gebhart/patrepeval huggingface dataset:
Three-dimensional structure of the kringle sequence: structure of prothrombin fragment 1 (1986)

The three-dimensional structure of bovine prothrombin fragment 1 has been solved at 2.8-A resolution. The electron density clearly reveals four disulfide bridges along with more than 80% of the side chains completely in density, which correspond faithfully to the kringle sequence, its preceding 30 residues, and the dodecapeptide carboxy terminal; the polysaccharide and the first 35 residues of the amino terminal of fragment 1 are disordered or about 40% of the structure. The folding of the kringle sequence is based upon close disulfide van der Waals contacts between Cys-87-Cys-127 and Cys-115-Cys-139 (4.1 A between midpoints of the bridges), two antiparallel strands of highly conserved (113-118, 124-129) beta-structure, and the stacking of some conserved aromatic residues, all near the center of the folded structure. Moreover, the overall folding appears to be duplicated as a pair of stacked duplex loops with an antiparallel open loop. The overall shape of the kringle structure approximates an eccentric oblate ellipsoid of dimensions 11 X 28 X 30 A. The residues immediately preceding the kringle are dominated by alpha-helical structure (Phe-41-Cys-48; Leu-56-Glu-63). Residues Phe-41-Trp-42 and Tyr-45, which are conserved in factor IX, factor X, protein C, and protein Z, form another aromatic stacked cluster while the Cys-48-Cys-61 disulfide loop corresponds to the well-known alpha/beta structural unit. The dodecapeptide carboxy-terminal interkringle chain extends along the periphery of the kringle in its plane and forms a beta-structure with the kringle-closing Ser-140-Val-143 tetrapeptide.
Compression of Large 3D Engineering Models using Automatic Discovery of Repeating Geometric Features (2001)

In this paper, we present a new geometry compression technique particularly suitable for 3D mesh models of engineering class -- architectural models, machine plants, factories, etc. We observe that such models have a number of repeating features at various levels of granularity. In most of the widely available models in this class, the geometric description of such features are also repeated.
An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells (2013)

The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1), which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near-complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant--but not IDH1-wild-type--glioma cells without appreciable changes in genome-wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects.
Anionic Surfactant Gel Treatment Fluid (2007)

Abstract Typical viscoelastic surfactant gels used for gravel packing and hydraulic fracturing have relied upon cationic, amphoteric, or zwitterionic surfactants as their primary gelling agent, complicating the stimulation of some wells due to wettability or formation fluid compatibility issues. This paper describes an anionic viscoelastic surfactant developed for fracturing and gravel packing applications. The performance of the gel as a function of temperature, salt type and concentration, and cosurfactant will be presented along with the chemical structure/activity relationship. Rheological measurements demonstrate that fluids made with the new anionic surfactant have effective performance over a range of conditions encountered in treating wells.
Temperature Monitoring and Perioperative Thermoregulation (2008)

Most clinically available thermometers accurately report the temperature of whatever tissue is being measured. The difficulty is that no reliably core-temperature-measuring sites are completely noninvasive and easy to use-especially in patients not undergoing general anesthesia. Nonetheless, temperature can be reliably measured in most patients. Body temperature should be measured in patients undergoing general anesthesia exceeding 30 min in duration and in patients undergoing major operations during neuraxial anesthesia. Core body temperature is normally tightly regulated. All general anesthetics produce a profound dose-dependent reduction in the core temperature, triggering cold defenses, including arteriovenous shunt vasoconstriction and shivering. Anesthetic-induced impairment of normal thermoregulatory control, with the resulting core-to-peripheral redistribution of body heat, is the primary cause of hypothermia in most patients. Neuraxial anesthesia also impairs thermoregulatory control, although to a lesser extent than does general anesthesia. Prolonged epidural analgesia is associated with hyperthermia whose cause remains unknown.
HER-2/neu Oncogene Characterization in Head and Neck Squamous Cell Carcinoma (1995)

The HER-2/neu oncogene is overexpressed in a subset of HNSCC tumors and cell lines. The results from Western blot and immunohistochemical analyses underscore a variable HER2/neu oncoprotein expression in HNSCC. Gene amplification was observed in a few of the cell lines, suggesting a potential mechanism of oncoprotein overexpression. Messenger RNA overexpression, however, can be seen in the absence of gene amplification, indicating that transcriptional or posttranscriptional control mechanisms must be involved. Further studies are indicated to determine the biologic role of HER-2/neu expression in the clinical progression of these lesions and to further define the molecular basis regulating its expression.
Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase (1998)

To investigate the role of neurofilaments in motor neuron disease caused by superoxide dismutase (SOD1) mutations, transgenic mice expressing a amyotrophic lateral sclerosis-linked SOD1 mutant (SOD1(G37R)) were mated with transgenic mice expressing human neurofilament heavy (NF-H) subunits. Unexpectedly, expression of human NF-H transgenes increased by up to 65%, the mean lifespan of SOD1(G37R) mice. Microscopic examination corroborated the protective effect of NF-H protein against SOD1 toxicity. Although massive neurodegeneration occurred in 1-yr-old mice expressing SOD1(G37R) alone, spinal root axons and motor neurons were remarkably spared in doubly SOD1(G37R);NF-H-transgenic littermates.
Persistent access control to prevent piracy of digital information (1999)

Marshall McLuhan's statement that "the medium is the message" captured the reality of communications until the digital age. Communicating digitally involves the transfer of information as streams of bits. No longer does matter need to be moved. In the case of data representing continuous waveforms, the communication is complete when the recipient possesses a digital representation of the original signal with a given fidelity criterion. This allows one to embed watermarks to deliver hidden information. In the case of discrete data files, the communication is complete when the recipient possesses the identical stream of bits delivered by the source: at that moment there are two, identical, streams of bits. It is impossible to characterize one as the original and the other as the copy. Consequently, one loses control of digital information after transmitting it to another. The recipient is free to use their original as they see fit. The ubiquitous PC and Internet provide the means easily and inexpensively to copy and distribute data files to anyone wishing to do so. We introduce a framework for persistent access control over digital data. That is, data remain under the control of their originator, even after another has received them. This requires the use of multiple levels of encryption, transmission of ciphering keys through licenses associated with the data, and of trusted hardware and trusted software (access control mechanism) to ensure that the originator's restrictions are not circumvented. We show how a PC or consumer electronics appliance can accommodate the required system-while remaining compatible with previously produced data. This material is the subject of a pending U.S. Patent Application (allowed) and foreign applications.
Specificity of Interactions Between Polysaccharide Helices and β-1,4-Linked Polysaccharides (1981)

It is now firmly established that agarose1, ι - carrageenan2 and probably also κ -carrageenan3 can adopt double helical conformations in the condensed phase. The evidence is also very strong that, in favourable conditions of temperature and concentration, and (for the carrageenans) ionic strength and appropriate counterions, these double helices can survive in highly hydrated solutions and gels4. We have reported previously5 that the double helices of agarose and κ-carrageenan (but not i-carrageenan) could bind in an ordered, cooperative fashion, to the unsubstituted sequences of 1,4-linked β-D-mannopyranose residues in certain plant galactomannans, and that such mixed polysaccharide systems can lead to unexpected and useful rheological properties. We proposed5, that the binding mechanism involves noncovalent association between unlike polysaccharide chains in ordered, complementary conformations - a double helix and a ribbon respectively - as shown schematically in Figure 1. We have not yet determined the stoichiometry of binding (ie. whether helices
Agreement in Risk Prediction Between the 21-Gene Recurrence Score Assay (Oncotype DX®) and the PAM50 Breast Cancer Intrinsic Classifier™ in Early-Stage Estrogen Receptor–Positive Breast Cancer (2012)

There is good agreement between the two assays for high (i.e., luminal B or RS > 31) and low (i.e., luminal B or RS < 18) prognostic risk assignment but PAM50 assigns more patients to the low risk category. About half of the intermediate RS group was reclassified as luminal A by PAM50.
l-amino acid oxidases of Proteus rettgeri (1975)

Proteus rettgeri has been found to contain two separable 1-amino acid oxidases. Both enzymes are particulate in nature, neither being ribosomal bound. One of these enzymes appears to have broad specificity, being active toward monoaminomonocarboxylic, imino, aromatic, sulfur-containing, and beta-hydroxyamino acids. The other enzyme has more limited specificity, catalyzing the oxidative deamination of the basic amino acids and citrulline. The affinity of this oxidase for the various substrates at pH 7.6 in decreasing order is arginine, histidine, ornithine, citrulline, and lysine. This enzyme has a particularly high affinity for arginine (Km equal to 0.27 mM), and anomalous kinetics are observed with increasing substrate concentrations. When concentrations of arginine greater than 1.0mM were added to the reaction containing histidine, imidazole pyruvate formation was completely inhibited.
Immune response to infection with Salmonella typhimurium in mice (2000)

Infection of mice with Salmonella typhimurium results in systemic infection and a disease similar to that seen in humans after infection with S. typhi. The innate immune system can restrict replication of S. typhimurium to a certain degree, but for effective control and eradication of bacteria, acquired immunity is essential. Salmonella infection induces the generation of specific CD4+ and CD8+ T cells, and both T cell populations are important for protection during primary and secondary responses, although the mechanisms underlying T cell-mediated protection are not yet completely understood. Infection with S. typhimurium also results in a strong antibody response to Salmonella antigens and, in contrast to most other intracellular bacteria, this antibody response participates in protection. In summary, the response to S. typhimurium involves both T and B cell-mediated immunity, and mechanisms mediated by both lymphocyte populations are important for control of primary infection and protection against secondary infection.
Ketoconazole and fluconazole drug interactions (1993)

This article reviews potential drug interactions that exist between ketoconazole or fluconazole and other drugs. English-language data sources included human subjects' computerized databases and published indexes. Case reports and studies demonstrate decreased dosage requirements of cyclosporine sodium, methylprednisolone sodium succinate, and possibly anticoagulants and phenytoin after ketoconazole or fluconazole administration, suggesting hepatic enzyme inhibition. Increased dosage requirements of ketoconazole are necessary after rifampin administration, suggesting rifampin's induction of hepatic microsomal enzymes. Possibly a similar effect may occur with concomitant fluconazole and rifampin. The effect of ketoconazole administration on prednisolone sodium phosphate and theophylline warrants further study. Fluconazole, a more selective agent for fungal P-450, seems to be of less concern regarding the potential for drug interactions than ketoconazole. (Arch Intern Med. 1993;153:1970-1976)
Vitamin D3 analogs and their 24‐Oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects (1997)

The seco-steroid hormone, 1α,25 dihydroxyvitamin D3 (1α,25(OH)2D3) binds to a specific nuclear receptor that acts as a ligand-inducible transcription factor. The resulting genomic effects include partial arrest in G0/G1 of the cell cycle and induction of differentiation; these effects have been observed in various types of cancer. Recently, we produced enzymatically the natural 24-oxo metabolites of 1α,25(OH)2D3 and two of its potent synthetic analogs (1α,25-(OH)2-16-ene-D3 and 1α,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1α,25(OH)2D3 and its analogs have either the same or greater antiproliferative activity against various cancer cells as their parental compounds. Notably, two cell lines (DU-145 (prostate cancer) and MDA-MB-436 [breast cancer]) that were extremely resistant to the antiproliferative effects of vitamin D3 analogs displayed greater sensitivity towards the 24-oxo metabolite of the vitamin D3 analog. Similarly, the 24-oxo metabolites had the capacity to induce differentiation and apoptosis and to diminish the proportion of cells in S phase. Most interestingly, while the analog 1α,25(OH)2-20-epi-D3 induced expression of BRCA1 in MCF-7 breast cancer cells; its 24-oxo metabolite dramatically suppressed BRAC1 expression. Thus, we have shown for the first time that the various biological activities produced by the hormone 1α,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1α,25(OH)2D3 and its natural 24-oxo metabolites. J. Cell. Biochem. 66:413–425, 1997. © 1997 Wiley-Liss, Inc.
Antifertility agents. 11. Secosteroids. 5. Synthesis of 9,11-secoestradiol (1975)

9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on hydrogenolysis gave methyl 17beta-hydroxy-3-methoxy-9,11-secoestra-1,3,5(10)-triene-11-carboxylate (3). The 17-O-THP derivative of 3 was treated with LiAlH4 to give 17beta-(O-tetrahydropyranyl)-3-methoxy-11-hydroxy-9,11-secoestra-1,3,5(10)-triene (5). The 11-O-mesylate of 5 on LiAlH4 reduction followed by mild acid treatment and demethylation under alkaline conditions gave 9. LiAlH4 reduction of 3 gave 9,11-seco-11-hydroxyestradiol 3-methyl ether (11) which on demethylation gave 9,11-seco-11-hydroxyestradiol (12).
Relative debugging and its application to the development of large numerical models (1995)

Because large scientific codes are rarely static objects, developers are often faced with the tedious task of accounting for discrepancies between new and old versions. In this paper, we describe a new technique called relative debugging that addresses this problem by automating the process of comparing a modified code against a correct reference code. We examine the utility of the relative debugging technique by applying a relative debugger called Guard to a range of debugging problems in a large atmospheric circulation model. Our experience confirms the effectiveness of the approach. Using Guard, we are able to validate a new sequential version of the atmospheric model, and to identify the source of a significant discrepancy in a parallel version in a short period of time.
Efficient data structures for tamper-evident logging (2009)

Many real-world applications wish to collect tamperevident logs for forensic purposes. This paper considers the case of an untrusted logger, serving a number of clients who wish to store their events in the log, and kept honest by a number of auditors who will challenge the logger to prove its correct behavior. We propose semantics of tamper-evident logs in terms of this auditing process. The logger must be able to prove that individual logged events are still present, and that the log, as seen now, is consistent with how it was seen in the past. To accomplish this efficiently, we describe a tree-based data structure that can generate such proofs with logarithmic size and space, improving over previous linear constructions. Where a classic hash chain might require an 800 MB trace to prove that a randomly chosen event is in a log with 80 million events, our prototype returns a 3 KB proof with the same semantics. We also present a flexible mechanism for the log server to present authenticated and tamper-evident search results for all events matching a predicate. This can allow large-scale log servers to selectively delete old events, in an agreed-upon fashion, while generating efficient proofs that no inappropriate events were deleted. We describe a prototype implementation and measure its performance on an 80 million event syslog trace at 1,750 events per second using a single CPU core. Performance improves to 10,500 events per second if cryptographic signatures are offloaded, corresponding to 1.1 TB of logging throughput per week. 1
Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant β 2 -microglobulin gene (2006)

Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I alpha-chain and beta(2)-microglobulin (beta(2)m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the alpha-chain gene sequences of the siblings were normal, the beta(2)m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble beta(2)m and HLA in the siblings' sera were <1% of normal. Transfection assays of beta(2)m-deficient cultured cells with beta(2)m cDNA indicated that the mutant beta(2)m supported <20% of normal expression of beta(2)m, MHC class I, and FcRn proteins. We concluded that a beta(2)m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and IgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds IgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations.
RAGE Blockade Stabilizes Established Atherosclerosis in Diabetic Apolipoprotein E–Null Mice (2002)

RAGE contributes not only to accelerated lesion formation in diabetic apoE-null mice but also to lesion progression. Blockade of RAGE may be a novel strategy to stabilize atherosclerosis and vascular inflammation in established diabetes.
TSCSP: Tabu search algorithm for VLSI module placement based on the clustering sequence-pair (2003)

Placement is an very important step in the physical design of VLSI circuits. It is the rectangular packing problem: Given a set of rectangular modules of arbitrary sizes, place them non-overlapping on a plane within a rectangle of minimum area. Since the variety of packing is uncountable infinite, the key issue is to find the optimal solution in the finite solution space, hence it is hard to be solved exactly in practical applications. In this paper, Tabu search algorithm is applied to solve module placement problem. Firstly, all modules are merged into some clusters according to the ratio-connectivity of circuit modules, the placement of the large modules (are included by some modules) is then represented by sequence-pairs. The searching of optimal solution of placement is performed by the tabu search algorithm. Some experiment results are shown in order to demonstrate the effectiveness of the proposed method.
Hypoxia- and non-hypoxia-related pulmonary hypertension — Established and new therapies (2006)

Pulmonary hypertension can occur as an isolated disease affecting the lung vessels only, in association with underlying hypoxic lung disorders, or due to chronic thromboembolic disease. Pulmonary hypertension caused by pulmonary venous congestion will not be focused on in this review. Regardless of the underlying disease, chronic cor pulmonale is associated with progressive clinical deterioration and a poor prognosis in most cases. The aim of specific therapies for pulmonary hypertension is to reduce pulmonary vascular resistance and thereby improve right ventricular function. Currently, three classes of drugs (prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors) are approved for the treatment of pulmonary arterial hypertension (PAH) in a defined patient population (group I according to the recent WHO classification). However, these medications may also lower pulmonary vascular resistance in patients with associated lung diseases (e.g. chronic obstructive pulmonary disease or lung fibrosis) and significant pulmonary hypertension, for whom these drugs are not yet approved. As non-selective vasodilators may induce gas-exchange disturbances, which preclude their long term use in these patients, such substances should be avoided in the hypoxemic patient. In this article we provide an update of the current understanding of hypoxia- and non-hypoxia-related pulmonary hypertension, addressing both the pathophysiological understanding of different disease aetiologies as well as the therapeutic options currently available.