gebhart/patrepeval huggingface dataset:
Genes involved in melanoma: an overview of INK4a and other loci. (1999)

Melanoma is the most aggressive of the skin cancers and its prognosis is often poor. The only known environmental risk factor for this tumour is ultraviolet light exposure. This fact together with the existence of melanoma-prone families has prompted investigation of genetic risk factors that may be involved in melanoma development. Inactivation of the INK4a/p16 gene is known to play a role in familial cases. Data on genes or loci involved in sporadic melanoma are less definitive and require more detailed research. In addition to the INK4a locus, other genes involved in melanoma development are discussed here, in particular those genes that participate in the same functional pathway, such as CDK4 and Rb, and p53, which is regulated by the alternative product of INK4a. Evidence showing the possible location of melanoma susceptibility genes on chromosomes 1p, 6, 10q and 11q is analysed along with data showing N-ras, betacatenin, c-myc and MC1R involvement. Melanoma is a well-characterized disease in terms of its progression stages; therefore obtaining precise genetic information is crucial in the development of a stepwise model of melanoma pathogenesis.
Organotrifluoroborates:  Protected Boronic Acids That Expand the Versatility of the Suzuki Coupling Reaction (2007)

Organotrifluoroborates represent an alternative to boronic acids, boronate esters, and organoboranes for use in Suzuki-Miyaura and other transition-metal-catalyzed cross-coupling reactions. The trifluoroborate moiety is stable toward numerous reagents that are often problematic for other boron species. Consequently, remote functional groups within the organotrifluoroborates can be manipulated, while retaining the valuable carbon-boron bond.
Preharvest 1-Methylcyclopropene Delays Fruit Maturity and Reduces Softening and Superficial Scald of Apples During Long-term Storage (2008)

Three experiments were undertaken to evaluate the effects of different preharvest 1-methylcyclopropene (1-MCP) spray treatments on apple ( Malus × domestica Borkh.) fruit maturity at harvest and quality after long-term storage in a regular atmosphere or controlled atmosphere (CA). Trees were sprayed within 7 days of the anticipated harvest date (H) and fruit for long-term storage were sampled at either H in the case of ‘Law Rome’ or at harvest dates that were delayed by up to 21 days (H + 21) in the case of ‘Golden Delicious’ and ‘Law Rome’. Preharvest 1-MCP sprays within 7 days of H reduced fruit drop, internal ethylene concentration, and starch index and reduced firmness loss during long-term storage of fruit at delayed harvest dates but had only minor effects on fruit maturity at H. Preharvest 1-MCP sprays reduced the incidence of superficial scald on ‘Law Rome’ apples more effectively than either diphenylamine or CA storage. Application of 1-MCP within 7 days of H may be used to delay harvest date, thereby allowing continued fruit growth without a concomitant advance in fruit maturity and to reduce firmness loss and superficial scald during long-term storage both for normal and delayed harvests.
A New Antigen Recognized by Cytolytic T Lymphocytes on a Human Kidney Tumor Results from Reverse Strand Transcription (1999)

By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2. This gene is transcribed in both directions. The antigenic peptide is not encoded by the sense transcript, RU2S, which is expressed ubiquitously. It is encoded by an antisense transcript, RU2AS, which starts from a cryptic promoter located on the reverse strand of the first intron and ends up on the reverse strand of the RU2S promoter, which contains a polyadenylation signal. This mechanism of antigen expression is unprecedented and further illustrates the notion that many peptides recognized by T cells cannot be predicted from the primary structure of the major product of the encoding gene. Antisense transcript RU2AS is expressed in a high proportion of tumors of various histological types. It is absent in most normal tissues, but is expressed in testis and kidney, and, at lower levels, in urinary bladder and liver. Short-term cultures of normal epithelial cells from the renal proximal tubule expressed significant levels of RU2AS message and were recognized by the CTLs. Therefore, this antigen is not tumor specific, but corresponds to a self-antigen with restricted tissue distribution.
Pharmacological Characterization of the αvβ6 Integrin Binding and Internalization Kinetics of the Foot-and-Mouth Disease Virus Derived Peptide A20FMDV2 (2016)

A20FMDV2 is a peptide derived from the foot-and-mouth disease virus with a high affinity and selectivity for the alpha-v beta-6 (αvβ6) arginyl-glycinyl-aspartic acid (RGD)-binding integrin. It has been shown to be an informative tool ligand in pre-clinical imaging studies for selective labelling of the αvβ6 integrin in a number of disease models. In a radioligand binding assay using a radiolabelled form of the peptide ([3H]A20FMDV2), its high affinity (K(D): 0.22 nmol/l) and selectivity (at least 85-fold) for αvβ6 over the other members of the RGD integrin family was confirmed. [3H]A20FMDV2 αvβ6 binding could be fully reversed only in the presence of EDTA, whereas a partial reversal was observed in the presence of excess concentrations of an RGD-mimetic small molecule (SC-68448) or unlabelled A20FMDV2. Using flow cytometry on bronchial epithelial cells, the ligand-induced internalization of αvβ6 by A20FMDV2 and latency-associated peptide-1 was shown to be fast (t(1/2): 1.5 and 3.1 min, respectively), concentration-dependent (EC50: values 1.1 and 3.6 nmol/l, respectively) and was followed by a moderately slow return of integrin to the surface. The results of the radioligand binding studies suggest that the binding of A20FMDV2 to the RGD-binding site on αvβ6 is required to maintain its engagement with the hypothesised A20FMDV2 synergy site on the integrin. In addition, there is evidence from flow cytometric studies that the RGD-ligand engagement of αvβ6 post-internalization plays a role in delaying recycling of the integrin to the cell surface. This mechanism may act as a homeostatic control of membrane αvβ6 following RGD ligand engagement.
Flow patterns in the human carotid artery bifurcation. (1984)

To elucidate the connection between blood flow and the localized genesis and development of atherosclerosis and thrombosis at the human carotid artery bifurcation, detailed studies of the flow patterns and distributions of fluid velocity and wall shear rate in this region were carried out using a transparent segment of the carotid artery, prepared from a human subject postmortem, and cinemicrographic techniques. It was found that a recirculation zone which consisted of a pair of complex spiral secondary flows, symmetrical about the common median plane of the bifurcation, was formed in the carotid sinus over wide ranges of inflow Reynolds numbers, Re0, and flow rate ratios, Q1/Q0 (internal/common). The formation and the size of the recirculation zone were largely dependent on Q1/Q0, as well as on Re0. The size of the recirculation zone increased from approximately 4 mm at Re0 = 300 to a maximum of approximately 9 mm at Re0 greater than 800. The results suggest that, under physiological conditions (Re0 approximately 600, Q1/Q0 approximately 0.7), a standing recirculation zone exists in the carotid sinus, thereby affecting local mass transfer and interactions of blood cells with the vessel wall, which may lead to the incidence of atherosclerosis and thrombosis in this region.
FABRICATION AND OPTICAL PROPERTIES OF NANOCOMPLEXES COMPOSED OF METAL NANOPARTICLES AND ORGANIC DYES (2004)

We have prepared nanocomplexes composed of silver or gold nanoparticles as a core and merocyanine or phthalocyanine as a shell portion by the co-reprecipitation method. From their absorption spectra, the core metal nanoparticles seemed to interact electronically with the shell layer of organic compounds in the nanocomplexes to give different electronic states from their original states. The morphology of their nanocomplexes was observed by electron microscopies.
High-Throughput Screening of a Corynebacterium glutamicum Mutant Library on Genomic and Metabolic Level (2014)

Due to impressive achievements in genomic research, the number of genome sequences has risen quickly, followed by an increasing number of genes with unknown or hypothetical function. This strongly calls for development of high-throughput methods in the fields of transcriptomics, proteomics and metabolomics. Of these platforms, metabolic profiling has the strongest correlation with the phenotype. We previously published a high-throughput metabolic profiling method for C. glutamicum as well as the automatic GC/MS processing software MetaboliteDetector. Here, we added a high-throughput transposon insertion determination for our C. glutamicum mutant library. The combination of these methods allows the parallel analysis of genotype/phenotype correlations for a large number of mutants. In a pilot project we analyzed the insertion points of 722 transposon mutants and found that 36% of the affected genes have unknown functions. This underlines the need for further information gathered by high-throughput techniques. We therefore measured the metabolic profiles of 258 randomly chosen mutants. The MetaboliteDetector software processed this large amount of GC/MS data within a few hours with a low relative error of 11.5% for technical replicates. Pairwise correlation analysis of metabolites over all genotypes showed dependencies of known and unknown metabolites. For a first insight into this large data set, a screening for interesting mutants was done by a pattern search, focusing on mutants with changes in specific pathways. We show that our transposon mutant library is not biased with respect to insertion points. A comparison of the results for specific mutants with previously published metabolic results on a deletion mutant of the same gene confirmed the concept of high-throughput metabolic profiling. Altogether the described method could be applied to whole mutant libraries and thereby help to gain comprehensive information about genes with unknown, hypothetical and known functions.
Visualizing Strain Evolution and Coordinated Buckling within CNT Arrays by In Situ Digital Image Correlation (2012)

Abstract Spatial mapping of strain fields within compressed carbon nanotube (CNT) array columns is achieved using digital image correlation (DIC) analysis of in situ scanning electron microscopy (SEM) image sequences. Full‐field displacement and strain maps are generated based upon the motion of the constituent CNTs, which serve as a traceable high‐contrast speckle pattern for DIC analysis. The deformation modes and CNT array buckling characteristics vary systematically as a function of column aspect ratio, including bending, crushing, and bottom‐up buckle accumulation behaviors. In spite of disparate appearing deformation modes, strain maps indicate that CNT array buckling consistently initiates at 5% local principal strain (ϵ 2 ) for all columns. The ability to quantitatively assess the deformation modes and buckling behavior of CNT arrays at the nanoscale will enable their improved design for high‐strain electrical contacts, compliant thermal interfaces, force sensors, energy‐absorbing foams, or other applications.
Genetic and functional characterization of human pemphigus vulgaris monoclonal autoantibodies isolated by phage display (2005)

Pemphigus is a life-threatening blistering disorder of the skin and mucous membranes caused by pathogenic autoantibodies to desmosomal adhesion proteins desmoglein 3 (Dsg3) and Dsg1. Mechanisms of antibody pathogenicity are difficult to characterize using polyclonal patient sera. Using antibody phage display, we have isolated repertoires of human anti-Dsg mAbs as single-chain variable-region fragments (scFvs) from a patient with active mucocutaneous pemphigus vulgaris. ScFv mAbs demonstrated binding to Dsg3 or Dsg1 alone, or both Dsg3 and Dsg1. Inhibition ELISA showed that the epitopes defined by these scFvs are blocked by autoantibodies from multiple pemphigus patients. Injection of scFvs into neonatal mice identified 2 pathogenic scFvs that caused blisters histologically similar to those observed in pemphigus patients. Similarly, these 2 scFvs, but not others, induced cell sheet dissociation of cultured human keratinocytes, indicating that both pathogenic and nonpathogenic antibodies were isolated. Genetic analysis of these mAbs showed restricted patterns of heavy and light chain gene usage, which were distinct for scFvs with different desmoglein-binding specificities. Detailed characterization of these pemphigus mAbs should lead to a better understanding of the immunopathogenesis of disease and to more specifically targeted therapeutic approaches.
Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients (2007)

NAFLD is extremely common in people with type 2 diabetes and is associated with a higher prevalence of CVD. Follow-up studies are needed to determine whether NAFLD predicts the development and progression of CVD.
Progress toward human gene therapy (1993)

THE TECHNOLOGY of gene transfer has evolved over nearly 50 years since studies of DNA-mediated bacterial transformation reported by Avery et al in 1944.<sup>1</sup>These earliest gene transfer experiments explored "the chemical nature of the substance inducing transformation of pneumococcal types."1 More than two decades later, mammalian cells were transformed with SV40 and polyoma papovavirus DNA by calcium phosphate—mediated cellular uptake.<sup>2-4</sup>In 1971, the first workshop on gene therapy was held.<sup>5</sup>Recombinant DNA technology provided the first approaches for cell transfer of disease-related genes (ie, β-globin [hemoglobinopathies] and hypoxanthine guanine phosphoribosyltransferase [Lesch-Nyhan syndrome]).<sup>6-10</sup>The Human Genome Project, with its high rate of heritable disease and cancer gene discoveries, fuels the opportunities for gene transfer therapy. Replication-defective viral vectors are essential vehicles for gene transfer. Safe viral vectors were developed in the laboratories of Mulligan, Verma, Miller, and Gilboa based on the basic research on the life
Management of Primary Hyperlipidemia (1995)

Epidemiologic, clinical, genetic, experimental, and pathological studies have clearly established the primary role of lipoproteins in atherogenesis.1,2 Lowering plasma cholesterol concentrations reduces the availability of atherogenic lipoproteins and also, presumably, the accumulation of cholesterol in the intima of arteries. Measures to lower plasma cholesterol have become fundamental to the practice of preventive cardiology, and their use in both patients who already have coronary disease and healthy people has materially contributed to the 50 percent reduction in mortality from coronary heart disease in the United States in the past two decades.3,4 Lowering the plasma cholesterol concentration by a variety . . .
Gonadotropin-Releasing Hormone and Its Analogues (1991)

RESEARCH into the neuroendocrine control of reproduction by gonadotropin-releasing hormone (GnRH) has witnessed a remarkable two decades. From the isolation and chemical characterization of GnRH in 1971 through the awarding of the Nobel Prize to Drs. Serially and Guillemin for these accomplishments shortly thereafter, the translation from basic discovery to clinical usefulness has been swift. Food and Drug Administration approvals of GnRH-agonist analogues for the treatment of prostate cancer, endometriosis, and precocious puberty, as well as the use of natural GnRH to induce ovulation, are examples of the clinical usefulness of these fundamental observations. Numerous clinical therapies designed to stimulate . . .
[Drug therapy in cardiopulmonary resuscitation]. (2001)

In the year 2000, new international guidelines for cardiopulmonary resuscitation (CPR) were published by the American Heart Association, and the European Resuscitation Council. These guidelines are evidence-based, indicating that these recommendations are based primarily on interpretation of data from clinical studies. Levels of recommendation range from class I (proven safe and useful), class IIa (intervention of choice), IIb (alternative intervention), indeterminate (research stage), and class III (unacceptable, no benefit). Administration of drugs during CPR should be performed intravenously or intraosseously (class IIa) or, as a second-line approach, endotracheally (class IIb). Due to lack of evidence, the standard dose of 1 mg epinephrine to treat ventricular fibrillation, pulseless electrical activity, or asystole was categorized as class indeterminate; while a single dose of 40 units vasopressin to treat adults with shock-refractory ventricular fibrillation received a IIb recommendation. Owing to a lack of clinical data, the use of vasopressin was neither recommended to treat adults with pulseless electrical activity or asystole, nor for the use in children. Both endothelin and calcium were not recommended for routine use (class indeterminate). Careful titration of acid-base status with 1 mL/kg 8.4% sodium bicarbonate should only be administered if indicated by blood gas analysis (class indeterminate). If 1 mg epinephrine fails to be effective in adult patients with pulseless electrical activity or asystole, 1 mg atropine can be administered (class indeterminate). Regarding antiarrhythmic drugs, 300 mg amiodarone (class IIb) showed the best results in shock-refractory ventricular fibrillation. The postresuscitation phase has the goal to achieve the best possible neurological performance after return of spontaneous circulation, which requires careful optimization of organ functions.
A novel approach for ground fault detection (2004)

Faulted lines must be repaired and returned to service in the shortest possible time to provide reliable service to the customers. Fault detection is an important aspect of system protection, as it involves personnel as well as equipment safety. The research on fault detection techniques is mainly based on conventional methods, not suitable for detecting high impedance ground faults. This paper discusses a novel approach for detecting high impedance ground faults using state-of-the-art signal processing technology. Some laboratory test results are reported. The reported work offers promise in realizing dependable and secure high impedance ground fault detection using latest technology.
Ca(2+)-dependent and Ca(2+)-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL-2H3 cells. Reconstitution of secretory responses with Ca2+ and purified isozymes in washed permeabilized cells. (1993)

Rat basophilic RBL-2H3 cells, which exhibit Ca(2+)-dependent secretion of granules when stimulated with antigen, contained the Ca(2+)-dependent alpha and beta and the Ca(2+)-independent delta, epsilon, and zeta isoforms of protein kinase C. These isoforms associated, to variable extents (i.e. delta the most and zeta the least), with the membrane fraction upon antigen stimulation but without external Ca2+; only the Ca(2+)-independent isoforms did so. Both types of isozymes were probably necessary for optimal responses to antigen as indicated by the following observations. All Ca(2+)-dependent isozymes were degraded in cells treated with 20 nM phorbol 12-myristate 13-acetate for 6 h, whereas the Ca(2+)-independent isozymes were not degraded and were retained when the cells were subsequently permeabilized and washed. Cells so treated still exhibited antigen-induced secretion (25-33% of normal) which was suppressed by selective inhibitors of protein kinase C (Ro31-7549 and calphostin C) thereby indicating a possible contribution of the Ca(2+)-independent isozymes in secretion. Normally, washed permeabilized cells lost all isozymes of protein kinase C and failed to secrete in response to antigen. A full secretory response to antigen could be reconstituted by the subsequent addition of nanomolar concentrations of either beta or delta isozymes of protein kinase C (other isozymes were much less effective) but only in the presence of 1 microM free Ca2+ to indicate distinct roles for Ca2+ and protein kinase C in exocytosis.
Differentiation of human monocytic cell lines confers susceptibility to Bacillus anthracis lethal toxin (2004)

Anthrax lethal toxin (LT) is comprised of protective antigen and lethal factor. Lethal factor enters mammalian cells in a protective antigen-dependent process and cleaves mitogen-activated protein kinase kinases. Although LT has no observable effect on many cell types, it causes necrosis in macrophages derived from certain mouse strains and apoptosis in activated mouse macrophages. In this study, we observed that LT treatment of three different human monocytic cell lines U-937, HL-60 and THP-1 did not induce cell death. Cells did become susceptible to the toxin, however, after differentiation into a macrophage-like state. Treatment with LT resulted in decreased phosphorylation of p38, ERK1/2 and JNK in both undifferentiated and differentiated HL-60 cells, suggesting that the change in susceptibility does not result from differences in toxin delivery or substrate cleavage. Death of differentiated HL-60 cells was accompanied by chromosome condensation and DNA fragmentation, but was not inhibited by the pan-caspase inhibitor Z-VAD-FMK. In addition, we observed that the macrophage differentiation process could be inhibited by LT. Our results indicate that LT-mediated death of mouse and human macrophages may occur through distinct processes and that the differentiation state of human cells can determine susceptibility or resistance to LT.
Health research with Aboriginal Australians: perceptions and realities (1999)

The author examines some of the complex historical and ethical issues surrounding health research, particularly with Indigenous peoples. In doing so, he reaches three conclusions. 1. Human history provides many examples of curiosity-driven research involving practices or experiments that would be regarded as unethical by contemporary standards. Indigenous people and others in disadvantaged situations have been at particular risk of exploitation. 2. The sharing of knowledge from past research, regardless of where it was carried out, has delivered major benefits to the health of both Indigenous and non- Indigenous populations. 3. Nevertheless, research with humans can never be justified on utilitarian grounds alone. It must also respect the autonomy, beliefs and wishes of potential research subjects and not expose them to any foreseeable physical or mental harm. (non-author abstract)