gebhart/patrepeval huggingface dataset:
A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells (2008)

Inappropriate activation of JAK/STAT signaling occurs with high frequency in human cancers and is associated with cancer cell survival and proliferation. Therefore, the development of pharmacologic STAT signaling inhibitors has therapeutic potential in the treatment of human cancers. Here, we report 2-[(3,5-bis-trifluoromethyl-phenyl)-hydroxy-methyl]-1-(4-nitro-phenylamino)-6-phenyl-1,2,4a,7a-tetrahydro-pyrrolo[3,4-b]-pyridine-5,7-dione (AUH-6-96) as a novel small-molecule inhibitor of JAK/STAT signaling that we initially identified through a cell-based high-throughput screening using cultured Drosophila cells. Treatment of Drosophila cells with AUH-6-96 resulted in a reduction of Unpaired-induced transcriptional activity and tyrosine phosphorylation of STAT92E, the sole Drosophila STAT homologue. In human cancer cell lines, AUH-6-96 inhibited both constitutive and interleukin-6-induced STAT3 phosphorylation. Specifically, in Hodgkin lymphoma L540 cells, treatment with AUH-6-96 resulted in reduced levels of tyrosine phosphorylated STAT3 and of the STAT3 downstream target gene SOCS3 in a dose- and time-dependent manner. In addition, AUH-6-96-treated L540 cells showed decreased expression of persistently activated JAK3, suggesting that AUH-6-96 inhibits the JAK/STAT pathway signaling in L540 cells by affecting JAK3 activity and subsequently blocking STAT3 signaling. Importantly, AUH-6-96 selectively affected cell viability only of cancer cells harboring aberrant JAK/STAT signaling. In support of the specificity of AUH-6-96 for inhibition of JAK/STAT signaling, treatment with AUH-6-96 decreased cancer cell survival by inducing programmed cell death by down-regulating the expression of STAT3 downstream target antiapoptotic genes, such as Bcl-xL. In summary, this study shows that AUH-6-96 is a novel small-molecule inhibitor of JAK/STAT signaling and may have therapeutic potential in the treatment of human cancers harboring aberrant JAK/STAT signaling.
Remineralization of enamel subsurface lesions in situ by the use of three commercially available sugar‐free gums (2008)

The superior remineralization activity of the TW gum in situ was attributed to the presence of casein phosphopeptide-amorphous calcium phosphate nanocomplexes.
Interleukin-6 production in high-grade B lymphomas: correlation with the presence of malignant immunoblasts in acquired immunodeficiency syndrome and in human immunodeficiency virus-seronegative patients (1992)

Abstract The mechanisms leading to malignant cell proliferation may differ between the different histologic forms of high-grade non-Hodgkin's lymphomas. To analyze the potential role of interleukin-6 (IL-6) as a growth factor for lymphomatous cells in these different forms, the in situ production of this cytokine was analyzed in lymphomatous samples taken from 24 patients, 18 of whom were human immunodeficiency virus (HIV) infected. Eleven Burkitt's lymphomas (BLs), seven diffuse large- cell lymphomas, and six immunoblastic lymphomas were studied. In situ hybridization experiments showed that the IL-6 gene was expressed in all tissues. The number of IL-6 gene-expressing cells was 7 times higher in the non-BLs than in the BLs, and it was 17 times higher than that of 14 control lymph nodes displaying a benign follicular hyperplasia. Analysis of individual cases indicated that the level of IL-6 gene expression was strongly correlated with the presence of immunoblasts within the malignant clone. In contrast, this level was not correlated with the presence of Epstein-Barr virus genome in the lymphoma or with the HIV status of patients. Immunohistochemical studies with an anti-IL-6 monoclonal antibody showed that IL-6 was produced in non-BLs, but not in BLs. In the former, IL-6 mainly originated from reactive, nonmalignant cells. Immunohistochemical analyses of non-BLs also showed that malignant cells produced the 80-Kd chain of the IL-6 receptor. Taken together, these results suggest that IL-6 may act as a growth factor in some forms of high-grade B lymphomas. The presence of immunoblasts may be an indicator of such forms.
Taxonomic Classification of Human Hepatitis B Virus (1986)

Sufficient data have accumulated to permit the ICTV Study Group on the Nomenclature of Hepatitis Viruses to recognize human hepatitis B virus as a member of a unique group of viruses and to classify it, together with a number of related animal viruses, into a new family called the Hepadnaviridae. Over the past decade, the International Committee on Taxonomy of Viruses (ICTV) has been active in the development of a classification system for viruses. The majority of viruses infecting vertebrate hosts have been classified into families and genera on the recommendations of the Vertebrate Virus Subcommittee (VVSC). In June 1980, the VVSC authorized the formation of an ad hoc Study Group on the Nomenclature of Hepatitis Viruses under the Chairmanship of Dr. Ian D. Gust. This paper represents the first report of the Study Group on the Taxonomic Classification of Human Hepatitis B Virus.
Stent-Assisted Coiling of Intracranial Aneurysms (2009)

Stents were associated with a significant decrease of angiographic recurrences, but they were associated with more lethal complications compared with coiling without stents.
Fundamental Elliptic Curve Cryptography Algorithms (2011)

This note describes the fundamental algorithms of Elliptic Curve Cryptography (ECC) as they were defined in some seminal references from 1994 and earlier. These descriptions may be useful for implementing the fundamental algorithms without using any of the specialized methods that were developed in following years. Only elliptic curves defined over fields of characteristic greater than three are in scope; these curves are those used in Suite B.
Borylation of primary and secondary alkyl bromides catalyzed by Cu2O nanoparticles (2015)

A Cu<sub>2</sub>O nanoparticle catalyzed borylation of alkylboronic esters is developed, with mild reaction conditions, high yield and in the absence of ligands which otherwise are essential in homogenous catalysis, using bis(pinacolato)diboron as the boron source.
Computerized detection of clustered microcalcifications in digital mammograms: Applications of artificial neural networks (1992)

Artificial neural networks have been applied to the differentiation of actual "true" clusters from normal parenchymal patterns and also to the differentiation of actual clusters from false-positive clusters as reported by a computerized scheme for the detection of microcalcifications in digital mammograms. The differentiation was carried out in both the spatial and frequency domains. The performance of the neural networks was evaluated quantitatively by means of receiver operating characteristic (ROC) analysis. It was found that the networks could distinguish clustered microcalcifications from normal nonclustered areas in the frequency domain, and that they could eliminate approximately 50% of false-positive clusters of microcalcifications while preserving 95% of the positive clusters, when applied to the results of the automated detection scheme. A large, comprehensive training database is needed for neural networks to perform reliably in clinical situations.
Repetitive elements and their genetic applications in zebrafish (1997)

Repetitive elements provide important clues about chromosome dynamics, evolutionary forces, and mechanisms for exchange of genetic information between organisms. Repetitive sequences, especially the mobile elements, have many potential applications in genetic research. DNA transposons and retroposons are routinely used for insertional mutagenesis, gene mapping, gene tagging, and gene transfer in several model systems. Once they are developed for the zebrafish, they will greatly facilitate the identification, mapping, and isolation of genes involved in development as well as the investigation of the evolutionary processes that have been shaping eukaryotic genomes. In this review repetitive elements are characterized in terms of their lengths and other physical properties, copy numbers, modes of amplification, and mobilities within a single genome and between genomes. Examples of how they can be used to screen genomes for species and individual strain differences are presented. This review does not cover repetitive gene families that encode well-studied products such as rRNAs, tRNAs, and the like.
Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. (1993)

Concentrations in plasma of clozapine and norclozapine, the major metabolite of clozapine, were measured in 59 treatment-resistant schizophrenic patients at a random time period during the course of treatment. A lower sum of the concentrations of clozapine and norclozapine or either alone predicted less improvement in the Brief Psychiatric Rating Scale (BPRS) Total and Positive symptoms in a multivariate analysis that controlled for baseline BPRS rating and dose. The mean doses of clozapine after 6 months of treatment and at the time of blood sampling were not significantly different in 30 responders and 29 nonresponders to clozapine, on the basis of the decrease in BPRS Total scores, whereas the concentrations in plasma in clozapine of norclozapine and the sum of their concentrations were significantly higher in responders. Clozapine and norclozapine concentrations in plasma correlated both with dose at the time of sampling and with dose at 6 months. A clozapine concentration of 370 ng/ml was the optimal cutoff for distinguishing responders from nonresponders. Clozapine and norclozapine concentrations did not differ in male smokers and nonsmokers.
Do nonimmunologically mediated pathways play a role in the pathogenesis of rheumatoid arthritis? (1993)

The association between elevated serum rheumatoid factor and rheumatoid arthritis (RA) has been confirmed repeatedly and interpreted as strong evidence for an immunologic basis for the disease. In recent years, considerable additional evidence supporting this view has been obtained, strongly suggesting a role for CD4+ T cells in the pathogenesis of RA. An alternative view has also gained support, however. Based on studies of animal models and of RA itself, several lines of evidence have emerged that indicate that nonimmunologic pathways are operative in established RA. These observations have fostered the hypothesis that the evolution of RA may be associated with the emergence of non-T-cell-dependent autonomous pathways that dominate the latter stages of the disease.
“Coherence Radar” and “Spectral Radar”—New Tools for Dermatological Diagnosis (1998)

"Coherence radar," an optical 3-D sensor based on short coherence interferometry, is used to measure skin surface topology. This method is called optical coherence profilometry (OCP) and it may be a useful tool for medical diagnosis in dermatology because different medical conditions show distinct alterations of the skin surface. The measuring uncertainty is less than 2 μm. The measuring time is about 4 s. in vivo 3-D mapping of naked skin was performed without preparation. For clinical application, a fiber optical implementation was introduced. Spectral radar is an optical sensor for the acquisition of skin morphology based on OCT techniques. The scattering amplitude a(z) along one vertical axis from the surface into the bulk can be measured within one exposure. No reference arm scanning is necessary. The theory of the sensor, including the dynamic range, is discussed and in vivo measurements of human skin by a fiber optical implementation of the sensor are demonstrated. © 1998 Society of Photo-Optical Instrumentation Engineers.
Instruments based on shape-memory alloy properties for minimal access surgery, interventional radiology and flexible endoscopy (2000)

AbstractInstrumental manipulations during minimal access surgery (MAS) are limited by the four degrees of freedom (d.o.f.) possible when long instruments are introduced into the peritoneal cavity through access ports. This is in sharp contrast to an equivalent instrument held in the hand by the surgeon during open conventional surgery, where six d.o.f. are available. Steerable motorised endo-effectors are one engineering option to overcome this intrinsic limitation of MAS. However, it is difficult to meet the torque requirements of such instruments using existing electric motor technology. We have sought a different, though not mutually-exclusive approach to the design and development of more effective instrumentation for MAS, based on shape-memory alloy (SMA). SMA formed from nickel-titanium (NiTi) has unique superelastic and shape-recovery properties, and are therefore an advantageous construction material for instrument components and devices within the limited size constraints imposed by the ports used in MAS. In general, novel MAS instrumentation based on SMA components falls into two categories, depending on whether superelastic, or shape recovery properties are utilised for a particular instrument design. This paper is based on research and development carried out in Dundee during the past 15 years on NiTi-SMA based instrumentation for MAS.Key Words: shape-memory alloyinstrumentationminimal access surgery
Near-IR multi-modal imaging of natural occlusal lesions (2009)

Reflectance and transillumination imaging show demineralization with high contrast in the near-IR. The objective of this study is to use lesion size and contrast acquired in reflectance and transillumination near-infrared imaging modes to estimate the severity of natural occlusal caries lesions. Previous studies have shown that near-infrared (NIR) light can be used to effectively image artificial carious lesions. However, its efficacy on natural lesions requires further exploration. Fifty extracted teeth with varying amounts of occlusal decay were examined using a NIR imaging system operating at 1310-nm. Image analysis software was used to calculate contrast values between sound and carious tooth structure. After imaging, teeth were histologically sampled at 1-mm intervals in order to determine lesion depth. Lesion contrast in transillumination mode significantly increased with lesion depth (p<0.001), while lesion contrast in reflectance mode did not increase. The lesion area demonstrated a significant increase with lesion severity in both imaging modes. These results suggest that lesion contrast and area can be used to estimate lesion severity in NIR images.
Terminal Riboadenylate Transferase from Escherichia coli (1976)

Catalytic properties of terminal riboadenylate transferase from Escherichia coli and the products of the enzymic reaction were investigated. The kinetic analysis revealed that the reaction obeys the sequential ordered bi‐bi mechanism. The application of conditions elaborated in this study resulted in the synthesis of products of defined size and efficient primer utilization. The tRNA(rA) n obtained was a good template for the synthesis of complementary DNA with réverse transcriptase.
DNA sequence and characterization of Haemophilus influenzae dprA+, a gene required for chromosomal but not plasmid DNA transformation (1995)

Natural genetic transformation in Haemophilus influenzae involves DNA binding, uptake, translocation, and recombination. In this study, we cloned and sequenced a 3.8-kbp H. influenzae DNA segment capable of complementing in trans the transformation defect of an H. influenzae strain carrying the tfo-37 mutation. We used subcloning, deletion analysis, and in vivo protein labeling experiments to more precisely define the gene required for efficient DNA transformation on the cloned DNA. A novel gene, which we called dprA+, was shown to encode a 41.6-kDa polypeptide that was required for efficient chromosomal but not plasmid DNA transformation. Analysis of the deduced amino acid sequence of DprA suggested that it may be an inner membrane protein, which is consistent with its apparent role in DNA processing during transformation. Four other open reading frames (ORFs) on the cloned DNA segment were identified. Two ORFs were homologous to the phosphofructokinase A (pfkA) and alpha-isopropyl malate synthase (leuA) genes of Escherichia coli and Salmonella typhimurium, respectively. Homologs for the two other ORFs could not be identified.
Carbon Nanotube Based Bearing for Rotational Motions (2004)

4 pages, 3 figures
Growth factors. Their biology and promise in dermatologic diseases and tissue repair (1989)

In the last few years, the field of peptide growth factors has exploded with new knowledge and potential therapeutic applications. We review some of these important aspects of growth factors with regard to the field of dermatology.
Derivation of Oocytes from Mouse Embryonic Stem Cells (2003)

Continuation of mammalian species requires the formation and development of the sexually dimorphic germ cells. Cultured embryonic stem cells are generally considered pluripotent rather than totipotent because of the failure to detect germline cells under differentiating conditions. Here we show that mouse embryonic stem cells in culture can develop into oogonia that enter meiosis, recruit adjacent cells to form follicle-like structures, and later develop into blastocysts. Oogenesis in culture should contribute to various areas, including nuclear transfer and manipulation of the germ line, and advance studies on fertility treatment and germ and somatic cell interaction and differentiation.
Acting via a Cell Surface Receptor, Thyroid Hormone Is a Growth Factor for Glioma Cells (2006)

Recent evidence suggests that the thyroid hormone L-thyroxine (T4) stimulates growth of cancer cells via a plasma membrane receptor on integrin alphaVbeta3. The contribution of this recently described receptor for thyroid hormone and receptor-based stimulation of cellular mitogen-activated protein kinase [MAPK; extracellular signal-regulated kinase 1/2 (ERK1/2)] activity, to enhancement of cell proliferation by thyroid hormone was quantitated functionally and by immunologic means in three glioma cell lines exposed to T4. At concentrations of 1 to 100 nmol/L, T4 caused proliferation of C6, F98, and GL261 cells, measured by accumulation of proliferating cell nuclear antigen (PCNA) and radiolabeled thymidine incorporation. This effect was inhibited by the T4 analogue, tetraiodothyroacetic acid, and by an alphaVbeta3 RGD recognition site peptide, both of which block T4 binding to integrin alphaVbeta3 but are not agonists. Activation of MAPK by T4 was similarly inhibited by tetraiodothyroacetic acid and the RGD peptide. The thyroid hormone 3,5,3'-triiodo-L-thyronine (T3) and T4 were equipotent stimulators of PCNA accumulation in C6, F98, and GL261 cells, but physiologic concentrations of T3 are 50-fold lower than those of T4. In conclusion, our studies suggest that glioblastoma cells are thyroid hormone dependent and provide a molecular basis for recent clinical observations that induction of mild hypothyroidism may improve duration of survival in glioblastoma patients. The present experiments infer a novel cell membrane receptor-mediated basis for the growth-promoting activity of thyroid hormone in such tumors and suggest new therapeutic approaches to the treatment of patients with glioblastoma.
Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. (1991)

To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte nuclei/yr in the left and right ventricular myocardium, respectively. This loss in muscle mass was accompanied by a progressive increase in myocyte cell volume per nucleus in both ventricles. Left ventricular myocytes enlarged by 110 microns3/yr, whereas right ventricular myocytes increased by 118 microns3/yr, resulting in a preservation of ventricular wall thickness. However, the cellular hypertrophic response was unable to maintain normal cardiac mass. Left and right ventricular weights decreased by 0.70 and 0.21 g/yr, respectively. In conclusion, loss of cells and enlargement of the remaining myocytes may represent the structural basis for the reduced compensatory capacity of the aged heart and together may contribute to the development of myocardial dysfunction and failure in the elderly.
Cloning, Characterization, and Functional Studies of a 47-kDa Platelet Receptor for Type III Collagen (2002)

A 1.2-kb cDNA fragment encoding a platelet 47-kDa protein has been isolated from a human bone marrow cDNA library by using a degenerate oligonucleotide of the sequenced amino terminus of the purified platelet protein with a poly(dT)(12).(dG) by polymerase chain reaction. A computer search revealed that the cDNA represents the coding sequence of a protein with a fragmentary homology to several proteins. Using a prokaryotic expression system, pBad TOPO-47 cDNA, a 47-kDa recombinant protein was obtained and purified to apparent homogeneity by nickel-nitrilotriacetic acid resin and collagen affinity column. The recombinant protein binds to type III but not type I collagen-Sepharose 2B affinity columns. Anti-47-kDa but not anti-65-kDa antibody inhibits the binding of the recombinant protein to the type III collagen-coated micro titer wells in a dose-dependent manner. Like the receptor protein purified from platelet membranes, the recombinant protein inhibits type III collagen-induced platelet aggregation also in a dose-dependent manner. We have defined two active peptides from the cloned deduced amino acid sequence. Both peptides inhibit type III but not type I collagen-induced platelet aggregation in a dose-dependent fashion. These results suggest that the active binding site of the platelet receptor to type III collagen resides in these portions of the protein.
Novel costimulators in the immune gene therapy of cancer. (1996)

One of the major goals of cancer immunotherapy is the induction of tumour-specific T-lymphocyte responses that will be effective in the rejection of established tumours. The prospects for such therapy rely on the identification of tumour antigens, and although there is persuasive evidence for the presence of such antigens,1,2 the occurrence of the disease does illustrate that the immune system is at least, on some occasions, unable to recognise and destroy these targets. Tumour antigens may be novel proteins (from genetic lesions or viral infections), modified existing antigens (eg, abnormally glycosylated cell surface proteins), or inappropriately expressed normal gene products (eg, CA125, carcinoembryonic antigen, and alpha-fetoprotein).1 Involvement of the immune system in the normal surveillance and suppression of cancer is further suggested by the increased incidence of tumours in immunocompromised patients.3 However, recent evidence has shown that, at least in model systems, cancer cells can be modulated in such a way that they stimulate cells of the immune system to recognise and destroy these malignant cells. This review summarizes the costimulatory molecules involved in the activation of such cells, the principles and mechanisms underlying their activation, and how such knowledge can be used to persuade the immune system to challenge cancer.