gebhart/patrepeval huggingface dataset:
T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes (2004)

The T-box transcription factor T-bet is known to control lineage commitment and interferon-gamma production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-gamma, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.
Flow Effects on Coagulation and Thrombosis (2006)

Thrombosis occurs in a dynamic rheological field that constantly changes as the thrombus grows to occlusive dimensions. In the initiation of thrombosis, flow conditions near the vessel wall regulate how quickly reactive components are delivered to the injured site and how rapidly the reaction products are disseminated. Whereas the delivery and removal of soluble coagulation factors to the vessel is thought to occur via classic convection-diffusion phenomena, the movement of cells and platelets to the injured wall is strongly augmented by flow-dependent cell-cell collisions that enhance their ability to interact with the wall. In addition, increased shear conditions have been shown to activate platelets, alter the cellular localization of proteins such as tissue factor (TF) and TF pathway inhibitor, and regulate gene production. In the absence of high shearing forces, red cells, leukocytes, and platelets can form stable aggregates with each other or cells lining the vessel wall, which, in addition to altering the biochemical makeup of the aggregate or vessel wall, effectively increases the local blood viscosity. Thus, hemodynamic forces not only regulate the predilection of specific anatomic sites to thrombosis, but they strongly influence the biochemical makeup of thrombi and the reaction pathways involved in thrombus formation.
The computation of line spectral frequencies using Chebyshev polynomials (1986)

Line spectral frequencies provide an alternate parameterization of the analysis and synthesis filters used in linear predictive coding (LPC) of speech. In this paper, a new method of converting between the direct form predictor coefficients and line spectral frequencies is presented. The system polynomial for the analysis filter is converted to two even-order symmetric polynomial with interlacing roots on the unit circle. The line spectral frequencies are given by the positions of the roots of these two auxiliary polynomials. The response of each of these polynomials on the unit circle is expressed as a series expansion in Chebyshev polynomials. The line spectral frequencies are found using an iterative root finding algorithm which searches for real roots of a real function. The algorithm developed is simple in structure and is designed to constrain the maximum number of evaluations of the series expansions. The method is highly accurate and can be used in a form that avoids the storage of trigonometric tables or the computation of trigonometric functions. The reconversion of line spectral frequencies to predictor coefficients uses an efficient algorithm derived by expressing the root factors as an expansion in Chebyshev polynomials.
The limits of the DNase I-sensitive domain of the human apolipoprotein B gene coincide with the locations of chromosomal anchorage loops and define the 5′ and 3′ boundaries of the gene (1989)

In eukaryotic cells, chromatin is organized as domains or loops that are generated by periodic attachment of the chromatin fiber to protein components of a nuclear matrix, or scaffold. These chromosomal loops may have a function in gene regulation. The length of the chromatin domain encompassing the human apolipoprotein B gene was studied by determining the locations of nuclear matrix attachment sites as well as the boundaries of the DNase I-sensitive domain in cells that express the gene (such as HepG2 and CaCo-2 cells) and in those that do not (HeLa cells). Three nuclear matrix attachment regions (MARs) of the human apolipoprotein B gene have been localized: a 3' -proximal MAR, between nucleotides +43,186 and +43,850; a 5' -proximal MAR, between nucleotides -2,765 and -1,801; and a 5' -distal MAR, between nucleotides -5,262 and -4,048. Both the 3' -proximal and the 5' -distal MARS were present in cells that express the gene (HepG2 and CaCo-2 cells) as well as in cells that do not (HeLa cells), whereas the 5' -proximal MAR was detected only in HepG2 cells. These MARs were located at the bases of chromosomal loops in histone-extracted nuclei in all three cell lines. Various classes of A/T-rich sequences resembling the recognition site for topoisomerase II were present within the MAR-containing fragments. The boundaries of the DNase I-sensitive domain coincide with the positions of the 3' -proximal and 5' -distal matrix attachment sites. These results suggest the existence of a 47.5-kilobase domain that represents a topologically sequestered functional unit containing the coding region and all known cis-acting regulatory elements of the human apolipoprotein B gene.
MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21 (2019)

Intrinsic resistance of unknown mechanism impedes the clinical utility of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) in malignancies other than breast cancer. Here, we used melanoma patient-derived xenografts (PDXs) to study the mechanisms for CDK4/6i resistance in preclinical settings. We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, and inhibition of this pathway improved CDK4/6i response in a p21-dependent manner. We showed that a target of p21, CDK2, was necessary for proliferation in CDK4/6i-treated cells. Upon treatment with CDK4/6i, melanoma cells up-regulated cyclin D1, which sequestered p21 and another CDK inhibitor, p27, leaving a shortage of p21 and p27 available to bind and inhibit CDK2. Therefore, we tested whether induction of p21 in resistant melanoma cells would render them responsive to CDK4/6i. Because p21 is transcriptionally driven by p53, we coadministered CDK4/6i with a murine double minute (MDM2) antagonist to stabilize p53, allowing p21 accumulation. This resulted in improved antitumor activity in PDXs and in murine melanoma. Furthermore, coadministration of CDK4/6 and MDM2 antagonists with standard of care therapy caused tumor regression. Notably, the molecular features associated with response to CDK4/6 and MDM2 inhibitors in PDXs were recapitulated by an ex vivo organotypic slice culture assay, which could potentially be adopted in the clinic for patient stratification. Our findings provide a rationale for cotargeting CDK4/6 and MDM2 in melanoma.
High Level Calcineurin Activity Predisposes Neuronal Cells to Apoptosis (1999)

Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase that is abundantly expressed in several specific areas of the brain, which are exceptionally vulnerable to stroke, epilepsy, and neurodegenerative diseases. In this study, we assessed the effects of high level activity of calcineurin on neuronal cells. Virus-mediated high level constitutive activity of calcineurin rendered neuronal cells susceptible to apoptosis induced by serum reduction or by a brief exposure to calcium ionophore. Adenovirus-mediated, high level forced activity of calcineurin induced cytochrome c/caspase-3-dependent apoptosis in neurons. Preincubation with the calcineurin inhibitors cyclosporin A and FK506 reduced susceptibility to apoptosis. High level constitutive expression of Bcl-2 or CrmA or incubation with a specific caspase-3 inhibitor inhibited the calcineurin-induced apoptosis. These data indicate that high level constitutive activity of calcineurin predisposes neuronal cells to cytochrome c/caspase-3 dependent apoptosis even under sublethal conditions.
A nitrogen-15 nuclear magnetic resonance study of the tetracycline antibiotics (1991)

Natural abundance 15 N NMR has been used to study several tetracycline antibiotics in the solid state and in solution. In the solid state, the 15 N chemical shifts of the tetracycline free bases are sensitive to the site of protonation in the "A" ring. A high frequency shift of 14 ppm is observed for the keto form of oxytetracycline (N protonated) relative to the enol form of oxytetracycline (O protonated). Comparison of 15 N chemical shifts in the solid and solution states indicates for the first time that the structural integrity (site of protonation and hence conformation) of the tetracyclines is maintained in (CD 3 ) 2 SO solutions. In addition, the solid state 15 N CP/MAS NMR spectra are sensitive to subtle conformational changes of the "A" ring amide substituent. Key words: antibiotics, tetracyclines, 15 N NMR, molecular structure.
An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota (2011)

Detailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.
Near‐infrared dyes for six‐color immunophenotyping by laser scanning cytometry (2002)

With this adaptation, it is possible to measure the tandem conjugates PE-Cy7 and APC-Cy7. This new setup opens the way for six-color immunophenotyping by LSC.
Enzyme Nomenclature. Recommendations 1992 (1994)

This document contains additions and amendments to Enzyme Nomenclature (1992) , published by Academic Press, Orlando, Florida. Comments and suggestions on enzyme classification and nomenclature may be sent to Prof. K. F. Tipton, Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland.
Effects of cyclo (his–pro) plus zinc on glucose metabolism in genetically diabetic obese mice (2003)

CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti-hyperglycaemic agent.
DNA transposon Hermes inserts into DNA in nucleosome-free regions in vivo (2010)

Transposons are mobile genetic elements that are an important source of genetic variation and are useful tools for genome engineering, mutagenesis screens, and vectors for transgenesis including gene therapy. We have used second-generation sequencing to analyze ≈2 × 10(5) unique de novo transposon insertion sites of the transposon Hermes in the Saccharomyces cerevisiae genome from both in vitro transposition reactions by using purified yeast genomic DNA, to better characterize intrinsic sequence specificity, and sites recovered from in vivo transposition events, to characterize the effect of intracellular factors such as chromatin on target site selection. We find that Hermes transposon targeting in vivo is profoundly affected by chromatin structure: The subset of genome-wide target sites used in vivo is strongly associated (P < 2e-16 by Fisher's exact test) with nucleosome-free chromatin. Our characterization of the insertion site preferences of Hermes not only assists in the future use of this transposon as a molecular biology tool but also establishes methods to more fully determine targeting mechanisms of other transposons. We have also discovered a long-range sequence motif that defines S. cerevisiae nucleosome-free regions.
Denosumab: An update (2011)

Denosumab is a fully human monoclonal antibody that inhibits the formation, function and survival of osteoclasts, preventing the interaction of tumor necrosis factor ligand superfamily member 11 (receptor activator of nuclear factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator of NF-KB, RANK). This results in a reduction in bone resorption and an increase in bone mineral density. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. A number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab is a new alternative for the prevention and treatment of postmenopausal osteoporosis and a promising agent for the treatment of other bone diseases associated with bone loss.
Liver transplantation in patients with HIV infection (2004)

1. Liver transplantation for human immunodeficiency virus (HIV)-positive patients with end-stage liver disease in the era of highly active retroviral therapy has proven to be an effective treatment. The concerns of HIV progression have not been borne out by the growing worldwide experience. 2. CD4 counts are stable and HIV viral load is controllable with medication following liver transplantation. 3. Hepatitis C virus (HCV) coinfection in HIV-positive recipients is universal, but the severity of recurrence does not appear to be different from that in HIV-negative patients with HCV liver disease. 4. Complex pharmacokinetic interactions between the calcineurin inhibitors used for immunosuppression along with protease inhibitors are present, but management directed at recognizing the need for monitoring levels does not appear to increase the risk of toxicity. 5. The degree of immunosuppression from iatrogenic drug therapy and HIV does not lead to increased risk of infectious complications.
Pituitary adenylyl cyclase-activating peptide: A pivotal modulator of glutamatergic regulation of the suprachiasmatic circadian clock (1999)

The circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus organizes behavioral rhythms, such as the sleep-wake cycle, on a near 24-h time base and synchronizes them to environmental day and night. Light information is transmitted to the SCN by direct retinal projections via the retinohypothalamic tract (RHT). Both glutamate (Glu) and pituitary adenylyl cyclase-activating peptide (PACAP) are localized within the RHT. Whereas Glu is an established mediator of light entrainment, the role of PACAP is unknown. To understand the functional significance of this colocalization, we assessed the effects of nocturnal Glu and PACAP on phasing of the circadian rhythm of neuronal firing in slices of rat SCN. When coadministered, PACAP blocked the phase advance normally induced by Glu during late night. Surprisingly, blocking PACAP neurotransmission, with either PACAP6-38, a specific PACAP receptor antagonist, or anti-PACAP antibodies, augmented the Glu-induced phase advance. Blocking PACAP in vivo also potentiated the light-induced phase advance of the rhythm of hamster wheel-running activity. Conversely, PACAP enhanced the Glu-induced delay in the early night, whereas PACAP6-38 inhibited it. These results reveal that PACAP is a significant component of the Glu-mediated light-entrainment pathway. When Glu activates the system, PACAP receptor-mediated processes can provide gain control that generates graded phase shifts. The relative strengths of the Glu and PACAP signals together may encode the amplitude of adaptive circadian behavioral responses to the natural range of intensities of nocturnal light.
Spatiotemporal Micropatterning of Cells on Arbitrary Substrates (2007)

This paper presents a readily accessible patterning platform--based upon geometric constraints, discrete cell suspension droplets, and controlled cell settling--that provides both temporal and spatial patterning capabilities. As a demonstration, single-cell (and bead) suspensions as well as multicellular human embryonic stem cell colonies are spatiotemporally patterned onto arbitrary substrates. These substrates include tissue culture surfaces, cell monolayers, protein-coated surfaces, and 3D gel matrices. The generation of soluble factor gradients is also demonstrated. This method is completely passive and does not require external power sources. Spatiotemporal patterning provides a foundation for future biological studies that explore the time-dependent relationships between cell-cell signaling and cellular responses.
Recent Developments in High-Energy Density Liquid Hydrocarbon Fuels (1999)

The evolution of high-energy density fuels over the past three decades is briefly described. This period can be characterized by exceedingly slow progress and notable lack of success toward the development of practical, economically viable fuel systems. Recently, two novel ultrahigh-energy density fuels, one naturally occurring and one synthetic, have emerged; these fuels, which are both composed of compact hydrocarbon molecules, have energy contents or heating values significantly greater than that of currently used standard missile fuel JP-10 (up to 160K Btu/gal (44.7K MJ/m3) vs 141.7K Btu/gal (39.6K MJ/m3)). In addition, these fuels also exhibit superior low-temperature, viscometric, flash-point, and other properties that are desired and, indeed, required for practical fuels. Initial research and development of these fuels are described, and their chemistries, properties, and, in the case of the naturally occurring fuel, engine test results are provided.
Treating Vaccine Reactions: Two Lifelines, But No Guarantees (2002)

The pictures are almost too gruesome to look at. Dozens of them, displayed in neat rows on an educational Web page* by the U.S. Centers for Disease Control and Prevention (CDC), remind viewers of the horrific side effects of the smallpox vaccine in a small minority of cases. Unfortunately, doctors will have only limited means to help such patients when the United States resumes vaccination. Although two treatments are recommended for vaccine complications, little hard evidence supports the efficacy of either one.
A systematic evaluation of immunoassay point-of-care testing to define impact on patients’ outcomes (2017)

Background Point-of-care testing has been developed to provide rapid test results. Most published studies focus on analytical performance, neglecting its impact on patient outcomes. Objective To review the analytical performance and accuracy of point-of-care testing specifically planned for immunoassay and to evaluate the impact of faster results on patient management. Methods A search of electronic databases for studies reporting immunoassay results obtained in both point-of-care testing and central laboratory scenarios was performed. Data were extracted concerning the study details, and the methodological quality was assessed. The analytical characteristics and diagnostic accuracy of six points-of-care testing: troponin, procalcitonin, parathyroid hormone, brain natriuretic peptide, C-reactive protein and neutrophil gelatinase-associated lipocalin were evaluated. Results A total of 116 scientific papers were analysed. Studies measuring procalcitonin, parathyroid hormone and neutrophil gelatinase-associated lipocalin reported a limited impact on diagnostic decisions. Seven studies measuring C-reactive protein claimed a significant reduction of antibiotic prescription. Several authors evaluated brain natriuretic peptide or troponin reporting faster decision-making without any improvement in clinical outcome. Forty-four per cent of studies reported analytical data, showing satisfactory correlations between results obtained through point-of-care testing and central laboratory setting. Half of studies defined the diagnostic accuracy of point-of-care testing as acceptable for troponin (median sensitivity and specificity: 74% and 94%, respectively), brain natriuretic peptide (median sensitivity and specificity: 82% and 88%, respectively) and C-reactive protein (median sensitivity and specificity 85%). Conclusions Point-of-care testing immunoassay results seem to be reliable and accurate for troponin, brain natriuretic peptide and C-reactive protein. The satisfactory analytical performance, together with an excellent practicability, suggests that it could be a consistent tool in clinical practice, but data are lacking regarding the patient outcomes.
Growth Phase-dependent Activation of Nitrogen-related Genes by a Control Network of Group 1 and Group 2 σ Factors in a Cyanobacterium (2005)

It has been reported that an RNA polymerase sigma factor, SigC, mainly contributes to specific transcription from the promoter PglnB-54,-53 under nitrogen-deprived conditions during the stationary phase of cell growth in the cyanobacterium Synechocystis sp. strain PCC 6803 (Asayama, M., Imamura, S., Yoshihara, S., Miyazaki, A., Yoshida, N., Sazuka, T., Kaneko, T., Ohara, O., Tabata, S., Osanai, T., Tanaka, K., Takahashi, H., and Shirai, M. (2004) Biosci. Biotechnol. Biochem. 68, 477-487). In this study, we further examined the functions of group 2 sigma factors of RNA polymerase in NtcA-dependent nitrogen-related gene expression in PCC 6803. Results indicated that SigB and SigC contribute to the transcription from PglnB-54,-53 with a sigma factor replaced in a growth phase-dependent manner. We also confirmed the contribution of SigB and SigC to the transcription of other NtcA-dependent genes, glnA, sigE, and amt1, as in the case of glnB. On the other hand, the transcription of glnN was dependent on SigB and SigE. In the SigB and SigC-based regulation, the level of SigB increased, but that of SigC was constant under conditions of nitrogen deprivation. Furthermore, it was found that SigC negatively and positively regulates the level of SigB in the log and stationary phase, respectively. SigC also had a positive effect on the level of sigB transcript during the stationary phase. In contrast, SigB acts positively on SigC levels in both growth phases. These results and previous findings indicated that multiple group 2 sigma factors take part in the control of NtcA-dependent nitrogen-related gene expression in cooperation with a group 1 sigma factor, SigA.
Exploiting Knowledge of R/Avr Genes to Rapidly Clone a New LZ-NBS-LRR Family of Late Blight Resistance Genes from Potato Linkage Group IV (2009)

In addition to the resistance to Phytophthora infestans (Rpi) genes Rpi-blb1 and Rpi-blb2, Solanum bulbocastanum appears to harbor Rpi-blb3 located at a major late blight resistance locus on LG IV, which also harbors Rpi-abpt, R2, R2-like, and Rpi-mcd1 in other Solanum spp. Here, we report the cloning and functional analyses of four Rpi genes, using a map-based cloning approach, allele-mining strategy, Gateway technology, and transient complementation assays in Nicotiana benthamiana. Rpi-blb3, Rpi-abpt, R2, and R2-like contain all signature sequences characteristic of leucine zipper nucleotide binding site leucine-rich repeat (LZ-NBS-LRR) proteins, and share amino-acid sequences 34.9% similar to RPP13 from Arabidopsis thaliana. The LRR domains of all four Rpi proteins are highly homologous whereas LZ and NBS domains are more polymorphic, those of R2 being the most divergent. Clear blocks of sequence affiliation between the four functional resistance proteins and those encoded by additional Rpi-blb3 gene homologs suggest exchange of LZ, NBS, and LRR domains, underlining the modular nature of these proteins. All four Rpi genes recognize the recently identified RXLR effector PiAVR2.