gebhart/patrepeval huggingface dataset:
Brd2 disruption in mice causes severe obesity without Type 2 diabetes (2009)

Certain human subpopulations are metabolically healthy but obese, or metabolically obese but normal weight; such mutations uncouple obesity from glucose intolerance, revealing pathways implicated in Type 2 diabetes. Current searches for relevant genes consume significant effort. We have reported previously a novel double bromodomain protein called Brd2, which is a transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin. In the present study, we show that wholebody disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue, heat production and expression of mitochondrial uncoupling proteins in brown adipose tissue, reduced macrophage infiltration in white adipose tissue, and lowered blood glucose, leading to an improved metabolic profile and avoiding eventual Type 2 diabetes. Brd2 is highly expressed in pancreatic beta-cells, where it normally inhibits beta-cell mitosis and insulin transcription. In 3T3-L1 pre-adipocytes, Brd2 normally co-represses PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) and inhibits adipogenesis. Brd2 knockdown protects 3T3-L1 adipocytes from TNF-alpha (tumour necrosis factor-alpha)-induced insulin resistance, thereby decoupling inflammation from insulin resistance. Thus hypomorphic Brd2 shifts energy balance toward storage without causing glucose intolerance and may provide a novel model for obese metabolically healthy humans.
High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization (2005)

High resolution CGH analysis of breast cancer reveals several regions where DNA copy number is commonly gained or lost, that non-random correlations between specific amplicons exist, and that specific genetic alterations are maintained in breast cancer cell lines despite repeat passage in tissue culture. These observations suggest that genes within these regions are critical to the malignant phenotype and may thus serve as future therapeutic targets.
[Induction of left ventricular remodeling and dysfunction in the recipient heart following donor heart myocardial infarction: new insights into the pathological role of tumor necrosis factor-alpha from a novel heterotopic transplant-coronary ligation model]. (2003)

We developed a novel heterotopic cardiac transplantation-coronary ligation model capable of inducing myocardial infarction in the absence of downstream hemodynamic effects, and allowing differential quantification of indexes of cardiac remodeling in vivo, such as the local and remote effects of angiotensin II and TNF-alpha on cardiac remodeling. Modification of activated cytokines, such as TNF-alpha induced by cardiac ischemic stress, might be a beneficial strategy for the treatment of cardiac dysfunction and subsequent cardiac remodeling after acute myocardial infarction.
EAP-TLS smarteards, from dream to reality (2004)

This paper presents the first implementation of the EAPTLS (Extensible Authentication Protocol-Transport Layer Security) protocol in smartcards. Tests, performed on two java devices, are discussed and analysed. Results show that TLS processing is slow, because smartcards are not (yet) optimized for that purpose; however we clearly demonstrate that TLS processing in smartcards is not today a dream, and can be realized with existing components.
High resolution on-chip spectroscopy based on miniaturized microdonut resonators (2011)

We experimentally demonstrate a high resolution integrated spectrometer on silicon on insulator (SOI) substrate using a large-scale array of microdonut resonators. Through top-view imaging and processing, the measured spectral response of the spectrometer shows a linewidth of ~0.6 nm with an operating bandwidth of ~50 nm. This high resolution and bandwidth is achieved in a compact size using miniaturized microdonut resonators (radius ~2 μm) with a high quality factor, single-mode operation, and a large free spectral range. The microspectrometer is realized using silicon process compatible fabrication and has a great potential as a high-resolution, large dynamic range, light-weight, compact, high-speed, and versatile microspectrometer.
ChemInform Abstract: Synthesis of Di(1‐isoquinolinyl) and Di(4‐quinazolinyl) Disulfides from 1(2H)‐Isoquinolinethiones and 4(3H)‐Quinazolinethiones, Respectively, with Tosyl Chloride and Sodium Ethoxide. (1983)

Abstract Die Titelumsetzung liefert die Disulfide (II) bzw. (IV) in über 70proz. Ausbeute.
On the role of surface tension in the stabilization of globular proteins (1996)

The stabilization of proteins by a variety of co-solvents can be related to their property of increasing the surface tension of water. It is demonstrated that, during the thermal unfolding of proteins, this increase of the surface tension can be overcome by the increase in the temperature of the solution at the midpoint of the transition, Tm, and the weak binding of co-solvent molecules. Three such co-solvents were studied: trehalose, lysine hydrochloride (LysHCl), and arginine hydrochloride (ArgHCl). Trehalose and LysHCl increase the midpoint of Tm. The increase of the surface tension by addition of trehalose is completely compensated by its decrease due to the increase in Tm. However, for LysHCl, the increase of the surface tension by the co-solvent is partly reduced by its binding to the protein. For trehalose, preferential interaction measurements with RNaseA demonstrate that it is totally excluded from the protein. In contrast, LysHCl gives evidence of binding to RNaseA. ArgHCl also increases the surface tension of water. Nevertheless, Tm of RNaseA decreases on addition of ArgHCl to the solution. Preferential interaction measurements showed very small values of preferential hydration of the native protein, indicating extensive binding of ArgHCl to the protein. During unfolding, the amount of additional ArgHCl binding is sufficiently large to counteract the surface tension effects, and the protein is destabilized. Therefore, although surface tension appears to be a critical factor in the stabilization of proteins, its increase by co-solvent does not ensure increased stabilization. The binding of ligands can reduce significantly, or even overwhelm, its effects.
Evaporative evolution of a Na–Cl–NO[sub 3]–K–Ca–SO[sub 4]–Mg–Si brine at 95 °C: Experiments and modeling relevant to Yucca Mountain, Nevada (2005)

A synthetic Topopah Spring Tuff water representative of one type of pore water at Yucca Mountain, NV was evaporated at 95°C in a series of experiments to determine the geochemical controls for brines that may form on, and possibly impact upon the long-term integrity of waste containers and drip shields at the designated high-level, nuclear-waste repository. Solution chemistry, condensed vapor chemistry, and precipitate mineralogy were used to identify important chemical divides and to validate geochemical calculations of evaporating water chemistry using a high temperature Pitzer thermodynamic database. The water evolved toward a complex "sulfate type" brine that contained about 45 mol % Na, 40 mol % Cl, 9 mol % NO3, 5 mol % K, and less than 1 mol % each of SO4, Ca, Mg, ∑CO2(aq), F, and Si. All measured ions in the condensed vapor phase were below detection limits. The mineral precipitates identified were halite, anhydrite, bassanite, niter, and nitratine. Trends in the solution composition and identification of CaSO4 solids suggest that fluorite, carbonate, sulfate, and magnesium-silicate precipitation control the aqueous solution composition of sulfate type waters by removing fluoride, calcium, and magnesium during the early stages of evaporation. In most cases, the high temperature Pitzer database, used by EQ3/6 geochemical code, sufficiently predicts water composition and mineral precipitation during evaporation. Predicted solution compositions are generally within a factor of 2 of the experimental values. The model predicts that sepiolite, bassanite, amorphous silica, calcite, halite, and brucite are the solubility controlling mineral phases.
The immune epitope database (IEDB) 3.0 (2014)

The IEDB, www.iedb.org, contains information on immune epitopes--the molecular targets of adaptive immune responses--curated from the published literature and submitted by National Institutes of Health funded epitope discovery efforts. From 2004 to 2012 the IEDB curation of journal articles published since 1960 has caught up to the present day, with >95% of relevant published literature manually curated amounting to more than 15,000 journal articles and more than 704,000 experiments to date. The revised curation target since 2012 has been to make recent research findings quickly available in the IEDB and thereby ensure that it continues to be an up-to-date resource. Having gathered a comprehensive dataset in the IEDB, a complete redesign of the query and reporting interface has been performed in the IEDB 3.0 release to improve how end users can access this information in an intuitive and biologically accurate manner. We here present this most recent release of the IEDB and describe the user testing procedures as well as the use of external ontologies that have enabled it.
Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid. (1997)

Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis. Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFalpha production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation. In BALB/c mice, a dose of 10 mg/kg LPS, injected i.p., caused 57% and 100% mortality, at 24 and 48 hr, respectively. HU-211, administered i.p. 30 min before lipopolysaccharide (LPS), reduced lethality to 9 and 67% at these time points (P < .05). When coinjected with D-galactoseamine (i.p.), LPS was 100% lethal within 24 hr, whereas eight hourly injections of HU-211 caused mortality of C57BL/6 mice to drop to 10% (P < .001). Administration of LPS to Sprague-Dawley rats resulted in a 30% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFalpha production and nitric oxide generation (by >90%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS. HU-211 may, therefore, have therapeutic implications in the treatment of TNFalpha-mediated pathologies.
<title>Large-scale experiments on low-bit-rate multimedia broadcast</title> (1998)

This paper contains our experience with low bit rate multimedia streaming and broadcast, as applied to the Internet/Intranet, and focuses on two of the enabling technologies: 100% Java clients and broadcast reflectors. Interpreted Java is slower than compiled C/C++ and Java platforms do not currently support video and audio synchronization. Various techniques to improve Java performance and to reduce code size are provided in detail. A novel video and audio synchronization mechanism for the pure Java environment is devised and instigated. This paper also describes a hierarchical reflector network architecture which, superimposed on the Internet, is a practical alternative for broadcasting of events to massive client audiences when multicast support of such audiences in the current Internet is questionable and remains untested.
Menopausal hormone replacement therapy and breast cancer: A meta‐analysis (1992)

A meta-analysis was performed to determine whether the scientific literature provides enough evidence that hormone replacement therapy after menopause increases the risk of breast cancer. Studies were located by MEDLINE, supplemented by a hand search of all the references in the articles located. The papers were graded as to quality. Those considered unbiased were combined using Woolf's method. Thirty-seven original studies were found: 23 case-control, 13 cohort, and one clinical trial. Overall, a small but statistically significant relative risk (RR) figure of 1.06 was calculated. Women who experienced natural menopause seemed to be at increased risk (RR = 1.13). A significant weighted RR was observed in current hormone replacement therapy users, especially in those who had natural menopause (RR = 1.63). A nonsignificant increasing trend was found between duration of hormone replacement therapy and breast cancer risk, although the opposite was seen when the association was analyzed by time since last use. These results imply that hormone replacement therapy could promote breast cancer.
Efficacy of colistin‐impregnated beads to prevent multidrug‐resistant A. baumannii implant‐associated osteomyelitis (2009)

Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dose delivery. To address this, we developed a mouse model with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic lesions that do not contain apparent biofilm. We also found that mice mount a specific IgG response against three proteins (40, 47, and 56 kDa) regardless of the strain used, suggesting that these may be immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a 100% infection rate with 75% of the MDR strains, and in vitro testing confirmed that all strains were sensitive to colistin. We also developed a real-time quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7 days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an unloaded PMMA bead control. While the parenteral colistin failed to demonstrate any significant effects versus the placebo, the colistin PMMA bead significantly reduced the infection rate such that only 29.2% of the mice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).
Dugald Arbuckle—Dialogue With Jerry Pine (1979)

Dugald S. Arbuckle, an advocate of human rights in counseling and writer on the implications of existential humanistic thought in psychotherapy and education, reflects on the roots of his humanistic thinking from his boyhood days in the mining country of the Western Canadian Rockies through more than 30 years of teaching and private practice. A major contributor to the literature that has shaped counseling and psychotherapy, Arbuckle is the founder of the graduate Program in Humanistic Counseling at Boston University and served as president of the American Personnel and Guidance Association (1959–60). In this dialogue he discusses a wide and provocative range of ideas with a former student, Gerald J. Pine, currently Professor of Counselor Education at the University of New Hampshire.
Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway (2006)

Cisplatin resistance occurs, at least in part, through the function of the Fanconi anemia (FA)/BRCA pathway, a DNA-damage response pathway required for repair of cisplatin cross-links. In the current study, we designed a cell-based screening strategy to identify small-molecule inhibitors of the FA/BRCA pathway with the hypothesis that such molecules could restore sensitivity to platinum agents. We identified four inhibitors, including three protein kinase inhibitors (wortmannin, H-9, and alsterpaullone) and one natural compound (curcumin) that inhibit the FA/BRCA pathway. We show that curcumin, a compound that is generally regarded as safe, inhibits the monoubiquitination of the FANCD2 protein as predicted by the screen and consequently sensitizes ovarian and breast tumor cell lines to cisplatin through apoptotic cell death. We believe that this study shows an efficient, high-throughput method for identifying new compounds that may sensitize cancer cells to DNA-damaging chemotherapy.
북,미간 영변 대포동, 금창리 핵/미사일 협상 결과의 결정요인 분석: 윈셋(win-set) 개념을 중심으로 (2005)

본 논문은 1990년대 북한과 미국 간의 영변, 금창리, 대포동, 핵·미사일 협상의 결과를 설명한다. 북한에 대해 군사적 공격을 계획했던 미국은 협상을 통해 북한에 경제적 지원을 하게 되었다. 북한과 미국 간의 협상은 비대칭적 협상에서 강대국이 약소국보다 협상에서 우월할 것이라는 기존의 체계적 접근 방법의 예상과는 다른 결과를 보여준다. 비대칭적 북·미간 핵·미사일 협상 결과에 영향을 준 요인은 미국의 힘만은 아닌 다양한 국내 변수 및 외압이 큰 역할을 한 것이다. 이런 맥락에서 미국의 민간 부문의 활동과 역할, 북한의 국내상황, 그리고 대외적인 외압들이 북한과 미국과의 협상 결과에 어떤 영향을 주었는지를 설명한다.
The adenovirus hexon protein. The primary structure of the polypeptide and its correlation with the hexon gene. (1981)

The primary structure of the adenovirus hexon polypeptide has been determined by amino acid sequence studies of peptides from all regions of the molecule combined with sequence analysis of selected areas of its gene. The sequence presented contains 966 unique amino acid residues. Overlapping peptides recovered from CNBr cleavage and from digestions with proteolytic enzymes were analyzed, as well as DNA segments around sites for restriction endonucleases in the hexon gene. The primary structure is in good agreement with the total composition of the protein, with the compositions of individual CNBr fragments, and with known locations of restriction enzyme cleavage sites in the gene. Distinct regions of internal homology do not occur in the structure. The entire hexon polypeptide is encoded by a contiguous DNA sequence without intervening sequences.
Phase II Trial of Gefitinib in Recurrent Glioblastoma (2003)

Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.
Cell micropatterning on an albumin‐based substrate using an inkjet printing technique (2009)

Positioning of cells in a desired pattern on a substrate is an important technique for cell-based technologies, including the fundamental investigation of cell functions, tissue-engineering applications, and the fabrication of cell-based biosensors and cell arrays. Recently, the inkjet printing technique was recognized as a promising approach to the creation of cellular patterns on substrates, and it has been achieved by the printing of living cells or cell adhesive proteins. In this article, we created complex cellular patterns by using an albumin-based substrate and inkjet printing technique. Albumin was cross-linked using ethylene glycol diglycidyl ether. Subsequent casting of the cross-linked albumin solution onto glass plates prevented cells from adhering to their surfaces. Through screening various chemical reagents, we found that these cross-linked albumin surfaces dramatically changed into cell adhesive surfaces after immersion in cationic polymer solutions. Based on this finding, cell adhesive regions were prepared with a desired pattern by printing the polyethyleneimine (PEI) solution onto a cross-linked albumin substrate using a modified commercial inkjet printer. Various cellular patterns including figures, letters, and gradients could be fabricated by seeding mouse L929 fibroblast cells or mouse Neuro-2a neuroblastoma cells onto the printed PEI-patterned substrate. Compared with the printing of fragile living cells or proteins, printing of stable PEI circumvents clogging of printer head nozzles and enables reproducible printing. Therefore, the present method will allow the creation of complex cell patterns.
Experimental aspects of high‐intensity transient signals in the detection of emboli (1995)

Experimental studies in the 1960s and 1970s demonstrated the high sensitivity of Doppler ultrasound in detecting gaseous bubbles. More recent studies have shown that microscopic air bubbles, as well as glass microspheres as small as 5 mu to 20 mu, cause characteristic high-intensity signals. Recently it has been demonstrated that less echogenic embolic materials such as thrombus, platelet aggregates, and atheroma can also be detected with a high sensitivity. Such "solid," or formed-element, emboli as small as 200 mu to 400 mu can be detected; the lower size limit of detection was due to an inability to make smaller embolic particles rather than to the sensitivity of the detection process itself. Analysis of the Doppler signals provides some information about embolus size and composition, but accurate characterization in clinical practice is not possible using current technology. Studies in experimental models have allowed the detailed description of embolic signals; they appear as a short-duration, frequency-focused increase in intensity, predominantly unidirectional in the direction of flow, and usually contained within the spectral envelope. In contrast, artifacts appear as a bidirectional, high-intensity increase with maximum intensity at low frequencies. These differences have been exploited to develop automatic embolus detection programs, and an off-line version has been successfully validated in an experimental model.
The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats (2002)

Abstract The favorable pharmacological profile exhibited by piracetam stimulated the synthesis of related compounds potentially endowed with a higher nootropic potency. The antiamnesic and procognitive activity of DM232 (unifiram), a new compound structurally related to piracetam, was investigated. Mouse passive avoidance and rat Morris water maze and Social learning tests were employed. DM232 (0.001–1 mg kg −1 i.p. – 0.01–0.1 1 mg kg −1 p.o.) prevented amnesia induced by scopolamine (1.5 mg kg −1 i.p.), mecamylamine (20 mg kg −1 i.p.), baclofen (2 mg kg −1 i.p.), and clonidine (0.125 mg kg −1 i.p.). Furthermore, The antiamnesic effect of the investigated compound was comparable to that exerted by well‐known nootropic drugs such as piracetam (30–100 mg kg −1 i.p.), aniracetam (100 mg kg −1 p.o.), rolipram (30 mg kg −1 p.o.), and nicotine (5 mg kg −1 i.p). DM232 (0.1 mg kg −1 i.p.) was also able to prevent amnesia induced by scopolamine (0.8 mg kg −1 i.p.) in the rat Morris watermaze test. In the rat social learning test, DM232 (0.1 mg kg −1 i.p.) injected in adults rats reduced the duration of active exploration of the familiar partner in the second session of the test. DM232, similarly to piracetam, reduced the duration of hypnosis induced by pentobarbital. At the highest effective doses, the investigated compound did not impair motor coordination (rota rod test), nor modified spontaneous (Animex). These results indicate DM232 (unifiram) as a novel cognition enhancer, strictly related to piracetam‐like compounds, able to ameliorate memory impairment at doses about 1,000 times lower than the most active available nootropic compounds. Drug Dev. Res. 56:23–32, 2002. © 2002 Wiley‐Liss, Inc.