gebhart/patrepeval huggingface dataset:
Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity (1971)

This study was designed to develop a method for quantitative assessment of infarct size in the conscious animal based on serial changes of serum creatine phosphokinase (CPK) activity. From 11 experiments in which myocardial CPK was injected intravenously in conscious dogs, the average CPK distribution space and average CPK fractional disappearance rate from serum were found to be 11.4% of body weight and 0.48% min respectively. In other experiments, myocardial infarction was produced in 22 conscious dogs by constriction of a left coronary artery snare and serum CPK activity was determined at frequent intervals for 24 hr. Since myocardial CPK depletion reflects infarct size, infarct size was determined directly by analysis of myocardial CPK content in the same animals 24 hr after coronary artery occlusion. CPK released from the infarct was determined from observed changes in serum CPK activity analyzed according to a model taking into account the fraction of CPK released from an infarct and the rates of appearance and disappearance of CPK activity from serum. Infarct size was calculated on the basis of observed changes in serum CPK and compared to infarct size determined directly by analysis of myocardial CPK depletion. Agreement was close and results from all experiments fit the equation: [infarct size (g) determined from serum CPK] = 1.13 x [infarct size (g) determined from myocardial CPK] - 1.3, r = 0.96, n = 22. The method described is useful for accurate assessment of infarct size in the conscious animal and for detection of modification of infarct size produced by pharmacologic interventions.
Targeting cancer stem cells: a new therapy to cure cancer patients. (2012)

Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. They have been identified in blood, breast, brain, colon, melanoma, pancreatic, prostate, ovarian, lung cancers and so on. It is often considered to be associated with chemo-resistance and radio-resistance that lead to the failure of traditional therapies. Most therapies are directed at the fast growing tumor mass but not the slow dividing cancer stem cells. Eradicating cancer stem cells, the root of cancer origin and recurrence, has been thought as a promising approach to improve cancer survival or even to cure cancer patients. Understanding the characteristics of cancer stem cells will help to develop novel therapies to eliminate the initiating cancer stem cell, and the relevant patents on the cancer stem cell and cancer therapy by cancer stem cells will be discussed.
Visual grasp affordances from appearance-based cues (2011)

In this paper, we investigate the prediction of visual grasp affordances from 2D measurements. Appearance-based estimation of grasp affordances is desirable when 3-D scans are unreliable due to clutter or material properties. We develop a general framework for estimating grasp affordances from 2-D sources, including local texture-like measures as well as object-category measures that capture previously learned grasp strategies. Local approaches to estimating grasp positions have been shown to be effective in real-world scenarios, but are unable to impart object-level biases and can be prone to false positives. We describe how global cues can be used to compute continuous pose estimates and corresponding grasp point locations, using a max-margin optimization for category-level continuous pose regression. We provide a novel dataset to evaluate visual grasp affordance estimation; on this dataset we show that a fused method outperforms either local or global methods alone, and that continuous pose estimation improves over discrete output models.
Purification, characterization, and cDNA cloning of an AU-rich element RNA-binding protein, AUF1. (1993)

The degradation of some proto-oncogene and lymphokine mRNAs is controlled in part by an AU-rich element (ARE) in the 3' untranslated region. It was shown previously (G. Brewer, Mol. Cell. Biol. 11:2460-2466, 1991) that two polypeptides (37 and 40 kDa) copurified with fractions of a 130,000 x g postribosomal supernatant (S130) from K562 cells that selectively accelerated degradation of c-myc mRNA in a cell-free decay system. These polypeptides bound specifically to the c-myc and granulocyte-macrophage colony-stimulating factor 3' UTRs, suggesting they are in part responsible for selective mRNA degradation. In the present work, we have purified the RNA-binding component of this mRNA degradation activity, which we refer to as AUF1. Using antisera specific for these polypeptides, we demonstrate that the 37- and 40-kDa polypeptides are immunologically cross-reactive and that both polypeptides are phosphorylated and can be found in a complex(s) with other polypeptides. Immunologically related polypeptides are found in both the nucleus and the cytoplasm. The antibodies were also used to clone a cDNA for the 37-kDa polypeptide. This cDNA contains an open reading frame predicted to produce a protein with several features, including two RNA recognition motifs and domains that potentially mediate protein-protein interactions. These results provide further support for a role of this protein in mediating ARE-directed mRNA degradation.
Diabetes expertise: a subspecialty on a general medical unit. (2002)

A medical unit developed a subspecialty in diabetes care by increasing the expertise of its staff nurses. A task force was formed to set goals and create an action plan. An educational curriculum was developed, implemented, and evaluated. Medical staff nurses were integrated as diabetes educators and now provide 24-hour diabetes specialty care coverage for the hospital.
Differential Site Accessibility Mechanistically Explains Subcellular-Specific N-Glycosylation Determinants (2014)

Glycoproteins perform extra- and intracellular functions in innate and adaptive immunity by lectin-based interactions to exposed glyco-determinants. Herein, we document and mechanistically explain the formation of subcellular-specific N-glycosylation determinants on glycoproteins trafficking through the shared biosynthetic machinery of human cells. LC-MS/MS-based quantitative glycomics showed that the secreted glycoproteins of eight human breast epithelial cells displaying diverse geno- and phenotypes consistently displayed more processed, primarily complex type, N-glycans than the high-mannose-rich microsomal glycoproteins. Detailed subcellular glycome profiling of proteins derived from three breast cell lines (MCF7/MDA468/MCF10A) demonstrated that secreted glycoproteins displayed significantly more α-sialylation and α1,6-fucosylation, but less α-mannosylation, than both the intermediately glycan-processed cell-surface glycoproteomes and the under-processed microsomal glycoproteomes. Subcellular proteomics and gene ontology revealed substantial presence of endoplasmic reticulum resident glycoproteins in the microsomes and confirmed significant enrichment of secreted and cell-surface glycoproteins in the respective subcellular fractions. The solvent accessibility of the glycosylation sites on maturely folded proteins of the 100 most abundant putative N-glycoproteins observed uniquely in the three subcellular glycoproteomes correlated with the glycan type processing thereby mechanistically explaining the formation of subcellular-specific N-glycosylation. In conclusion, human cells have developed mechanisms to simultaneously and reproducibly generate subcellular-specific N-glycosylation using a shared biosynthetic machinery. This aspect of protein-specific glycosylation is important for structural and functional glycobiology and discussed here in the context of the spatio-temporal interaction of glyco-determinants with lectins central to infection and immunity.
Cerebral blood flow response pattern during balloon test occlusion of the internal carotid artery. (1994)

For achieving a minimal hemodynamic related-stroke rate associated with permanent clinical internal carotid artery occlusion we suggest integration of a thorough analysis of quantitative cerebral blood flow data before and during balloon test occlusion.
Camera calibration method with a coplanar target and three-dimensional reconstruction (2009)

This essay proposes a method for camera calibration. This method calibrates camera's all intrinsic parameters and extrinsic parameters step-by-step under the condition of considering the first order radial distortion. Compared with Tsai's two-stage method, this method only needs to use a coplanar target and can calibrate the image center and the scale factor. It also introduces a new distortion model and then can completely calibrate camera linearly, avoiding the trouble and the instability of non-linear optimization. It's simpler. Then, this essay introduces a computing model of three-dimensional reconstruction of the two cameras' system, and proves that this calibration method has high accuracy after the three-dimensional reconstruction.
A Series of 2,4-Disubstituted Quinolines as a New Class of Allosteric Enhancers of the Adenosine A3Receptor (2009)

The adenosine receptor subfamily consists of the adenosine A(1), A(2A), A(2B), and A(3) receptors, which are localized in a variety of tissues throughout the human body. It is, therefore, a challenge to develop receptor specific ligands with improved tissue selectivity. Allosteric modulators could have these therapeutic advantages over orthosteric ligands. In the present study, a series of 2,4-disubstituted quinolines were synthesized on the basis of the structure of LUF6000 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist binding to a similar extent as 34. In addition, this new compound showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, compound 27 showed improved activity in comparison to 34, as it increased both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA at the human adenosine A(3) receptor.
Electric field effect in high T c superconducting ultrathin YBa2Cu3O7−x films (1991)

A multilayer high Tc superconducting field-effect transistor-like structure was made from ultrathin YBa2Cu3O7−x films. An epitaxially grown dielectric SrTiO3 insulation layer, which had a forward bias breakdown voltage of about 20 V, allowed an electric field induced change in the channel layer of 1.25×1013 carrier/cm2 per volt of the gate voltage. A significant modulation of the normal state and superconducting properties was observed in samples with YBa2Cu3O7−x channel layers of a few unit cells thick. By applying gate voltage of different polarities, Tc was both suppressed and enhanced by ∼1 K. The resistance was modulated by as much as 20% in the normal state and by over 1500% near the zero resistance temperature.
Fine mapping of the MHC Class III region demonstrates association of AIF1 and rheumatoid arthritis (2008)

The results of the genotyping and expression studies presented here suggest a role for AIF1 in both the aetiology and pathogenesis of RA.
Risks of double-counting in deep sequencing (2014)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Transdifferentiation of Human Islet Cells in a Long-term Culture (2001)

It has been established that ductal cells or precursor cells within the ductal tree of the pancreas can differentiate into islet cells. Although islet cells can also form exocrine cells, it is unclear whether they arise from precursor (stem) cells or from mature endocrine cells by transdifferentiation. Using a defined culture medium and technique for islet purification, for the first time we were able to maintain human islets in culture for more than a year. Multilabeling immunohistochemical and immunoelectron microscopic examination of the islets at different days of culture using islet cell markers (antibodies to hormones, neuron-specific enolase, chromogranin A) and ductal cell markers (cytokeratins 7 and 19, carbonic anhydrase II, DU-PAN2, CA 19-9, and MUC1) revealed that endocrine cells gradually transdifferentiate to ductal, acinar, and intermediary cells. Although islet hormone secretion ceased after day 28 in culture, endocrine cells were still detectable at day 60. However, later, all endocrine and exocrine cells were replaced by undifferentiated cells that expressed neuron-specific enolase, chromogranin A, laminin, vimentin, cytokeratin 7 and 19, alpha-1-antitrypsin, transforming growth factor-alpha, and epidermal growth factor receptor. Our data thus show that, under proper conditions, human islets can be maintained in vitro over a long period and that, in the culture condition, islet cells seem to transdifferentiate to exocrine cells and undifferentiated cells, which may be considered pancreatic precursor (stem) cells.
Current therapy in oncology (1993)

A multidisciplinary reference work in oncology providing discussions of the biology, diagnosis and treatment of a broad range of clinical cancer problems. The book presents an integrated approach to the treatment of patients with cancer covering medical oncology, radiation and more.
Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models (2012)

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × less effective than Nec-1 in inhibiting human RIPK1 kinase activity in vitro, it was only 10 times less potent than Nec-1 and Nec-1s in a mouse necroptosis assay and became even equipotent at high concentrations. Along the same line, in vivo, high doses of Nec-1, Nec-1i and Nec-1s prevented tumor necrosis factor (TNF)-induced mortality equally well, excluding the use of Nec-1i as an inactive control. Paradoxically, low doses of Nec-1 or Nec-1i, but not Nec -1s, even sensitized mice to TNF-induced mortality. Importantly, Nec-1s did not exhibit this low dose toxicity, stressing again the preferred use of Nec-1s in vivo. Our findings have important implications for the interpretation of Nec-1-based data in experimental disease models.
Herpes Simplex Virus Vaccines (1977)

Journal Article Herpes Simplex Virus Vaccines Get access Thomas G. Wise, Thomas G. Wise Division of Virology, Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland The present address of Dr. Thomas G. Wise is Massachusetts General Hospital, Boston, Massachusetts, and of Dr. Peter R. Pavan is Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter R. Pavan, Peter R. Pavan Division of Virology, Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Francis A. Ennis Francis A. Ennis Division of Virology, Bureau of Biologics, Food and Drug Administration, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 136, Issue 5, November 1977, Pages 706–711, https://doi.org/10.1093/infdis/136.5.706 Published: 01 November 1977 Article history Received: 18 February 1977 Revision received: 20 June 1977 Published: 01 November 1977
Bovine endothelial cell plasminogen activator inhibitor (1988)

A plasminogen activator inhibitor (PAI) was purified from bovine endothelial cell conditioned medium by a simple procedure in the absence of protein denaturant. The yield was 2.2 mg from 1.61 conditioned medium in a typical experiment. The purified inhibitor showed a single band on sodium dodecyl sulfate/polyacrylamide gel electrophoresis and reverse fibrin autography with an apparent molecular mass of 45 kDa. The amino-terminal 40-amino-acid sequence was determined and found to be 70% similar to the reported corresponding sequence of human PAI-1. The amino acid composition also revealed a close relationship between bovine PAI and human PAI-1. The purified PAI was substantially inactive (570 U/mg) but it could be activated by treatment with protein denaturants such as 1% SDS (1.8 X 10(5) U/mg) and 4 M guanidine-HCl (1.5 X 10(5) U/mg). A more effective activation of this latent PAI was achieved by heat treatment at 100 degrees C for 2.5 min, generating the specific activity of 1.0 X 10(6) U/mg. The heat-activated PAI lost its activity during incubation at 56 degrees C for 30 min, but repeated heat at 100 degrees C for 2.5 min could regenerate about 70% of the initial activity. Treatment at 37 degrees C, 56 degrees C and 80 degrees C, however, failed to activate the latent PAI at all. These findings suggest that the buried reactive site of the latent PAI is exposed as a result of a heat-induced, specific conformational change, but tends to be masked again during renaturation under mild conditions, i.e. the PAI protein takes on preferentially a latent form.
Shadow edge lithography for nanoscale patterning and manufacturing (2007)

We demonstrate a wafer-scale nanofabrication method using the shadow effect in physical vapor deposition. An analytical model is presented to predict the formation of nanoscale gaps created by the shadow effect of a prepatterned edge on a deposition plane. The theoretical prediction agrees quantitatively with the widths of the fabricated nanogaps and nanochannels. In the diffusion experiments, both λ-DNA and fluorescein molecules were successfully introduced into the nanochannels. The proposed shadow edge lithography has potential to be a candidate for mass-producing nanostructures.
In vitro and in vivo targeting of gene expression to melanoma cells. (1993)

Gene therapy protocols for cancer usually involve removal of tumor cells, culture in vitro to allow gene transfer, and subsequent reintroduction in vivo. Targeting therapeutic genes to tumor cells in situ requires an accuracy of gene delivery that currently is not possible with the use of existing techniques. To overcome these limitations we have used two promoters, which are preferentially active in melanocytic cells, to direct gene expression specifically to melanoma cells both in vitro and in vivo. Here we describe experiments showing that as little as 769 base pairs of the 5'-flanking regions of the tyrosinase, and 1.4 kilobase pair of the tyrosinase-related protein 1, genes are sufficient to direct expression of the beta-galactosidase gene to both human and murine melanoma cells and melanocytes, while not permitting expression in a range of other cell types in vitro. These promoters showed high levels of activity in 12 of 14 murine and human melanoma cell lines tested but showed only basal levels of activity, similar to that of a promoterless construct, in a range of 12 other cell types. Cell type specificity is maintained when the construct is delivered to cells either by physical means or by inclusion of the cell type-specific expression cassette into a retroviral vector. Direct injection of DNA, encoding the beta-galactosidase gene expressed from either promoter, into established B16 melanomas or Colo 26 tumors in syngeneic mice resulted in extensive transduction of tumor cells in the B16 melanomas (approximately 10% of tumor cells expressing 10 days after DNA injection), whereas no blue-staining cells were seen in the Colo 26 tumors. The reporter gene was expressed in melanoma cells and in some normal melanocytes but not in other surrounding normal tissue. We propose that the combination of a tissue-specific promoter driving a therapeutic gene, with delivery of such a construct directly to sites of tumor growth in vivo, either by direct DNA injection or by retroviral infection, may provide significantly enhanced safety for gene therapy for solid tumors.
Scanning polyhedra without Do-loops (1998)

We study in this paper the problem of polyhedron scanning which appears for example when generating code for transformed loop nests in automatic parallelization. After a review of related works, we detail our method to scan affine images of polyhedra. After some experimental results we show how our method applies to unions of affine images of polyhedra. We have taken the option to generate low level code without loops. This has allowed us to have a completely general and fully parameterized method without losing efficiency.
HbF-Associated Genetic Variation Marks an Erythroid Regulatory Element Essential for BCL11A Transcription and Subsequent Stage-Specific Globin Expression (2012)

Abstract Abstract 828 Genome-wide association studies (GWAS) have identified common genetic variation within a 14-kb segment of intron-2 of the BCL11A gene that is associated with the level of fetal hemoglobin (HbF) and the clinical severity of the β-globin disorders sickle cell disease and β-thalassemia. Functional studies have validated BCL11A as a major repressor of HbF. Here, we explore the consequences of genetic variation on BCL11A expression. The HbF-associated variants overlap BCL11A sequences that possess an evolutionarily conserved enhancer chromatin signature, including the presence of H3K4me1 and H3K27ac and the absence of H3K4me3 histone modifications. Moreover, these sequences show a unique pattern of DNase I hypersensitivity in erythroid precursors compared to other BCL11A-expressing lineages including fetal brain and B-lymphocytes. Occupancy of the major erythroid transcription factors GATA1 and TAL1 is observed at these DNase I hypersensitive sites (DHS). Chromosome conformation capture studies demonstrate that these DHSs form a long-range interaction with the BCL11A promoter. To address the function of the putative regulatory element, we generated transgenic mice with the 12-kb intronic region attached to a minimal promoter and reporter gene. The element enhanced reporter gene expression in an erythroid-lineage restricted, definitive erythroid stage-specific manner. The minimal enhancer activity was mapped to the +58-kb DHS. Similar enhancer activity was observed in primary human erythroid precursors. To address the possible requirement of this element for BCL11A expression, we deleted the corresponding region in adult-stage murine erythroleukemia cells with TALEN-mediated gene targeting. Expression of BCL11A was dramatically reduced and embryonic globins Hbby and Hbb-bh1 were markedly derepressed with concomitant reduction of adult globin Hbb-b1. Analysis of heterozygous primary human erythroid precursors revealed that low-HbF haplotype alleles are preferentially occupied by GATA1 and TAL1 at sequences surrounding rs1427407. A composite half-E-box–GATA motif is disrupted at this SNP in the high-HbF allele. Furthermore, the low-HbF haplotype allele of BCL11A is expressed at a 1.7-fold higher level relative to the high-HbF allele. These data demonstrate that HbF-associated genetic variation in BCL11A modulates the function of a critical erythroid enhancer of BCL11A, and consequently expression of BCL11A itself. The quantitative level of BCL11A in turn regulates the relative expression of the stage-specific globin genes. The essential erythroid enhancer of the BCL11A gene might itself serve as a target for genetic manipulation as a novel approach to the human β-globin disorders. Disclosures: Porteus: Alex's Lemonade Stand Foundation: Research Funding.