gebhart/patrepeval huggingface dataset:
Mutational Analysis of the Human Immunodeficiency Virus Type 1 Vpu Transmembrane Domain That Promotes the Enhanced Release of Virus-Like Particles from the Plasma Membrane of Mammalian Cells (1998)

Human immunodeficiency virus type 1 Vpu is a multifunctional phosphoprotein composed of the N-terminal transmembrane (VpuTM) and C-terminal cytoplasmic domains. Each of these domains regulates a distinct function of the protein; the transmembrane domain is critical in virus release, and phosphorylation of the cytoplasmic domain is necessary for CD4 proteolysis. We carried our experiments to identify amino acids in the VpuTM domain that are important in the process of virus-like particle (VLP) release from HeLa cells. VLPs are released from the plasma membrane of HeLa cells at constitutive levels, and Vpu expression enhanced the release of VLPs by a factor of 10 to 15. Deletion of two to five amino acids from both N- and C-terminal ends or the middle of the VpuTM domain generated mutant Vpu proteins that have lost the ability to enhance VLP release. These deletion mutants have not lost the ability to associate with the wild-type or mutant Vpu proteins and formed complexes with equal efficiency. They were also transported normally to the Golgi complex. Furthermore, a Vpu protein having the CD4 transmembrane and Vpu cytoplasmic domains was completely inactive, and Vpu proteins harboring hybrid Vpu-CD4 TM domains were also defective in the ability to enhance the release of VLPs. When tested for functional complementation in cotransfected cells, two inactive proteins were not able to reconstitute Vpu activity that enhances the release of Gag particles. Coexpression of functional CD4/Vpu hybrids or wild-type Vpu with inactive mutant CD4/Vpu proteins revealed that mutations in the VpuTM domain could dominantly interfere with Vpu activity in Gag release. Taken together, these results demonstrated that the structural integrity of the VpuTM domain is critical for Vpu activity in the release of VLPs from the plasma membrane of mammalian cells.
Crystal Structure of the Human RORα Ligand Binding Domain in Complex with Cholesterol Sulfate at 2.2 Å (2004)

The retinoic acid-related orphan receptor alpha (RORalpha) is an orphan member of the subfamily 1 of nuclear hormone receptors. Our recent structural and functional studies have led to the hypothesis that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. We have now solved the x-ray crystal structure of the ligand binding domain of RORalpha in complex with cholesterol-3-O-sulfate following a ligand exchange experiment. In contrast to the 3-hydroxyl of cholesterol, the 3-O-sulfate group makes additional direct hydrogen bonds with three residues of the RORalpha ligand binding domain, namely NH-Gln(289), NH-Tyr(290), and NH1-Arg(370). When compared with the complex with cholesterol, seven well ordered water molecules have been displaced, and the ligand is slightly shifted toward the hydrophilic part of the ligand binding pocket, which is ideally suited for interactions with a sulfate group. These additional ligand-protein interactions result in an increased affinity of cholesterol sulfate when compared with cholesterol, as shown by mass spectrometry analysis done under native conditions and differential scanning calorimetry. Moreover, mutational studies show that the higher binding affinity of cholesterol sulfate translates into an increased transcriptional activity of RORalpha. Our findings suggest that cholesterol sulfate could play a crucial role in the regulation of RORalpha in vivo.
The Basis of Ammonium Release in nifL Mutants of Azotobacter vinelandii (1999)

In Azotobacter vinelandii, nitrogen fixation is regulated at the transcriptional level by an unusual two-component system encoded by nifLA. Certain mutations in nifL result in the bacterium releasing large quantities of ammonium into the medium, and earlier work suggested that this occurs by a mechanism that does not involve NifA, the activator of nif gene transcription. We have investigated a number of possible alternative mechanisms and find no evidence for their involvement in ammonium release. Enhancement of NifA-mediated transcription, on the other hand, by either elimination of nifL or overexpression of nifA, resulted in ammonium release, correlating with enhanced levels of nifH mRNA, raised levels of nitrogenase and acetylene-reducing activity, and increased concentrations of intracellular ammonium. Up to 35 mM ammonium can accumulate in the medium. Where measured, intracellular levels exceeded extracellular levels, indicating that rather than being actively transported, ammonium is lost from the cell passively, possibly by reversal of an NH(4)(+) uptake system. The data also indicate that in the wild type the bulk of NifA is inactivated by NifL during steady-state growth on dinitrogen.
Reducing file system latency using a predictive approach (1994)

Despite impressive advances in file system throughput resulting from technologies such as high-bandwidth networks and disk arrays, file system latency has not improved and in many cases has become worse. Consequently, file system I/O remains one of the major bottlenecks to operating system performance [10]. This paper investigates an automated predictive approach towards reducing file latency. Automatic Prefetching uses past file accesses to predict future file system requests. The objective is to provide data in advance of the request for the data, effectively masking access latencies. We have designed and implement a system to measure the performance benefits of automatic prefetching. Our current results, obtained from a trace-driven simulation, show that prefetching results in as much as a 280% improvement over LRU especially for smaller caches. Alternatively, prefetching can reduce cache size by up to 50%. 1 Motivation Rapid improvements in processor and memory speeds have created...
Topic-based Vector Space Model (2003)

This paper motivates and presents the Topic-based Vector Space Model (TVSM), a new vector-based approach for document comparison. The approach does not assume independence between terms and it is flexible regarding the specification of term-similarities. Stop-word-list, stemming and thesaurus can be fully integrated into the model. This paper shows further how the TVSM can be fully implemented within the context of relational databases. This facilitates the use of this approach by generic applications. At the end short comparisons with other vector-based approaches namely the Vector Space Model (VSM) and the Generalized Vector Space Model (GVSM) are presented. 1.
The spectrum of complement alternative pathway‐mediated diseases (2008)

The complement system has once again come into prominence in the therapeutic development arena. The recent approval of an inhibitory monoclonal antibody, eculizumab, which is directed against complement component C5 for the disease paroxysmal nocturnal hemoglobinuria has provided the initial validation of this system as a therapeutic target. Preclinical studies using animal models and human-derived samples demonstrate that inhibition of complement ameliorates many inflammatory and autoimmune disease manifestations. Major efforts continue to define the most optimal means to block complement activation in a cost-effective manner. Because the system is initiated through three pathways and generates at least six immunoregulatory and pro-inflammatory mediators, there is substantial complexity to this problem. One pathway, designated the alternative pathway, has recently been shown to play a particularly important role in preclinical disease models. Further evidence of the importance of the alternative pathway has been provided by studies of human diseases, where mutations or dysfunctional polymorphisms that promote activation of this pathway are highly associated with the diseases atypical hemolytic uremic syndrome, dense deposit disease, and age-related macular degeneration. This article reviews evidence in support of the essential role of the alternative pathway in the generation of tissue injury and the rationale for development of therapies that modulate its activity.
Tannins and related compounds. XXIX. Seven new methyl derivatives of flavan-3-ols and a 1,3-diarylpropan-2-ol from Cinnamomum cassia, C. obtusifolium and Lindera umbellata var. membranacea. (1985)

Seven new methyl derivatives of flavan-3-ols (compounds 1-7) and one 1, 3-diarylpropan-2-ol (compound 8) were isolated from three Lauraceous plants (1, and 3-7 from Cinnamomum cassia, 1, 3 and 4 from Cinnamomum obtusifolium, and 1-4 and 8 from Lindera umbellata var. membranacea). Their structures were characterized mainly by proton nuclear magnetic resonance (1H-NMR) examination combined with nuclear Overhauser effect (NOE) experiments as the 3'-O-methylate (1), 3', 4'-di-O-methylate (2), 5, 3'-di-O-methylate (3) and 5, 7, 3'-tri-O-methylate (4) of (-)-epicatechin, the 4'-O-methylate (5), 7, 4'-di-O-methylate (6) and 5, 7, 4'-tri-O-methylate (7) of (+)-catechin, and 1-(4', 6'-dihydroxy-2'-methoxyphenyl)-3-(4'-hydroxy-3"-methoxyphenyl)-propan-2-ol (8).
The dependence of the radiation damage formation on the substrate implant temperature in GaN during Mg ion implantation (2005)

In pursuit of p-type doping, we have implanted GaN with Mg ions at 200 and 500keV with the substrate temperature maintained at −150 (cold) or +300°C (hot) during ion irradiation. The samples have been annealed at 1000°C postion implantation. The radiation damage peak position (and its profile), the dopant distribution, and the damage stability during annealing were all shown to be dependent upon the GaN substrate temperature during implantation. The damage peak position in the solid was reduced for cold implantation. The dopant distribution in the solid depends upon the implant temperature and in agreement with the damage measurements, the Mg range is shallower in GaN for cold implants when compared to hot implants. The trends observed suggest that the dynamic defect annealing rate during irradiation is reduced for cold implantation, and the subsequent increase in the damage level (scattering centers) formed during the damage buildup reduces the ion range in the solid. In turn, the reduced ion range subsequently limits the final damage range. The rate of damage removal during thermal annealing in the samples implanted at cold temperature was increased: this is explained by the greater complexity of defects caused during high-temperature implantation, due to the raised level of dynamic defect annealing.
Low SOX17 expression is a prognostic factor and drives transcriptional dysregulation and esophageal cancer progression (2013)

The transcriptional network of the SRY (sex determining region Y)-box 17 (SOX17) and the prognostic impact of SOX17 protein expression in human cancers remain largely unclear. In this study, we evaluated the prognostic effect of low SOX17 protein expression and its dysregulation of transcriptional network in esophageal squamous cell carcinoma (ESCC). Low SOX17 protein expression was found in 47.4% (73 of 154) of ESCC patients with predicted poor prognosis. Re-expression of SOX17 in ESCC cells caused reduced foci formation, cell motility, decreased ESCC xenograft growth and metastasis in animals. Knockdown of SOX17 increased foci formation in ESCC and normal esophageal cells. Notably, 489 significantly differential genes involved in cell growth and motility controls were identified by expression array upon SOX17 overexpression and 47 genes contained putative SRY element in their promoters. Using quantitative chromatin immunoprecipitation-PCR and promoter activity assays, we confirmed that MACC1, MALAT1, NBN, NFAT5, CSNK1A1, FN1 and SERBP1 genes were suppressed by SOX17 via the SRY binding-mediated transcriptional regulation. Overexpression of FN1 and MACC1 abolished SOX17-mediated migration and invasion suppression. The inverse correlation between SOX17 and FN1 protein expression in ESCC clinical samples further strengthened our conclusion that FN1 is a transcriptional repression target gene of SOX17. This study provides compelling clinical evidence that low SOX17 protein expression is a prognostic biomarker and novel cell and animal data of SOX17-mediated suppression of ESCC metastasis. We establish the first transcriptional network and identify new suppressive downstream genes of SOX17 which can be potential therapeutic targets for ESCC.
Single-wafer cluster tool performance: an analysis of the effects of redundant chambers and revisitation sequences on throughput (1996)

Recent trends in the semiconductor industry indicate the need to explore alternatives to batch-wafer manufacturing. One proposed alternative is a micro-factory based on cluster tools. This paper presents an analysis of the effect of redundant chambers and chamber revisitation process sequences on the throughput in an individual cluster tool. Theoretical models which quantify the time required to process a lot of wafers in a cluster tool are developed for these situations. The differences between scheduling algorithms which use the load-lock as a queue and those that do not are also explored. Finally, the models developed in the work are integrated into a model which bounds the minimum theoretical turn-around-time which can be achieved in a cluster based fab.
Ocular Imaging of Attentional Bias Among College Students: Automatic and Controlled Processing of Alcohol-Related Scenes (2009)

Ocular-imaging methods are a valuable tool for use in the study of attentional bias to alcohol-related images in college drinkers. Further research is needed to determine the potential application of these methods to the prevention and treatment of alcohol misuse on college campuses.
Tailoring structure-function and pharmacokinetic properties of single-chain Fv proteins by site-specific PEGylation (2003)

The utility of single-chain Fv proteins as therapeutic agents would be realized if the circulating lives of these minimal antigen-binding polypeptides could be both prolonged and adjustable. We have developed a general strategy for creating tailored monoPEGylated single-chain antibodies. Free cysteine residues were engineered in an anti-TNF-alpha scFv at the C-terminus or within the linker segments of both scFv orientations, V(L)-linker-V(H) and V(H)-linker-V(L). High-level expression of 10 designed variant scFv proteins in Pichia pastoris allowed rapid purification. Optimization of site-specific conjugate preparation with 5, 20 and 40 kDa maleimide-PEG polymers was achieved and a comparison of the structural and functional properties of the scFv proteins and their PEGylated counterparts was performed. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the unique attachment site for each PEG polymer. Independent biochemical and bioactivity analyses, including binding affinities and kinetics, antigenicity, flow cytometric profiling and cell cytotoxicity rescue, demonstrated that the functional activities of the 10 designed scFv conjugates are maintained, while scFv activity variations between these alternative assays can be correlated with conjugate and analytical designs. Pharmacokinetic studies of the PEGylated scFv in mice demonstrated up to 100-fold prolongation of circulating lives, in a range comparable to clinical antibodies.
Langage et temps de dicto (1985)

Martin Robert. Langage et temps de dicto. In: Langue française, n°67, 1985. La pragmatique des temps verbaux, sous la direction de Co Vet. pp. 23-37.
The Effects of Adrenomedullin Overexpression in Breast Tumor Cells (2002)

These results further support the role of adrenomedullin as a survival factor for tumors. Development of physiologically efficient inhibitors of adrenomedullin may prove useful in the clinical management of cancer.
In Vivo Assessment of HER2 Receptor Density in HER2-positive Tumors by Near-infrared Imaging, Using Repeated Injections of the Fluorescent Probe (2013)

HER2 overexpression and amplification of the HER2/neu gene have been found in approximately 25% of invasive breast carcinomas. They are associated with a poor prognosis and resistance to therapy in breast cancer patients. Up to now, clinical evaluation of human epidermal growth factor receptor 2 (HER2) expression is based on ex vivo methods (immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) staining of biopsied tissue). Our goal is to realize "image and treat" paradigm using targeted fluorescent probes to evaluate expression levels of cell biomarkers responsible for cancer progression and to monitor the efficacy of corresponding monoclonal antibody treatments. We used fluorescent Affibody-based probes for in vivo analysis of HER2 receptors using near-infrared optical imaging that do not interfere with binding of the therapeutic agents to these receptors. We have analyzed two types of breast carcinoma xenografts with significant differences in HER2 expression (31 and 21 according to classification) in the mouse model. Using our kinetic model to analyze the temporal variations of the fluorescence intensity in the tumor area after two subsequent injections allowed us to assess quantitatively the difference in HER2 expression levels for two tumor types (BT-474 and MD-MBA-361). This result was substantiated by ELISA ex vivo assays of HER2 expression in the same tumors.
On-chip culture system for observation of isolated individual cells (2001)

To investigate the properties of isolated single cells with their environment, we developed the differential analysis method for single cells using an on-chip microculture system. The advantages of the system are, (i). continuous cultivation of a series of isolated single cells or a group of cells under contamination free conditions, (ii). continuous observation and comparison of those cells with 0.2 microm spatial resolution by a phase-contrast/fluorescent microscopy system with digital image processing. The core of the system is an n x n (n = 20-50) array of chambers, where each is 20-70 microm in diameter and 5-30 microm deep holes etched into a biotin-coated 0.17 mm thick glass slide. The biotin-coated glass slide is covered with the streptavidin coated cellulose semipermeable membrane, which is fixed on the surface of the glass slide by streptavidin-biotin attachment, separating those holes from the nutrient medium circulating through a 'cover chamber' above. A single cell or group of cells can thus be isolated from environment perfused with the same medium, and the medium in each chamber can be changed within the diffusion time (<1/30 s). In addition, the microchamber volumes of specific cells or cell groups can be controlled by the sizes of the chambers. By using this system we found that the length of isolated Escherichia coli increased at 0.06 microm min(-1) between cell divisions regardless of the chamber volume, and that the cell concentration reached 10(12) cells ml(-1) under contamination free conditions. The system is thus particularly useful for one cell level analysis because the direct descendants of single cells can be cultured and compared in the isolated microchambers, and the physical properties of the cells in each microchamber can be continuously observed and compared.
Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells (2008)

Members of the carcinoembryonic antigen family (CEACAMs) are widely expressed, and, depending on the tissue, capable of regulating diverse functions including tumor promotion, tumor suppression, angiogenesis, and neutrophil activation. Four members of this family, CEACAM1, CEACAM8, CEACAM6, and CEACAM3 (recognized by CD66a, CD66b, CD66c, and CD66d mAbs, respectively), are expressed on human neutrophils. CD66a, CD66b, CD66c, and CD66d antibodies each increase neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies is blocked by CD18 mAbs and is associated with upregulation of CD11/CD18 on the neutrophil surface. To examine potential interactions of CEACAMs in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a set of CD66 mAbs was tested following desensitization to stimulation by various combinations of these mAbs. Addition of a CD66 mAb in the absence of calcium results in desensitization of neutrophils to stimulation by that CD66 mAb. The current data show that desensitization of neutrophils to any two CEACAMs results in selective desensitization to those two CEACAMs, while the cells remain responsive to the other two neutrophil CEACAMs. In addition, cells desensitized to CEACAM-3, -6, and -8 were still responsive to stimulation of CEACAM1 by CD66a mAbs. In contrast, desensitization of cells to CEACAM1 and any two of the other CEACAMs left the cells unresponsive to all CD66 mAbs. Cells desensitized to any combination of CEACAMs remained responsive to the unrelated control protein CD63. Thus, while there is significant independence of the four neutrophil CEACAMs in signaling, CEACAM1 appears to play a unique role among the neutrophil CEACAMs. A model in which CEACAMs dimerize to form signaling complexes could accommodate the observations. Similar interactions may occur in other cells expressing CEACAMs.
The impact on retrieval effectiveness of skewed frequency distributions (1999)

We present an analysis of word senses that provides a fresh insight into the impact of word ambiguity on retrieval effectiveness with potential broader implications for other processes of information retrieval. Using a methodology of forming artifically ambiguous words, known as pseudowords, and through reference to other researchers' work, the analysis illustrates that the distribution of the frequency of occurrance of the senses of a word plays a strong role in ambiguity's impact of effectiveness. Further investigation shows that this analysis may also be applicable to other processes of retrieval, such as Cross Language Information Retrieval, query expansion, retrieval of OCR'ed texts, and stemming. The analysis appears to provide a means of explaining, at least in part, reasons for the processes' impact (or lack of it) on effectiveness.
Changes in Gene Expression Associated With Response to Neoadjuvant Chemotherapy in Breast Cancer (2005)

No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.