gebhart/patrepeval huggingface dataset:
DNA methylation profiling in Barrett’s esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses (2011)

Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified, squamous esophageal epithelium is replaced by specialized intestinal epithelium. Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma (EAC), a solid tumor that is rapidly increasing in incidence in western countries. BE evolves into EAC through intermediate steps that involve increasing degrees of dysplasia. Current histologic criteria are quite subjective and the clinical behavior of BE is highly variable and difficult to predict using these standards. It is widely believed that molecular alterations present in BE and EAC will provide more precise prognostic and predictive markers for these conditions than the current clinical and histologic features in use. In order to further define molecular alterations that can classify unique groups of BE and EAC, we utilized methylation microarrays to compare the global gene methylation status of a collection of normal squamous, BE, BE + high-grade dysplasia (HGD), and EAC cases. We found distinct global methylation signatures, as well as differential methylation of specific genes, that discriminated these histological groups. We also noted high and low methylation epigenotypes among the BE and EAC cases. Additional validation of those CpG sites that distinguished BE from BE + HGD and EAC may lead to the discovery of useful biomarkers with potential clinical applications in the diagnosis and prognosis of BE and EAC.
CD8+ T cells in psoriatic lesions preferentially use T-cell receptor V beta 3 and/or V beta 13.1 genes. (1994)

Psoriasis is an inflammatory skin disorder characterized by epidermal keratinocyte hyperproliferation in association with a cellular infiltrate. There is evidence that activated T cells play a role in psoriatic plaque formation. We examined the T-cell receptor beta-chain variable gene segment (V beta) use of epidermal T cells in shave biopsies of psoriatic lesions. Our results show increased expression of V beta 3 and/or V beta 13.1 messages in the CD8+, but not CD4+, T cells in the lesions of a majority of patients studied. Sequence analysis of complementarity-determining region 3 (CDR3) of these two V beta genes from the skin demonstrated monoclonality or marked oligoclonality. A second biopsy from the same or different lesions, performed 3.5-8 months later in four patients, again revealed increased V beta 3 and/or V beta 13.1 expression and clonality. Moreover, in three of the four patients, the same V beta CDR3 rearrangement was found in both biopsies, although there was no V beta CDR3 homology between patients. In two patients in which V beta 3 and/or V beta 13.1 was not increased, an increase in V beta 17 gene use and clonality was found. The clonality of V beta sequence data indicates these cells are recruited and expanded in situ. The persistence of V beta 3-and/or V beta 13.1-bearing CD8+ T cells in lesions that did not undergo resolution suggests their role as effector cells rather than as regulatory cells.
Electrochemical approaches to alleviation of the problem of carbon dioxide accumulation (2001)

Abstract The electrochemical reduction of CO2, which includes a number of different specific approaches, may show promise as a means to help slow down the accumulation of this greenhouse gas in the atmosphere. Two types of approaches are examined briefly here. First, CO2 can be used as a reagent in the electrocarboxylation reaction to produce organic carboxylic acids, for example, the pharmaceutical ibuprofen. Second, CO2 can be converted to a fuel, either directly or via synthesis gas. The latter can be produced with reasonably good energy efficiency in a gas-diffusion, electrode-based cell even at present with existing electrocatalysts. Oxygen gas is produced as a by-product. Further work is needed to improve the selectivity and efficiency in this and other approaches.
A reappraisal of non-consensus mRNA splice sites (1991)

Journal Article A reappraisal of non-consensus mRNA splice sites Get access Lan J. Jackson Lan J. Jackson MRC Human Genetics Unit, Western General HospitalCrewe Road, Edinburgh EH4 2XU, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 14, 25 July 1991, Pages 3795–3798, https://doi.org/10.1093/nar/19.14.3795 Published: 25 July 1991 Article history Received: 06 June 1991 Accepted: 18 June 1991 Published: 25 July 1991
Clinical Pharmacokinetics of Frovatriptan (2002)

Frovatriptan can be taken without regard for food intake, and because of the large therapeutic margin and shallow dose-response curve, there is no need for dosage adjustment in the elderly, in women taking a combined oral contraceptive, in patients with mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or according to gender. The long duration of exposure may reduce the likelihood of early migraine recurrence.
Recent Patents on PCSK9: A New Target for Treating Hypercholesterolemia (2009)

Proprotein convertase subtilisin/kexin type 9 (PCSK9), the ninth member of the proprotein convertase (PC)family, has emerged as a potential target for reducing plasma low-density lipoprotein cholesterol (LDL-c) levels. PCSK9post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) in the liver by binding to the epidermalgrowth factor-like repeat A (EGF-A) domain of the LDLR and thereby controls the level of LDL-c in plasma. Some of its natural mutations called gain-of-function mutations cause hypercholesterolemia and coronary heart disease (CHD), whereas loss-of-function mutations in the PCSK9 gene are associated with hypocholesterolemia. This review summarizes the current understanding of PCSK9 and recently published patent and patent applications on methods and techniques that may efficiently reduce plasma LDL-c levels through inhibiting PCSK9 expression by antisense oligonucleotides, small interference RNAs (siRNAs), specific antibodies, or other small molecules.
Wafer to wafer direct bonding using surfaces activated by hydrogen plasma treatment (2003)

This paper describes a method of direct wafer bonding using surfaces activated by RF hydrogen plasma for silicon on insulator (SOI) applications. The hydrogen plasma cleaning of silicon in the RIE mode is investigated as a pretreatment for Si direct bonding. Gas-phase cleaning using hydrogen plasma is considered an especially effective way of removing hydrocarbon and fluorocarbon contaminants from the Si surface, and the cleaned Si surface is successfully terminated by hydrogen. The hydrogen-terminated surfaces are rendered hydrophilic. The effect of plasma treatment on the surface chemistry is investigated by Auger electron spectrometry (AES). It is revealed that the carbon impurity concentration at the surface can be reduced below the 5 at.% level. Volatile hydrogen compounds are formed during the plasma procedure and pumped away, resulting in substrate surfaces free from carbon contamination. Atomic force microscopy (AFM) is used to estimate the surface roughness and morphology as a function of plasma exposure time and power. The surface becomes smoother with decreasing plasma exposure time and power. When the exposure time exceeds 10 min at constant plasma power of 100 W and the plasma power increases over 130 W at a constant exposure time of 3 min, roughness increases rapidly. The increase in roughness is caused by Si{111} platelet defects and the Si etching reaction occurs preferentially at positions where the Si{111} platelets intersect the surface. The initial interfacial energy measured by the crack propagation method is 506 mJ/m/sup 2/, which is 3 times stronger than that of a conventional RCA cleaning method.
An investigation of the lexical dimension of the IELTS Speaking Test (2006)

This is a report of a research project to investigate vocabulary use by candidates in the current (since 2001) version of the IELTS Speaking Test, in which Lexical resource is one of the four criteria applied by examiners to rate candidate performance. For this purpose, a small corpus of texts was created from transcriptions of 88 IELTS Speaking Tests recorded under operational conditions at 21 test centres around the world. The candidates represented a range of proficiency levels from Band 8 down to Band 4 on the nine-band IELTS reporting scale. The data analysis involved two phases: the calculation of various lexical statistics based on the candidates’ speech, followed by a more qualitative analysis of the full transcripts to explore, in particular, the use of formulaic language. In the first phase, there were measures of lexical output, lexical variation and lexical sophistication, as well as an analysis of the vocabulary associated with particular topics in Parts 2 and 3 of the test.
The CCN3 (NOV) cell growth regulator: a new tool for molecular medicine (2003)

The CCN genes encode secreted signaling proteins that participate in fundamental processes including cell adhesion, proliferation and differentiation, embryogenesis, tissue remodeling and patterning. Abnormal expression of CCN proteins is associated with several pathological conditions, including vascular diseases, fibrosis and cancer. Understanding the structural and functional basis for the variety of biological properties attributed to CCN proteins is an important challenge. It will help the understanding of their roles in the control of cellular proliferation, differentiation and death, thereby allowing their use for early diagnosis and therapy. In an attempt to evaluate the relevance of CCN3 as a useful tool in modern biomedical technologies, the biological properties of the CCN proteins and the data that established their potential usefulness will briefly be reviewed.
Recombinant Polyketide Synthesis in Streptomyces : Engineering of Improved Host Strains (1999)

Efficient polyketide synthesis derived from plasmid-borne heterologous Streptomyces polyketide synthase (PKS) gene clusters necessitates a suitable host strain. Well-characterized laboratory strains such as Streptomyces coelicolor or Streptomyces lividans and their frequently used derivatives carry endogenous genes for the synthesis of actinorhodin (among other PKS genes), which might interfere with the efficient production of extrachromosomally encoded PKS proteins and the quantitative analysis of their secreted polyketide products. To circumvent this problem, a frequently used S. coelicolor derivative, designated CH999, was engineered to lack most of the actinorhodin gene cluster. However, this strain can only be transformed with methyl-free DNA. Additionally, unlike its otherwise isogenic parent CH1, CH999 exhibits low transformation efficiencies. Here, we report the construction of two S. lividans host strains, K4-114 and K4-155. With respect to the actinorhodin gene cluster, both are genotypically identical to CH999; however, both can be transformed at considerably higher frequencies and also with methylated DNA. Upon transformation with the appropriate expression vector, CH999, K4-114 and K4-155 all produce the erythromycin precursor 6-deoxyerythronolide B (6-dEB) equally well.
Rates of ligand binding to periplasmic proteins involved in bacterial transport and chemotaxis. (1983)

The ligand reactions of three binding proteins involved in bacterial transport and chemotaxis have been examined by stopped flow, rapid mixing techniques. The processes measured were: L-arabinose, D-galactose, and D-fucose binding to the Escherichia coli L-arabinose-binding protein; L-histidine binding to the Salmonella typhimurium L-histidine-binding protein; and D-maltose, maltotriose, cyclic maltohexaose, and cyclic maltoheptaose binding to the E. coli D-maltose-binding protein. Changes in tryptophan fluorescence were monitored, and the resultant time courses were analyzed quantitatively in terms of a simple one-step binding process. The fitted association rate constants for sugar binding are all about 1-3 X 10(7) M-1 s-1; variation in the affinity constants is expressed primarily by changes in the dissociation rate constants, 1-100 s-1. The sugar-binding proteins react at equal rates with the alpha and beta anomeric forms of their substrates. The ligand dissociation rates measured in vitro are consistent with the corresponding Vmax values observed for in vivo active transport. The association rate constant for the L-histidine-binding protein is 5-10 times greater than the corresponding rate constants for the sugar-binding proteins. A similar, large bimolecular rate, approximately 1 X 10(8) M-1 s-1, has been observed for the E. coli L-glutamine-binding protein (Weiner, J. H., and Heppel, L. A. (1971) J. Biol. Chem. 246, 6933-6941) and appears to reflect favorable electrostatic interactions between the charged amino acid and the surface of the protein molecule.
Withholding Proven Treatment in Clinical Research (2001)

The use of placebo-controlled trials began just before World War II, and the Declaration of Helsinki, which arose from the Nuremberg Code, was formulated after the war. Placebo-controlled studies soon became the gold standard of evidence, and the Declaration of Helsinki became the gold standard of research ethics. However, the practices of the first collided with the principles of the second, and researchers and ethicists have been trying to resolve this problem ever since. The debate over placebo-controlled trials is implicitly and inextricably linked to concern about withholding treatment — specifically, withholding proven or standard treatment — in the course . . .
Noninvasive Glucose Monitoring Systems: Will We Ever Have Such Sensors for Practical Use? (2007)

It is still the dream of patients with diabetes and diabetologists to be able to monitor glucose changes in the human body over prolonged periods of time without hurting the patients, i.e. without having the need to break the skin barrier. This commentary tries to highlight why we should invest more brain power and money in this area of research while also raising the following critical question: Can we be sure that a reliable system for noninvasive glucose monitoring will ever be possible? Finally, I propose establishing an international working group for glucose monitoring. Such an independent group of researchers (which would not focus on noninvasive approaches only) might be very instrumental in bringing a critical and constructive approach in this area of research forward.
Mouse complement regulatory protein Crry/p65 uses the specific mechanisms of both human decay-accelerating factor and membrane cofactor protein. (1995)

Normal host cells are protected from the destructive action of complement by cell surface complement regulatory proteins. In humans, decay-accelerating factor (DAF) and membrane cofactor protein (MCP) play such a biologic role by inhibiting C3 and C5 convertases. DAF and MCP accomplish this task by specific mechanisms designated decay-accelerating activity and factor I cofactor activity, respectively. In other species, including mice, structural and/or functional homologues of these proteins are not yet well characterized. Previous studies have shown that the mouse protein Crry/p65 has certain characteristics of self-protecting complement regulatory proteins. For example, Crry/p65 is expressed on a wide variety of murine cells, and when expressed on human K562 erythroleukemic cells, it prevents deposition of mouse C3 fragments on the cell surface during activation of either the classical or alternative complement pathway. We have now studied factor I cofactor and decay-accelerating activities of Crry/p65. Recombinant Crry/p65 demonstrates cofactor activity for factor I-mediated cleavage of both mouse C3b and C4b. Surprisingly, Crry/p65 also exhibits decay-accelerating activity for the classical pathway C3 convertase strongly and for the alternative pathway C3 convertase weakly. Therefore, mouse Crry/p65 uses the specific mechanisms of both human MCP and DAF. Although Crry/p65, like MCP and DAF, contains tandem short consensus repeats (SCR) characteristic of C3/C4 binding proteins, Crry/p65 is not considered to be a genetic homologue of either MCP or DAF. Thus, Crry/p65 is an example of evolutionary conservation of two specific activities in a single unique protein in one species that are dispersed to individual proteins in another. We propose that the repeating SCR motif in this family has allowed this unusual process of evolution to occur, perhaps driven by the use of MCP and DAF as receptors by human pathogens such as the measles virus.
Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation (2011)

We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell transplantation recipients with biopsy-proven EBV-lymphoproliferative disease (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions in 73% and 68% of treated patients including 74% and 72% of patients surviving ≥ 8 days after infusion, respectively. Reversible acute GVHD occurred in recipients of DLIs (17%) but not EBV-CTLs. The probability of complete response was significantly lower among patients with multiorgan involvement. In responders, DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not increase and EBV viremia persisted. Treatment failures were correlated with impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the patient's blood or biopsied tumor or they failed to lyse their targets because they were selectively restricted by HLA alleles not shared by the EBV-LPD. Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to impaired T-cell recognition of tumor-associated viral antigens or their presenting HLA alleles.
Reductive Amination of Piperidines with Aldehydes Using Borane-Pyridine (1993)

Abstract Borane-pyridine complex (BAP) was found to be an excellent replacement for NaCNBH3 in the Borch reduction. Assorted aromatic, heterocyclic and aliphatic aldehydes were reacted with various substituted piperidines using standardized conditions.
Screening of cell-drug interactions using acoustic trapping and MALDI MS (2015)

The properties of liquid and gas flows in microscale systems differ from those in macroscale; microfluidics is a field of science in which these properties are investigated and utilized for the development of microscale systems. Acoustofluidics is a branch of microfluidics focusing on the movement (acoustophoresis) or localization (acoustic trapping) of particles in microchannels using ultrasound. \nIn this work, the suitability of a new miniaturized method for the screening of cell-drug interactions was investigated. In the method, the cells were acoustically trapped within a glass capillary, enabling liquid movement (generated with a syringe pump) in the capillary while the trapped cell cluster remains stationary. In this manner, the trapping of cells, their incubation with a drug solution, rinsing, and the elution could be done using the same capillary. The sample preparation was done using a miniaturized solid phase extraction technique (integrated selective enrichment target, ISET), and the analysis was done with matrix assisted laser desorption/ionization mass spectrometry (MALDI MS). The drug compounds investigated were selective serotonin reuptake inhibitors (SSRI). \n\nThe research was conducted in five phases. In the first phase, a suitable solid phase extraction method for the drug compounds was investigated. In the second phase, the performance of the acoustic trap was investigated by acoustically trapping polystyrene beads and Coulter counting them. In the third phase, the method was modelled by conducting drug binding studies using cation exchange beads instead of cells. In the fourth phase, the drug binding studies were conducted by investigating the binding of drug compounds to human platelets and yeast cells. Platelets were chosen due to the expression of serotonin transporter, the molecular target of SSRI drugs, on their cell membranes. Also a cell membrane preparation containing serotonin transporter was used for the binding studies. In addition, memory effects occurring in the method were investigated. In the fifth phase, comparative drug binding studies without acoustic trapping were conducted. \n\nThe suitability of the method for the screening of cell-drug interactions could not be thoroughly substantiated, but further research and method development are required. The reason for this was the inadequate sensitivity of the method, because of which large drug concentrations had to be used. This lead to the increased occurrence of memory effects.
[Determination of Keganmin tablet with multi-wavelength K-factor spectrophotometry]. (1997)

The contents of phenacetin, aminopyrine and caffeine in Keganmin tablet were determined simultaneonsly with multiwavelength K -factor spectrophotometry. The result is accurate and the method is rapid. The average recoveries and relative standard deviations of the analysis for phenacetin, aminopyrine and caffeine were 99.91%, 0.41%; 100.1%, 0.29%; 100.1%, 0.56%, respectively.
The enhancement of PCR amplification by low molecular weight amides (2001)

Amplification of a DNA target by the polymerase chain reaction (PCR) often requires laborious optimization efforts. In this regard, the use of certain organic chemicals such as dimethyl sulfoxide, polyethylene glycol, betaine and formamide as cosolvents has been found to be very helpful. Unfortunately, very little is known about the precise structural features that make these additives effective and, accordingly, the number of such chemicals currently known to enhance PCR is limited. In order to address these issues, we decided to focus on formamide and undertook an extensive study of low molecular weight amides as a class to see how changing the substituents in the amide structure influences its effect on PCR. We describe here the results of this study, which involved 11 different amides, and present observations that provide a cohesive picture of structure-activity relations in this group of additives. We found several of these amides to be exceptionally effective and introduce them as novel PCR enhancers.