gebhart/patrepeval huggingface dataset:
Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression. Implications for AIDS-Kaposi’s sarcoma pathogenesis (1992)

Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency. These data have suggested that products from activated immune cells may affect the development of AIDS-KS. Here we report that conditioned media from activated or dysregulated T cells contain a variety of cytokines that promote the growth of spindle cells derived from KS lesions of AIDS patients (AIDS-KS cells) and induce normal vascular cells, potential cell progenitors of the AIDS-KS cells, to acquire features of the KS cell phenotype ("spindle" cell morphology and growth responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein). The same conditioned media or cytokines promote HIV-1 gene expression and rescue defective HIV-1 proviruses, interrupting HIV-1 latency and increasing Tat production. The cellular and viral effects of cytokines are increased in an additive or synergistic manner by picomolar concentrations of extracellular Tat. These data suggest that cytokines produced by activated immune cells cooperate with HIV-1 infection in AIDS-KS pathogenesis.
A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation (1997)

The equine SCID defect is more severe than its murine counterpart in that SCID foals are incapable of forming either coding or signal joints, whereas SCID mice manifest normal signal joint formation. To determine the basis of this difference and whether DNA-dependent kinase, catalytic subunit (DNA-PK(CS)), is involved in signal joint formation, equine DNA-PK(CS) transcripts were cloned and sequenced from normal and SCID cell lines. In the mutant allele, a frame-shift mutation truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family resulting in complete absence of full length DNA-PK(CS) and accounting for the kinase-negative phenotype of these cells; the mutation in SCID mice allows for some DNA-PK(CS) expression. The difference in DNA-PK(CS) expression in SCID mice and foals explains the more severe phenotype of equine SCID, and definition of DNA-PK(CS) as the defect in equine SCID demonstrates that DNA-PK(CS) is required for both coding and signal joint formation.
Growth Fraction of Myelocytes In Normal Human Granulopoiesis (1986)

The labelling index (LI) of myelocytes (M) after flash labelling of normal human bone marrow cells with [3H]-thymidine ([3H]TdR) is always lower that the LI obtained for myeloblasts (MB) and for promyelocytes (PM). This fact can be interpreted in two ways: it may mean that the duration of the G1 phase of the cell cycle is longer in M than in MB or PM, or it may mean that the proportion of cells in cycle, i.e., the growth fraction (GF), is lower in the M population than in MB or PM. The evolution of the LI and of the mean number of grains per cell was monitored in [3H]TdR-labelled normal bone marrow during in vitro incubation for 50 hr. The generation time, measured by the halving time of the mean number of grains per cell after flash labelling, was similar for M to that for MB and PM. During continuous labelling, the LI of MB and PM reached 1 and the LI value for M never rose to more than 50% of the values recorded for MB and PM after 30 hr. These findings give support to the second hypothesis, i.e., a lower GF in the M population. Good correlation was found between the LI of M and the proportion of mature polymorphonuclear cells in the bone marrow of normal subjects and of patients with chronic benign neutropenia or hyperleucocytosis. Variations in the M growth fraction could be a medium-term (2-3 days) regulatory factor in granulocyte production.
NFAT Transcription Factors Are Critical Survival Factors That Inhibit Cardiomyocyte Apoptosis During Phenylephrine Stimulation In Vitro (2003)

Biomechanical stress on the heart results in activation of numerous signaling cascades, leading to cardiomyocyte hypertrophy, apoptosis, and ultimately, heart failure. The Ca2+-dependent phosphatase calcineurin is an essential mediator of cardiac hypertrophy, and in most but not all studies, calcineurin inhibition attenuated cardiac hypertrophy in vivo. However, calcineurin inhibition has been reported to have adverse effects on cardiac remodeling and cardiomyocyte apoptosis. Calcineurin regulates the activity of a number of downstream targets, including the transcription factors NFAT, MEF2, and NF-kappaB, and the apoptotic factor Bad. To evaluate the contribution of NFAT activation by calcineurin to cardiomyocyte responses to hypertrophic stimulation, we used adenovirus to express VIVIT, a selective peptide inhibitor of calcineurin-mediated NFAT activation. We found that selective NFAT inhibition during phenylephrine stimulation inhibited hypertrophy but resulted in increased cardiomyocyte apoptosis. In contrast, nonselective inhibition of calcineurin by cyclosporin A did not cause cardiomyocyte apoptosis after phenylephrine stimulation. Cyclosporin A suppressed the effect of VIVIT on cardiomyocyte apoptosis. These results demonstrate that during phenylephrine stimulation calcineurin activates both pro- and antiapoptotic pathways in cardiomyocytes, and that NFAT activity is a critical component of the antiapoptotic pathway that regulates whether the outcome of calcineurin activation is cardiomyocyte apoptosis or survival.
Ribosome display for improved biotherapeutic molecules (2006)

Ribosome display presents an innovative in vitro technology for the rapid isolation and evolution of high-affinity peptides or proteins. Displayed proteins are bound to and recovered from target molecules in multiple rounds of selection in order to enrich for specific binding proteins. No transformation step is necessary, which could lead to a loss of library diversity. A cycle of display and selection can be performed in one day, enabling the existing gene repertoire to be rapidly scanned. Proteins isolated from the panning rounds can be further modified through random or directed molecular evolution for affinity maturation, as well as selected for characteristics such as protein stability, folding and functional activity. Recently, the field of display technologies has become more prominent due to the generation of new scaffolds for ribosome display, isolation of high-affinity human antibodies by phage display, and their implementation in the discovery of novel protein-protein interactions. Applications for this technology extend into the broad field of antibody engineering, proteomics, and synthetic enzymes for diagnostics and therapeutics in cancer, autoimmune and infectious diseases, neurodegenerative diseases and inflammatory disorders. This review highlights the role of ribosome display in drug discovery, discusses advantages and disadvantages of the system, and attempts to predict the future impact of ribosome display technology on the development of novel engineered biopharmaceutical products for biological therapies.
Culture in the historiography of modem South Africa (1988)

Notoriously, there are almost as many definitions of the concept of culture as there are people who use the term.In a very broad sense though, the various meanings cluster around three fields, which can perhaps best be described by their respective students.Culture, in the singular or plural, is studied by (some) biologists and microbiologists, by (most) anthropologists and by (virtually all) art historians, musicologists and literary critics.Thus the high points of culture in these visions would be, say, a colony of penicillin on a laboratory dish, the kinship system of the Australian Aranda -though it would never be described as the highest, for all cultures are equal in the eyes of the anthropologists' God -and the works of Shakespeare, Rembrandt and Mozart.For historians, at least those writing in English, the first of these meanings is not so relevant, and is divorced from the others, especially as it is semantically substantially narrower than in Dutch.(Thus we translate "Kultuurstelsel" as "Cultivation System").The latter two, in contrast, are of great importance, but luckily they are closely related to each other at a theoretical level.They can be seen as two realisations of the underlying value system of a society (as it was continuously changing, a historian is bound to add), on the one hand in social structure, institutions, religion and so forth, and, on the other, in its art.The one is what Durkheim called the "representations collectives" of a society; the other, at least given the Western tradition of the artist as a man or woman apart, as the "representations individuelles".This is of course a highly "idealist" vision of the underlying forces within society.It assumes that it is the order which is imposed on the chaos of the world by human intelligences which provides the basis for culture in all its manifestations.This makes a survey of the historiography of culture in South Africa particulary difficult, since the majority of the most creative
A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. (1984)

Forty-eight patients with rheumatoid arthritis refractory to other treatments were studied in a placebo controlled trial of methotrexate (MTX) in 2 institutions. Once weekly for 6 weeks, the patients were injected with placebo (Group 1), MTX 10 mg (Group 2), or MTX 25 mg (Group 3). Then, for the next 6 weeks, Group 1 received MTX, either 10 or 25 mg/wk, and Groups 2 and 3 continued their same dose. Adverse reactions necessitated change from 25 mg to 10 mg in some patients, but no major side effects of MTX were noted. At 6 weeks, the effect of the 2 MTX doses did not differ significantly but patients on MTX had fared significantly better (p less than 0.005 - less than 0.001) than those given placebo. At 12 weeks, all indices showed significant improvement in Group 1 and maintenance or enhancement of the improvement in Groups 2 and 3. We conclude that weekly low dose MTX therapy is efficacious for refractory rheumatoid arthritis.
Baricitinib for the treatment of rheumatoid arthritis (2016)

Introduction: Rheumatoid arthritis (RA) is characterized by systemic synovitis causing joint destruction. With the development of biological disease-modifying anti-rheumatic drugs (bDMARDs) and combination of conventional DMARDs, clinical remission is perceived as an appropriate and realistic goal in many patients. However, bDMARDs require intravenous or subcutaneous injection and some patients fail to respond to bDMARDs or lose their primary response. Under the circumstances, targeted synthetic DMARDs (tsDMARDs), which are orally available low-molecular weight products, have been emerging. Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and naïve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs. There was a favorable response for clinical and functional parameters in studies with placebo, MTX and adalimumab as comparator. It is also reported that safety was tolerable within the limited study period.Areas covered: We here review the recent progress in the development of baricitinib and its potential for the treatment of RA.Expert commentary: Although baricitinib is only one of the highly effective DMARDs that has a new mode of action, it will bring new concepts for rheumatology in the future.
T Cell Production Slowed, Not Exhausted? (1999)

Ever since the very early days of the AIDS epidemic, almost 2 decades ago, researchers have recognized the disease by its signature symptom: a progressive loss of CD4 T lymphocytes, the primary immune cell targeted by HIV. Yet just how HIV causes T cell depletion is still the subject of vigorous debate. Does it destroy T cells so quickly and efficiently that the immune system exhausts itself trying to replace them? Or does it disrupt the immune system's ability to produce T cells in the first place? Now, in the January issue of Nature Medicine, a team led by immunologist Joseph McCune of the University of California, San Francisco, and endocrinologist Marc Hellerstein of UC Berkeley reports results obtained by using a new technique that for the first time provides a direct measure of how many new cells are produced over a given time period. The findings, the team says, support the notion that HIV's most important and insidious talent is to interfere with T cell production.
Achievable rates for multiple descriptions (1982)

Consider a sequence of independent identically distributed (i.i.d.) random variables <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X_{l},X_{2}, \cdots, X_{n}</tex> and a distortion measure <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d(X_{i},X̂_{i})</tex> on the estimates <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X̂_{i}</tex> of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X_{i}</tex> . Two descriptions <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i(X)\in \{1,2, \cdots ,2^{nR_{1}\}</tex> and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j(X)\in \{1,2, \cdots,2^{nR_{2}\}</tex> are given of the sequence <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X=(X_{1}, X_{2}, \cdots ,X_{n})</tex> . From these two descriptions, three estimates <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(i(X)), X2(j(X))</tex> , and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\hat{X}_{O}(i(X),j(X))</tex> are formed, with resulting expected distortions <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">E \frac{1/n} \sum^{n}_{k=1} d(X_{k}, \hat{X}_{mk})=D_{m}, m=0,1,2.</tex> We find that the distortion constraints <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D_{0}, D_{1}, D_{2}</tex> are achievable if there exists a probability mass distribution <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p(x)p(\hat{x}_{1},\hat{x}_{2},\hat{x}_{0}|x)</tex> with <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Ed(X,\hat{x}_{m})\leq D_{m}</tex> such that <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_{1}&gt;I(X;\hat{X}_{1}),</tex> <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R_{2}&gt;I(X;\hat{X}_{2}),</tex> where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">I(\cdot)</tex> denotes Shannon mutual information. These rates are shown to be optimal for deterministic distortion measures.
Frequent amplification of the bcl-1 locus in poorly differentiated squamous cell carcinoma of the lung. The Lung Cancer Study Group. (1990)

The bcl-1 locus on chromosome 11 at band q13 has been shown to be rearranged in some chronic B lymphoid malignancies with the t(11;14)(q13;q32). Chromosome 11 abnormalities occur in solid tumors including squamous cell cancers and adenocarcinomas. We have recently reported the frequency amplification of the bcl-1 locus in squamous cell carcinomas of head and neck origin, and increased copy number also has been found in some breast adenocarcinomas. In this investigation, we analyzed the arrangement, copy number and expression of this locus in 111 primary non-small cell lung cancers. Bcl-1 was found to be amplified three- to 10-fold in seven fresh tumors. Whereas none of 51 adenocarcinomas showed bcl-1 amplification, six of 46 squamous cell carcinomas revealed an increase in bcl-1 copy number. This amplification was more frequently associated with larger and more poorly differentiated tumors. None of the cancers showed rearrangement of this locus.
Quality Specifications for B-Type Natriuretic Peptide Assays (2005)

These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.
Rapid Diagnosis of Methicillin-Resistant Staphylococcus aureus Bacteremia by Nested Polymerase Chain Reaction (1996)

This method, as a sensitive and rapid monitoring system for MRS bacteremia, would be clinically beneficial for prevention of cross infection and for early determination of appropriate treatment for infected patients.
Educational Rights of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder (2008)

Adolescent Medicine: State of the Art Reviews(formerly Adolescent Medicine Clinics) is the official publication of the AAP Section on Adolescent Health. This widely respected resource continues to deliver practice-focused, useful information you won't see anywhere else.Topics in ADHD/Learning Disorders include:Attention-Deficit/Hyperactivity Disorder: A Personal PerspectiveAttention-Deficit/Hyperactivity Disorder and Complementary/Alternative MedicineCommon Comorbidities Seen in Adolescents with Attention-Deficit/Hyperactivity DisorderEducational Rights of Children and Adolescents with Attention-Deficit/Hyperactivity DisorderFamily Intervention for Home-Based Problems of Adolescents with Attention-Deficit/Hyperactivity DisorderMedications for Adolescents with Attention-Deficit/Hyperactivity DisorderOverview of Epidemiology, Clinical Features, Genetics, Neurobiology, and Prognosis of Adolescent Attention-Deficit/Hyperactivity DisorderAnd more!
Characterization of an animal model of hepatic metastasis (1996)

The experimental study of possible therapies for control of the growth of liver metastases requires the availability of a model which is technically feasible and appears to exhibit growth characteristics similar to human tumours. We report on the development of an intrasplenic injection model of liver metastases, and describe the histology, growth pattern and blood flow demonstrated by light microscopy, stereology and laser Doppler flowmetry. The hepatic metastases were induced in mice by intrasplenic injection of dimethylhydrazine (DMH) induced primary colonic carcinoma cells (10(6) cells in 1 mL). The growth and development of metastases was studied over a period of 3 weeks at predetermined time points. Tumour cells were visible in the hepatic sinusoids by day 7 by light microscopy. Macroscopically visible tumours with a diameter of 0.18 +/- 0.02 cm (mean +/- s.d.) were seen by day 10. By this time the tumours had derived a blood supply from the hepatic sinusoids adjacent to the tumour periphery. With further vascularization the tumours reached a diameter of 0.96 +/- 0.50 cm by day 22. Metastatic growth was quantitated by stereological analysis of tumour volume in relation to non-diseased hepatic tissue. Normal mouse liver had a mean volume of 1.13 +/- 0.14 cm3. Tumour growth occurred in three phases. During the initial slow phase the volume of metastases increased from 0.03 +/- 0.02 cm3 at day 10 to 0.22 +/- 0.24 cm3 by day 16. Rapid tumour growth, occurring over the next 3 days, constituted the intermediate phase with metastatic volume reaching 1.21 +/- 0.74 cm3 by day 19 (P = 0.0003 compared with day 16). This growth was followed by a plateau phase when the metastatic volume was 1.40 +/- 0.55 cm3 at day 22. The volume of total liver and of tumour necrosis followed a similar growth pattern. A necrotic tumour volume of 0.004 +/- 0.006 cm3 first seen on day 10 increased to 0.05 +/- 0.06 cm3 by day 16, and to 0.25 +/- 0.20 cm3 by day 22 (P = 0.0022 compared with day 16). The blood flow in metastases measured by laser Doppler flowmetry was lower compared to the non-diseased liver. Tumour blood flow, expressed as a percentage of normal liver blood flow, was 63.31 +/- 26.28% at day 10 and diminished to 27.91 +/- 8.99% by day 22, with an increase in tumour size and age. The decrease in flow was significant between days 13 and 16 (P = 0.0015). This intrasplenic mouse model of metastases is reproducible and should prove useful in the study of treatment of hepatic metastases.
CRISPR-Cas9-Mediated Single-Gene and Gene Family Disruption in Trypanosoma cruzi (2014)

Trypanosoma cruzi, the causative agent of human Chagas disease, is the leading worldwide cause of infectious myocarditis. Diagnostics for the infection are relatively poor, treatment options are limited and of variable effectiveness, and suitable vaccines are nonexistent. The T. cruzi genome is replete with genes of unknown function and greatly expanded gene families with hundreds of members. The absence of facile genetic engineering tools, including RNA interference, for T. cruzi has prevented elucidation of gene and gene family function and the development of better infection prevention and control measures. In this study, we demonstrate that the CRISPR-Cas9 system is a versatile and powerful tool for genome manipulations in T. cruzi, bringing new opportunities for unraveling the functions of previously uncharacterized genes and how this human pathogen engages its large families of genes encoding surface proteins to interact with human and animal hosts.
Detection Limits for Nanoscale Biosensors (2005)

We examine through analytical calculations and finite element simulations how the detection efficiency of disk and wire-like biosensors in unmixed fluids varies with size from the micrometer to nanometer scales. Specifically, we determine the total flux of DNA-like analyte molecules on a sensor as a function of time and flow rate for a sensor incorporated into a microfluidic system. In all cases, sensor size and shape profoundly affect the total analyte flux. The calculations reveal that reported femtomolar detection limits for biomolecular assays are very likely an analyte transport limitation, not a signal transduction limitation. We conclude that without directed transport of biomolecules, individual nanoscale sensors will be limited to picomolar-order sensitivity for practical time scales.