gebhart/patrepeval huggingface dataset:
The glutamate dehydrogenase gene of Clotridium symbiosum (1992)

The gene encoding the NAD(+)-dependent glutamate dehydrogenase (GDH) of Clostridium symbiosum was cloned using the polymerase chain reaction (PCR) because it could not be recovered by standard techniques. The nucleotide sequence of the gdh gene was determined and it was overexpressed from the controllable tac promoter in Escherichia coli so that active clostridial GDH represented 20% of total cell protein. The recombinant plasmid complemented the nutritional lesion of an E. coli glutamate auxotroph. There was a marked difference between the nucleotide compositions of the coding region (G + C = 52%) and the flanking sequences (G + C = 30% and 37%). The structural gene encoded a polypeptide of 450 amino acid residues and relative molecular mass (M(r) 49,295 which corresponds to a single subunit of the hexameric enzyme. The DNA-derived amino acid sequence was consistent with a partial sequence from tryptic and cyanogen bromide peptides of the clostridial enzyme. The N-terminal amino acid sequence matched that of the purified protein, indicating that the initiating methionine is removed post-translationally, as in the natural host. The amino acid sequence is similar to those of other bacterial GDHs although it has a Gly-Xaa-Gly-Xaa-Xaa-Ala motif in the NAD(+)-binding domain, which is more typical of the NADP(+)-dependent enzymes. The sequence data now permit a detailed interpretation of the X-ray crystallographic structure of the enzyme and the cloning and expression of the clostridial gene will facilitate site-directed mutagenesis.
Broad-Range and Binary-Range Acyl-Acyl-Carrier-Protein Thioesterases Suggest an Alternative Mechanism for Medium-Chain Production in Seeds (1997)

In the current model of medium-chain (C8-14) fatty acid biosynthesis in seeds, specialized FatB acyl-acyl-carrier-protein (ACP) thioesterases are responsible for the production of medium chains. We have isolated and characterized FatB cDNAs from the maturing seeds of elm (Ulmus americana) and nutmeg (Myristica fragrans), which accumulate predominantly caprate (10:0)- and myristate (14:0)-containing oils, respectively. In neither species were we able to find cDNAs encoding enzymes specialized for these chain lengths. Nutmeg FatB hydrolyses C14-18 substrates in vitro and expression in Brassica napus seeds leads to an oil enriched in C14-18 saturates. Elm FatB1 displays a binary specificity: one activity is centered on 10:0-ACP, and a second is centered on palmitate (16:0)-ACP. After expression in B. napus seeds the oil is enriched in C10-18 saturates, predominantly 16:0, 14:0, and 10:0. The composition of free fatty acids produced by elm FatB1 in Escherichia coli shifts from C14-16 to mostly C8-10 by increasing the rate of chain termination by this enzyme. These results suggest the existence of an alternative mechanism used in the evolution of medium-chain production, a model of which is presented.
Crystallization analysis fractionation: A new technique for the analysis of branching distribution in polyolefins (1994)

Abstract A new technique to analyze the short‐chain branching distribution (SCBD) in linear lowdensity polyethylene has been developed. The technique referred as crystallization analysis fractionation is based on a stepwise precipitation approach. By monitoring the polymer solution concentration during crystallization, the cumulative and differential SCBD can be obtained without the need of physical separation of fractions. The new technique has been shown to provide similar results to temperature rising elution fractionation but in a shorter time and with a simplified apparatus. It allows the simultaneous analysis of various samples and could also be used for analysis of polypropylene and other semicrystalline polymers that can be fractionated on the basis of crystallizability. © 1994 John Wiley &amp; Sons, Inc.
Silo: Predictable Message Completion Time in the Cloud (2013)

Many cloud applications need predictable completion of application tasks. To achieve this, they require predictable completion time for network messages. We identify three key requirements for such predictability: guaranteed network bandwidth, guaranteed per-packet delay and guaranteed burst allowanace. We present Silo, a network architecture for public cloud datacenters that offers these guarantees. Silo leverages the fact that guaranteed bandwidth and delay are tightly coupled: controlling tenant bandwidth yields deterministic bounds on network queuing delay. Silo builds upon network calculus to determine how tenants with competing requirements can coexist, using a novel packet pacing mechanism to ensure the requirements are met. We have implemented a Silo prototype comprising a VM placement manager and a Windows Hyper-V network driver. Silo does not require any changes to applications, VMs and network switches. Through testbed experiments and large scale simulations, we show that Silo can ensure predictable message latency for competing applications in cloud datacenters.
A Transcriptively Active Complex of APP with Fe65 and Histone Acetyltransferase Tip60 (2001)

Amyloid-beta precursor protein (APP), a widely expressed cell-surface protein, is cleaved in the transmembrane region by gamma-secretase. gamma-Cleavage of APP produces the extracellular amyloid beta-peptide of Alzheimer's disease and releases an intracellular tail fragment of unknown physiological function. We now demonstrate that the cytoplasmic tail of APP forms a multimeric complex with the nuclear adaptor protein Fe65 and the histone acetyltransferase Tip60. This complex potently stimulates transcription via heterologous Gal4- or LexA-DNA binding domains, suggesting that release of the cytoplasmic tail of APP by gamma-cleavage may function in gene expression.
Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment (2018)

Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of proinflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the BM microenvironment and that the BM stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a<sup>+</sup> senescent BM stromal cells in vivo improved the survival of mice with leukemia. Next, we find that the leukemia-driven senescent tumor microenvironment is caused by AML-induced NOX2-derived superoxide. Finally, using the p16-3MR mouse model, we show that by targeting NOX2 we reduced BM stromal cell senescence and consequently reduced AML proliferation. Together, these data identify leukemia-generated NOX2-derived superoxide as a driver of protumoral p16INK4a-dependent senescence in BM stromal cells. Our findings reveal the importance of a senescent microenvironment for the pathophysiology of leukemia. These data now open the door to investigate drugs that specifically target the "benign" senescent cells that surround and support AML.
Effect of Pulse Pressure on Vascular Smooth Muscle Cell Migration: The Role of Urokinase and Matrix Metalloproteinase (1999)

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248+/-14%). Both u-PA and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti-u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7% for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.
The differential effects of EPA and DHA on cardiovascular risk factors (2011)

Compelling evidence exists for the cardioprotective benefits resulting from consumption of fatty acids from fish oils, EPA (20:5n-3) and DHA (22:6n-3). EPA and DHA alter membrane fluidity, interact with transcription factors such as PPAR and sterol regulatory element binding protein, and are substrates for enzymes including cyclooxygenase, lipoxygenase and cytochrome P450. As a result, fish oils may improve cardiovascular health by altering lipid metabolism, inducing haemodynamic changes, decreasing arrhythmias, modulating platelet function, improving endothelial function and inhibiting inflammatory pathways. The independent effects of EPA and DHA are poorly understood. While both EPA and DHA decrease TAG levels, only DHA appears to increase HDL and LDL particle size. Evidence to date suggests that DHA is more efficient in decreasing blood pressure, heart rate and platelet aggregation compared to EPA. Fish oil consumption appears to improve arterial compliance and endothelial function; it is not yet clear as to whether differences exist between EPA and DHA in their vascular effects. In contrast, the beneficial effect of fish oils on inflammation and insulin sensitivity observed in vitro and in animal studies has not been confirmed in human subjects. Further investigation to clarify the relative effects of consuming EPA and DHA at a range of doses would enable elaboration of current understanding regarding cardioprotective effects of consuming oily fish and algal sources of long chain n-3 PUFA, and provide clearer evidence for the clinical therapeutic potential of consuming either EPA or DHA-rich oils.
Statistical methods for analyzing immunosignatures (2011)

Based on this research, we lay out an analytic framework illustrating how immunosignatures may be useful as a general method for screening and presymptomatic screening of disease as well as antibody discovery.
Synergy between angiostatin and endostatin: inhibition of ovarian cancer growth. (2000)

Ovarian cancer is the leading cause of fatality among gynecological malignancies. Ovarian cancer growth is angiogenesis-dependent, and an increased production of angiogenic growth factors such as vascular endothelial growth factor is prognostically significant even during early stages of the disease. Therefore, we investigated whether antiangiogenic treatment can be used to inhibit the growth of ovarian cancer in an experimental model system. Mouse angiostatin (kringle 1-4) and endostatin were expressed in yeast. Purified angiostatin and endostatin were then used to treat established ovarian cancers in athymic mice. These studies showed that both angiostatin and endostatin inhibited tumor growth. However, angiostatin treatment was more effective in inhibiting ovarian cancer growth when compared with endostatin in parallel experiments. Residual tumors obtained from angiostatin- and endostatin-treated animals showed decreased number of blood vessels and, as a consequence, increased apoptosis of tumor cells. Subsequently, the efficacy of a combined treatment with angiostatin and endostatin was investigated. In the presence of both angiostatic proteins, endothelial cell proliferation was synergistically inhibited. Similarly, a combination regimen using equal amounts of angiostatin and endostatin showed more than additive effect in tumor growth inhibition when compared with treatment with individual angiostatic protein. These studies demonstrate synergism between two angiostatic molecules and that antiangiogenic therapy can be used to inhibit ovarian cancer growth.
美国社会科学研究处于困境:由于匮乏,还是密谋? (1984)

社会科学正处于困境之中。这在更大程度上可以这样说,但这不是从经济状况可以看出或可作为依据而得出的简单推断。我们知道,对于学术研究的开展,经费方面造成的威胁是十分明显的,虽然知识界对此还没有全面了解。单纯地解释为经费“匮乏”还说明不了造成这种困境的原因所在。还有另一些同样严重的威胁虽然不十分明显,但对我们合法地位的受到进一步损害和把研究成果应用于制定国家政策以及基础研究工作的开展等方面将产生严重深远的影响。此外,社会科学界获得信息的途径也受到限制,提供可靠数据的能力减弱了,当前一些公共研究私营化了,华盛顿的专业研究人员和同行评论家政治化了,宪法规定给予从事研究的
N-degron and C-degron pathways of protein degradation (2019)

This perspective is partly review and partly proposal. N-degrons and C-degrons are degradation signals whose main determinants are, respectively, the N-terminal and C-terminal residues of cellular proteins. N-degrons and C-degrons include, to varying extents, adjoining sequence motifs, and also internal lysine residues that function as polyubiquitylation sites. Discovered in 1986, N-degrons were the first degradation signals in short-lived proteins. A particularly large set of C-degrons was discovered in 2018. We describe multifunctional proteolytic systems that target N-degrons and C-degrons. We also propose to denote these systems as "N-degron pathways" and "C-degron pathways." The former notation replaces the earlier name "N-end rule pathways." The term "N-end rule" was introduced 33 years ago, when only some N-terminal residues were thought to be destabilizing. However, studies over the last three decades have shown that all 20 amino acids of the genetic code can act, in cognate sequence contexts, as destabilizing N-terminal residues. Advantages of the proposed terms include their brevity and semantic uniformity for N-degrons and C-degrons. In addition to being topologically analogous, N-degrons and C-degrons are related functionally. A proteolytic cleavage of a subunit in a multisubunit complex can create, at the same time, an N-degron (in a C-terminal fragment) and a spatially adjacent C-degron (in an N-terminal fragment). Consequently, both fragments of a subunit can be selectively destroyed through attacks by the N-degron and C-degron pathways.
Innovative antifibrotic therapies in systemic sclerosis (2012)

Many antifibrotic candidate therapies have proven efficacy and tolerability in preclinical models of SSc. So far, early clinical studies have tested only few of these agents. Besides discovering novel molecular treatment strategies, SSc research will now have to translate its findings into clinical practice.
Detector optimization at CEPC (2016)

The detector optimization is a critical task in the design of the CEPC detector to ensure that the physics goals of the CEPC project will be achieved. On one hand, in order to make the best use of all Higgs bosons generated at CEPC, the detector design should consider high-efficiency reconstruction and precision measurement of all the physics objects including leptons and jets, and of other key spatial and kinematic variables including the displaced vertices, charged track trajectories, missing energy and momentum of jets. . On the other hand, the cost and the operation of the detector , such as power consuming and active cooling, should also be taken into account. Starting from a baseline that follows the ILD detector design, a series of detector optimization studies have been performed. This report will summarize the progresses and results.
Characterization of the targeted nuclear accumulation of GFP within the cells of transgenic plants (1997)

The soluble proteins of the nucleoplasm are synthesized on cytoplasmic ribosomes. Proteins larger than about 40 kDa are post‐translationally targeted to the nucleus via energy‐dependent processes, passing through the nuclear pore complex into the nucleoplasm. Targeting involves nuclear localization signals (NLSs) found within the primary sequences of the imported proteins. In higher plants, information has come primarily from study of proteins carrying ‘classical’ NLSs, comprising stretches of basic amino acids, and has required assays to measure nuclear uptake both in vitro and in vivo . In general, these assays are not entirely satisfactory; they are either technically demanding, are of limited accuracy and statistical rigor, or are unsuitable for in vivo applications.
Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers (2006)

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.
Micropatterning of Copper on a Poly(ethylene terephthalate) Substrate Modified with a Self-Assembled Monolayer (2005)

We have developed a technique for the site-selective electroless deposition of Cu on poly(ethylene terephthalate) (PET) substrate modified with an organic self-assembled monolayer (SAM). The PET substrate was first modified with a silica-like layer by being dip-coated in an acetone solution of 3-aminopropyltrimethoxysilane and treated with UV light. The PET substrate was further modified with thiol groups using a 3-mercaptopropyltrimethoxysilane-SAM and then irradiated by UV light through a photomask to prepare thiol-group regions and OH-group regions. Cu was then deposited on only the thiol-group regions of the substrate by electroless deposition in a neutral solution with no catalysts by using dimethylamineborane as a reducing reagent. This site-selective deposition process can control the deposition conditions by an organic thin film fabricated on a surface-modified PET substrate, and thus can be applied to other low heat-resistant substrates.
Comparing skin staples to sutures. (1989)

In a prospective randomized study, 52 lacerations requiring closure in the emergency department were either stapled or sutured. Six participating emergency physicians closed the wounds and recorded data about the laceration and the treatment provided. Patients visited their own family physicians for removal of the closures. Forty family physicians removed closures from 44 lacerations and reported follow-up data on discomfort levels, ease of closure removal, and cosmetic results. Lacerations were closed 2.7 times faster by the staple method (p<0.001), and there were no clinically significant differences between the two methods with respect to discomfort, infection rates, cosmetic result, or ease of removal. The staple device we used was more expensive than sutures. We concluded that the staple method of closure is safe, comfortable, and effective in the emergency department setting, and that the method's speed offsets its greater expense in some circumstances.
Phase II Study of Erlotinib (OSI-774) in Patients With Advanced Hepatocellular Cancer (2005)

Results of this trial suggest a benefit for EGFR/HER1 blockade with erlotinib in patients with HCC manifested by disease control. Additional studies with erlotinib as a single agent or in combination with other agents are warranted.
Clinical use of E. coli Nissle 1917 in inflammatory bowel disease (2008)

The probiotic Escherichia coli strain Nissle 1917 is in addition to some Lactobacilli sp. one of the best-studied probiotic strains. This particular E. coli strain was isolated in 1917 based on its potential to protect from presumably infectious gastroenteritis. Initial therapeutic success was noted in the management of gastrointestinal infectious disorders and infections affecting the urinary tract; the focus shifted later to chronic inflammatory conditions. The unique combination of fitness and survival factors to support intestinal survival, the lack of virulence, and obvious probiotic properties make this microorganism a safe and effective candidate in the treatment of chronic inflammatory bowel diseases. Three large clinical trials have assessed the potential in the maintenance of remission of ulcerative colitis and equivalence to standard 5-ASA medication was documented. This review aims to discuss important mechanisms of E. coli Nissle 1917 and will review the available literature regarding treatment of inflammatory bowel diseases.
Stereoselective synthesis of pyrrolo[2,3‐d]pyrimidine α‐ and β‐D‐ribonucleosides from anomerically pure D‐ribofuranosyl chlorides: Solid‐Liquid Phase‐Transfer Glycosylation and 15N‐NMR Spectra (1988)

Abstract Solid‐liquid phase‐transfer glycosylation (KOH, tris[2‐(2‐methoxyethoxy)ethye]amine ( = TDA‐1), MeCN) of pyrrolo[2,3‐ d ]pyrimidines such as 3a and 3b with an equimolar amount of 5‐ O ‐[(1,1 ‐dimethylethyl)dimethylsilyl]‐2,3‐ O ‐(1‐methylethylidene)‐α‐ D ‐ribofuranosyl chloride (1) [6] gave the protected β‐ D ‐nucleosides 4a and 4b , respectively, stereoselectively (Scheme). The β‐ D ‐anomer 2 [6] yielded the corresponding α‐ D ‐nucleosides 5a and 5b with traces of the β‐ D ‐compounds. The 6‐substituted 7‐deazapurine nucleosides 6a , 7a , and 8 were converted into tubercidin (10) or its α‐ D ‐anomer (11) . Spin‐lattice relaxation measurements of anomeric ribonucleosides revealed that T 1 values of HC(8) in the α‐ D ‐series are significantly increased compared to HC(8) in the β‐ D ‐series while the opposite is true for T 1 of HC(1′). 15 N‐NMR data of 6‐substituted 7‐deazapurine D ‐ribofuranosides were assigned and compared with those of 2′‐deoxy compounds. Furthermore, it was shown that 7‐deaza‐2′deoxyadenosine ( = 2′‐deoxytubercidin; 12 ) is protonated at N(1), whereas the protonation site of 7‐deaza‐2′‐deoxyguanosine ( 20 ) is N(3).