gebhart/patrepeval huggingface dataset:
Nature of the charged-group effect on the stability of the C-peptide helix. (1985)

The residues responsible for the pH-dependent stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A) have been identified by chemical synthesis of analogues and measurement of their helix-forming properties. Each of the residues ionizing between pH 2 and pH 8 has been replaced separately by an uncharged residue. Protonation of Glu-2- is responsible for the sharp decrease in helix stability between pH 5 and pH 2, and deprotonation of His-12+ causes a similar decrease between pH 5 and pH 8. Glu-9- is not needed for helix stability. The results cannot be explained by the Zimm-Bragg model and host-guest data for alpha-helix formation, which predict that the stability of the C-peptide helix should increase when Glu-2- is protonated or when His-12+ is deprotonated. Moreover, histidine+ is a strong helix-breaker in host-guest studies. In proteins, acidic and basic residues tend to occur at opposite ends of alpha-helices: acidic residues occur preferentially near the NH2-terminal end and basic residues near the COOH-terminal end. A possible explanation, based on a helix dipole model, has been given [Blagdon, D. E. & Goodman, M. (1975) Biopolymers 14, 241-245]. Our results are consistent with the helix dipole model and they support the suggestion that the distribution of charged residues in protein helices reflects the helix-stabilizing propensity of those residues. Because Glu-9 is not needed for helix stability, a possible Glu-9-...His-12+ salt bridge does not contribute significantly to helix stability. The role of a possible Glu-2-...Arg-10+ salt bridge has not yet been evaluated. A charged-group effect on alpha-helix stability in water has also been observed in a different peptide system [Ihara, S., Ooi, T. & Takahashi, S. (1982) Biopolymers 21, 131-145]: block copolymers containing (Ala)20 and (Glu)20 show partial helix formation at low temperatures, pH 7.5, where the glutamic acid residues are ionized. (Glu)20(Ala)20Phe forms a helix that is markedly more stable than (Ala)20(Glu)20Phe. The results are consistent with a helix dipole model.
Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine (1968)

DL-threo- and DL-erythro-β-Hydroxyisoleucine were prepared from cis- and trans-3-methylpent-2-enoic acids, respectively. The configuration of the erythro isomer was established from its synthesis by two independent routes. The diastereoisomers, and those of other β-hydroxy amino acids, can be distinguished by examination of their proton magnetic resonance spectra.
PIK3CA mutations in advanced ovarian carcinomas (2005)

PIK3CA belongs to the phosphatidylinositol 3-kinases (PI3Ks) family, which play an important role in proliferation, adherence, transformation and cell survival through the PI3K/AKT signaling pathway. Somatic activating mutations of this gene have recently been detected in several types of cancers. In the present study, 109 advanced ovarian carcinomas were analyzed for PIK3CA mutations in exon 9 and exon 20 by direct sequencing. Activating missense mutations were observed in 4 of the 109 tumors in addition to one variant leading no change of the PIK3CA protein. Two of the cases with mutations were mucinous and clear cell tumors, suggesting that PIK3CA mutations are more common in these rare histological types.
Evidence that p53 behaves as a tumour suppressor gene in sporadic breast tumours. (1990)

Using the polymerase chain reaction, we have amplified exons 5 and 6 of the human p53 gene from paired samples of tumour and blood DNA of 60 patients with sporadic breast tumours and from placental or tonsil DNA of 30 normal controls. The patients' DNAs were previously examined for loss of heterozygosity of markers distal to the p53 gene on chromosome 17p and tumour samples were assayed for p53 mRNA levels. Hydroxylamine modification of mismatched base pairs was used to identify mutations in the amplified product. We have directly sequenced many of the samples including all those with mutations and have identified the particular mutation in each case. Exons 5 and 6 code for amino acids 126 through to 224 and constitute approximately 25% of the total coding region of the gene. They encompass part of the SV40 binding region as well as 2 of 5 areas known to be highly conserved in evolution and mutations in this region have been shown to be associated with tumorigenicity. We have found mutations in 13% of the primary tumours (8/60), all of which show allele loss of markers in the 17p region. No mutations were found in exons 5 and 6 of 30 normal controls. Our results are the first to identify mutations in p53 in primary breast tumours. Since our analysis has so far been confined to only part of the coding region of the gene, it is likely that further studies will reveal a mutation frequency in excess of 13%.
Smad4 and β-Catenin Co-activators Functionally Interact with Lymphoid-enhancing Factor to Regulate Graded Expression of Msx2 (2003)

Recent in vivo evidence suggests that Wnt signaling plays a central role in determining the fate of stem cells in the ectoderm and in the neural crest by modulating bone morphogenetic protein (BMP) levels, which, in turn, influence Msx gene expression. However, the molecular mechanism regulating the expression of the Msx genes as key regulators of cell fate has not been elucidated. Here we show in murine embryonic stem cells that BMP-dependent activation of Msx2 is mediated via the cooperative binding of Smad4 at two Smad binding elements and of lymphoid enhancing factor (Lef1) at two Lef1/TCF binding sites. Lef1 can synergize with Smad4 and Smad1 to activate Msx2 promoter, and this transcriptional complex is assembled on the endogenous promoter in response to BMP2. The Wnt/beta-catenin signaling pathway can activate Msx2 via the binding of Lef1 to its promoter and synergizes with BMP2 to activate Msx2 expression, possibly via enhanced recruitment of the p300/cAMP-response element-binding protein-binding protein co-factor. Interestingly, the Wnt/beta-catenin-dependent activation of Msx2 was defective in Smad4-deficient embryonic stem cells or when Smad binding elements were mutated but persisted in the presence of various BMP antagonists, indicating that Smad4 was involved in transducing the Wnt/beta-catenin signals in the absence of a BMP autocrine loop. A chromatin immunoprecipitation analysis revealed that endogenous Smad4, but not Smad1, was part of the Lef1 transcriptional complex in response to beta-catenin activation, dismissing any implication of BMP signaling in this response. We propose that Wnt signaling pathway could dictate cell fate not only by modulating BMP levels but also by directly regulating cooperatively BMP-target genes.
Starch-Deficient Maize Mutant Lacking Adenosine Diphosphate Glucose Pyrophosphorylase Activity (1966)

The maize mutant shrunken-2 synthesizes only 25 to 30 percent as much starch as normal maize; it completely lacks adenosine diphosphate glucose pyrophosphorylase activity in both endosperm and embryo tissue. Identification of the mutant block indicates that the greater portion of starch in the endosperm of normal maize is synthesized by way of enzyme systems that utilize adenosine diphosphate glucose as a substrate, and that the latter is formed chiefly by adenosine diphosphate glucose pyrophosphorylase.
Optimizing SPARQLeR using short circuit evaluation of filter clauses (2009)

The discovery of semantic relationships between two entities is an area of interest and study in the Semantic Web. Regarding the data in an RDF store as a graph allows the utilization of path searches, but with large ontologies exhaustive searches are not practical. SPARQLeR, an extension of SPARQL, sought to utilize regular expressions in the search and construction of a path which helped avoid exhaustive searches by limiting the search space during evaluation. Still, due to the filter constraint evaluation occurring after a path was constructed, the actual search space of the beginning and ending resources was not being limited. To address this problem, an optimization is proposed that uses a form of short circuit evaluation of the filter constraints in a SPARQL query to limit the search space as early as possible to avoid costly path searches between two nodes.
Predictive markers in rapidly progressing rheumatoid arthritis. (2007)

The emphasis in rheumatoid arthritis (RA) management today is on early diagnosis and intervention, but the choice of intervention has become increasingly complex. The number of disease modifying antirheumatic drugs available for treatment of RA has increased significantly. The efficacy, toxicity, and cost of those agents vary widely. And the progression of joint damage in RA is highly unpredictable and variable, ranging from self-limited disease to rapid progressive destruction. Prognostic markers that could identify patients with aggressive, rapidly progressing disease and predict the response to therapy would provide a rational basis for early, aggressive treatment. They would also protect patients with less aggressive disease from possible overtreatment and toxicities, and could have a significant influence on allocation of healthcare resources. The search for predictive markers of arthritis outcome has been and undoubtedly will continue to be the subject of many studies. This article will review both established and emerging predictive markers in RA.
Practical aerobic membrane filtration blood culture technique: clinical blood culture trial (1975)

During the course of preliminary clinical trials of an improved membrane filter blood culture system, filter plugging produced by a gelling of the lysing solution was observed when the patients had high leukocyte counts. A solution of streptokinase-streptodornase (Varidase, Lederle Laboratories) dissolved or prevented the gel and permitted rapid filtration without plugging. With streptokinase-streptodornase incorporated in the filtration procedure, a comparison of several culture systems was carried out on 176 blood cultures. Brucella broth with and without sodium polyanethol sulfonate, a prereduced osmotically stabilized broth, pour plates, and an improved aerobic membrane filter system were compared. The membrane filter system yielded 29 of the total of 37 positive cultures, far surpassing all other systems. Eight of these cultures were detected first by the filter technique, and 13 were positive only in this system. Nineteen of the 37 positive cultures were from patients on antimicrobial agents. Fourteen of these were detected by the filter, twice the number detected by any of the other systems.
Severe alcoholic hepatitis-current concepts, diagnosis and treatment options (2014)

Alcoholic hepatitis (AH) is an acute hepatic manifestation occurring from heavy alcohol ingestion. Alcoholic steatohepatitis (ASH) is histologically characterized by steatosis, inflammation, and fibrosis in the liver. Despite the wide range of severity at presentation, those with severe ASH (Maddrey's discriminant function ≥ 32) typically present with fever, jaundice, and abdominal tenderness. Alcohol abstinence is the cornerstone of therapy for AH and, in the milder forms, is sufficient for clinical recovery. Severe ASH may progress to multi-organ failure including acute kidney injury and infection. Thus, infection and renal failure have a major impact on survival and should be closely monitored in patients with severe ASH. Patients with severe ASH have a reported short-term mortality of up to 40%-50%. Severe ASH at risk of early death should be identified by one of the available prognostic scoring systems before considering specific therapies. Corticosteroids are the mainstay of treatment for severe ASH. When corticosteroids are contraindicated, pentoxifylline may be alternatively used. Responsiveness to steroids should be assessed at day 7 and stopping rules based on Lille score should come into action. Strategically, future studies for patients with severe ASH should focus on suppressing inflammation based on cytokine profiles, balancing hepatocellular death and regeneration, limiting activation of the innate immune response, and maintaining gut mucosal integrity.
Role of amine activators on the curing parameters, properties and toxicity of acrylic bone cements (1998)

A review about the accelerating effect of tertiary aromatic amines used as activator in the benzoyl peroxide/amine system for the curing of acrylic resins is presented. The kinetics, mechanism and activation energy of the reaction are considered, together with some toxicity, residuals and leaching data concerned with biomedical applications of this system, e.g. denture resins or acrylic bone cements. Furthermore, some results relating the effect of the temperature of the surroundings on the curing parameters of the cements prepared with three amines (N,N-dimethyl-4-toluidine, N,N-dimethylbenzyl alcohol and N,N-dimethylbenzyl methacrylate) are shown. The results indicate that the temperature has a significant effect on the curing parameters, and must be considered in the evaluation of new activators. The relevance of these results lies with the importance of thermal trauma generally associated with the implantation of acrylic bone cements. © 1998 SCI.
SOI material technology using plasma immersion ion implantation (2002)

Silicon on insulator (SOI) devices have many attractive applications in integrated circuit technology. The high cost of manufacturing the SOI wafers, however, prevents it from being widely accepted for mass production. Separation by plasma implantation of oxygen (SPIMOX), an extremely high through-put SIMOX formation process using plasma immersion ion implantation (PIII) has demonstrated promising results. In this paper, an improvement on the SPIMOX process is presented. High-dose implantation is a costly procedure for the "smart cut" process. A low cost, high through-put implantation by hydrogen or helium plasma is demonstrated as a feasible, novel process for SOI technology using PIII.
An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non–Small-Cell Lung Cancer (2008)

Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant therapy.
STO-609, a Specific Inhibitor of the Ca2+/Calmodulin-dependent Protein Kinase Kinase (2002)

STO-609, a selective inhibitor of Ca(2+)/calmodulin-dependent protein kinase kinase (CaM-KK) was synthesized, and its inhibitory properties were investigated both in vitro and in vivo. STO-609 inhibits the activities of recombinant CaM-KK alpha and CaM-KK beta isoforms, with K(i) values of 80 and 15 ng/ml, respectively, and also inhibits their autophosphorylation activities. Comparison of the inhibitory potency of the compound against various protein kinases revealed that STO-609 is highly selective for CaM-KK without any significant effect on the downstream CaM kinases (CaM-KI and -IV), and the IC(50) value of the compound against CaM-KII is approximately 10 microg/ml. STO-609 inhibits constitutively active CaM-KK alpha (glutathione S-transferase (GST)-CaM-KK-(84-434)) as well as the wild-type enzyme. Kinetic analysis indicates that the compound is a competitive inhibitor of ATP. In transfected HeLa cells, STO-609 suppresses the Ca(2+)-induced activation of CaM-KIV in a dose-dependent manner. In agreement with this observation, the inhibitor significantly reduces the endogenous activity of CaM-KK in SH-SY5Y neuroblastoma cells at a concentration of 1 microg/ml (approximately 80% inhibitory rate). Taken together, these results indicate that STO-609 is a selective and cell-permeable inhibitor of CaM-KK and that it may be a useful tool for evaluating the physiological significance of the CaM-KK-mediated pathway in vivo as well as in vitro.
High-definition television update (1988)

Developments in high-definition television (HDTV) in the US, Europe, and Japan are reviewed. The Japanese direct-broadcast-satellite HDTV system is described, and its advantages and drawbacks are examined. European activity is briefly described. The FCC enquiry into HDTV in the US is discussed. The focus is on the issues of standards and compatibility.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Short‐term modulation of glycogen metabolism, glycolysis and gluconeogenesis by physiological oxygen concentrations in hepatocyte cultures (1983)

The influence of different oxygen concentrations (0% to 20%, v/v) on the main pathways of carbohydrate metabolism was studied in rat hepatocyte cultures. Cells resembling the periportal or the perivenous cell type were obtained after 48 h culture under different hormonal conditions; they are referred to as 'periportal' or 'perivenous', respectively. Using radiochemical techniques the metabolic rates of the two cell types were measured between 48 h and 50 h under different oxygen tensions. Standard physiological substrates of 5 mM glucose, 2 mM lactate and endogenous glycogen were used. In cells incubated under 4% O2, mimicking hepatovenous oxygen levels, compared to cells assayed under 13% O2, mimicking arterial levels, glycogen degradation to free glucose and to lactate was faster while glycogen synthesis was slower; glycolysis, from glucose to lactate, was faster and gluconeogenesis, from lactate to glucose, was only slightly slower. Under anoxic conditions glycogen breakdown was maximal and glycogen synthesis minimal; gluconeogenesis was also minimal, but glycolysis was not maximal, it reached its peak rate at 4% O2. CO2-formation increased up to 6% and then stayed essentially constant at higher O2 tensions. Net glycogen metabolism: in 'perivenous' cells net glycogen synthesis was observed above, net glycogen degradation below 4% O2. In 'periportal' cells, which had a very low glycogen content, net glycogen metabolism was very small. Net glucose metabolism: in 'perivenous' cells net glucose formation was only seen under anoxic conditions. Net glucose utilization was observed at about the same rate under all physiological O2 tensions. In 'periportal' cells net glucose formation increased clearly up to 6% O2 and then remained almost constant. Net lactate metabolism: in 'perivenous' cells net lactate formation occurred below, and net lactate utilization above, 6% O2. In 'periportal' cells a pronounced net lactate utilization was observed under all physiological O2 tensions. Net flow between glucose-6-phosphate and pyruvate was observed in the glycolytic direction in 'perivenous' and in the gluconeogenic direction in 'periportal' cells except under anoxic conditions. When O2 tensions were lowered, the percentage of 'futile cycling' was decreased in the 'perivenous', glycolytic hepatocytes; conversely, it was increased in the 'periportal', gluconeogenic hepatocytes. It is concluded that physiological oxygen concentrations modulate hepatic carbohydrate metabolism and that they contribute further to the proposed metabolic differences between periportal and perivenous cells in vivo.
Principles of Knowledge Representation (1996)

The book contains a collection of eight survey papers written by some of the most excellent researchers in foundations of knowledge representation and reasoning. It covers topics like theories of uncertainty, nonmonotonic and causal reasoning, logic programming, abduction, inductive logic programming, description logics, complexity in Artificial Intelligence, and model based diagnosis. It thus provides an up-to-date coverage of recent approaches to some of the most challenging problems underlying knowledge representation and Artificial Intelligence in general.
Function and Signal Transduction Mediated by the Interleukin 3 Receptor System in Hematopoiesis (1996)

Interleukin 3 (IL-3) promotes development of hematopoietic cells through activation of the IL-3 receptor (IL-3R) complex consisting of alpha and beta subunits. The alpha subunit binds IL-3 with low affinity and forms a high-affinity receptor with the common beta subunit (beta c). The beta c subunit does not bind any cytokine by itself but is involved in the formation of high-affinity functional receptors for IL-5 and GM-CSF. As the alpha subunits provide the specificity to cytokines and beta c plays a major role in signal transduction, IL-3, GM-CSF and IL-5 exhibit similar functions when they act on the same cells. Surprisingly, no apparent hematological defect other than a reduced number of eosinophils was found in knock-out mice lacking an entire function of IL-3, GM-CSF and IL-5; this indicates a remarkable functional overlap with other cytokine systems for hematopoiesis. Binding of the cytokines to the receptor induces activation of the JAK2 tyrosine kinase that associates with beta c and triggers the signaling events. The membrane proximal region of beta c is responsible for activation of JAK2 and STAT5, as well as for induction of c-myc. The signals induced by this region are required for cell-cycle progression and DNA synthesis. Activation of the Ras pathway requires the distal region of beta c and is involved in the suppression of apoptosis. Proliferation of hematopoietic cells requires signals for both DNA synthesis and anti-apoptosis. In this review, we describe the recent findings of the function and signal transduction mediated by the IL-3R system.
DNA methylation: past, present and future directions (2000)

DNA methylation, or the covalent addition of a methyl group to cytosine within the context of the CpG dinucleotide, has profound effects on the mammalian genome. These effects include transcriptional repression via inhibition of transcription factor binding or the recruitment of methyl-binding proteins and their associated chromatin remodeling factors, X chromosome inactivation, imprinting and the suppression of parasitic DNA sequences. DNA methylation is also essential for proper embryonic development; however, its presence can add an additional burden to the genome. Normal methylation patterns are frequently disrupted in tumor cells with global hypomethylation accompanying region-specific hypermethylation. When these hypermethylation events occur within the promoter of a tumor suppressor gene they will silence the gene and provide the cell with a growth advantage in a manner akin to deletions or mutations. Recent work indicating that DNA methylation is an important player in both DNA repair and genome stability as well as the discovery of a new family of DNA methyltransferases makes now a very exciting period for the methylation field. This review will highlight the major findings in the methylation field over the past 20 years then summarize the most important and interesting future directions the field is likely to take in the next millennium.
Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. (2002)

CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that is involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Because CTCF targets include oncogenes and tumor suppressor genes, we screened over 100 human tumor samples for mutations that might disrupt CTCF activity. We did not observe any CTCF mutations leading to truncations/premature stops. Rather, in breast, prostate, and Wilms' tumors, we observed four different CTCF somatic missense mutations involving amino acids within the ZF domain. Each ZF mutation abrogated CTCF binding to a subset of target sites within the promoters/insulators of certain genes involved in regulating cell proliferation but did not alter binding to the regulatory sequences of other genes. These observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function."