gebhart/patrepeval huggingface dataset:
The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma (2000)

BACKGROUND The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas. Cancer 2000;88:1378–83. © 2000 American Cancer Society.
Why now? Moving from stroke risk factors to stroke triggers (2007)

Confirmation of these findings in further studies may help elucidate the mechanisms behind this short-term increase in stroke risk. Improved methods of assessment of this period of heightened susceptibility could lead to more temporally focused preventive interventions.
Lithographic patterning of nanoparticle films self-assembled from organic solutions by using a water-soluble mask (2005)

A lithographic technique is described that enables the highly selective patterning of thin films from gold nanoparticles and organic linker molecules, which are formed via repetitive self-assembly from organic solution. The key element of this method is the application of a calcium oxide∕hydroxide mask, which withstands the application of organic solvents during film deposition and which prevents deposition of nanoparticles on protected parts of the substrate. After film assembly the mask is removed by dissolution in water at room temperature. The method was used to pattern chemiresistor-type vapor sensors based on gold nanoparticle∕nonanedithiol films. Comparative experiments with nonpatterned reference sensors reveal that the patterning process does not degrade the sensing properties of the films.
Antioxidant activity of 3,4-DHPEA-EA and protocatecuic acid: a comparative assessment with other olive oil biophenols (1999)

Olive oil contains several phenolic compounds with antioxidant activity, whose levels depend strongly on the kind of cultivar grown, fruit ripening effects and the oil extraction process. Therefore, the beneficial effects exerted by olive oil consumption on the resistance of low density lipoproteins (LDLs) to oxidation depend not only on an increased intake of mono-unsaturated fatty acids (e.g. oleate) which are less prone to oxidation, but also phenolic antioxidants. The aim of this study was to analyze in vitro effects exerted on the oxidative modification of Cu-stimulated human LDL by two olive oil biophenols, i.e. 3,4-dihydroxyphenylethanol-elenolic acid (3,4-DHPEA-EA) and protocatecuic acid. These compounds have not been investigated in as much detail as the better-known olive oil biophenols - such as tyrosol (p-HPEA), o-coumaric acid, vanillic acid, caffeic acid, oleuropein and 3,4-dihydroxyphenylethanol (3,4-DHPEA). Modification of LDL was tested by measuring the formation of intermediate and end products of lipid peroxidation such as conjugated dienes, lipid hydroperoxides, cholesterol and cholesteryl ester oxides, as well as studying the decrease in oxidizable substrates like polyunsaturated fatty acids. In addition, the increase in LDL negative charges was evaluated. The results demonstrate the two-tested olive oil biophenols show high antioxidant activities. In particular, protocatecuic acid and 3,4-DHPEA-EA show an antioxidant activity comparable with that of caffeic acid, oleuropein and 3,4-DHPEA. They are not only able to retard lipid peroxidation, but also to reduce the extent of its activity.
Architecture of the U5 Small Nuclear RNA (1994)

We have used comparative sequence analysis and deletion analysis to examine the secondary structure of the U5 small nuclear RNA (snRNA), an essential component of the pre-mRNA splicing apparatus. The secondary structure of Saccharomyces cerevisiae U5 snRNA was studied in detail, while sequences from six other fungal species were included in the phylogenetic analysis. Our results indicate that fungal U5 snRNAs, like their counterparts from other taxa, can be folded into a secondary structure characterized by a highly conserved stem-loop (stem-loop 1) that is flanked by a moderately conserved internal loop (internal loop 1). In addition, several of the fungal U5 snRNAs include a novel stem-loop structure (ca. 30 nucleotides) that is adjacent to stem-loop 1. By deletion analysis of the S. cerevisiae snRNA, we have demonstrated that the minimal U5 snRNA that can complement the lethal phenotype of a U5 gene disruption consists of (i) stem-loop 1, (ii) internal loop 1, (iii) a stem-closing internal loop 1, and (iv) the conserved Sm protein binding site. Remarkably, all essential, U5-specific primary sequence elements are encoded by a 39-nucleotide domain consisting of stem-loop 1 and internal loop 1. This domain must, therefore, contain all U5-specific sequences that are essential for splicing activity, including binding sites for U5-specific proteins.
Enzyme Promiscuity: A Mechanistic and Evolutionary Perspective (2010)

Many, if not most, enzymes can promiscuously catalyze reactions, or act on substrates, other than those for which they evolved. Here, we discuss the structural, mechanistic, and evolutionary implications of this manifestation of infidelity of molecular recognition. We define promiscuity and related phenomena and also address their generality and physiological implications. We discuss the mechanistic enzymology of promiscuity--how enzymes, which generally exert exquisite specificity, catalyze other, and sometimes barely related, reactions. Finally, we address the hypothesis that promiscuous enzymatic activities serve as evolutionary starting points and highlight the unique evolutionary features of promiscuous enzyme functions.
Deletion of the Gene Encoding the Cyclin-Dependent Protein Kinase Pho85 Alters Glycogen Metabolism in Saccharomyces cerevisiae (1996)

Pho85, a protein kinase with significant homology to the cyclin-dependent kinase, Cdc28, has been shown to function in repression of transcription of acid phosphatase (APase, encoded by PHO5) in high phosphate (Pi) medium, as well as in regulation of the cell cycle at G1/S. We described several unique phenotypes associated with the deletion of the PHO85 gene including growth defects on a variety of carbon sources and hyperaccumulation of glycogen in rich medium high in Pi. Hyperaccumulation of glycogen in the pho85 strains is independent of other APase regulatory molecules and is not signaled through Snfl kinase. However, constitutive activation of cAPK suppresses the hyperaccumulation of glycogen in a pho85 mutant. Mutation of the type-1 protein phosphatase encoded by GLC7 only partially suppresses the glycogen phenotype of the pho85 mutant. Additionally, strains containing a deletion of the PHO85 gene show an increase in expression of GSY2. This work provides evidence that Pho85 has functions in addition to transcriptional regulation of APase and cell-cycle progression including the regulation of glycogen levels in the cell and may provide a link between the nutritional state of the cell and these growth related responses.
Platelet-Rich Plasma: A Review of Biology and Applications in Plastic Surgery (2006)

Healing of hard and soft tissue is mediated by a complex array of intracellular and extracellular events that are regulated by signaling proteins, a process that is, at present, incompletely understood. What is certain, however, is that platelets play a prominent if not deciding role. Controlled animal studies of soft and hard tissues have suggested that the application of autogenous platelet-rich plasma can enhance wound healing. The clinical use of platelet-rich plasma for a wide variety of applications has been reported; however, many reports are anecdotal and few include controls to definitively determine the role of platelet-rich plasma. The authors describe platelet biology and its role in wound healing; the preparation, characterization, and use of platelet-rich plasma; and those applications in plastic surgery for which it may be useful.
Emesa and Baalbek: Where is the Temple of Elahagabal? (2003)

The great Sun temple of Emesa, mentioned by Herodian in his account of the revolt of Elagabalus, has never been found. Recently, Warwick Ball has suggested that it is to be identified with the temple complex at Baalbek. The evidence which he provides for this assertion, however, does not prove his case and in some cases rests upon false assumptions. When the textual, archaeological and epigraphic evidence is examined, it is clear that the temple must have been in the city of Emesa itself, and therefore it is yet to be located.
Antibody fragments as tools in crystallography (2011)

While antibody-based therapeutics have become firmly established as front-line drugs, the use of antibodies as research tools in small molecule drug discovery is still in its infancy. In this review we focus on the use of antibody fragments as crystallization chaperones to aid the structural determination of otherwise 'uncrystallizable' or 'undruggable' target proteins. We also highlight a potential application for this technology, in which antibody-mediated structures may be used to inform the design of new chemical entities.
A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients (2004)

The association between polymorphisms in the programmed death (PD-1) gene and susceptibility to systemic lupus erythematosus (SLE) was determined using genomic DNA, isolated from a population-based cohort of 95 SLE patients and 155 healthy controls. Polymorphisms in the complete PD-1 gene except the large intron 1 were detected by sequencing. Furthermore, the patients were stratified according to the presence or absence of lupus nephropathy. The influence of the detected single nuclear polymorphisms (SNPs) on this specific clinical disease parameter was determined. In total, we identified 12 single nucleotide polymorphisms, of which six were novel and eight were considered to be rare (the frequency of the minor allele of these was less than 1% in our study populations). We found a significant association of an intronic 6867C/G SNP in the PD-1 gene with the presence of lupus nephropathy. As the 6867C/G SNP is located in a putative binding site for the transcriptional repressor ZEB, the associated allele of this SNP potentially alters the transcriptional regulation of PD-1. This report, for the first time, indicates that a 6867C/G SNP of the PD-1 gene is associated with lupus nephropathy in Caucasian SLE patients.
Optimal inverter VAR control in distribution systems with high PV penetration (2012)

The intent of the study detailed in this paper is to demonstrate the benefits of inverter var control on a fast timescale to mitigate rapid and large voltage fluctuations due to the high penetration of photovoltaic generation and the resulting reverse power flow. Our approach is to formulate the volt/var control as a radial optimal power flow (OPF) problem to minimize line losses and energy consumption, subject to constraints on voltage magnitudes. An efficient solution to the radial OPF problem is presented and used to study the structure of optimal inverter var injection and the net benefits, taking into account the additional cost of inverter losses when operating at non-unity power factor. This paper will illustrate how, depending on the circuit topology and its loading condition, the inverter's optimal reactive power injection is not necessarily monotone with respect to their real power output. The results are demonstrated on a distribution feeder on the Southern California Edison system that has a very light load and a 5 MW photovoltaic (PV) system installed away from the substation.
Inhibition of Pulmonary and Skeletal Metastasis by a Transforming Growth Factor-β Type I Receptor Kinase Inhibitor (2006)

Transforming growth factor-beta (TGF-beta) signaling has been shown to promote invasion and metastasis in various models of human cancers. In this study, we investigated the efficacy of a TGF-beta type I receptor kinase inhibitor (TbetaRI-I) to limit early systemic metastases in an orthotopic xenograft model of lung metastasis and in an intracardiac injection model of experimental bone and lung metastasis using human breast carcinoma MDA-MB-435-F-L cells, a highly metastatic variant of human breast cancer MDA-MB-435 cells, expressing the enhanced green fluorescent protein (EGFP). Treatment of the cells with the TbetaRI-I had no effect on their growth but blocked TGF-beta-stimulated expression of integrin alpha(v)beta(3) and cell migration in vitro. Systemic administration of the TbetaRI-I via i.p. injection effectively reduced the number and size of the lung metastasis in both orthotopic xenograft and experimental metastasis models with no effects on primary tumor growth rate compared with controls. TbetaRI-I treatment also reduced the incidence of widespread early skeletal metastases in the femur, tibia, mandible, and spine detected by whole-body EGFP fluorescence imaging. Tumor burden in femora and tibiae was also reduced after TbetaRI-I treatment as detected by histomorphometry analysis compared with the placebo controls. Our results indicate for the first time that abrogation of TGF-beta signaling by systemic administration of the TbetaRI-I can inhibit both early lung and bone metastasis in animal model systems and suggest antimetastatic therapeutic potential of the TbetaRI-I.
Conformational fluctuations in single DNA molecules (1997)

Measurement of fluorescent lifetimes of dye-tagged DNA molecules reveal the existence of different conformations. Conformational fluctuations observed by fluorescence correlation spectroscopy give rise to a relaxation behavior that is described by "stretched" exponentials and indicates the presence of a distribution of transition rates between two conformations. Whether this is an inhomogeneous distribution, where each molecule contributes with its own reaction rate to the overall distribution, or a homogeneous distribution, where the reaction rate of each molecule is time-dependent, is not yet known. We used a tetramethylrhodamine-linked 217-bp DNA oligonucleotide as a probe for conformational fluctuations. Fluorescence fluctuations from single DNA molecules attached to a streptavidin-coated surface directly show the transitions between two conformational states. The conformational fluctuations typical for single molecules are similar to those seen in single ion channels in cell membranes.
240-km repeater spacing in a 5280-km WDM system experiment using 8 x 2.5 Gb/s NRZ transmission (1998)

A repeater spacing of 240 km was experimentally demonstrated over a distance of 5280 km in an 8/spl times/2.5 Gb/s wavelength-division-multiplexing (WDM) transmission experiment. This long-span length was achieved by a combination of Raman amplification, a locally pumped erbium-doped fiber (EDF), and two remotely pumped EDFs. The total gain obtained from those four gain elements was about 50 dB. The performance demonstrated in this experiment was comparable to that of a system of similar length and capacity using conventional erbium-doped fiber amplifier (EDFA) technology at a repeater spacing of 80 km.
Peripheral lung remodelling in asthma and chronic obstructive pulmonary disease (2004)

In this issue of the European Respiratory Journal , Vignola et al. 1 report an association between high-resolution computed tomography (HRCT) scan abnormalities of the conducting airways and an analysis of markers of the tissue remodelling process. They demonstrate an association between the level of HRCT abnormality in the airways and increased levels of active elastase with overproduction of tissue-inhibitor metalloproteinase-1 over metalloproteinase-9 in the sputum. The study design is cross-sectional in nature and based on small numbers of patients collected into three groups, according to whether they had newly diagnosed and untreated asthma, treated asthma or chronic obstructive pulmonary disease (COPD). The design does not include a control group with normal lung function and lacks longitudinal data collection to ensure that the sputum markers and HRCT abnormalities change in the expected directions with disease progression. After the first reading, the notion that editorial writers have been described as “the sort of people who come down from …
Mechanism of ribosome recruitment by hepatitis C IRES RNA (2001)

Many viruses and certain cellular mRNAs initiate protein synthesis from a highly structured RNA sequence in the 5' untranslated region, called the internal ribosome entry site (IRES). In hepatitis C virus (HCV), the IRES RNA functionally replaces several large initiation factor proteins by directly recruiting the 43S particle. Using quantitative binding assays, modification interference of binding, and chemical and enzymatic footprinting experiments, we show that three independently folded tertiary structural domains in the IRES RNA make intimate contacts to two purified components of the 43S particle: the 40S ribosomal subunit and eukaryotic initiation factor 3 (eIF3). We measure the affinity and demonstrate the specificity of these interactions for the first time and show that the high affinity interaction of IRES RNA with the 40S subunit drives formation of the IRES RNA-40S-eIF3 ternary complex. Thus, the HCV IRES RNA recruits 43S particles in a mode distinct from both eukaryotic cap-dependent and prokaryotic ribosome recruitment strategies, and is architecturally and functionally unique from other large folded RNAs that have been characterized to date.
Gene expression profiling identifies clinically relevant subtypes of prostate cancer (2004)

Prostate cancer, a leading cause of cancer death, displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. To explore potential molecular variation underlying this clinical heterogeneity, we profiled gene expression in 62 primary prostate tumors, as well as 41 normal prostate specimens and nine lymph node metastases, using cDNA microarrays containing approximately 26,000 genes. Unsupervised hierarchical clustering readily distinguished tumors from normal samples, and further identified three subclasses of prostate tumors based on distinct patterns of gene expression. High-grade and advanced stage tumors, as well as tumors associated with recurrence, were disproportionately represented among two of the three subtypes, one of which also included most lymph node metastases. To further characterize the clinical relevance of tumor subtypes, we evaluated as surrogate markers two genes differentially expressed among tumor subgroups by using immunohistochemistry on tissue microarrays representing an independent set of 225 prostate tumors. Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were strong predictors of tumor recurrence independent of tumor grade, stage, and preoperative prostate-specific antigen levels. Our results suggest that prostate tumors can be usefully classified according to their gene expression patterns, and these tumor subtypes may provide a basis for improved prognostication and treatment stratification.
Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. (2003)

On the basis of our data, CAIX is the most significant molecular marker described in kidney cancer to date. Decreased CAIX levels are independently associated with poor survival in advanced RCC. CAIX reflects significant changes in tumor biology, which should be used to predict clinical outcome and identify high-risk patients in need for adjuvant immunotherapy and CAIX-targeted therapies.
Psychiatric endophenotypes and the development of valid animal models (2005)

Endophenotypes are quantifiable components in the genes-to-behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.
Preparation of aromatic polyesters by direct polycondensation with thionyl chloride in pyridine (1986)

Abstract Mechanistic features of the reaction with thionyl chloride in pyridine were studied in a model reaction of benzoic acid with p ‐chlorophenol or aniline. The yields were significantly affected by the amounts of pyridine, favorably by four equivalents, and the nature of pyridine, suggesting that pyridines are not only HCl scavengers, but are also involved in the reaction itself. The reaction was assumed to proceed via a carboxylic sulfinic‐anhydride intermediate different from acyl chloride, and the intermediate was found to be not so reactive that it was completely alcoholyzed by the phenol at high temperatures of more than 60°C. The reaction was successfully applied to the preparation of aromatic polyesters of high molecular weights by the direct polycondensation of aromatic dicarboxylic acids and bisphenols in pyridine at 80°C.
ChemInform Abstract: Multiple‐Echo Magnetic Resonance (2012)

Abstract Review: 32 refs.