gebhart/patrepeval huggingface dataset:
Human Bitter Taste Perception (2005)

Bitter taste perception is innate and induces aversive reactions. Since numerous harmful compounds, including secondary plant metabolites, synthetic chemicals, inorganic ions and rancid fats, do taste bitter, this basic taste modality may be considered as a defence mechanism against the ingestion of potential poisons. For a complete understanding of this defence mechanism it is obligatory to identify and characterize the chemical detectors of the bitter compounds, which display the remarkable ability to recognize thousands of different chemicals. Screening of the genome data bases ultimately led to the discovery of a novel gene family of ∼40 members in mice and ∼30 in humans. Some of the genes identified by this approach are located within chromosomal loci associated with tasting various distinct bitter compounds (Adler et al., 2000; Matsunami et al., 2000; Bufe et al., 2002). Therefore, these genes encoding G-proteincoupled receptors, TAS2Rs (previously referred to as T2Rs or TRBs), have been suggested to represent bitter taste receptors. Several lines of independent evidence further support this assumption (Adler et al., 2000; Chandrashekar et al., 2000; Matsunami et al., 2000). First, the expression pattern of these genes on the rodent tongue was consistent with that of bitter taste receptors. Secondly, functional expression studies identified the bitter compound cycloheximide as an agonist for mTAS2R105. Thirdly, mice strains with impaired cycloheximide tasting have variant mTAS2R105 genes encoding receptors that are less responsive to cycloheximide. Fourthly, mTAS2R105 couples in vitro to α-gustducin (Chandrashekar et al., 2000), a G-protein α-subunit expressed in taste tissue that has amply been shown before to play a role in bitter taste transduction (Margolskee, 2002). Although this question has not been directly addressed, these investigations led to the impression of a narrow tuning of bitter taste receptors and raised the intriguing problem of how organisms that are equipped with a limited number of TAS2R genes are able to perceive numerous chemicals bitter. In the present report we address two questions that are important for the understanding of bitter taste in general and human bitter taste in particular. First, given the largely uncharacterized receptor repertoire, are all TAS2Rs true bitter taste receptors and, secondly, can their broad tuning explain how humans equipped with a fairly small number of TAS2R genes are able to perceive thousands of bitter compounds.
Sputtered permanent magnet arrays for MR sensor bias (1987)

Magnetic field sensors consisting of four magnetoresistive elements in a bridge configuration are capable of detecting very low magnetic fields. These sensors require the application of a bias field to maximise the sensitivity and prevent domain wall formation which gives rise to Barkhausen noise. The design of thin film permanent magnet arrays for the production of sensor bias fields is considered. A simple charge sheet model is used to calculate the field from thin-film PtCo magnet arrays and the criteria for the production of sufficiently large and uniform bias fields are discussed. The use of these magnet arrays is shown to enable the simple construction of sensors with excellent vector response and allow the possibility of producing sensors capable of measuring fields up to 100 Oe with a linearity better than 1%.
TGF‐β1 calcium signaling increases α5 integrin expression in osteoblasts (2002)

TGF-beta1 is a potent osteoactive factor and exhibits a wide variety of effects on osteoblasts, most of which are mediated through receptor associated Smad proteins. We have recently reported a novel TGF-beta1 intracellular Ca2+ signaling pathway in osteoblasts, and found that this signaling is required for the TGF-beta1 mediated enhancement of osteoblast adhesion to substrate. Given that interaction between the extracellular matrix protein fibronectin and alpha5beta1 integrin on the cell surface is principally responsible for osteoblast substrate adhesion, we examined here whether the TGF-beta1 stimulated Ca2+ signal is involved in this pathway. Our results show that, in primary human osteoblasts, the TGF-beta1 induced intracellular Ca2+ signal is responsible, in part, for the stimulation of expression of alpha5 integrin, but not of beta1 integrin or fibronectin. Increased levels of alpha5 integrin protein and mRNA were seen as early as 12 h after TGF-beta1 treatment, but were inhibited by co-treatment of cells with nifedipine, a selective L-type Ca2+ channel blocker. TGF-beta1 treatment increased both fibronectin and beta1 integrin protein production within 48 h, in a manner unaffected by co-treatment with nifedipine. Immunofluorescence observations revealed that TGF-beta1 treatment resulted in increased alpha5 integrin staining, and more prominent alpha5 integrin clustering, with increased co-localization with the actin cytoskeleton, effects that were blocked by co-treatment with nifedipine. The TGF-beta1 induced intracellular Ca2+ signal in human osteoblasts is thus an important mechanistic step in the regulation of alpha5 integrin expression, later contributing to enhanced cell adhesion.
Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367 (2014)

Artificial transcription factors are powerful tools for regulating gene expression. Here we report results with engineered zinc-finger transcription factors (ZF-TFs) targeting four protein-coding genes, OCT4, SOX2, KLF4 and c-MYC, and one noncoding ribonucleic acid (RNA) gene, the microRNA (miRNA) miR302/367 cluster. We designed over 300 ZF-TFs whose targets lie within 1 kb of the transcriptional start sites (TSSs), screened them for increased messenger RNA or miRNA levels in transfected cells, and identified potent ZF-TF activators for each gene. Furthermore, we demonstrate that selected ZF-TFs function with alternative activation domains and in multiple cell lines. For OCT4, we expanded the target range to -2.5 kb and +500 bp relative to the TSS and identified additional active ZF-TFs, including three highly active ZF-TFs targeting distal enhancer, proximal enhancer and downstream from the proximal promoter. Chromatin immunoprecipitation (FLAG-ChIP) results indicate that several inactive ZF-TFs targeting within the same regulatory region bind as well as the most active ZF-TFs, suggesting that efficient binding within one of these regulatory regions may be necessary but not sufficient for activation. These results further our understanding of ZF-TF design principles and corroborate the use of ZF-TFs targeting enhancers and downstream from the TSS for transcriptional activation.
Enzyme with dual lipoxygenase activities catalyzes leukotriene A4 synthesis from arachidonic acid. (1984)

When arachidonic acid was incubated with homogenates of potato tubers, two isomers of 6-trans-leukotriene B4, epimeric at C-12, were formed in addition to the major product, (5S-hydroperoxy-6-trans-8,11,14-cis-icosatetraenoic acid (5-HPETE). To elucidate the mechanism of biosynthesis of the dihydroxy-acids, the lipoxygenase from the potato tubers was purified to apparent homogeneity by a combination of conventional chromatographic procedures and high-performance liquid chromatography equipped with a chromatofocusing column (Mono-P). The purified lipoxygenase acted on arachidonic acid and bishomo-gamma-linolenic acid to yield (5S)-hydroperoxy- and (8S)-hydroperoxyicosanoids, respectively. Furthermore, the purified enzyme converted 5-HPETE to leukotriene A4, with the presence of the epoxide intermediate being demonstrated by 18O2 experiments, methanol trapping, as well as further conversion to leukotriene B4 by the purified leukotriene A4 hydrolase. Several experiments, including those with lipoxygenase inhibitors, heat treatment, and competitive inhibition, indicated that both the 5-lipoxygenase and leukotriene A4 synthase activities resided in the same protein and that the formation of leukotriene A4 from 5-HPETE was catalyzed by the 8-lipoxygenase activity of the enzyme.
Reciprocal regulation of IL‐23 and IL‐12 following co‐activation of Dectin‐1 and TLR signaling pathways (2009)

Recognition of microbial products by germ-line-encoded PRR initiates immune responses, but how PRR mediate specific host responses to infectious agents is poorly understood. We and others have proposed that specificity is achieved by collaborative responses mediated between different PRR. One such example comprises the fungal beta-glucan receptor Dectin-1, which collaborates with TLR to induce TNF production. We show here that collaborative responses mediated by Dectin-1 and TLR2 are more extensive than first appreciated, and result in enhanced IL-23, IL-6 and IL-10 production in DC, while down-regulating IL-12 relative to the levels produced by TLR ligation alone. Such down-regulation occurred with multiple MyD88-coupled TLR, was dependent on signaling through Dectin-1 and also occurred in macrophages. These findings explain how fungi can induce IL-23 and IL-6, while suppressing IL-12, a combination which has previously been shown to contribute to the development of Th17 responses found during fungal infections. Furthermore, these data reveal how the collaboration of different PRR can tailor specific responses to infectious agents.
Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon (1986)

We treated 10 patients who had chronic non-A,non-B hepatitis with recombinant human alpha interferon in varying doses (0.5 to 5 million units) daily, every other day, or three times weekly for up to 12 months. In 8 of the 10 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. In two of these patients, the interferon therapy was stopped after four months, and in both cases, a prompt return of aminotransferase activities to pretreatment values occurred. Prolonged treatment was associated with a sustained improvement in aminotransferase levels; in three cases, biopsy specimens obtained after one year of therapy showed marked improvement in hepatic histology, even though low doses of alpha interferon had been used. These preliminary findings, although not adequately controlled, suggest that long-term, low-dose alpha interferon therapy may be effective in controlling the disease activity in some patients with chronic non-A,non-B hepatitis. A prospective controlled trial is now needed to assess the role of interferon therapy in this disease.
Component-based security model for XML messaging services (2003)

The objective of the paper is to enlighten the applicability of component technology in deploying security models to protect Web transactions. The proposed component-based security model is a substitutive methodology for conventional methods that are vendor dependent. The model prefers the Extensible Markup Language (XML) format to represent Web transactions, because of the multi-platform nature of modern Web applications. A granular approach is adopted in signing and encrypting the XML document. The paper also describes a distinct method used for key distribution. In addition, access control measures are also recommended in the model to protect data resources at the server against unauthorized access.
Lung neutrophils in the adult respiratory distress syndrome. Clinical and pathophysiologic significance. (1986)

Although neutrophils are of pathogenetic importance in various animal models of acute lung injury, their role in the adult respiratory distress syndrome (ARDS) is unclear. To study the significance of lung neutrophils in this disorder, patients with ARDS (n = 11) were evaluated by bronchoalveolar lavage within 24 h of admission to the intensive care unit. Patients with non-ARDS respiratory failure requiring mechanical ventilation (n = 4) and normal volunteers (n = 12) were also studied. Neutrophils constituted 67.6 +/- 9.8% of recovered lavage cells in patients with ARDS compared with only 4.0 +/- 2.4% of cells in mechanically ventilated control patients and 0.8 +/- 0.2% in normal volunteers (p less than 0.005, both comparisons). Furthermore, in patients with ARDS (n = 6) evaluated serially by bronchoalveolar lavage at 72-h intervals, neutrophil percentages decreased from 91 +/- 3.2% (initial lavage) to 42.8 +/- 12% (final lavage) (p less than 0.005). Lung neutrophils also predicted the severity of abnormalities in gas exchange and lung protein permeability. That is, the percentage of neutrophils correlated directly with the alveolar-arterial Po2 difference (r = 0.69, p less than 0.01) and lavage fluid total protein concentrations (r = 0.62, p less than 0.01). Because large numbers of lung neutrophils were present in these patients, ARDS lavage fluid was assayed for neutrophil mediators relevant to the pathogenesis of acute lung injury. Neutrophil elastase activity was not detected in any ARDS lavages, although elastase was antigenically present in most samples and appeared to be complexed to alpha-1-antitrypsin. In contrast to elastase, neutrophil collagenase was readily detectable in ARDS fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
A Newton-Raphson Iterative Scheme for Integrating Multiphase Production Data into Reservoir Models (2000)

Abstract This paper presents a new linearized iterative algorithm for building reservoir models conditioned to multiphase production data and geostatistical data. The significant feature of the proposed algorithm is that the computation of the sensitivity coefficients of production data with respect to model parameters can be avoided. This leads to dramatic reduction of computational cost. Instead of generating the sensitivity matrix as required for the least-squares algorithms, the proposed approach relies on solving the inversion equations which are derived from the necessary conditions for a functional extremum. It is proved that the proposed method requires considerably less computational effort than the traditional algorithms such as the Gauss-Newton method, the Levenberg-Marquardt method and the generalized pulse-spectrum technique (GPST). This is because the computation of the sensitivity coefficients makes the traditional algorithms computationally intensive. However, for the proposed linearized iterative scheme, the computational requirement only depends on the time steps used in the reservoir simulator rather than the number of parameters or the number of observed data. The linearized iteration scheme converges fast since the inversion equations can be solved through the Newton-Raphson method. At each iteration, the new approach requires solving the finite difference equations and the linear adjoint equations only once, respectively. Since the solver for the flow equations can be used to solve both the adjoint equations and the inversion equations, the proposed algorithm can be easily applied to commercial reservoir simulators. In this paper, two numerical examples for incorporating water oil rate data into geostatistical models are given to prove the efficiency of the proposed algorithm.
A diphtheria toxin-interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors. (2002)

The relative cytotoxicity of a diphtheria toxin (DT) human interleukin 3(IL3) fusion protein (DT(388)IL3) was tested against primitive normal (n = 3)and acute myeloid leukemia (AML) progenitors (n = 7). After 24-h culture with 50 ng/ml DT(388)IL3, the mean percentages of kill of AML colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and suspension culture-ICs (SC-ICs) were 82% (range, 47-100), 56% (range, 28-91), and 74% (range, 43-87), respectively, with most surviving progenitors being cytogenetically normal. Engraftment of DT(388)IL-3-treated AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice followed for 16 weeks was eradicated for two of these samples. In contrast, with normal bone marrow, mean percentages of CFC kill of 49 and 64% were seen with 50 or 250 ng/ml DT(388)IL3, respectively, whereas no significant kills were observed in the LTC-IC and SC-IC assays. The NOD/SCID mouse repopulating cell (RC) frequency in normal BM cells was also not reduced by DT(388)IL3 treatment. In subsequent experiments, NOD/SCID mice that received AML blasts i.v. followed in 24 h by 0.045 microg/g DT(388)IL3 daily i.p. x 5 showed mean percentages of reduction in AML engraftment of 83% (range, 14-100) and 57% (range, 0-98) after 4 and 12 weeks, respectively (n = 6). No evidence of leukemia was detected with two of six AML samples 12 weeks after one 5-day course of DT(388)IL3. Repeating the DT(388)IL3 treatment every 4 weeks enhanced its effectiveness against two additional samples. Thus, DT(388)IL3 kills primitive leukemic progenitors from a proportion of AML patients but shows no significant toxicity against equivalent normal cells.
The Role of the CXCL10/CXCR3 System in Type 1 Diabetes (2009)

Despite intervention with insulin, type 1 diabetes gradually deteriorates the patients' quality of life. The disease is characterized by an immune-mediated destruction of pancreatic beta-cells. Its etiology, however, remains controversial. Some studies argue that glutamic acid decarboxylase (GAD) antigen and GAD-reactive T cells are critical players in the development of diabetes by affecting the Th cell balance. A T-helper 1 (Th1)-dominant immune response is considered to be important in beta-cell failure in both human and animal models of type 1 diabetes. The Th1-type chemokine, CXCL10, and its receptor, CXCR3, are involved not only in the immune response, but also in the suppression of beta-cell proliferation. Thus, understanding the CXCL10/CXCR3 system may be important for finding a cure. In this short review, we discuss the role of the CXCL10/CXCR3 system in type 1 diabetes and propose relevant treatment options.
Detecting past and present intrusions through vulnerability-specific predicates (2005)

Most systems contain software with yet-to-be-discovered security vulnerabilities. When a vulnerability is disclosed, administrators face the grim reality that they have been running software which was open to attack. Sites that value availability may be forced to continue running this vulnerable software until the accompanying patch has been tested. Our goal is to improve security by detecting intrusions that occurred before the vulnerability was disclosed and by detecting and responding to intrusions that are attempted after the vulnerability is disclosed. We detect when a vulnerability is triggered by executing vulnerability-specific predicates as the system runs or replays. This paper describes the design, implementation and evaluation of a system that supports the construction and execution of these vulnerability-specific predicates. Our system, called IntroVirt, uses virtual-machine introspection to monitor the execution of application and operating system software. IntroVirt executes predicates over past execution periods by combining virtual-machine introspection with virtual-machine replay. IntroVirt eases the construction of powerful predicates by allowing predicates to run existing target code in the context of the target system, and it uses checkpoints so that predicates can execute target code without perturbing the state of the target system. IntroVirt allows predicates to refresh themselves automatically so they work in the presence of preemptions. We show that vulnerability-specific predicates can be written easily for a wide variety of real vulnerabilities, can detect and respond to intrusions over both the past and present time intervals, and add little overhead for most vulnerabilities.
Nitric Oxide Synthase in the Human Glaucomatous Optic Nerve Head (1997)

The 3 isoforms of NOS are present in apparently increased amounts in the optic nerve head of patients with primary open-angle glaucoma. The increased presence of NOS-1 and the induction of NOS-2 in astrocytes of the lamina cribrosa suggest that the glaucomatous optic nerve head is exposed to excessive levels of nitric oxide, which may be neurodestructive, locally, to the axons of the retinal ganglion cells. Conversely, the increased presence of NOS-3 in vascular endothelia may be neuroprotective by causing vasodilation and increased blood flow in the tissue.
Crystallization and preliminary crystallographic analysis of cabbage histidinol dehydrogenase (1996)

Recombinant Brassica oleracea histidinol dehydrogenase (HDH) has been crystallized in various space groups using the method of vapour diffusion. The presence or absence of inhibitors and substrates as well as the use of different precipitants has enabled the growth of five different crystal forms. Extensive searches with the first crystal form (A) failed to produce any useful heavy-atom derivatives, mainly because of the instability of the crystals. This provoked the search for further crystal forms in the hope of finding more suitable crystals. At least two of these crystal forms are of interest for further study.
Identification of a novel factor X deletion in combination with a missense mutation in the F10 gene - Genotype-phenotype correlation in a girl with severe factor X deficiency. (2009)

The genotype-phenotype relationship of compound heterozygous factor X deficiency in a young girl with severe factor X deficiency and bleeding symptoms is characterized. We identified a novel deletion of exon 6 and a missense mutation (c.856G>A, Val286Met) in exon 7 of the F10 gene leading to a compound heterozygous state and causing severe factor X deficiency. Therapeutic options for patients with symptomatic factor X deficiency are demonstrated.
Fusion of maintenance and control data: A need for the process (2012)

A process control system deals with disperse information sources mostly related with operation and maintenance issues. For integration purposes, a data collection and distribution system based on the concept of cloud computing is proposed to collect data or information pertaining to the assets of a process plant from various sources or functional areas of the plant inc1uding, for example, the process control functional areas, the maintenance functional areas and the process performance monitoring functional areas. This data and information is manipulated in a coordinated manner by the cloud using XML for data exchange, and is redistributed to other applications where is used to perform overall better or more optimal control, maintenance and business activities. From maintenance point of view, the benefit is that information or data may be collected by maintenance functions pertaining to the health, variability, performance or utilization of an asset. The end user, i.e. operators and maintainers are also considered. A user interface becomes necessary in order to enable users to access and manipulate the data and optimize plant operation. Furthermore, applications, such as work order generation applications may automatically generate work orders, parts or supplies orders, etc. based on events occurring within the plant due to this integration of data and creation of new knowledge as a consequence of such process.