gebhart/patrepeval huggingface dataset:
Hyperplasia, hyperkeratosis and benign tumor production in transgenic mice by a targeted v-fos oncogene suggest a role for fos in epidermal differentiation and neoplasia. (1993)

A vector, derived from the human K1 keratin gene, has been employed to target v-fos expression exclusively in the epidermis of transgenic mice. Adult transgenic mice expressors (3-4 months) displayed hyperplasia and hyperkeratosis, initially in wounded (tagged) ears, which later became bilateral. This phenotype appeared at other epidermal sites, most notably in the axilla and inguinal areas. This indicates that a second promoting event, such as wounding or friction, is required to elicit these pathological changes. Highly keratotic benign ear lesions and benign squamous papillomas appeared after long latency at sites of phenotypic epidermis. These data suggest that v-fos may be interfering with c-fos function in normal keratinocyte differentiation, but by itself is insufficient to elicit overt benign lesions.
Variability in physician referral decisions. (2003)

This study revealed unexplained variability among family physicians in the specialists to whom patients are referred for specific conditions. Why some patients with the same condition are referred to surgeons and others to medical specialists is unclear, at least in the context of expectations for referral as being long-term vs short-term or consultative vs referral for definitive management. The impact of this variability on costs and outcome could be considerable and deserves more intensive study.
Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin (1992)

Cholera and the related Escherichia coli-associated diarrheal disease are important problems confronting Third World nations and any area where water supplies can become contaminated. The disease is extremely debilitating and may be fatal in the absence of treatment. Symptoms are caused by the action of cholera toxin, secreted by the bacterium Vibrio cholerae, or by a closely related heat-labile enterotoxin, produced by Escherichia coli, that causes a milder, more common traveler's diarrhea. Both toxins bind receptors in intestinal epithelial cells and insert an enzymatic subunit that modifies a G protein associated with the adenylate cyclase complex. The consequent stimulated production of cyclic AMP, or other factors such as increased synthesis of prostaglandins by intoxicated cells, initiates a metabolic cascade that results in the excessive secretion of fluid and electrolytes characteristic of the disease. The toxins have a very high degree of structural and functional homology and may be evolutionarily related. Several effective new vaccine formulations have been developed and tested, and a growing family of endogenous cofactors is being discovered in eukaryotic cells. The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins. This information may improve our understanding of the disease process itself, as well as illuminate the role of the toxin in studies of signal transduction and G-protein function.
Study of normal and malignant white blood cells by time domain dielectric spectroscopy (2001)

The aim of this paper is to present a comprehensive theoretical and experimental study by means of time domain dielectric spectrometer (TDDS) of static and dynamic dielectric properties of normal and malignant blood cells. The successful use of the TDDS method as a tool of human cell study required a special protocol and algorithms for all stages of cell preparation, measurements and data treatment. The routine developed in this study was used in the experimental analysis of nine lines of malignant, transformed and normal lymphocytes. It was shown that dielectric permittivity, capacitance and conductivity values of the cell membrane are higher for normal lymphocytes in comparison with malignant ones.
The Diversity Challenge in Directed Protein Evolution (2006)

Over the past decade, we have witnessed a bloom in the field of evolutive protein engineering which is fueled by advances in molecular biology techniques and high-throughput screening technology. Directed protein evolution is a powerful algorithm using iterative cycles of random mutagenesis and screening for tailoring protein properties to our needs in industrial applications and for elucidating proteins' structure function relationships. This review summarizes, categorizes and discusses advantages and disadvantages of random mutagenesis methods used for generating genetic diversity. These random mutagenesis methods have been classified into four main categories depending on the method employed for nucleotide substitutions: enzyme based methods (Category I), synthetic chemistry based methods (Category II), whole cell methods (Category III) and combined methods (Category I-II, I-III and II-III). The basic principle of each method is discussed and varied mutagenic conditions are summarized in Tables and compared (benchmarked) to each other in terms of: mutational bias, controllable mutation frequency, ability to generate consecutive nucleotide substitutions and subset diversity, dependency on gene length, technical simplicity/robustness and cost-effectiveness. The latter comparison shows how highly-biased and limited current diversity creating methods are. Based on these limitations, strategies for generating diverse mutant libraries are proposed and discussed (RaMuS-Flowchart; KISS principle). We hope that this review provides, especially for researchers just entering the field of directed evolution, a guide for developing successful directed evolution strategies by selecting complementary methods for generating diverse mutant libraries.
A matched set of rat/mouse chimeric antibodies. Identification and biological properties of rat H chain constant regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha. (1989)

Rat C regions mu, gamma 1, gamma 2a, gamma 2b, gamma 2c, epsilon, and alpha have been characterized by means of chimeric antibody technology. A set of rat/mouse Ag-specific (anti-4-hydroxy-3-nitrophenacetyl) antibodies was constructed that differ only in the H chain constant region but carry identical V region and L chain, both of which are of mouse origin. All rat constant regions could be expressed and m.w. were as expected from the protein sequence. A slight variation in mobility within the IgG subclasses allowed us to establish a hierarchy for the sizes of the four gamma H chains; gamma 2b greater than gamma 1 greater than gamma 2c greater than gamma 2a. Rat IgG2c and IgG2b could be purified on both protein A and protein G while rat IgG2a could only be purified on protein G. Rat IgM and IgG2b were the most potent in C-mediated hemolysis. This was not simply a consequence of the amount of C1q bound because IgG2c bound C1q efficiently but was relatively poor in cell lysis. In ADCC using human effector and target cells, IgG2b and IgG1 were the most effective.
Gemini: A Noninferiority Study of Saquinavir/Ritonavir Versus Lopinavir/Ritonavir as Initial HIV-1 Therapy in Adults (2009)

: In treatment-naive, HIV-1-infected patients, SQV/r treatment was noninferior in virologic suppression at 48 weeks to LPV/r treatment and offered a better triglyceride profile.
Chemoselective Formation of Successive Triazole Linkages in One Pot:  “Click−Click” Chemistry (2006)

A methodology for the successive regiospecific "clicking" together of three components in one pot via two triazole linkages is reported. The protocol utilizes copper(I)-mediated alkyne-azide cycloaddition reactions combined with a silver(I)-catalyzed TMS-alkyne deprotection under mild hydroalcoholic conditions. We exemplify the approach with peptide-based components to illustrate its compatibility with polyfunctionalized biomolecules. The method constitutes a promising tool for peptide ligation. We also provide a procedure for directly using TMS-alkynes as the cycloaddition partner in classical "click" chemistry.
Efficient Depletion of Host DNA Contamination in Malaria Clinical Sequencing (2012)

The cost of whole-genome sequencing (WGS) is decreasing rapidly as next-generation sequencing technology continues to advance, and the prospect of making WGS available for public health applications is becoming a reality. So far, a number of studies have demonstrated the use of WGS as an epidemiological tool for typing and controlling outbreaks of microbial pathogens. Success of these applications is hugely dependent on efficient generation of clean genetic material that is free from host DNA contamination for rapid preparation of sequencing libraries. The presence of large amounts of host DNA severely affects the efficiency of characterizing pathogens using WGS and is therefore a serious impediment to clinical and epidemiological sequencing for health care and public health applications. We have developed a simple enzymatic treatment method that takes advantage of the methylation of human DNA to selectively deplete host contamination from clinical samples prior to sequencing. Using malaria clinical samples with over 80% human host DNA contamination, we show that the enzymatic treatment enriches Plasmodium falciparum DNA up to ∼9-fold and generates high-quality, nonbiased sequence reads covering >98% of 86,158 catalogued typeable single-nucleotide polymorphism loci.
Cellular receptors for type beta transforming growth factor. Ligand binding and affinity labeling in human and rodent cell lines. (1985)

Type beta transforming growth factor (beta TGF) purified from human platelets to homogeneity as judged by NH2-terminal amino acid sequence analysis has been labeled with 125I to characterize its interaction with cellular receptors. Binding of 125I-beta TGF to target cells is temperature- and time-dependent, specific, saturable, and reversible. About 1.6-1.9 X 10(4) binding sites/cell with high affinity for beta TGF (Kd = 5.6-7.8 X 10(-11) M and 9.1-14 X 10(-11) M, respectively) are found in NRK-49F and BALB/c 3T3 cells. beta TGF receptors do not appear to undergo acute down-regulation by the ligand. Specific binding of 125I-beta TGF has been observed in several human, rat, and mouse fibroblast lines and in some, but not all, tumor-derived cell lines examined. 125I-beta TGF has been cross-linked to intact cells and isolated membrane preparations using disuccinimidyl suberate. Cells and isolated membranes from human, rat, and mouse origin affinity labeled with 125I-beta TGF exhibit a major labeled species of approximately 280 kilodaltons that has the properties of high affinity and specificity expected from a physiologically relevant beta TGF receptor. Minor labeled species of 70-90 kilodaltons are also labeled by 125I-beta TGF, but they correspond to molecular species with low apparent affinity (Kd approximately 10(-8) M) for 125I-beta TGF.
Knowledge-based management of cellular clone fraud (2003)

The authors discuss the problems of fraudulent use of cellular networks, and in particular, the detection and management of cellular clone fraud, a new and fast-developing form of fraud with potentially large impact on carrier revenues. They discuss the problem, industry-proposed solutions, and the utility of knowledge-based techniques for detecting cellular clone fraud and managing it by recommending appropriate fraud-containment actions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Simultaneous host and parasite expression profiling identifies tissue-specific transcriptional programs associated with susceptibility or resistance to experimental cerebral malaria (2006)

These data show that host and parasite gene expression profiles can be simultaneously analysed using a single "combination" microarray, and that both the mouse and malaria parasite display distinct tissue- and strain-specific responses during infection. This technology facilitates the dissection of host-pathogen interactions in experimental cerebral malaria and could be extended to other disease models.
The Development of the Ideas and Policy of the British Union of Fascists, 1932-40 (1987)

Until the appearance of Neill Nugent's article on the ideas of the British Union of Fascists (BUF) in 1977,' this aspect of British fascism had been largely ignored. Previous work on the BUF concentrated mainly upon questions related to the character of Sir Oswald Mosley, the movement's leader and prime mover, and the novel features of the BUF's organization and campaigns, together with such aspects as anti-semitism and violence. Indeed, recent work on the topic has returned to questions of organization and historical narrative; for example, Gerry Webber's interesting contribution to the question of BUF membership,2 and J.D. Brewer's study of the BUF in the West Midlands.3 However, to date, Nugent's article remains the main commentary on the ideological orientation of Britain's primary fascist movement. Nugent's article was the first attempt to provide a clearer explanation of the BUF's ideas than that contained in the standard works on the movement.4 In addition, he provided a useful framework within which to analyze the differing elements in the hierarchy of BUF ideas and policy. Nugent divided the various elements of BUF thought into five sections, namely: the speeches and writings of Mosley, the contributions of the 'inner core' of the BUF's hierarchy, the periodic publications of the movement, the speeches and writings of the lesser leaders of the movement, and, finally, all other pronouncements. It is the first two 'authoritative' categories that Nugent concentrated on in his article. It seems that this five-part categorization of BUF ideas is essentially a correct interpretation of the importance of the various elements of thought within the BUF, bearing in mind that it was a strictly hierarchical movement, based upon the principles of leadership, and led by the charismatic figure of Mosley. However, the further content of the article merely provides a stepping-off point for further discussion.
Tandir burns in and around Diyarbakir, Turkey. (2010)

Tandir burn is a severe burn with a higher morbidity and mortality.
Concordant KRAS Mutations in Primary and Metastatic Colorectal Cancer Tissue Specimens: A Meta-Analysis and Systematic Review (2012)

A meta-analysis was performed to compare KRAS gene mutations in colorectal cancer tissue samples with primary and metastatic colorectal cancers. A total of 19 publications with 986 paired primary and distant metastases and 171 paired primary and lymph node metastases showed that KRAS genotype was highly concordant in primary and distant metastatic tumors, indicating that either type of tumor tissue could be useful as a source to detect KRAS mutations for selection of anti-EGFR therapy. However, lymph-node-metastatic tumors might not be suitable for diagnostic analysis of KRAS mutations due to an obvious discordant rate between primary and lymph-node-metastatic tumors.
Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-α in human prostate cancer cells (1999)

The epidermal growth factor receptor (EGFR) plays an important role in the development and progression of prostate cancer and its overexpression is associated with decreased survival. With progression, prostate cancer cells switch from epidermal growth factor (EGF) to transforming growth factor alpha (TGF-alpha) synthesis, which contributes to autocrine growth and unrestrained proliferation. To define the molecular mechanisms involved in the regulation of EGFR expression by EGF and TGF-alpha we studied three human prostate cancer cell lines, androgen-responsive (LNCaP) and -unresponsive (DU145 and PC3). Here we show that TGF-alpha stabilized EGFR mRNA two- to threefold in all three cell lines, whilst EGF stabilized EGFR mRNA approximately twofold in LNCaP and DU145 cells, but not in PC3 cells. Both ligands increased EGFR transcription in LNCaP and DU145 cells, with less effect in PC3 cells. In all three cell lines EGF reduced total EGFR protein levels more than TGF-alpha, but this was associated with a greater increase in de novo protein synthesis with EGF compared to TGF-alpha. Only EGF, however, shortened EGFR protein stability (half-life decreased from 5 h to 120 min), resulting in rapid disappearance of newly synthesized EGFR protein. Both ligands increased total LNCaP and DU145 cell numbers. These studies demonstrate that the EGF- and TGF-alpha-induced upregulation of EGFR mRNA and protein in human prostate cancer cell lines is complex and occurs at multiple, transcriptional and post-transcriptional levels. Taken together, these data provide novel insight into the molecular mechanisms by which TGF-alpha would preferentially maintain an autocrine loop in human prostate cancer cells. Furthermore, this work suggests that in human prostate cancer cells ligand-specific differential intracellular trafficking of the EGFR plays a major role in regulating its expression.
High-resolution image reconstruction from multiple differently exposed images (2006)

Super-resolution reconstruction is the process of reconstructing a high-resolution image from multiple low-resolution images. Most super-resolution reconstruction methods assume that exposure time is fixed for all observations, which is not necessarily true. In reality, cameras have limited dynamic range and nonlinear response to the quantity of light received, and exposure time might be adjusted automatically or manually to capture the desired portion of the scene's dynamic range. In this letter, we propose a Bayesian super-resolution algorithm based on an imaging model that includes camera response function, exposure time, sensor noise, and quantization error in addition to spatial blurring and sampling.
Proton Insertion into Oxide Cathodes during Chemical Delithiation (2006)

A quantitative determination of proton contents in various chemically delithiated oxide cathodes has been carried out with prompt gamma-ray activation analysis (PGAA), and the results are complemented by mass spectrometric and thermogravimetric analysis data. While the delithiated layered , , and show a significant amount of proton in the lattice at deep lithium extraction, orthorhombic , spinel , and olivine do not encounter such proton insertion. Interestingly, spinel shows both proton insertion and oxygen loss at deep lithium extraction. The differences are attributed to the differences in the chemical instability of the various cathodes.
NG2‐expressing cells as oligodendrocyte progenitors in the normal and demyelinated adult central nervous system (2005)

The mammalian adult central nervous system (CNS) is known to respond rapidly to demyelinating insults by regenerating oligodendrocytes for remyelination from a dividing precursor population. A widespread population of cells exists within the adult CNS that is thought to belong to the oligodendrocyte lineage, but which do not express proteins characteristic of mature myelinating oligodendrocytes, such as myelin basic protein (MBP) and 2,3-cyclic nucleotide 3-phosphodiesterase (CNP). Instead, these cells have phenotypic characteristics of a more immature stage of the oligodendrocyte lineage. They express the NG2 chondroitin sulphate proteoglycan, in addition to O4 and the platelet-derived growth factor alpha-receptor, all widely accepted as markers for oligodendrocyte progenitor cells (OPCs) throughout development. However, NG2+ cells residing in the adult CNS do not resemble embryonic or neonatal NG2+ cells in terms of their morphology or proliferation characteristics, but instead represent a unique type of glial cell that has the ability to react rapidly to CNS damage. In this review, we present the evidence that adult NG2+ cells are part of the oligodendrocyte lineage and are capable of giving rise to new oligodendrocytes under both normal and demyelinating conditions. We also review the literature that these cells may have multiple functional roles within the adult CNS, notwithstanding their primary role as OPCs.
Application of Machine Learning To Epileptic Seizure Detection (2010)

We present and evaluate a machine learning approach to constructing patient-specific classifiers that detect the onset of an epileptic seizure through analysis of the scalp EEG, a non-invasive measure of the brain’s electrical activity. This problem is challenging because the brain’s electrical activity is composed of numerous classes with overlapping characteristics. The key steps involved in realizing a high performance algorithm included shaping the problem into an appropriate machine learning framework, and identifying the features critical to separating seizure from other types of brain activity. When trained on 2
Factors contributing to the inhibition of HIV reverse transcriptase by chain‐terminating nucleotides in vitro and in vivo (1991)

Arguments are presented leading to the conclusion that two major factors contribute to the potency of inhibition of DNA-polymerase activity by chain-terminating nucleotides. The relative significance of these factors varies with the reaction conditions, particularly with the length of the template and the concentration ratio of enzyme (reverse transcriptase or other DNA polymerase) to primer. It is concluded that potent inhibition of HIV-reverse transcriptase activity under typical in vitro and in vivo conditions arises from different features of the interaction of chain terminators with the enzyme. A new method of testing for the parameter important under in vivo conditions is suggested.
Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction (2008)

Mammalian cells fuel their growth and proliferation through the catabolism of two main substrates: glucose and glutamine. Most of the remaining metabolites taken up by proliferating cells are not catabolized, but instead are used as building blocks during anabolic macromolecular synthesis. Investigations of phosphoinositol 3-kinase (PI3K) and its downstream effector AKT have confirmed that these oncogenes play a direct role in stimulating glucose uptake and metabolism, rendering the transformed cell addicted to glucose for the maintenance of survival. In contrast, less is known about the regulation of glutamine uptake and metabolism. Here, we report that the transcriptional regulatory properties of the oncogene Myc coordinate the expression of genes necessary for cells to engage in glutamine catabolism that exceeds the cellular requirement for protein and nucleotide biosynthesis. A consequence of this Myc-dependent glutaminolysis is the reprogramming of mitochondrial metabolism to depend on glutamine catabolism to sustain cellular viability and TCA cycle anapleurosis. The ability of Myc-expressing cells to engage in glutaminolysis does not depend on concomitant activation of PI3K or AKT. The stimulation of mitochondrial glutamine metabolism resulted in reduced glucose carbon entering the TCA cycle and a decreased contribution of glucose to the mitochondrial-dependent synthesis of phospholipids. These data suggest that oncogenic levels of Myc induce a transcriptional program that promotes glutaminolysis and triggers cellular addiction to glutamine as a bioenergetic substrate.