gebhart/patrepeval huggingface dataset:
Regulation of the expression of theKluyveromyces lactis PDC1 gene: carbon source-responsive elements and autoregulation (1999)

The yeast Kluyveromyces lactis has a single structural gene coding for pyruvate decarboxylase (KIPDC1). In order to study the regulation of the expression of KIPDC1, we have sequenced (EMBL Accession No. Y15435) its promoter and have fused the promoter to the reporter gene lacZ from E. coli. Transcription analysis in a Klpdc1 delta strain showed that KIPDC1 expression is subject to autoregulation. The PDC1 gene from Saccharomyces cerevisiae was able to complement the Rag- phenotype of the Klpdc1 delta mutant strain and it could also repress transcription of the KIPDC1-lacZ fusion on glucose. A deletion analysis of the promoter region was performed to study carbon source-dependent regulation and revealed that at least two cis-acting regions are necessary for full induction of gene expression on glucose. Other cis-elements mediate repression on ethanol.
Engineering Antibodies for Therapy (1992)

For most MAb-based therapies single doses of MAbs or MAb conjugates will not be curative. Rodent MAbs are highly immonogenic in almost all patients. The HAMA response abrogates efficacy and can cause toxicity in organs of clearance, especially for MAb-cytotoxic agent conjugates. Humanization is the most promising generally applicable approach to overcoming the immunogenicity of rodent MAbs. Chimerization reduces immunogenicity in patients significantly, but not completely. Full humanization of rodent antibodies with retention of most of their antigen binding activity is now a routine procedure. The studies with 4D5 (Kelley et al., 1992), however, illustrate that even when antigen binding activity is retained, humanization may affect the overall conformation of the antibody in ways which influence its interaction with cells (for example when the antigen is internalized or involved in signal transduction) and hence its in vivo properties. As yet there are not sufficient data to judge whether full humanization will (in practical terms) completely overcome the immunogenicity problem in patients, but these data will be available within a year. Antibody fragments are the most promising general approach to manipulating the pharmacokinetics and biodistribution of therapeutic MAbs. Such fragments are clearly superior to whole IgGs for tumour detection and will very likely prove superior for tumour therapy also. MAb targeting of highly potent cytotoxic agents to tumours represents a much-needed approach to improving therapeutic ratios in cancer treatment. Radioisotopes and highly potent low molecular weight drugs are the most promising cell-killing agents for MAb targeting, and conjugation technology suitable for clinical use of some of the best of these agents has now been developed. Very encouraging data have already been obtained in clinical studies of haematopoietic malignancies with MAb-isotope conjugates. Tumour loading data from clinical studies suggest that killing of solid tumours in patients will be achievable in the near future with repeated administration of humanized antibody fragments carrying the superior isotopes or highly potent drugs which are now available.
A new mechanism for the control of a prokaryotic transcriptional regulator: antagonistic binding of positive and negative effectors (2000)

MalT, the transcriptional activator of the Escherichia coli maltose regulon, self-associates, binds promoter DNA and activates initiation of transcription only in the presence of ATP and maltotriose, the inducer. In vivo studies have revealed that MalT action is negatively controlled by the MalY protein. Using a biochemical approach, we analyse here the mechanism whereby MalY represses MalT activity. We show that MalY inhibits transcription activation by MalT in a purified transcription system. In vitro, a constitutive MalT variant (which is partially active in the absence of maltotriose) is less sensitive than wild-type MalT to repression by MalY, as observed in vivo. We demonstrate that MalY forms a complex with MalT only in the absence of maltotriose and that, conversely, MalY inhibits maltotriose binding by MalT. Together, these results establish that MalY acts directly upon MalT without the help of any factor, and that MalY is a negative effector of MalT competing with the inducer for MalT binding.
Degree of electron-nuclear entanglement in the E x e Jahn-Teller system (1999)

Jahn-Teller systems exhibit strong coupling between the electronic and nuclear degrees of freedom. We analyse how linear and quadratic coupling affect the electron-nuclear entanglement in the $E\otimes \epsilon$ system. A measure of quantum entanglement, recently developed by Shimony [Ann. New York Acad. Sci. 755, 675 (1995)], is used. States in the adiabatic regime with quadratic coupling are analysed. The electron-nuclear entanglement in vibronic states of the linear Exe model is calculated numerically. The physical significance of electron-nuclear entanglement is discussed in terms of reduction factors and magnetic vibrational circular dichroism.
Gene mention normalization and interaction extraction with context models and sentence motifs (2008)

Our methods for gene, protein, and species identification, and extraction of protein-protein are available as part of the BioCreative Meta Services (BCMS), see http://bcms.bioinfo.cnio.es/.
[Acquired Immunodeficiency Syndrome (AIDS)] (1994)

A surveillance report from the Dallas County AIDS Cases tracking the spread of the disease by categorizes of disease, age, cases, and patient groups.
Intronic Single Nucleotide Polymorphisms in theRETProtooncogene Are Associated with a Subset of Apparently Sporadic Pheochromocytoma and May Modulate Age of Onset (2003)

Approximately 75% of pheochromocytomas are sporadic. Germline mutations in RET, VHL, SDHB, and SDHD have been shown to cause the 25% that are hereditary. Germline high penetrance gain-of-function RET mutations cause multiple endocrine neoplasia type 2, of which medullary thyroid carcinoma (MTC) and pheochromocytoma are components, whereas loss-of-function mutations cause Hirschprung disease (HSCR). A low-penetrance founder locus, in linkage disequilibrium with a RET ancestral haplotype comprising specific alleles at three intron (IVS) 1 single nucleotide polymorphisms (SNPs) (haplotype 0) and SNP A45A, predisposes to the majority of isolated HSCR. A different low-penetrance locus, in linkage disequilibrium with IVS 1 haplotype 2 and SNP S836S, was associated with a subset of sporadic MTC. We, therefore, sought to determine whether RET might also be a low-penetrance gene for apparently sporadic pheochromocytoma. We analyzed 104 pheochromocytoma cases without germline mutations in RET, VHL, SDHD, and SDHB for their status at A45, S836, three IVS 1 SNPs, and a novel upstream insertion/deletion variant. Pheochromocytoma cases were not associated with either A45A or S836S, but we found that cases were associated with haplotype 0 (P = 0.032). However, unlike HSCR, this pheochromocytoma-associated haplotype 0 was not associated with A45A. Taken together with the strengthening of association with the addition of the 5' insertion/deletion variant data (P = 0.016), our observations suggest the presence of a low-penetrance pheochromocytoma susceptibility locus in a region upstream of the putative loci for HSCR and apparently sporadic MTC.
Overview of theCCP4 suite and current developments (2011)

The CCP4 (Collaborative Computational Project, Number 4) software suite is a collection of programs and associated data and software libraries which can be used for macromolecular structure determination by X-ray crystallography. The suite is designed to be flexible, allowing users a number of methods of achieving their aims. The programs are from a wide variety of sources but are connected by a common infrastructure provided by standard file formats, data objects and graphical interfaces. Structure solution by macromolecular crystallography is becoming increasingly automated and the CCP4 suite includes several automation pipelines. After giving a brief description of the evolution of CCP4 over the last 30 years, an overview of the current suite is given. While detailed descriptions are given in the accompanying articles, here it is shown how the individual programs contribute to a complete software package.
Stereocontrolled Alkylative Construction of Quaternary Carbon Centers (2008)

Protocols for the stereodefined formation of alpha,alpha-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of alpha,alpha-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine alpha-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the alpha-C-H bond with alpha-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common pi-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine alpha-phenylbutyramides are found to undergo highly stereoselective but not stereospecific alpha-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that alpha,alpha-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an alpha-alkyl-alpha,beta-unsaturated pseudoephedrine amide, providing alpha,alpha-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the alpha-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes.
PPARadigms and PPARadoxes: expanding roles for PPARγ in the control of lipid metabolism (2002)

The nuclear receptor PPARgamma is a central regulator of adipose tissue development and an important modulator of gene expression in a number of specialized cell types including adipocytes, epithelial cells, and macrophages. PPARgamma signaling pathways impact both cellular and systemic lipid metabolism and have links to obesity, diabetes, and cardiovascular disease. The ability to activate this receptor with small molecule ligands has made PPARgamma an attractive target for intervention in human metabolic disease. As our understanding of PPARgamma biology has expanded, so has the therapeutic potential of PPARgamma ligands. Recent studies have provided insight into the paradoxical relationship between PPARgamma and metabolic disease and established new paradigms for the control of lipid metabolism. This review focuses on recent advances in PPARgamma biology in the areas of adipocyte differentiation, insulin resistance, and atherosclerosis.
Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer (2011)

Previously, we showed that high-energy metabolites (lactate and ketones) "fuel" tumor growth and experimental metastasis in an in vivo xenograft model, most likely by driving oxidative mitochondrial metabolism in breast cancer cells. To mechanistically understand how these metabolites affect tumor cell behavior, here we used genome-wide transcriptional profiling. Briefly, human breast cancer cells (MCF7) were cultured with lactate or ketones, and then subjected to transcriptional analysis (exon-array). Interestingly, our results show that treatment with these high-energy metabolites increases the transcriptional expression of gene profiles normally associated with "stemness," including genes upregulated in embryonic stem (ES) cells. Similarly, we observe that lactate and ketones promote the growth of bonafide ES cells, providing functional validation. The lactate- and ketone-induced "gene signatures" were able to predict poor clinical outcome (including recurrence and metastasis) in a cohort of human breast cancer patients. Taken together, our results are consistent with the idea that lactate and ketone utilization in cancer cells promotes the "cancer stem cell" phenotype, resulting in significant decreases in patient survival. One possible mechanism by which these high-energy metabolites might induce stemness is by increasing the pool of Acetyl-CoA, leading to increased histone acetylation, and elevated gene expression. Thus, our results mechanistically imply that clinical outcome in breast cancer could simply be determined by epigenetics and energy metabolism, rather than by the accumulation of specific "classical" gene mutations. We also suggest that high-risk cancer patients (identified by the lactate/ketone gene signatures) could be treated with new therapeutics that target oxidative mitochondrial metabolism, such as the anti-oxidant and "mitochondrial poison" metformin. Finally, we propose that this new approach to personalized cancer medicine be termed "Metabolo-Genomics," which incorporates features of both 1) cell metabolism and 2) gene transcriptional profiling. Importantly, this powerful new approach directly links cancer cell metabolism with clinical outcome, and new therapeutic strategies for inhibiting the TCA cycle and mitochondrial oxidative phosphorylation in cancer cells.
A Study of Concept Extraction Across Different Types of Clinical Notes. (2015)

Our research investigates methods for creating effective concept extractors for specialty clinical notes. First, we present three new "specialty area" datasets consisting of Cardiology, Neurology, and Orthopedics clinical notes manually annotated with medical concepts. We analyze the medical concepts in each dataset and compare with the widely used i2b2 2010 corpus. Second, we create several types of concept extraction models and examine the effects of training supervised learners with specialty area data versus i2b2 data. We find substantial differences in performance across the datasets, and obtain the best results for all three specialty areas by training with both i2b2 and specialty data. Third, we explore strategies to improve concept extraction on specialty notes with ensemble methods. We compare two types of ensemble methods (Voting/Stacking) and a domain adaptation model, and show that a Stacked ensemble of classifiers trained with i2b2 and specialty data yields the best performance.
Human skin fibroblasts in vitro differentiate along a terminal cell lineage. (1988)

Secondary mitotic human skin fibroblast populations in vitro underwent 53 +/- 6 cumulative population doublings (CPD) in 302 +/- 27 days. When the growth capacity of the mitotic fibroblasts is exhausted, and if appropriate methods are applied, the fibroblasts differentiate spontaneously into postmitotic fibroblast populations, which were kept in stationary culture for up to 305 +/- 41 additional days. Mitotic and postmitotic fibroblast populations are heterogeneous populations with reproducible changes in the proportions of mitotic fibroblasts F I, F II, and F III, and postmitotic fibroblasts F IV, F V, F VI, and F VII. This process makes it evident that the fibroblasts differentiate spontaneously along a seven-stage terminal cell lineage F I-F II-F III-F IV-F V-F VI-F VII. Shifts in the frequencies of the mitotic and postmitotic fibroblasts in mass populations are accompanied by alterations in the [35S]methionine polypeptide pattern of the developing mass populations. The [35S]methionine polypeptide patterns of homogeneous subpopulations of F I, F II, F III, F IV, F V, and F VI isolated from heterogeneous mass populations reveal that the six fibroblast morphotypes studied express their cell-type-specific [35S]methionine polypeptide pattern in the heterogeneous mass populations.
Optical and Photocatalytic Properties of Heavily F–-Doped SnO2 Nanocrystals by a Novel Single-Source Precursor Approach (2011)

Heavily F-doped SnO(2) nanocrystals were successfully prepared by a novel synthetic approach involving low-temperature oxidation of a Sn(2+)-containing fluoride complex KSnF(3) as the single-source precursor with H(2)O(2). The F-doped SnO(2) powder was characterized by powder X-ray diffraction, TG-MS, BET surface area, diffuse reflectance spectroscopy, XPS, PL, FTIR spectroscopy, Raman spectroscopy, EPR spectroscopy, SEM, and TEM. Broadening of the diffracted peaks, signifying the low crystallite size of the products, was quite evident in the powder X-ray diffraction pattern of SnO(2) obtained from KSnF(3). It was indexed in a tetragonal unit cell with lattice constants a = 4.7106 (1) Å and c = 3.1970 (1) Å. Agglomeration of particles, with an average diameter of 5-7 nm, was observed in the TEM images whose spotwise EDX analysis indicated the presence of fluoride ions. In the core level high-resolution F 1s spectrum, the peak observed at 685.08 eV was fitted by the Gaussian profile yielding the fluoride ion concentration to be 21.23% in the SnO(2) lattice. Such a high fluoride ion concentration is reported for the first time in powders. SnO(2):F nanocrystals showed greater thermal stability up to 300 °C when heated in a thermobalance under flowing helium, after which generation of small quantities of HF was observed in the TG coupled mass spectrometry analysis. The band gap value, estimated from the Kubelka-Munk function, showed a large shift from 3.52 to 3.87 eV on fluoride ion doping, as observed in the diffuse reflectance spectrum. Such a large shift was corroborated to the overdoped situation due to the Moss-Burstein effect with an increase in the carrier concentration. In the photoluminescence (PL) spectrum, SnO(2):F nanocrystals exhibited a broad green emission arising from the singly ionized oxygen vacancies created due to higher dopant concentration. The evidence for singly ionized vacancies was arrived from the presence of a signal with a g value of 1.98 in the ESR spectrum of SnO(2):F at room temperature. The disordered nature of the rutile lattice and the enormous oxygen vacancies created due to fluoride ion doping were evident from the broad bands observed at 455, 588, and 874 cm(-1) in the room-temperature Raman spectrum of SnO(2):F. As the consequence of the oxygen vacancies, F-doped SnO(2) was examined for the function as a photocatalyst in the degradation of aqueous RhB dye solution under UV irradiation. A very high photocatalytic efficiency was observed for the F-doped SnO(2) nanocrystals as compared to pure SnO(2). The BET surface area of pure SnO(2) was quite high (207.81 m(2)/g) as compared to the F-doped SnO(2) nanocrystals (45.16 m(2)/g). Pore size analysis showed a mean pore diameter of 1.97 and 13.97 nm for the pure and doped samples. The increased photocatalytic efficiency was related to the very high concentration of oxygen vacancies in SnO(2) induced by F doping.
Effect of polar organic compounds on leukemic cells: Butyrate-induced partial remission of acute myelogenous leukemia in a child (1983)

Polar organic compounds, such as dimethylsulfoxide and butyric acid, are known to induce differentiation in Friend erythroleukemia cells as well as in other cell types. It has been found that many of the compounds that induce cellular differentiation, inhibit 3H-thymidine incorporation and induce cell damage when incubated with leukemic cells from patients with acute or chronic myelogenous or acute lymphocytic leukemia. These effects are time and dose dependent. Among the compounds tested, butyrate was the most potent. Parenteral administration of butyrate (500 mg/kg/day) for ten days to a child with acute myelogenous leukemia in relapse, and resistant to conventional therapy, resulted in elimination of myeloblasts from the peripheral blood, an increase in mature myeloid cells and a reduction in 3H-thymidine uptake by the patient's peripheral blood cells. Bone marrow myeloblasts were reduced from 70-80% to 20% following the course of intravenous butyrate. No impairment of liver or renal function and no coagulation abnormalities were observed during butyrate treatment. Organic agents that induce cell differentiation may provide additional reagents for the clinical management of selected cases of leukemia.
DNA-Photocleavage Agents (2001)

This review describes recent advances in the development of DNA-photocleavage agents. Major mechanisms of photosensitized DNA photocleavage are presented and the most popular categories of compounds are considered, which include metal complexes and many organic functional derivatives. DNA-targeted conjugates of photosensitizers are also described and discussed.
Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. (1992)

The activation of the insulin-like growth factor 1 (IGF-1) receptor by its ligand plays a central role in the growth of most cell types. We have used the techniques of computational chemistry in order to design and synthesize several novel analogues of IGF-1. These analogues were able to inhibit the autophosphorylation of the IGF-1 receptor as well as the growth of several different cell types, including prostate carcinoma cells and SV40-transformed cells. Additionally, we have found that D-amino acid analogues of these peptides are apparently resistant to the proteolytic degradation that occurs in the presence of whole sera. Consequently, these analogues seem to show great potential both as probes of the structure/function activities of the IGF-1 signalling pathway and as novel clinical strategies in controlling abnormal cellular growth.
Body Temperature Change During Anesthesia for Electroconvulsive Therapy: Implications for Quality Incentives in Anesthesiology (2008)

We conclude that there was no consistent change in temperature during anesthesia between our study patients when anesthesia was administered to facilitate ECT. If patients' tympanic temperatures were below 36 degrees C upon admission to the PACU, it would be incorrect to conclude that intraprocedural temperature management measures were substandard. Also, current methods of measuring temperature may be inadequate to ascertain if patients are hypothermic after surgery. As the avoidance of hypothermia is a meritorious goal, anesthesia departments need to ensure that their temperature monitoring equipment is adequate to ensure accurate measurement of postanesthetic temperature if this variable is to be used as a quality incentive.
Sequence Mapping by Electronic PCR (1997)

The highly specific and sensitive PCR provides the basis for sequence-tagged sites (STSs), unique landmarks that have been used widely in the construction of genetic and physical maps of the human genome. Electronic PCR (e-PCR) refers to the process of recovering these unique sites in DNA sequences by searching for subsequences that closely match the PCR primers and have the correct order, orientation, and spacing that they could plausibly prime the amplification of a PCR product of the correct molecular weight. A software tool was developed to provide an efficient implementation of this search strategy and allow the sort of en masse searching that is required for modern genome analysis. Some sample searches were performed to demonstrate a number of factors that can affect the likelihood of obtaining a match. Analysis of one large sequence database record revealed the presence of several microsatellite and gene-based markers and allowed the exact base-pair distances among them to be calculated. This example provides a demonstration of how e-PCR can be used to integrate the growing body of genomic sequence data with existing maps, reveal relationships among markers that existed previously on different maps, and correlate genetic distances with physical distances.