gebhart/patrepeval huggingface dataset:
The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated. (1995)

The envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) were found to be modified by fatty acylation of the transmembrane protein subunit gp41. The precursor gp160 was also palmitoylated prior to its cleavage into the gp120 and gp41 subunits. The palmitic acid label was sensitive to treatment with hydroxylamine or 2-mercaptoethanol, indicating that the linkage is through a thioester bond. Treatment with cycloheximide did not prevent the incorporation of [3H]palmitic acid into the HIV envelope protein, indicating that palmitoylation is a posttranslation modification. In contrast to other glycoproteins, which are palmitoylated at cysteine residues within or close to the membrane-spanning hydrophobic domain, the palmitoylation of the HIV-1 envelope proteins occurs on two cysteine residues, Cys-764 and Cys-837, which are 59 and 132 amino acids, respectively, from the proposed membrane-spanning domain of gp41. Sequence comparison revealed that one of these residues (Cys-764) is conserved in the cytoplasmic domains of almost all HIV-1 isolates and is located very close to an amphipathic region which has been postulated to bind to the plasma membrane.
Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21waf1/cip1 (1998)

These data suggest that micromolar concentrations of tamoxifen inhibit prostate cancer cell growth by inhibition of PKC, resulting in induction of the p21(waf1/cip1) protein.
An Electrophysiological Analysis of the Anticonvulsant Action of Cannabidiol on Limbic Seizures in Conscious Rats (1979)

The effects of cannabidiol (CBD) on electrically evoked kindled seizures were studied in conscious, unrestrained rats with chronically implanted cortical and limbic electrodes, and the results were compared with those of delta 9-tetrahydrocannabinol (delta 9-THC), phenytoin (PHT), and ethosuximide (ESM). All drugs were anticonvulsant, but there were marked differences in their effects on afterdischarge (AD) threshold, duration, and amplitude. CBD, like PHT and delta 9-THC, elevated the AD threshold; in contrast, ESM decreased the threshold but suppressed AD spread. CBD, however, also resembled ESM inasmuch as both drugs decreased AD duration and amplitude. Electrophysiologically, the antiseizure effects of CBD were a combination of those of PHT and ESM. The combination of effects may account for the observation that CBD was the most efficacious of the drugs tested against limbic ADs and convulsions. Other properties of CBD were also noted: For example, compared with delta 9-THC, it is a much more selective anticonvulsant vis-à-vis motor toxicity. CBD also lacks the CNS excitatory effects produced by delta 9-THC, PHT, and ESM. These characteristics, combined with its apparently unique set of electrophysiological properties, support the suggestion that CBD has therapeutic potential as an antiepileptic.
Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1α–initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine–Chemokine Axis (1999)

The impact of lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-alpha-initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1-10 nM, the LXA4 and ATL analogues each inhibited TNF-alpha-stimulated superoxide anion generation and IL-1beta release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-alpha, as these responses were not altered with either GM-CSF- or zymosan-stimulated cells. TNF-alpha-induced IL-1beta gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-alpha-stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1beta, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-alpha-directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.
Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system (2010)

Botulinum neurotoxins (BoNTs) are the most potent natural toxins known. The effects of BoNT serotype A (BoNT/A) can last several months, whereas the effects of BoNT serotype E (BoNT/E), which shares the same synaptic target, synaptosomal-associated protein 25 (SNAP25), last only several weeks. The long-lasting effects or persistence of BoNT/A, although desirable for therapeutic applications, presents a challenge for medical treatment of BoNT intoxication. Although the mechanisms for BoNT toxicity are well known, little is known about the mechanisms that govern the persistence of the toxins. We show that the recombinant catalytic light chain (LC) of BoNT/E is ubiquitylated and rapidly degraded in cells. In contrast, BoNT/A LC is considerably more stable. Differential susceptibility of the catalytic LCs to ubiquitin-dependent proteolysis therefore might explain the differential persistence of BoNT serotypes. In this regard we show that TRAF2, a RING finger protein implicated in ubiquitylation, selectively associates with BoNT/E LC and promotes its proteasomal degradation. Given these data, we asked whether BoNT/A LC could be targeted for rapid proteasomal degradation by redirecting it to characterized ubiquitin ligase domains. We describe chimeric SNAP25-based ubiquitin ligases that target BoNT/A LC for degradation, reducing its duration in a cellular model for toxin persistence.
65 Gbits/in.2 quantum magnetic disk (abstract) (1996)

Quantum magnetic disk (QMD), proposed recently, offers a new paradigm for ultrahigh density magnetic recording. In a QMD, each bit is represented by a prepatterned nanoscale single-domain magnetic pillar or bar that was uniformly embedded in a nonmagnetic material on a disk. The size and shape of each bit is well controlled during the fabrication to ensure single magnetic domain formation, therefore the magnetic moment of each bit has only two quantized states: equal in magnitude but opposite in direction. Compared to conventional magnetic disks, the QMD offers many unique advantages in writing, reading, and tracking. In this article, we report the fabrication of both longitudinal and perpendicular magnetization QMDs and their investigation with scanning electron microscopy, atomic force microscopy, and magnetic force microscopy. Both QMDs were fabricated using electron beam nanolithography, reactive ion etching, and chemical mechanical polishing. We will also discuss QMD fabrication techniques which do not involve conventional lithography. The perpendicular QMD structure consists of 50-nm-diam nickel pillars uniformly embedded in 200 nm thick SiO2 with a surface roughness of 0.5 nm rms. The pillar array has a period of 100 nm which corresponds to a magnetic storage density of 65 Gbits/in2—over two orders of magnitude greater than the current state-of-the-art magnetic storage density.
Maintenance of remission in patients with ulcerative colitis with once- or twice-daily MMX™ mesalazine: results of an international multicentre randomised trial (2008)

Introduction: MMX Multi Matrix System® (MMX) mesalazine (MEZAVANT™; MEZAVANT™ XL [UK and Ireland]; LIALDA™ [USA]) is a once daily, high-strength (1.2g/tablet), prolonged-release formulation of 5-aminosalicylic acid (5-ASA). In this study, the safety and efficacy of MMX mesalazine when dosed once or twice daily, was evaluated in patients whose ulcerative colitis (UC) was in remission.
Preparation and Purification of an End to End Coupled mEGF−Dextran Conjugate (1997)

The amino terminus of mouse epidermal growth factor (mEGF) was coupled directly to the aldehyde end of dextran through a reductive amination procedure. The highest coupling efficiency was approximately 80% and could be reached after approximately 24 h of reaction time at pH 8. Gel filtration on Sephadex G-50 Fine removed free mEGF from the conjugate. Preparative polyacrylamide gel electrophoresis was used to separate the conjugate from excess noncharged dextran. The conjugate bound specifically to the EGF receptor on cultured glioma cells as shown in displacement tests with free mEGF. The conjugate was stable in the pH interval 4-9, in 2 M sodium chloride, in 7 M urea, and in human serum and could still bind to the EGF receptor after such treatments. The conjugates are candidates for targeted nuclide therapy.
Characterization of Self-Assembled Organic Films Using Differential Charging in X-ray Photoelectron Spectroscopy (2006)

Differential charging is often regarded as a problem in X-ray photoelectron spectroscopic studies, especially for insulating or partially conducting samples. Application of a positive bias can reduce the effect of differential charging by attracting stray electrons from the system, thereby compensating for the electron loss. On the other hand, differential charging effect can be enhanced by the application of a negative bias to the sample during spectrum acquisition. The successful use of the differential charging technique to distinguish between multi- and monolayer organophosphonate films on oxide-covered silicon has been reported. A detailed description of this technique is now presented which shows how differential charging can be used as an important tool for the characterization of self-assembled films deposited on various surfaces. The dependence of this technique on the conductivity of the substrate has been investigated by studying the spectral behavior of the deposited films of phosphonic acid on conducting, semiconducting, and insulating samples (stainless steel, silicon, and glass). Application of either positive or negative dc electrical bias affects the carbon core-level (C1s) line shape and intensity, which is dependent on the atom's physical location above the surface.
Saving and Empowering Young Lives in Europe (SEYLE): a randomized controlled trial (2010)

The German Clinical Trials Register, DRKS00000214.
T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38‐kDa antigen in patients with active disease (1992)

It is generally accepted that both host protection and pathogenic reactions in tuberculosis are mediated by T lymphocytes. However, little is known about the structures and discreet functions of epitopes stimulating the immune response. In this study, proliferative responses of blood T lymphocytes to synthetic peptides derived from the sequence of the 38-kDa antigen from Mycobacterium tuberculosis have been investigated in 41 healthy individuals and in 36 patients with active tuberculosis. Of the healthy purified protein derivative (PPD)-positive donors, 90% responded to a permissively recognized peptide, 38.G (residues 350-359), located at the carboxy terminus of the molecule. Four other permissively recognized epitopes of this molecule (38.A, 38.I, 38.E, 38.K) were stimulatory for more than 50% of healthy PPD-positive individuals. Patients with lymphatic tuberculosis responded to these peptides in a similar manner. In contrast, we observed a selective anergy to stimulation with peptide 38.G in the majority of patients with pulmonary (11% responders) and nonlymphatic extrapulmonary tuberculosis (25% responders). The lack of responsiveness to 38.G was epitope specific since the degree of responsiveness to the other four permissively recognized peptide epitopes was similar for patients and PPD-positive controls. Using the PEPSCAN technology and truncated peptides, the core epitope of 38.G was localized to a peptide 10 amino acids long (HFQPLPPAVV). This minimal structure was capable of inducing a proliferative response in all healthy 38.G responders tested. The mechanisms influencing this epitope-specific anergy in patients could give new insights into the immunopathogenesis of tuberculosis.
The Role of the Amadori Product in the Complications of Diabetes (2008)

Strong evidence has emerged in recent years in support of an association between advanced glycation and the complications of diabetes, whereby both glycoxidation products and oxoaldehydes have been implicated. In contrast, except for the fact that skin collagen-linked fructosamine (Amadori product) is a strong predictor of the risk of progression of microvascular disease in humans, Amadori products have not been associated with complications in most animal experiments. Below we develop the hypothesis that glucose-derived advanced glycation end products (AGEs), such as glucosepane, may inflict sustained damage to the extracellular matrix in diabetes and contribute to tissue stiffening and accelerated sclerosis in arteries, kidneys, and other organs as supported by immunochemical studies using a glucosepane antibody. We also hypothesize that many more structures derived from Amadori products with nucleophiles, such as primary amines and thiols, are expected. The selective prevention of Amadori-derived AGEs using deglycating enzymes would be desirable. However, x-ray diffraction studies of Amadoriase I crystals show that the active site of the enzyme is deeply embedded, explaining why this approach is unlikely to succeed in vivo. Preliminary experiments with nucleophiles show that aminoguanidine and other compounds block glucosepane in vitro.
Novel Aspects of Oxidative Stress in Cardiovascular Diseases (2009)

Oxygen radicals, and other reactive oxygen species, may play an important role in the pathophysiology of atherosclerosis, stroke, and other cardiovascular diseases. Mechanisms that account for oxidative stress in different cardiovascular diseases are diverse; for example, increases in activity of NAD(P)H oxidase, "uncoupling" of nitric oxide synthase, and maladaptive changes in expression of antioxidants can all contribute to increases in oxidative stress. Very different patterns of pro-and antioxidant mechanisms that contribute to increases in oxygen radicals in atherosclerotic plaques, hemorrhagic strokes, and aortic valve stenosis have been observed. A disappointment, in relation to the hypothesis that oxygen radicals contribute to cardiovascular risk, is that many studies indicate that antioxidant vitamins fail to reduce the risk of cardiovascular disease. Better understanding of mechanisms that lead to increases in oxidative stress in different cardiovascular diseases may lead to more effective antioxidant prevention or treatment of diseases.
Comparison of different analytical methods for assessing total antioxidant capacity of human serum (1998)

Three assays were compared for the determination of total antioxidant capacity in human serum: the oxygen radical absorbance capacity (ORAC) assay, the Randox Trolox-equivalent antioxidant capacity (Randox-TEAC) assay, and the ferric reducing ability (FRAP) assay. There was a weak but significant linear correlation between serum ORAC and serum FRAP. There was no correlation either between serum ORAC and serum TEAC or between serum FRAP and serum TEAC. The effect of dilution on the serum TEAC value and the use of inhibition percentage at a fixed time, without considering the length of inhibition time in the quantitation of results, adversely affected the Randox-TEAC assay. The FRAP assay is simple and inexpensive but does not measure the SH-group-containing antioxidants. The ORAC assay has high specificity and responds to numerous antioxidants. By utilizing different extraction techniques in the ORAC assay, one can remove serum proteins and also make some gross differentiation between aqueous and lipid-soluble antioxidants. However, the ORAC assay requires approximately 60 min more than the FRAP or Randox-TEAC assay to quantitate results.
Fine-grained adaptive biased locking (2011)

Mutual-exclusion locking is the prevailing technique for protecting shared resources in concurrent programs. Fine-grained locking maximizes the opportunities for concurrent execution while preserving correctness, but increases both the number of locks and the frequency of lock operations. Adding to the frequency of these operations is the practice of using locks defensively --- such as in library code designed for use in both concurrent and single-threaded scenarios. If the library does not protect itself with locks, an engineering burden is placed on the library's users; if the library does use locks, it punishes those who use it only from a single thread. Biased locking is a dynamic protocol for eliminating this trade-off, in which the underlying run-time system optimizes lock operations by biasing a lock to a specific thread when the lock is dynamically found to be thread-local. Biased locking protocols are distinguished by how many opportunities for optimization are found, and what performance trade-offs for non-local locks are experienced. Of particular concern is the relatively high cost involved in revoking the bias of a lock, which makes existing biased locking protocols susceptible to performance pathologies for programs with specific patterns of contention.
评《保罗·萨缪尔森与现代经济理论》 (1988)

保罗·萨缪尔森同本文集作者们的交往是多方面的:作为一位学者,萨缪尔森极大地改变了经济分析的方法;作为一位教师,他使许多课程变得有血有肉,并促进了经济研究;同时,他又是某些作者的同窗,或如萨缪尔森本人所言,是战壕中的战友;他还是另外一些作者的乐于助人的同事,一位热心和大方的朋友。因为保罗是这样独恃的人,我们认为写一组文章赞扬他在经济分析的各个领域所作的诸多贡献,将成为献给他的一件别致的礼物——为这位已经拥有了一切的人再增加一件东西。1940年,萨缪尔森刚刚结束了在哈佛大学担任初级研究员的三年任期,这是一个他称之为“黄金般的和富有创造力的”时期。那
Genome-Wide Identification of S accharomyces cerevisiae Genes Required for Maximal Tolerance to Ethanol (2009)

The understanding of the molecular basis of yeast resistance to ethanol may guide the design of rational strategies to increase process performance in industrial alcoholic fermentations. In this study, the yeast disruptome was screened for mutants with differential susceptibility to stress induced by high ethanol concentrations in minimal growth medium. Over 250 determinants of resistance to ethanol were identified. The most significant gene ontology terms enriched in this data set are those associated with intracellular organization, biogenesis, and transport, in particular, regarding the vacuole, the peroxisome, the endosome, and the cytoskeleton, and those associated with the transcriptional machinery. Clustering the proteins encoded by the identified determinants of ethanol resistance by their known physical and genetic interactions highlighted the importance of the vacuolar protein sorting machinery, the vacuolar H(+)-ATPase complex, and the peroxisome protein import machinery. Evidence showing that vacuolar acidification and increased resistance to the cell wall lytic enzyme beta-glucanase occur in response to ethanol-induced stress was obtained. Based on the genome-wide results, the particular role of the FPS1 gene, encoding a plasma membrane aquaglyceroporin which mediates controlled glycerol efflux, in ethanol stress resistance was further investigated. FPS1 expression contributes to decreased [(3)H]ethanol accumulation in yeast cells, suggesting that Fps1p may also play a role in maintaining the intracellular ethanol level during active fermentation. The increased expression of FPS1 confirmed the important role of this gene in alcoholic fermentation, leading to increased final ethanol concentration under conditions that lead to high ethanol production.
Polymer-stabilized optically isotropic liquid crystals for next-generation display and photonics applications (2011)

Polymer-stabilized optically isotropic liquid crystals, including blue phases, are emerging as a strong contender for next-generation display technology because they exhibit some revolutionary features such as no need for surface alignment, submillisecond response time, isotropic dark state, and cell gap insensitivity. The basic material properties, including electric field-induced birefringence, dispersion relation of Kerr constant, and temperature dependent Kerr constant, are reviewed. Recent progress on blue phase liquid crystal material development and device structures for lowering the operating voltage are introduced. Promising applications and remaining technical challenges are also discussed.
Clustered syk tyrosine kinase domains trigger phagocytosis. (1996)

Phagocytosis is a phylogenetically primitive mechanism adapted by specialized cells of the immune system to ingest particulate pathogens. Recent evidence suggests that the program of specific cytoskeletal rearrangements that underlies phagocytosis may share elements with the antigen receptor signaling pathway in lymphocytes. Tyrosine phosphorylation, necessary for both lymphocyte effector function and phagocytosis, is thought to allow cytoskeletal elements to couple to the intracellular domains of antigen and Fc receptor subunits. We show here that the intracellular domains of the receptors are not inherently required for cytoskeletal coupling. Chimeric transmembrane proteins bearing syk but not src family tyrosine kinase domains are capable of autonomously triggering phagocytosis and redistribution of filamentous actin in COS cells. These responses cannot be initiated by a receptor chimera bearing a point mutation in the syk catalytic domain, and the kinase domain alone is sufficient for initiating cytoskeletal coupling.
Identification of CHIP, a Novel Tetratricopeptide Repeat-Containing Protein That Interacts with Heat Shock Proteins and Negatively Regulates Chaperone Functions (1999)

The chaperone function of the mammalian 70-kDa heat shock proteins Hsc70 and Hsp70 is modulated by physical interactions with four previously identified chaperone cofactors: Hsp40, BAG-1, the Hsc70-interacting protein Hip, and the Hsc70-Hsp90-organizing protein Hop. Hip and Hop interact with Hsc70 via a tetratricopeptide repeat domain. In a search for additional tetratricopeptide repeat-containing proteins, we have identified a novel 35-kDa cytoplasmic protein, carboxyl terminus of Hsc70-interacting protein (CHIP). CHIP is highly expressed in adult striated muscle in vivo and is expressed broadly in vitro in tissue culture. Hsc70 and Hsp70 were identified as potential interaction partners for this protein in a yeast two-hybrid screen. In vitro binding assays demonstrated direct interactions between CHIP and both Hsc70 and Hsp70, and complexes containing CHIP and Hsc70 were identified in immunoprecipitates of human skeletal muscle cells in vivo. Using glutathione S-transferase fusions, we found that CHIP interacted with the carboxy-terminal residues 540 to 650 of Hsc70, whereas Hsc70 interacted with the amino-terminal residues 1 to 197 (containing the tetratricopeptide domain and an adjacent charged domain) of CHIP. Recombinant CHIP inhibited Hsp40-stimulated ATPase activity of Hsc70 and Hsp70, suggesting that CHIP blocks the forward reaction of the Hsc70-Hsp70 substrate-binding cycle. Consistent with this observation, both luciferase refolding and substrate binding in the presence of Hsp40 and Hsp70 were inhibited by CHIP. Taken together, these results indicate that CHIP decreases net ATPase activity and reduces chaperone efficiency, and they implicate CHIP in the negative regulation of the forward reaction of the Hsc70-Hsp70 substrate-binding cycle.