gebhart/patrepeval huggingface dataset:
Receptor (SLAM [CD150]) Recognition and the V Protein Sustain Swift Lymphocyte-Based Invasion of Mucosal Tissue and Lymphatic Organs by a Morbillivirus (2006)

Experimental infections of ferrets with canine distemper virus (CDV) recapitulate many hallmarks of measles: rash, high fever, viremia, depression of delayed-type hypersensitivity responses, lowered leukocyte counts, and reduced lymphocyte proliferation activity. To understand how a morbillivirus invades the host and causes immunosuppression, we generated CDV either unable to recognize one of the receptors or incapable of expressing either one or both of the candidate interferon antagonist proteins V and C. Variants of these viruses expressing green fluorescent protein were also generated. Striking similarities between CDV infection of ferrets and human immunodeficiency virus host invasion were documented: first, massive early replication in the gut-associated lymphatic tissue, including intestinal Peyer's patches, followed by extensive infection of lymphatic organs, including thymus and circulating lymphocytes. Moreover, T cells were selectively depleted. Thus, CDV takes advantage of mucosal surfaces for host invasion and lymphocytes for swift dissemination. A CDV unable to recognize the signaling lymphocytic activation molecule (SLAM [CD150]) that is expressed in lymphocytes and other immune cells did not spread. A V-defective CDV multiplied with reduced efficiency in lymphocytes and did not inhibit the interferon and cytokine responses. Protein C affected the severity of rash and digestive symptoms elicited by V-defective CDV, but it was dispensable for the invasion of the lymphatic organs. These findings prove formally that SLAM recognition is necessary for morbillivirus virulence. They also reveal how two viral proteins affect pathogenesis: V sustains the swift lymphocyte-based invasion of mucosal tissue and lymphatic organs, whereas C sustains subsequent infection phases.
A role for mitogen‐activated protein kinases in the etiology of diabetic neuropathy (2001)

The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen-activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin-induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose-induced oxidative stress.
100ml 机舱“面子问题” (2008)

今年3月14日,民航总局发布了《关于禁止旅客随身携带液态物品乘坐国内航班的公告》,该公告调整了旅客随身携带液态物品乘坐国内航班的相关规定。其中,针对旅客携带的化妆品也做出了规定:每种化妆品限带一件,其容器容积不得超过100ml,并应置于独立袋内,接受开瓶检查。相信很多注重保养的旅客不免都要皱起了眉头。其实,100ml 照样可以搞定机舱内的皮肤保养工作。
Stargardt's Disease and Fundus Flavimaculatus (1979)

A study of 67 patients with a diagnosis of Stargardt's disease (juvenile macular degeneration) or fundus flavimaculatus showed that, apart from the ophthalmoscopic appearance, there is no clear distinction between these two disorders. The disease is an autosomal recessive macular degeneration that is bilateral and symmetrical in appearance, with diminished central vision as the hallmark symptom. The onset of symptoms usually occurred in the first or second decade, but a substantial number of patients were asymptomatic until the fourth or fifth decade. Psychophysical and electrophysiologic tests indicated that this is a localized and not a generalized retinal dystrophy. While the initial vision in the better eye was 6/12 (20/40) or better in one third of the patients, follow-up studies showed progression to levels between 6/30 (20/100) and 6/60 (20/400).
LE-ACS4, a fruit ripening and wound-induced 1-aminocyclopropane-1-carboxylate synthase gene of tomato (Lycopersicon esculentum). Expression in Escherichia coli, structural characterization, expression characteristics, and phylogenetic analysis. (1993)

ACC (1-aminocyclopropane-1-carboxylic acid) synthase is the key regulatory enzyme in the biosynthetic pathway of the plant hormone ethylene and is encoded by a highly divergent multigene family in tomato (Rottmann, W. H., Peter, G. F., Oeller, P. W., Keller, J. A., Shen, N. F., Nagy, B. P., Taylor, L. P., Campbell, A. D., and Theologis, A. (1991) J. Mol. Biol. 222, 937-961). Two members of the family, LE-ACS2 and LE-ACS4, are induced during fruit ripening and upon treatment of mature green fruits with exogenous ethylene (C2H4) in a dose-dependent manner. Both genes are superinduced by wounding of pericarp tissue during various stages of ripening. The wound-induced accumulation of LE-ACS2 mRNA is more rapid and greater than that of LE-ACS4. Both mRNAs accumulate in the absence of protein synthesis, suggesting that their induction is a primary response to the inducer. The LE-ACS4 gene was isolated and structurally characterized. The function of the LE-ACS4 protein (53,509 Da, pI 5.4) was verified by expression experiments in Escherichia coli. The promoters of LE-ACS2 and LE-ACS4 contain potential cis-acting regulatory elements responsible for induction by ethylene, wounding, and anaerobiosis. In addition, elements for binding the transcriptional factors EmBP1, GBF-1, and OCSBF-1 are also present. Phylogenetic analysis of 20 ACC synthases from dicots and monocots indicate that the LE-ACS2 and LE-ACS4 proteins belong to an unique sublineage that includes an additional member of the tobacco family, NT-ACS1. The divergence of this sublineage is a relatively recent event in the evolution of ACC synthase protein.
Retinopathy of Coton de Tulear dogs: clinical manifestations, electroretinographic, ultrasonographic, fluorescein and indocyanine green angiographic, and optical coherence tomographic findings (2008)

Multifocal retinopathy of Coton de Tulear dogs is inherited as an autosomal recessive condition. The retinopathy manifests early in life as nonprogressive multifocal bullous retinal detachments. The blood ocular barrier remains intact. Photopic and scotopic electroretinography are minimally diminished compared to age-matched dogs.
Microscale Thermophoresis for the Assessment of Nuclear Protein-Binding Affinities (2013)

The rapid advance in our knowledge of cellular regulatory mechanisms, including those involving chromatin-based processes, stems in part from the development of biophysical techniques such as fluorescence spectroscopy, surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC). Despite their widespread utility, each of these techniques has its pros and cons, and new techniques are still required. Here we describe the application of microscale thermophoresis (MST), a novel technique based on thermophoresis, to characterize the binding between histone peptides and a histone chaperone protein, in free solution, with high sensitivity and low sample consumption.
Chiral separation of chiral compounds on cellulose chiral column by HPLC (2006)

The chiral separations of three chiral compounds were directly performed on polysaccharide-based chiral OJ-H.The influence of the mobile phase modifier and the structures and types of alcohol on the chiral separation were investigated.Results indicated that the chiral separation depends strongly upon hydrogen bonding and the π-π interaction between the analyte and CSP molecules.Moreover,the carbon number of the alcohol in the mobile phase also affects the retention and resolution of the chiral compound.
Circuit-level techniques for reliable Physically Uncloneable Functions (2009)

In this paper we study the effect of transistor supply voltage and body bias on the performance of ring oscillator Physically Uncloneable Functions (PUFs). The uniqueness (ability to identify a PUF) and reproducibility (ability to reproduce the same output) of PUFs increase drastically in the subthreshold region of operation. Also, the reproducibility of PUFs increase when the transistors are forward body biased. A ring oscillator PUF was tested and it achieved a uniqueness of 47.8% and reproducibility of 100% when operating at a supply voltage of 0.2 V. Compared to a base line configuration, our method improved the uniqueness by 18% and reproducibility by 7%. Therefore, apart from architectural optimizations, circuit level considerations like supply voltage and body bias can improve the reliability of PUFs.
Thermostabilization of the Neurotensin Receptor NTS1 (2009)

Structural studies on G-protein-coupled receptors have been hampered for many years by their instability in detergent solution and by the number of potential conformations that receptors can adopt. Recently, the structures of the beta(1) and beta(2) adrenergic receptors and the adenosine A(2a) receptor were determined in the antagonist-bound state, a receptor conformation that is thought to be more stable than the agonist-bound state. In contrast to these receptors, the neurotensin (NT) receptor NTS1 is much less stable in detergent solution. We have therefore used a systematic mutational approach coupled with activity assays to identify receptor mutants suitable for crystallization, both alone and in complex with the peptide agonist NT. The best receptor mutant NTS1-7m contained four point mutations. It showed increased stability compared to the wild-type receptor, in the absence of ligand, after solubilization with a variety of detergents. In addition, NTS1-7m bound to NT was more stable than unliganded NTS1-7m. Of the four thermostabilizing mutations, only one residue (A86L) is predicted to be in the lipid environment. In contrast, I260A appears to be buried within the transmembrane helix bundle, F342A may form a distant part of the putative ligand-binding site, whereas F358A is likely to be in a region that is important for receptor activation. NTS1-7m binds NT with a similar affinity for the wild-type receptor. However, agonist dissociation was slower, and NTS1-7m activated G-proteins poorly. The affinity of NTS1-7m for the antagonist SR48692 was also lower than that of the wild-type receptor. Thus, we have successfully stabilized NTS1 in an agonist-binding conformation that does not efficiently couple to G-proteins.
Apoptotic Activity and Mechanism of 2-Cyano-3,12-Dioxoolean-1,9-Dien-28-Oic-Acid and Related Synthetic Triterpenoids in Prostate Cancer (2008)

Synthetic triterpenoids 2-cyano-3, 12-dioxooleana-1, 9-(11)-dien-28-oic acid (CDDO) and CDDO-Me (CDDO-methyl ester) have entered clinical trials for cancer. We determined that CDDO analogues at submicromolar concentrations induce apoptosis of cultured prostate cancer cell lines, LNCaP, ALVA31, Du145, PC3, and PPC1, with lethal dose 50% approximately 1 micromol/L for CDDO-Me and an imidazole analogue (CDDO-Im). These compounds induced apoptosis of prostate cancer cells as characterized by cleavage of caspase-3, caspase-7, caspase-8, caspase-9, caspase-10, BID, and poly(ADP)ribose polymerase and by dependence on caspase activity. Moreover, triterpenoid-induced cell death was abolished by caspase-8-targeting small interfering (si) RNA. To explore the mechanism(s) involved in caspase-8 activation, we examined cell surface expression of death receptor (DR)4 and DR5 after triterpenoid treatment. Cell surface DR4 and DR5 expression was significantly up-regulated by CDDO or CDDO-Im but not by CDDO-Me. DR4 and DR5 knockdown with siRNA significantly inhibited apoptosis induced by CDDO and CDDO-Im but had no effect on CDDO-Me-induced killing, suggesting that CDDO and CDDO-Im induce apoptosis by a different mechanism than CDDO-Me. In addition to activating the caspase-8-dependent extrinsic apoptosis pathway, we observed that Bcl-X(L) overexpression inhibited triterpenoid-mediated killing of prostate cancer cell line Du145, suggesting that the intrinsic pathway (via mitochondria) also participates in triterpenoid-mediated killing. In vivo antitumor activity of CDDO-Me was shown using a Du145 tumor xenograft model in nude rats. Altogether, these findings suggest CDDO and related synthetic triterpenoids should be further evaluated as potential novel therapeutics for hormone refractory prostate cancers.
Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin (1996)

Photoreceptors of the Xenopus laevis retina are the site of a circadian clock. As part of a differential display screen for rhythmic gene products in this system, we have identified a photoreceptor-specific mRNA expressed in peak abundance at night. cDNA cloning revealed an open reading frame encoding a putative 388 amino acid protein that we have named "nocturnin" (for night-factor). This protein has strong sequence similarity to the C-terminal domain of the yeast transcription factor, CCR4, as well as a leucine zipper-like dimerization motif. Nocturnin mRNA levels exhibit a high amplitude circadian rhythm and nuclear run-on analysis indicates that it is controlled by the retinal circadian clock at the level of transcription. Our observations suggest that nocturnin may function through protein-protein interaction either as a component of the circadian clock or as a downstream effector of clock function.
Antibody–Cytotoxic Agent Conjugates: Preparation and Characterization (2008)

Conjugates of antibodies with cytotoxic agents offer a targeted therapeutic strategy against cancer cells expressing target antigens. Several antibodies against various cancer cell-surface antigens have been conjugated with different cytotoxic agents that inhibit essential cellular targets such as microtubules or DNA. Antibody-cytotoxic agent conjugates (ACCs) against several types of cancer are currently in advanced stages of clinical trials and one, gemtuzumab ozogamicin (Mylotarg), is approved for the treatment of acute myeloid leukemia. The linker group connecting the antibody to the cytotoxic agent is an important feature of the ACC, modulating the release of the active cytotoxic agent in the targeted cell. Several linker strategies employed for ACCs in current clinical trials include cleavable linkers with disulfide, hydrazone, lysosomal protease-substrate groups, and non-cleavable linkers. This chapter describes the methods of preparation of conjugates of antibodies with small-molecule cytotoxic agents (maytansinoids, calicheamicin, and auristatins) bearing different linkers. Methods to evaluate the in vitro cytotoxicity and in vivo anti-tumor efficacy of ACC are described in brief. Analytical methods are described to evaluate the mechanism of cellular processing of the ACCs with different linkers and the generation of the active metabolites.
Inhibition of Alzheimer's disease β‐amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: implications for Alzheimer's therapy (2001)

ABSTRACT Alzheimer's disease (AD) is a major public health problem, and there is currently no clinically accepted treatment to cure it or to stop its progression. Fibrillar aggregates of the β–amyloid peptide (Aβ) are major constituents of the senile plaques found in the brains of AD patients and have been related to AD neurotoxicity. Here it is shown that nitrophenols prevent aggregation and cause disaggregation of Aβ fibrils and that they strongly prevent the neurotoxicity of Aβ to rat hippocampal neurons in culture. Furthermore, by using an in vivo model system of cerebral amyloid deposition, it is shown that nitrophenols cause a marked reduction in the volume occupied by amyloid deposits in the hippocampi of rats. These results raise the possibility that nitrophenols or their derivatives may be useful lead compounds for the development of drugs to prevent the neurotoxicity and deposition of Aβ in AD.
Scaling Internet services by LinuxDirector (2000)

LinuxDirector is a software tool that directs network connections to multiple servers that share their workload, which can be used to build highly scalable and highly available services. LinuxDirector extends the TCP/IP stack of the Linux kernel to support three IP load balancing techniques, which can make parallel services of different kinds of server clusters to appear as a service on a single IP address. Four scheduling algorithms have been implemented to assign connections to different servers, and a simple distributed lock manager is provided for applications on different servers to access shared data consistently. Scalability is achieved by transparently adding or removing a node in the cluster and high availability is provided by detecting node or daemon failures and reconfiguring the system appropriately. This paper describes the design and implementation of LinuxDirector and presents several of its features including scalability, high availability, connection affinity and icmp handling.
A Novel Erasing Technology for 3.3V Flash Memory with 64Mb Capacity and Beyond (1992)

A novel erasing scheme has been develaped to suppress the distribution of the erased cell threshold voltage(erased-V,.J. The new 2-step erasing scheme consists of two step of the cell gate bias conditions, that is to apply I) negative high voltage on the control gate to erase the cell data, and successive 2) positive high voltage to inject a few electrons from the substrate back to the floating gate. The suppressing effect of the erased-V, distribution was also contiied using a 16K bit Flash memory cell array, the erased-V, distribution drastically decreases from 2.0V by the conventional erasing scheme to 0.9V using the 2-step erasing scheme.
Inhibition of adhesive activity of K88 fibrillae by peptides derived from the K88 adhesin (1987)

A cyanogen bromide fragment derived from the K88ab adhesin inhibited the hemagglutinating activity of K88 fibrillae. Smaller fragments which inhibited the adherence of K88 fibrillae to erythrocytes or to intestinal epithelial cells were obtained by digestion of K88ab fibrillae with alpha-chymotrypsin. Active peptides were isolated from the digestion mixture and identified as Ser-Leu-Phe and Ala-Ile-Phe. Both tripeptides correspond to the peptide stretches Ser-148-Leu-Phe-150 and Ala-156-Ile-Phe-158, respectively, which are part of conserved regions in the primary structure of the K88 variants ab, ac, and ad. The isolated tripeptides inhibited the hemagglutinating activity of purified K88 fibrillae in the 1 to 5 microM range, while adherence of the fibrillae to intestinal epithelial cell brush borders was inhibited in the 10 to 50 microM range. Furthermore, the tripeptides were capable of eluting attached bacteria from agglutinated erythrocytes. The inhibitory activity of the isolated peptides was confirmed by testing various synthetic peptides for their ability to inhibit the interaction of the different K88 variants with various species of erythrocytes. The significance of these findings for the localization of the receptor-binding domain is discussed.
Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib (‘Iressa’, ZD1839) in non-small-cell lung cancer (2004)

Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has demonstrated antitumour activity and favourable tolerability in Phase II studies. We investigated whether EGFR expression levels could predict for response to gefitinib in patients with advanced non-small-cell lung cancer (NSCLC), who received gefitinib (250 mg day(-1)) as part of a worldwide compassionate-use programme. Tissue samples were analysed by immunohistochemistry to assess membrane EGFR immunoreactivity. Of 147 patients enrolled in our institution, 50 patients were evaluable for assessment of both clinical response and EGFR expression. The objective tumour response rate was 10% and disease control was achieved in 50% of patients. Although high EGFR expression was more common in squamous-cell carcinomas than adenocarcinomas, all objective responses were observed in patients with adenocarcinoma. Response and disease control with gefitinib were not associated with high EGFR expression. Overall, median survival was 4 months, and the 1-year survival rate was 18%. Strong EGFR staining correlated with shorter survival time for all patients. Gefitinib demonstrated promising clinical activity in this group of patients with NSCLC. These results have also shown that EGFR expression is not a significant predictive factor for response to gefitinib.
Increased plasma interleukin-8 concentrations in alcoholic hepatitis (1993)

Patients with alcoholic hepatitis often have hepatic polymorphonuclear leukocyte infiltration and neutrophilia. Interleukin-8 is a cytokine that stimulates neutrophil chemotaxis and release of lysosomal enzymes. It is made by several types of cells, including fibroblasts, Kupffer cells and hepatocytes. In this study, serial plasma interleukin-8 concentrations were measured with enzyme-linked immunosorbent assay in 40 consecutive patients with moderate-to-severe alcoholic hepatitis over a 6-mo period. Two control groups included 10 patients without clinically important liver disease admitted for treatment of alcohol dependence and 12 healthy male volunteers. The mean plasma interleukin-8 level on admission was markedly increased: 695 ± 146 pg/ml in the alcoholic hepatitis patients. The alcohol-dependent control group and the normal volunteer controls had mean interleukin-8 concentrations of 106 ± 28 pg/ml and 10 ± 5 pg/ml, respectively. Initially increased interleukin-8 levels in alcoholic hepatitis patients decreased to a meals of 182 ± 42 pg/ml over the first month; levels had decreased further to 124 ± 79 pg/ml after 6 mo. Increased interleukin-8 concentrations in patients with alcoholic hepatitis suggest a role for interleukin-8 in the neutrophilia and hepatic polymorphonuclear leukocyte infiltration of alcoholic hepatitis. (HEPATOLOGY 1993;18:576-580.)
Benefits and limitations of tapping into stored energy for datacenters (2011)

Datacenter power consumption has a significant impact on both its recurring electricity bill (Op-ex) and one-time construction costs (Cap-ex). Existing work optimizing these costs has relied primarily on throttling devices or workload shaping, both with performance degrading implications. In this paper, we present a novel knob of energy buffer (eBuff) available in the form of UPS batteries in datacenters for this cost optimization. Intuitively, eBuff stores energy in UPS batteries during "valleys" - periods of lower demand, which can be drained during "peaks" - periods of higher demand. UPS batteries are normally used as a fail-over mechanism to transition to captive power sources upon utility failure. Furthermore, frequent discharges can cause UPS batteries to fail prematurely. We conduct detailed analysis of battery operation to figure out feasible operating regions given such battery lifetime and datacenter availability concerns. Using insights learned from this analysis, we develop peak reduction algorithms that combine the UPS battery knob with existing throttling based techniques for minimizing datacenter power costs. Using an experimental platform, we offer insights about Op-ex savings offered by eBuff for a wide range of workload peaks/valleys, UPS provisioning, and application SLA constraints. We find that eBuff can be used to realize 15-45% peak power reduction, corresponding to 6-18% savings in Op-ex across this spectrum. eBuff can also play a role in reducing Cap-ex costs by allowing tighter overbooking of power infrastructure components and we quantify the extent of such Cap-ex savings. To our knowledge, this is the first paper to exploit stored energy - typically lying untapped in the datacenter - to address the peak power draw problem.