gebhart/patrepeval huggingface dataset:
HMGB1 in Sepsis (2003)

HMGB1 is a member of the high-mobility group protein superfamily that has been widely studied as nuclear proteins that bind DNA, stabilize nucleosomes and facilitate gene transcription. A series of recent discoveries revealed a cytokine activity of HMGB1, that when secreted into the extracellular milieu, mediates downstream inflammatory responses in endotoxemia, arthritis and sepsis. HMGB1 is properly defined as a cytokine because it stimulates proinflammatory responses in monocytes/macrophages, is produced during inflammatory responses in vivo in standardized models of systemic and local inflammation, mediates delayed endotoxin lethality, and is required for the full expression of inflammation in animal models of endotoxemia, sepsis and arthritis. HMGB1 is either actively secreted by monocytes/macrophages or passively released from necrotic cells from any tissue. These pathways are central for the biology of HMGB1 as a cytokine, since they provide key mechanisms that integrate the inflammatory response to infectious and non-infectious cell injuries. Receptor signal transduction of HMGB1 occurs in part through the receptor for advanced glycation end-products (RAGE) expressed on monocytes/macrophages, endothelial cells, neurons and smooth-muscle cells. HMGB1 is a late-acting cytokine, because it first appears in the extracellular milieu 8-12 h after the initial macrophage response to proinflammatory stimuli. Knowledge of the cytokine role of HMGB1 has implications for understanding downstream cytokine cascades, regulation of delayed innate immune responses and targeting treatment towards these processes. Effectiveness of delayed treatment with HMGB1 blockade up to 24 h after induction of experimental sepsis offers a unique window of opportunities to allow rescue from lethal sepsis.
Endothelial dysfunction in hypertension: fact or fancy? (1998)

Endothelium can deeply influence vascular tone and structure. The main endothelium-derived factor is nitric oxide (NO), which not only is a potent vasodilator but also inhibits platelet aggregation, smooth muscle cell proliferation, monocyte adhesion, and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. In human hypertension, endothelial dysfunction has been documented in peripheral and coronary macro- and microcirculation and in renal circulation. Impaired endothelium-dependent vasodilatation associated with essential hypertension appears to be a primary phenomenon because it can be detected in the offspring of essential hypertensive patients, shows no clear correlation with blood pressure value, and is not normalized by the mere reduction of blood pressure. The phenomenon responsible for endothelial alteration in essential hypertensive patients appears to be the activation of an alternative pathway involving cyclo-oxygenase (COX), which reduces NO availability through production of oxidative stress. This alteration in the NO pathway could be the main mechanism through which a dysfunctional endothelium may promote atherosclerosis and thrombosis in essential hypertension. Therefore, an important aim of antihypertensive therapy would be not only to normalize blood pressure values but also to reverse endothelial dysfunction by restoring NO availability. Evidence indicates that different classes of antihypertensive compounds have different effects on this alteration. Dihydropiridine calcium antagonists appear to act specifically on the NO pathway by a mechanism that is probably related to antioxidant activity.
A Powerful Brønsted Acid Catalyst for the Organocatalytic Asymmetric Transfer Hydrogenation of Imines (2005)

A little goes a long way: A 1 mol % loading of the chiral phosphoric acid catalyst 2 converts aromatic and aliphatic imines such as 1 into the corresponding amines (4) in high yields and enantioselectivities if treated with Hantzsch dihydropyridine 3.
Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal humans to endotoxin (1992)

Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction that characterizes Gram-negative sepsis. In animal models of endotoxemia, pretreatment with ibuprofen or pentoxifylline attenuates some of these cardiovascular changes. To evaluate the effects of these agents on the human cardiovascular response to endotoxemia, hemodynamic variables were measured serially in 24 normal subjects who were given intravenous endotoxin. The subjects were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no medication before endotoxin administration (n = 5). The subjects were volume loaded 3-5 h after endotoxin administration, and hemodynamic measurements were reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had significant increases in heart rate, cardiac index, oxygen delivery, and oxygen consumption, while systemic vascular resistance index decreased significantly from baseline. The oxygen extraction ratio remained unchanged. After volume loading, the left ventricular ejection fraction and left ventricular end-diastolic and end-systolic volume indexes did not differ among the groups. The hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence of fever and is not significantly ameliorated by oral cyclooxygenase or phosphodiesterase inhibition.
The Reactivity and Oxidation Pathway of Cysteine 232 in Recombinant Human α1-Antitrypsin (2002)

Oxidative damage to the sulfur-containing amino acids, methionine and cysteine, is a major concern in biotechnology and medicine. alpha1-Antitrypsin, which is a metastable and conformationally flexible protein that belongs to the serpin family of protease inhibitors, contains nine methionines and a single cysteine in its primary sequence. Although it is known that methionine oxidation in the protein active site results in a loss of biological activity, there is little specific knowledge regarding the reactivity of its unpaired thiol, Cys-232. In this study, the thiol-modifying reagent NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazole) was used to label peroxide-modified alpha1-antitrypsin and demonstrate that the Cys-232 in vitro oxidation pathway begins with a stable sulfenic acid intermediate and is followed by the formation of sulfinic and cysteic acid in successive steps. pH-dependent reactivity with hydrogen peroxide showed that Cys-232 has a pK(a) of 6.86 +/- 0.05, a value that is more than 1.5 pH units lower than that of a typical protein thiol. pH-induced conformational changes in the region surrounding Cys-232 were also examined and indicate that mildly acidic conditions induce a conformation that enhances Cys-232 reactivity. In summary, this work provides new insights into alpha1-antitrypsin reactivity in oxidizing environments and shows that a unique structural environment renders its unpaired thiol, Cys-232, its most reactive amino acid.
Detection of adenovirus in clinical specimens by polymerase chain reaction and liquid-phase hybridization quantitated by time-resolved fluorometry (1993)

In addition to tests for the group-specific hexon antigen of adenoviruses, adenoviruses can be detected in clinical specimens by hybridization assays utilizing the widely shared base sequences of the region of the hexon gene that codes for the group-reactive determinants. We have developed a liquid-phase hybridization system with biotin- and europium-labeled probes which are reacted after DNA amplification of a 161-bp region of the hexon gene and which are quantitated by time-resolved (TR) fluorometry in streptavidin-coated microtiter wells. Polymerase chain reaction (PCR)-TR fluorometry is not a rapid test in the usual sense, but it is highly useful for specimens with inherent toxicity or with low virus yield, such as organ minces and specimens obtained late in the course of an illness. In a survey of 103 specimens tested by this method, including urine, stool, and tissue suspensions, the agreement with the hexon-specific TR fluoroimmunoassay antigen test for positive specimens was 100% and the sensitivity compared with that of virus culture was 91%. The PCR-TR fluorometry system was also shown to be advantageous as a quantitative measure of PCR products.
Effect of Thymectomy on Human Peripheral Blood T Cell Pools in Myasthenia Gravis (2001)

The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immunodeficiency in humans. Because thymectomy in humans is performed for treatment of myasthenia gravis (MG), we have studied patients with MG for effects of thymectomy on peripheral blood (PB) naive (CD45RA(+), CD62L(+)) and memory (CD45RO(+)) T cells. We have also determined the effect of thymectomy on levels of PB cells containing signal joint TCR delta excision circles (TRECs), a molecular marker of thymus emigrants that have divided few times after leaving the thymus. In 17 nonthymectomized and 26 thymectomized MG patients studied at varying times after thymectomy (1 day to 41 years), we found no significant mean difference in PB T cell TREC levels between ages 40 and 80 years. However, both thymectomized and nonthymectomized MG patients had lower PB T cell TREC levels than did age-matched normal subjects (p < 0.0001 for both). These data demonstrated that MG itself or treatment for MG decreased thymopoiesis independent of thymectomy. Next, to control for disease activity and treatment, we prospectively studied 10 MG patients before and from 27 to 517 days after thymectomy. We found that thymectomy decreased CD4 or CD8 T cell TREC concentrations most when thymopoiesis was active before thymectomy (six of six patients), but had little effect in patients when thymopoiesis was minimal (four of four patients). In contrast, there was no significant effect of thymectomy on absolute numbers of naive PB T cells. Thus, in MG, removal of a thymus with active thymopoiesis resulted in a significant fall in PB TREC(+) T cells postthymectomy.
Synthesis, Material Properties, and Transistor Performance of Highly Pure Thiophene Oligomers (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, Material Properties, and Transistor Performance of Highly Pure Thiophene OligomersH. E. Katz, L. Torsi, and A. DodabalapurCite this: Chem. Mater. 1995, 7, 12, 2235–2237Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/cm00060a007https://doi.org/10.1021/cm00060a007research-articleACS PublicationsRequest reuse permissionsArticle Views617Altmetric-Citations111LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Model for Automatically Repairing Execution Integrity (2007)

Many users value applications that continue execution in the face of attacks. Current software protection techniques typically abort a process after an intrusion attempt ({\it e.g.}, a code injection attack). We explore ways in which the security property of integrity can support availability. We extend the Clark-Wilson Integrity Model to provide primitives and rules for specifying and enforcing repair mechanisms and validation of those repairs. Users or administrators can use this model to write or automatically synthesize \emph{repair policy}. The policy can help customize an application's response to attack. We describe two prototype implementations for transparently applying these policies without modifying source code.
Barriers to Superfast Water Transport in Carbon Nanotube Membranes (2013)

Carbon nanotube (CNT) membranes hold the promise of extraordinary fast water transport for applications such as energy efficient filtration and molecular level drug delivery. However, experiments and computations have reported flow rate enhancements over continuum hydrodynamics that contradict each other by orders of magnitude. We perform large scale molecular dynamics simulations emulating for the first time the micrometer thick CNTs membranes used in experiments. We find transport enhancement rates that are length dependent due to entrance and exit losses but asymptote to 2 orders of magnitude over the continuum predictions. These rates are far below those reported experimentally. The results suggest that the reported superfast water transport rates cannot be attributed to interactions of water with pristine CNTs alone.
Analysis of volatile components of drugs and explosives by solid phase microextraction‐ion mobility spectrometry (2008)

Current ion mobility spectrometry (IMS) devices are used to detect drugs and explosives in the form of particles and, in cases where the vapor pressure of the drugs or explosives is sufficiently high, the gas can be sampled and detected directly. The aim of this study is to demonstrate the use of solid phase microextraction (SPME) as a preconcentration technique coupled to an IMS for the detection of odor signature compounds of drugs and explosives. The reduced mobilities (K(o)) and IMS operating conditions for the odor signature compounds of cocaine, marijuana, and 3,4-methylenedioxy-N-methylamphetamine (MDMA) are reported for the first time. LODs, linear dynamic ranges (LDRs), and the precision of the analysis of these odor signature compounds, and the explosive taggant 2,3-dimethyl-2,3-dinitrobutane (DMNB) were obtained by SPME-IMS and normal IMS conditions. The systematic optimization of the IMS operating parameters for the detection of these odor compounds is also reported incorporating the use of genetic algorithms (GAs) for finding the optimal settings for the detection of these compounds of interest. These results support the case for targeting volatile components as a presumptive detection for the presence of the parent compounds of drugs and explosives. Furthermore, the IMS-specific GA developed can be used as an optimization tool for the detection of other compounds of interest in future work.
Incidence and Duration of Side Effects and Those Rated as Bothersome With Selective Serotonin Reuptake Inhibitor Treatment for Depression (2004)

Side effects associated with SSRIs are common and bothersome to patients. Treatment-emergent side effects tend to persist during the first 3 months of treatment.
Prolonged Hypoxia Differentially Regulates Hypoxia-inducible Factor (HIF)-1α and HIF-2α Expression in Lung Epithelial Cells (2004)

Transcriptional adaptations to hypoxia are mediated by hypoxia-inducible factor (HIF)-1, a heterodimer of HIF-alpha and aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1alpha and HIF-2alpha subunits both undergo rapid hypoxia-induced protein stabilization and bind identical target DNA sequences. When coexpressed in similar cell types, discriminating control mechanisms may exist for their regulation, explaining why HIF-1alpha and HIF-2alpha do not substitute during embryogenesis. We report that, in a human lung epithelial cell line (A549), HIF-1alpha and HIF-2alpha proteins were similarly induced by acute hypoxia (4 h, 0.5% O(2)) at the translational or posttranslational level. However, HIF-1alpha and HIF-2alpha were differentially regulated by prolonged hypoxia (12 h, 0.5% O(2)) since HIF-1alpha protein stimulation disappeared because of a reduction in its mRNA stability, whereas HIF-2alpha protein stimulation remained high and stable. Prolonged hypoxia also induced an increase in the quantity of natural antisense HIF-1alpha (aHIF), whose gene promoter contains several putative hypoxia response elements to which (as we confirm here) the HIF-1alpha or HIF-2alpha protein can bind. Finally, transient transfection of A549 cells by dominant-negative HIF-2alpha, also acting as a dominant-negative for HIF-1alpha, prevented both the decrease in the HIF-1alpha protein and the increase in the aHIF transcript. Taken together, these data indicate that, during prolonged hypoxia, HIF-alpha proteins negatively regulate HIF-1alpha expression through an increase in aHIF and destabilization of HIF-1alpha mRNA. This trans-regulation between HIF-1alpha and HIF-2alpha during hypoxia likely conveys target gene specificity.
Glycosylation catalyzed by lysyl hydroxylase 3 is essential for basement membranes (2006)

Lysyl hydroxylase 3 (LH3) is a multifunctional enzyme possessing lysyl hydroxylase (LH), hydroxylysyl galactosyltransferase (GT) and galactosylhydroxylysyl glucosyltransferase (GGT) activities in vitro. To investigate the in vivo importance of LH3-catalyzed lysine hydroxylation and hydroxylysine-linked glycosylations, three different LH3-manipulated mouse lines were generated. Mice with a mutation that blocked only the LH activity of LH3 developed normally, but showed defects in the structure of the basement membrane and in collagen fibril organization in newborn skin and lung. Analysis of a hypomorphic LH3 mouse line with the same mutation, however, demonstrated that the reduction of the GGT activity of LH3 disrupts the localization of type IV collagen, and thus the formation of basement membranes during mouse embryogenesis leading to lethality at embryonic day (E) 9.5-14.5. Strikingly, survival of hypomorphic embryos and the formation of the basement membrane were directly correlated with the level of GGT activity. In addition, an LH3-knockout mouse lacked GGT activity leading to lethality at E9.5. The results confirm that LH3 has LH and GGT activities in vivo, LH3 is the main molecule responsible for GGT activity and that the GGT activity, not the LH activity of LH3, is essential for the formation of the basement membrane. Together our results demonstrate for the first time the importance of hydroxylysine-linked glycosylation for collagens.
Long non-coding RNA FTH1P3 facilitates uveal melanoma cell growth and invasion through miR-224-5p (2017)

Growing evidences indicated that Long noncoding RNAs (lncRNAs) played important roles in tumor initiation and progression. However, the function and mechnism of lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) remain unknown in uveal melanoma. We showed that the expression level of FTH1P3 was upregulated in uveal melanoma cell lines and tissues. Elevated expression of FTH1P3 promoted uveal melanoma cell proliferation, cell cycle and migration. Moreover, we found that FTH1P3 was a direct target gene of miR-224-5p in uveal melanoma cell. Overexpression of FTH1P3 suppressed miR-224-5p expression and promoted the expression of Rac1 and Fizzled 5, which were the direct target genes of miR-224-5p. Furthermore, we showed that miR-224-5p expression level was downregulated in uveal melanoma cell lines and tissues. FTH1P3 expression was inversely correlated with the miR-224-5p expression in uveal melanoma tissues. Ectopic expression of miR-224-5p decreased uveal melanoma cell proliferation, cell cycle and migration. Elevated expression of FTH1P3 enhanced uveal melanoma cell proliferation and migration by inhibiting miR-224-5p expression. These results suggest that lncRNA FTH1P3 plays a crucial role in uveal melanoma. Investigation of the underlying mechanism may be a target for the treatment of uveal melanoma.
The Mercury System: Exploiting Truly Fast Hardware in Data Mining (2003)

In many data mining applications, the size of the database is not only extremely large, it is also growing rapidly. Even for relatively simple searches, the time required to move the data off magnetic media, cross the system bus into main memory, copy into processor cache, and then execute code to perform a search is prohibitive. We are building a system in which a significant portion of the data mining task (i.e., the portion that examines the bulk of the raw data) is implemented in fast hardware, close to the magnetic media on which it is stored. Furthermore, this hardware can be replicated allowing mining tasks to be performed in parallel, thus providing further speedup for the overall mining application. In this paper, we describe a general framework under which this can be accomplished and provide initial performance results for a set of applications.
The Progression in the Mouse Skin Carcinogenesis Model Correlates With ERK1/2 Signaling (2002)

These data suggest, for the first time, that oncogenicity and the degree of progression in the mouse skin carcinogenesis model correlates with ERK1/2 signaling.
Chromosomal localization of two genes encoding human ras exchange factors: SOS1 maps to the 2p22→p16 region and SOS2 to the 14q21→q22 region of the human genome (1994)

The human SOS1 and SOS2 genes encode proteins that control GDP-->GTP exchange on ras proteins and are involved in signal transduction by tyrosine kinase receptors. In situ hybridization shows that SOS1 maps to 2p22-->p16 and SOS2 to 14q21-->q22 in the human genome.
Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes (1994)

We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis.