T-cell receptor; and (K)v, voltage-gated.
Scanning Mutagenesis of ω-Atracotoxin-Hv1a Reveals a Spatially Restricted Epitope That Confers Selective Activity against Insect Calcium Channels (2004)

We constructed a complete panel of alanine mutants of the insect-specific calcium channel blocker omega-atracotoxin-Hv1a. Lethality assays using these mutant toxins identified three spatially contiguous residues, Pro10, Asn27, and Arg35, that are critical for insecticidal activity against flies (Musca domestica) and crickets (Acheta domestica). Competitive binding assays using radiolabeled omega-atracotoxin-Hv1a and neuronal membranes prepared from the heads of American cockroaches (Periplaneta americana) confirmed the importance of these three residues for binding of the toxin to target calcium channels presumably expressed in the insect membranes. At concentrations up to 10 microm, omega-atracotoxin-Hv1a had no effect on heterologously expressed rat Cav2.1, Cav2.2, and Cav1.2 calcium channels, consistent with the previously reported insect selectivity of the toxin. 30 microm omega-atracotoxin-Hv1a inhibited rat Cav currents by 10-34%, depending on the channel subtype, and this low level of inhibition was essentially unchanged when Asn27 and Arg35, which appears to be critical for interaction of the toxin with insect Cav channels, were both mutated to alanine. We propose that the spatially contiguous epitope formed by Pro10, Asn27, and Arg35 confers specific binding to insect Cav channels and is largely responsible for the remarkable phyletic selectivity of omega-atracotoxin-Hv1a. This epitope provides a structural template for rational design of chemical insecticides that selectively target insect Cav channels.
Omega 3 Fatty Acids in Bipolar Disorder (1999)

Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. (1988)

We developed a method for immunoaffinity purification of Saccharomyces cerevisiae adenylyl cyclase based on creating a fusion with a small peptide epitope. Using oligonucleotide technology to encode the peptide epitope we constructed a plasmid that expressed the fusion protein from the S. cerevisiae alcohol dehydrogenase promoter ADH1. A monoclonal antibody previously raised against the peptide was used to purify adenylyl cyclase by affinity chromatography. The purified enzyme appeared to be a multisubunit complex consisting of the 200-kilodalton adenylyl cyclase fusion protein and an unidentified 70-kilodalton protein. The purified protein could be activated by RAS proteins. Activation had an absolute requirement for a guanine nucleoside triphosphate.
论“资本主义中心”国家和“发展中的外围”国家的相互关系 (1990)

《和平与社会主义问题》杂志1989年第6期刊登了黎巴嫩共产党中央政治局委员P.萨姆洪就“资本主义中心”国家和“发展中的外围”国家的相互关系问题回答该刊编辑B.加夫里洛夫的提问,摘译如下。