gebhart/patrepeval huggingface dataset:
Alterations in Adenosine Metabolism and Signaling in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis (2010)

These findings suggest that components of adenosine metabolism and signaling are altered in a manner that promotes adenosine production and signaling in the lungs of patients with COPD and IPF, and provide proof of concept information that these disorders may benefit from adenosine-based therapeutics. Furthermore, this study provides the first evidence that A(2B)R signaling can promote the production of inflammatory and fibrotic mediators in patients with these disorders.
Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells (2011)

The goal of cancer immunotherapy is the generation of an effective, stable, and self-renewing antitumor T-cell population. One such approach involves the use of high-affinity cancer-specific T-cell receptors in gene-therapy protocols. Here, we present the generation of functional tumor-specific human T cells in vivo from genetically modified human hematopoietic stem cells (hHSC) using a human/mouse chimera model. Transduced hHSC expressing an HLA-A*0201-restricted melanoma-specific T-cell receptor were introduced into humanized mice, resulting in the generation of a sizeable melanoma-specific naïve CD8(+) T-cell population. Following tumor challenge, these transgenic CD8(+) T cells, in the absence of additional manipulation, limited and cleared human melanoma tumors in vivo. Furthermore, the genetically enhanced T cells underwent proper thymic selection, because we did not observe any responses against non-HLA-matched tumors, and no killing of any kind occurred in the absence of a human thymus. Finally, the transduced hHSC established long-term bone marrow engraftment. These studies present a potential therapeutic approach and an important tool to understand better and to optimize the human immune response to melanoma and, potentially, to other types of cancer.
Loss-of-function mutations in the maize homeobox gene, knotted1, are defective in shoot meristem maintenance (1997)

The product of the maize homeobox gene, knotted1 (kn1), localizes to the nuclei of cells in shoot meristems, but is absent from portions of the meristem where leaf primordia or floral organs initiate. Recessive mutant alleles of kn1 were obtained by screening for loss of the dominant leaf phenotype in maize. Mutant kn1 alleles carrying nonsense, splicing and frame shift mutations cause severe inflorescence and floral defects. Mutant tassels produce fewer branches and spikelets. Ears are often absent, and when present, are small with few spikelets. In addition, extra carpels form in female florets and ovule tissue proliferates abnormally. Less frequently, extra leaves form in the axils of vegetative leaves. These mutations reveal a role for kn1 in meristem maintenance, particularly as it affects branching and lateral organ formation.
Consequences of AhR Activation in Steady-State Dendritic Cells (2010)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the prototypical aryl hydrocarbon receptor (AhR) ligand and a potent immunotoxicant. However, the mechanisms underlying TCDD-induced immunomodulation remain to be defined. Dendritic cells are professional antigen-presenting cells that constitutively express the AhR and are sensitive to TCDD-induced AhR activation. We hypothesized that AhR activation alters the differentiation and function of steady-state bone marrow-derived dendritic cells (BMDCs). To test this hypothesis, steady-state BMDCs from C57BL/6 mice were grown in the presence of TCDD or vehicle. TCDD-treated steady-state BMDCs (TCDD-BMDCs) displayed decreased expression of CD11c and CD11a, whereas increasing the frequency of major histocompatibility complex class II, CD86, CD80, and CD54. Similar phenotypic alterations were observed with the AhR ligands 6-formylindolo[3,2-b]carbazole and 2-(1H-indole-3'-carbonyl)-thiazole-4-carboxylic acid (ITE). TCDD-BMDCs from AhR(-/-) mice were refractory to TCDD-induced surface marker alterations, whereas TCDD-BMDCs from AhR(dbd/dbd) mice displayed similar phenotypic alterations as AhR(+/+) TCDD-BMDCs. Following lipopolysaccharide (LPS), cytosine-phosphate-guanine (CpG), or Imiquimod stimulation, TCDD-BMDCs secreted less interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-10, and IL-12. TCDD also altered NF-κB family member-binding activity in unstimulated and LPS- or CpG-stimulated steady-state BMDCs. The internalization of the soluble antigens, ovalbumin, and acetylated low-density lipoprotein was decreased, whereas internalization of latex beads was increased in TCDD-BMDCs when compared with vehicle-BMDCs. TCDD-BMDCs displayed increased messenger RNA expression of the regulatory gene IDO2 and following LPS stimulation upregulated IDO1, IDO2, TGFβ1, and TGFβ3 gene expression. Additionally, TCDD-BMDCs increased the generation of CD4(+) CD25(+) FoxP3(+) Tregs in vitro in an IDO-dependent fashion. However, TCDD-treated BMDCs did not alter antigen-specific T-cell activation in vivo. Overall, TCDD-induced AhR activation alters the differentiation, activation, innate, and immunoregulatory function but not the T cell-activating capacity of steady-state BMDCs.
Obesity: assessment and management in primary care. (2001)

Obesity is a complex, multifactorial condition in which excess body fat may put a person at health risk. National data indicate that the prevalence of obesity in the United States is increasing in children and adults. Reversing these trends requires changes in individual behavior and the elimination of societal barriers to healthy lifestyle choices. Basic treatment of overweight and obese patients requires a comprehensive approach involving diet and nutrition, regular physical activity, and behavioral change, with an emphasis on long-term weight management rather than short-term extreme weight reduction. Physicians and other health professionals have an important role in promoting preventive measures and encouraging positive lifestyle behaviors, as well as identifying and treating obesity-related comorbidities. Health professionals also have a role in counseling patients about safe and effective weight loss and weight maintenance programs. Recent evidence-based guidelines from the National Heart, Lung, and Blood Institute, as well as recommendations from the American Academy of Pediatrics, American Association of Clinical Endocrinologists/American College of Endocrinology, American Obesity Association, U.S. Clinical Preventive Services Task Force, Institute of Medicine, and World Health Organization can be consulted for information and guidance on the identification and management of overweight and obese patients.
Learning people detection models from few training samples (2011)

People detection is an important task for a wide range of applications in computer vision. State-of-the-art methods learn appearance based models requiring tedious collection and annotation of large data corpora. Also, obtaining data sets representing all relevant variations with sufficient accuracy for the intended application domain at hand is often a non-trivial task. Therefore this paper investigates how 3D shape models from computer graphics can be leveraged to ease training data generation. In particular we employ a rendering-based reshaping method in order to generate thousands of synthetic training samples from only a few persons and views. We evaluate our data generation method for two different people detection models. Our experiments on a challenging multi-view dataset indicate that the data from as few as eleven persons suffices to achieve good performance. When we additionally combine our synthetic training samples with real data we even outperform existing state-of-the-art methods.
Accurate fault location technique for power transmission lines (1990)

The paper describes a very accurate fault location technique which uses post-fault voltage and current derived at both line ends. Fault location is independent of fault resistance and the method does not require any knowledge of source impedance. It maintains high accuracy for untransposed lines and no fault type identification is required. The paper presents the theory of the technique and the results of simulation studies to determine its performance.
The Clinical Assessment of Intraventricular Flows (2014)

Recent advances in imaging techniques have allowed physicians to obtain robust measurements of intracardiac flows in the clinical setting. Consequently, the physiological implications of intraventricular fluid dynamics are beginning to be understood. Initial data show that these flows involve complex fluid-structure interactions and mixing phenomena that are modified by disease. Here we critically review the most important aspects of intraventricular fluid mechanics relevant for clinical applications. We discuss current image and numerical methods for assessing intraventricular flows, as well as implemented approaches to analyze their impact on cardiac function. The physiological and clinical insights provided by such techniques are discussed both in health and in disease. The final goal is to encourage research in the application of fluid dynamic foundations to patient-based clinical data. A huge potential is anticipated not only in terms of the basic science of large-scale biological systems, but also in practical terms of improving patient care.
From Inverse Problems in Mathematical Physiology to Quantitative Differential (2007)

The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting), using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge). We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of differential diagnoses. We outline possible steps toward translating this computational approach to the bedside, to supplement today’s evidence-based medicine with a quantitatively founded model-based medicine that integrates mechanistic knowledge with patient-specific information.
Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce (2006)

Peer Reviewed
A general method for locating the X-ray source point in Kossel diffraction (1977)

A development of a conic fitting procedure is described which enables the X-ray source point in Kossel diffraction to be determined solely by analysis of shadows cast on the recording film and so dispenses, in subsequent analysis of the pattern, with the need to have prior knowledge of the crystal structure of the specimen or to have accurately manufactured cameras. The technique involves a conic fitting analysis of the shadows cast by spheres positioned between the recording film and X-ray source. Two or more shadows provide data from which the pattern centre and specimen to film distance are evaluated, so locating the X-ray source. The technique has been used in conjunction with new experiments in the development of suitable procedures for adaptation of Kossel diffraction for use in scanning electron microscopes. The paper includes a numerical analysis of errors involved in source location and in subsequent evaluation of lattice spacing and the technique is tested with studies on iron, copper and copper-bismuth alloy. It is shown that the standard deviation of errors in locating the X-ray source amounts to 1 part in 3000 and in lattice-spacing measurement, to 1 part in 7000. The lattice parameters found for the three materials tested were for iron 2.8653±0.0005 Å, for copper 3.61715±0.0005 Å, for copper–bismuth 3.6155±0.0005 Å. The crystal volume yielding the patterns for which these data were obtained is estimated as 260 × 10−9 mm3.
Methotrexate analogs. 4. 7-Methyl derivatives of methotrexate and dichloromethotrexate. New synthesis and some biological studies (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethotrexate analogs. 4. 7-Methyl derivatives of methotrexate and dichloromethotrexate. New synthesis and some biological studiesAndre Rosowsky and Katherine K. N. ChenCite this: J. Med. Chem. 1974, 17, 12, 1308–1311Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://pubs.acs.org/doi/10.1021/jm00258a016https://doi.org/10.1021/jm00258a016research-articleACS PublicationsRequest reuse permissionsArticle Views157Altmetric-Citations12LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Identification of a precursor in the biosynthesis of the p21 transforming protein of harvey murine sarcoma virus (1982)

The p21 transforming protein coded for by the v-ras gene of Harvey murine sarcoma virus (Ha-MuSV) migrates as a doublet band between 21,000 and 23,000 daltons during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lower band of the doublet is designated p21, and the upper band is designated pp21 since it comigrates with the phosphorylated form of p21. By pulse-labeling with [35S] methionine, we detected a p21 precursor, pro-p21, which migrated as if it was approximately 1,000 daltons larger than p21. The precursor-product relationship was established by pulse-chase experiments with [25S] methionine in the presence of 100 micrograms of cycloheximide per ml, which inhibited all de novo protein biosynthesis. Within 4 h, pro-p21 was completely chased into p21, and during the next 24 h pp21 accumulated. Thus, formation of pp21 from p21 did not require de novo protein synthesis. By subcellular fractionation into cytosol amd membrane fractions, we found that pro-p21 was synthesized in a non-membrane-bound state and that shortly after its complete synthesis, the p21 product was associated with the membrane fraction. By selective cleavage of p21 at a unique aspartic acid-proline residue with 70% formic acid or with Staphylococcus aureus V8 protease, we found that the intramolecular site of pro-p21 processing was located in the C-terminal portion of the pro-p21 molecule. The possibilities that the precursor was involved in the assembly of p21 into the plasma membrane and, alternatively, that the processing was a step in the activation of p21 biochemical activities are discussed.
1058. Adeno-Associated Virus Serotype 6 (AAV-6) Vector Mediated Gene Transfer of Soluble VEGF Receptors for the Treatment of Glioblastoma Multiforme (2004)

Thomas C. Harding,1 Alshad S. Lalani,1 Jian Min Lin,1 Satyasri Yendluri,1 Bo Luan,1 Kathryn E. Koprivnikar,1 Guang Tu,1 Melissa A. Gonzalez-Edick,1 Wei Wei Wu-Prior,1 Melinda VanRoey,1 Byron Roberts,2 Richard LeCouter,2 Pete Dickinson,2 Karin Jooss.1
Initiation of protein synthesis in bacteria at a translational start codon of mamalian cDNA: effects of the preceding nucleotide sequence. (1980)

Plasmids containing a mouse cDNA sequence encoding the enzyme dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3) have been used to study the efficiency of initiation of protein synthesis at an ATG (AUG) translational start codon indigenous to the eukaryotic CDNA. differences in DHFR production assayed phenotypically, enzymatically, and immunologically were correlated with the primary structure of the DNA segment that precedes the translational start codon. Our results indicate that initiation of a structurally discrete and biologically functional eukaryotic protein can occur in bacteria on a fused mRNA molecule, and that the efficiency of expression is strongly affected by: (i) the extent of homology of the translational control region with the 3'-OH end of 16S ribosomal RNA, and (ii) the distance between the protein start codon and the ribosome-binding sequence on the mRNA.
WisecondorX: improved copy number detection for routine shallow whole-genome sequencing (2018)

Shallow whole-genome sequencing to infer copy number alterations (CNAs) in the human genome is rapidly becoming the method par excellence for routine diagnostic use. Numerous tools exist to deduce aberrations from massive parallel sequencing data, yet most are optimized for research and often fail to redeem paramount needs in a clinical setting. Optimally, a read depth-based analytical software should be able to deal with single-end and low-coverage data-this to make sequencing costs feasible. Other important factors include runtime, applicability to a variety of analyses and overall performance. We compared the most important aspect, being normalization, across six different CNA tools, selected for their assumed ability to satisfy the latter needs. In conclusion, WISECONDOR, which uses a within-sample normalization technique, undoubtedly produced the best results concerning variance, distributional assumptions and basic ability to detect true variations. Nonetheless, as is the case with every tool, WISECONDOR has limitations, which arise through its exclusiveness for non-invasive prenatal testing. Therefore, this work presents WisecondorX in addition, an improved WISECONDOR that enables its use for varying types of applications. WisecondorX is freely available at https://github.com/CenterForMedicalGeneticsGhent/WisecondorX.
Orthomolecular Methods In Medicine (1967)

The top of this essay reads: "Contribution to the volume Functional Biochemistry of Cell Structures, dedicated to the memory of Academician N.M. Sissakian."
Amplification of N- myc in Untreated Human Neuroblastomas Correlates with Advanced Disease Stage (1984)

A domain of DNA designated N-myc is amplified 20- to 140-fold in human neuroblastoma cell lines but not in cell lines from other tumor types. N-myc has now been found to be amplified in neuroblastoma tissue from 24 of 63 untreated patients (38 percent). The extent of amplification appears to be bimodal, with amplification of 100- to 300-fold in 12 cases and 3- to 10-fold in 10 others. Amplification was found in 0 of 15 patients with stage 1 or 2 disease, whereas 24 of 48 cases (50 percent) with stage 3 or 4 had evidence of N-myc amplification. These data indicate that N-myc amplification is a common event in untreated human neuroblastomas. Furthermore, N-myc amplification is highly correlated with advanced stages of disease (P less than 0.001) and with the ability to grow in vitro as an established cell line, both of which are associated with a poor prognosis.
A novel functional domain of an alpha-like DNA polymerase. The binding site on the herpes simplex virus polymerase for the viral UL42 protein. (1990)

Most DNA-dependent DNA polymerases exist as a complex with one or more noncovalently bound accessory proteins, whose presence is necessary for the correct functioning of the holoenzyme. Using the herpes simplex virus DNA polymerase as a representative member of the alpha-polymerase family, we have recreated the association between the polymerase and its accessory protein UL42 in vitro through the translation in rabbit reticulocyte lysate of bacteriophage RNA polymerase-generated transcripts encoding the two polypeptides. Study of the ability of deleted versions of the polymerase protein to bind UL42, as detected by coimmunoprecipitation of the two polypeptides, defined a carboxyl-terminal region of the DNA polymerase that was both necessary and sufficient for the association. This domain is distinct from regions of the protein previously characterized as involved in catalysis. The results suggest a strategy for the design of novel targeted antiviral drugs, which would disrupt the DNA polymerase-UL42 complex.
Pharmacological activation of plasma‐membrane KATP channels reduces reoxygenation‐induced Ca2+ overload in cardiac myocytes via modulation of the diastolic membrane potential (2004)

1. The opening of cardiac plasma-membrane ATP-sensitive K(+) channels (pmK(ATP)) can protect the heart against ischaemia/reperfusion injury. We recently demonstrated that the resting membrane potential (E(m)) of ventricular myocytes strongly modulates reoxygenation-induced Ca(2+) overload. This led to the hypothesis that activation of pmK(ATP) can influence the extent of chemically induced hypoxia (CIH)/reoxygenation Ca(2+) overload via hyperpolarization of the diastolic membrane potential of ventricular myocytes. 2. The membrane potential (E(m)) of isolated rat myocytes was determined using the perforated patch-clamp technique and DiBac(4)(3) imaging. Intracellular Ca(2+) ([Ca(2+)](i)) was monitored using FURA-2 imaging. 3. CIH/reoxygenation caused a significant depolarization of E(m) and a substantial increase in [Ca(2+)](i). The K(ATP) opener pinacidil (100 microm) and the pmK(ATP) opener P-1075 (100 microm) hyperpolarized the E(m) of normoxic myocytes. Pinacidil (100 microm) and P-1075 (10 and 100 microm), applied during reoxygenation, hyperpolarized E(m) and prevented reoxygenation-induced increases in [Ca(2+)](i). 4. Myocyte hypercontracture and death increased in parallel with an E(m) depolarization of 10-15 mV and increases in [Ca(2+)](i). Under these conditions, the selective pmK(ATP) channel inhibitor HMR 1098 further depolarized myocyte membrane potential and increased hypercontracture. 5. In conclusion, activation of pmK(ATP) channels can prevent CIH/reoxygenation-induced Ca(2+) overload via a mechanism that is dependent on hyperpolarization of diastolic membrane potential. Hyperpolarization toward normal resting membrane potential favours the Ca(2+) extrusion mode of Na(+)/Ca(2+) exchange.