gebhart/patrepeval huggingface dataset:
Phantom studies for estimation of defect size on cardiac (18)F SPECT and PET: implications for myocardial viability assessment. (2001)

SPECT with (18)F-FDG has emerged as an alternative to dedicated PET for the assessment of myocardial viability. However, whether FDG SPECT can reliably quantify the extent of viable and scarred myocardium is uncertain. The aim of this study was to investigate whether SPECT with an (18)F-labeled agent would provide information on defect size similar to that provided by dedicated PET.Imaging was performed using an elliptic cylinder chest phantom with simulated bone, lung, mediastinum, liver, and heart. (18)F was administered into the myocardium, mediastinum, right and left ventricular cavities, and liver. Plastic inserts (n = 11) ranging in size from 2% to 60% of the myocardium were used to simulate transmural myocardial infarctions. The chest phantom was imaged with a dedicated PET camera and with a double-head SPECT camera equipped with ultra-high-energy collimators. Both SPECT and PET data were analyzed using a semiquantitative polar map approach. Defects were quantified using various cutoff thresholds ranging from 30% to 80% of peak activity and were expressed as a percentage of the left ventricular myocardium. Defect size as measured by SPECT or PET was compared with true defect size.The measured SPECT defect size was highly variable depending on the cutoff used, whereas PET defect size was relatively constant over the range of cutoffs tested. The mean absolute difference between measured and true defect sizes was minimal at a cutoff of 50% of peak activity for both SPECT (3.3% +/- 3.3%) and PET (2.7% +/- 2.5%). For this threshold, both SPECT and PET measurements showed an excellent correlation with true defect size (r = 0.98 for SPECT and 0.99 for PET). The correlation between SPECT and PET measurements was also excellent (r = 0.99; P < 0.01).If an appropriate threshold is used to define a defect, SPECT with an (18)F-labeled agent can accurately measure defect size similarly to the manner of PET.
<i>In Situ</i> Electrochemical Scanning Tunneling Microscopy: Adlayers of Organic Molecules (2001)

Until recently, there had been only few in situ methods available for the structural determination of an electrode surface in solution at the atomic level. Now, several recent investigations have demonstrated scanning tunneling microscopy (STM) to be a powerful new technique for in situ characterization, with atomic resolution, of electrode surfaces under potentiostatic control. It has been demonstrated that the in situ STM makes it possible to monitor with atomic resolution a wide variety of electrode processes such as the adsorption of inorganic and organic species, the dissolution and deposition of metals and semiconductors. Owing to limitations on space, the focus is on the adsorption of organic molecules such as benzene and related compounds.
Evaluation of 0.4% Ketorolac Tromethamine Ophthalmic Solution Versus 0.5% Ketorolac Tromethamine Ophthalmic Solution After Phacoemulsification and Intraocular Lens Implantation (2006)

Treatment with 0.4% ketorolac tromethamine ophthalmic solution is as effective as 0.5% ketorolac tromethamine ophthalmic solution in reducing inflammation after routine cataract surgery. Patients reported less discomfort using 0.4% ketorolac.
Corn metabolites affect growth and virulence of Agrobacterium tumefaciens. (1990)

Homogenates of corn seedlings inhibit both growth of Agrobacterium tumefaciens and induction of its Ti plasmid virulence (vir) genes by acetosyringone (AS). The heat-labile inhibitor has been identified as 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), present in 2-week-old seedlings (B73) at a concentration of 1.5 mM or greater. A concentration of 0.3 mM DIMBOA is sufficient to block growth of A. tumefaciens completely for 220 hr. DIMBOA at 0.1 mM concentration completely inhibited vir gene induction by 100 microM AS and reduced growth rate by 50%. Thus, DIMBOA can be expected to have a significant effect on attempts to transform corn by using A. tumefaciens as a vector.
Primary structure of alpha 2-macroglobulin receptor-associated protein. Human homologue of a Heymann nephritis antigen (1991)

The alpha 2-macroglobulin (alpha 2M) receptor complex as purified by affinity chromatography contains three polypeptides: a 515-kDa heavy chain, an 85-kDa light chain, and a 39-kDa associated protein. Previous studies have established that the 515/85-kDa components are derived from a 600-kDa precursor whose complete sequence has been determined by cDNA cloning (Herz, J., Hamann, U., Rogne, S., Myklebost, O., Gassepohl, H., and Stanley, K. (1988) EMBO J. 7,4119-4127). We have now determined the primary structure of the human 39-kDa polypeptide, termed alpha 2M receptor-associated protein, by cDNA cloning. The deduced amino acid sequence contains a putative signal sequence that precedes the 323-residue mature protein. Comparative sequence analysis revealed that alpha 2M receptor-associated protein has 73% identity with a rat protein reported to be a pathogenic domain of Heymann nephritis antigen gp 330 and 77% identity to a mouse heparin-binding protein termed HBP-44. The high overall identity suggests that these molecules are interspecies homologues and indicates that the pathogenic domain, previously thought to be a portion of gp 330, is in fact a distinct protein. Further, the 120-residue carboxyl-terminal region of alpha 2M receptor-associated protein has 26% identity with a region of apolipoprotein E containing the low density lipoprotein receptor binding domain. Pulse-chase experiments revealed that the newly formed alpha 2M receptor-associated protein remains cell-associated, while surface labeling experiments followed by immunoprecipitation suggest that this protein is present on the cell surface forming a complex with the alpha 2M receptor heavy and light chains.
Crystallographic and Biochemical Investigations of Kumamolisin-As, a Serine-Carboxyl Peptidase with Collagenase Activity (2004)

Kumamolisin-As (previously called ScpA) is the first known example of a collagenase from the sedolisin family (MEROPS S53). This enzyme is active at low pH and in elevated temperatures. In this study that used x-ray crystallographic and biochemical methods, we investigated the structural basis of the preference of this enzyme for collagen and the importance of a glutamate residue in the unique catalytic triad (Ser(278)-Glu(78)-Asp(82)) for enzymatic activity. Crystal structures of the uninhibited enzyme and its complex with a covalently bound inhibitor, N-acetyl-isoleucyl-prolyl-phenylalaninal, showed the occurrence of a narrow S2 pocket and a groove that encompasses the active site and is rich in negative charges. Limited endoproteolysis studies of bovine type-I collagen as well as kinetic studies using peptide libraries randomized at P1 and P1', showed very strong preference for arginine at the P1 position, which correlated very well with the presence of a negatively charged residue in the S1 pocket of the enzyme. All of these features, together with those predicted through comparisons with fiddler crab collagenase, a serine peptidase, rationalize the enzyme's preference for collagen. A comparison of the Arrhenius plots of the activities of kumamolisin-As with either collagen or peptides as substrates suggests that collagen should be relaxed before proteolysis can occur. The E78H mutant, in which the catalytic triad was engineered to resemble that of subtilisin, showed only 0.01% activity of the wild-type enzyme, and its structure revealed that Ser(278), His(78), and Asp(82) do not interact with each other; thus, the canonical catalytic triad is disrupted.
High Throughput Quantitative Analysis of Serum Proteins Using Glycopeptide Capture and Liquid Chromatography Mass Spectrometry (2004)

It is expected that the composition of the serum proteome can provide valuable information about the state of the human body in health and disease and that this information can be extracted via quantitative proteomic measurements. Suitable proteomic techniques need to be sensitive, reproducible, and robust to detect potential biomarkers below the level of highly expressed proteins, generate data sets that are comparable between experiments and laboratories, and have high throughput to support statistical studies. Here we report a method for high throughput quantitative analysis of serum proteins. It consists of the selective isolation of peptides that are N-linked glycosylated in the intact protein, the analysis of these now deglycosylated peptides by liquid chromatography electrospray ionization mass spectrometry, and the comparative analysis of the resulting patterns. By focusing selectively on a few formerly N-linked glycopeptides per serum protein, the complexity of the analyte sample is significantly reduced and the sensitivity and throughput of serum proteome analysis are increased compared with the analysis of total tryptic peptides from unfractionated samples. We provide data that document the performance of the method and show that sera from untreated normal mice and genetically identical mice with carcinogen-induced skin cancer can be unambiguously discriminated using unsupervised clustering of the resulting peptide patterns. We further identify, by tandem mass spectrometry, some of the peptides that were consistently elevated in cancer mice compared with their control littermates.
Bone Marrow-Derived Hemopoietic Precursors Commit to the T Cell Lineage Only after Arrival in the Thymic Microenvironment (2007)

T lymphocytes develop in the thymus from hemopoietic precursors that commit to the T cell lineage under the influence of Notch signals. In this study, we show by single cell analyses that the most immature hemopoietic precursors in the adult mouse thymus are uncommitted and specify to the T cell lineage only after their arrival in the thymus. These precursors express high levels of surface Notch receptors and rapidly lose B cell potential upon the provision of Notch signals. Using a novel culture system with complexed, soluble Notch ligands that allows the titration of T cell lineage commitment, we find that these precursors are highly sensitive to both Delta and Jagged ligands. In contrast, their phenotypical and functional counterparts in the bone marrow are resistant to Notch signals that efficiently induce T cell lineage commitment in thymic precursors. Mechanistically, this is not due to differences in receptor expression, because early T lineage precursors, bone marrow lineage marker-negative, Sca-1-positive, c-Kit-positive and common lymphoid progenitor cells, express comparable amounts of surface Notch receptors. Our data demonstrate that the sensitivity to Notch-mediated T lineage commitment is stage-dependent and argue against the bone marrow as the site of T cell lineage commitment.
Asymmetric Dimethylarginine Increases Mononuclear Cell Adhesiveness in Hypercholesterolemic Humans (2000)

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is elevated in hypercholesterolemia. This study was designed to determine the role of ADMA in the increased mononuclear cell adhesiveness observed in human hypercholesterolemia. In patient studies, plasma ADMA levels were determined by high-performance liquid chromatography. Functional mononuclear leukocyte adhesion assays were performed in parallel, and flow cytometry was used to characterize bound monocytes and T lymphocytes. Hypercholesterolemic patients were then placed on an oral L-arginine regimen of 14 or 21 g/d and studied over 12 weeks. In cell culture studies, bovine aortic endothelial cells were incubated with varied concentrations of ADMA. Monocytoid cells were cocultured with these bovine aortic endothelial cells, and their adhesiveness was assessed by use of a binding assay. Flow cytometry was used to quantify adhesion molecule expression. Plasma ADMA levels and adhesiveness of mononuclear cells (specifically, monocytes and T lymphocytes) were elevated in hypercholesterolemic patients. Adhesiveness was inversely correlated with the plasma L-arginine/ADMA ratio. Oral administration of L-arginine normalized plasma L-arginine/ADMA ratios and attenuated monocyte and T-lymphocyte adhesiveness. ADMA had no direct effect on the adhesiveness of mononuclear cells. However, monocytes became hyperadhesive when cocultured with ADMA-exposed endothelial cells. In human hypercholesterolemia, the plasma L-arginine/ADMA ratio is inversely correlated with mononuclear cell adhesiveness. Restoration of the L-arginine/ADMA ratio to control levels normalizes mononuclear cell adhesiveness. Our studies suggest that the elaboration of endothelium-derived nitric oxide affects the behavior of circulating T lymphocytes and monocytes.
A sensitive ristocetin co-factor activity assay with recombinant glycoprotein Ibalpha for the diagnosis of patients with low von Willebrand factor levels. (2004)

This ELISA assay can be useful in the identification and classification of VWD patients in that it may provide a more accurate distinction between type 2 with abnormal VWF function and type 1 with a low plasma VWF concentration.
Response of Extraintestinal Pathogenic Escherichia coli to Human Serum Reveals a Protective Role for Rcs-Regulated Exopolysaccharide Colanic Acid (2013)

Extraintestinal Escherichia coli (ExPEC) organisms are the leading cause of Gram-negative bacterial bloodstream infections. These bacteria adapt to survival in the bloodstream through expression of factors involved in scavenging of nutrients and resisting the killing activity of serum. In this study, the transcriptional response of a prototypic ExPEC strain (CFT073) to human serum was investigated. Resistance of CFT073 to the bactericidal properties of serum involved increased expression of envelope stress regulators, including CpxR, σE, and RcsB. Many of the upregulated genes induced by active serum were regulated by the Rcs two-component system. This system is triggered by envelope stress such as changes to cell wall integrity. RcsB-mediated serum resistance was conferred through induction of the exopolysaccharide colanic acid. Production of this exopolysaccharide may be protective while cell wall damage caused by serum components is repaired.
Dysplasia Associated With Atypical Glandular Cells on Cervical Cytology (2005)

These data suggest that women with atypical glandular cells are at substantial risk for dysplasia and malignancy. The rate of disease varies with the method of Pap test collection, age, presence of persistent AGUS Pap tests, and AGUS subclassification.
Variational shape approximation (2004)

A method for concise, faithful approximation of complex 3D datasets is key to reducing the computational cost of graphics applications. Despite numerous applications ranging from geometry compression to reverse engineering, efficiently capturing the geometry of a surface remains a tedious task. In this paper, we present both theoretical and practical contributions that result in a novel and versatile framework for geometric approximation of surfaces. We depart from the usual strategy by casting shape approximation as a variational geometric partitioning problem. Using the concept of geometric proxies, we drive the distortion error down through repeated clustering of faces into best-fitting regions. Our approach is entirely discrete and error-driven, and does not require parameterization or local estimations of differential quantities. We also introduce a new metric based on normal deviation, and demonstrate its superior behavior at capturing anisotropy.
A New Member of the hsp90 Family of Molecular Chaperones Interacts with the Retinoblastoma Protein during Mitosis and after Heat Shock (1996)

A gene encoding a new heat shock protein that may function as a molecular chaperone for the retinoblastoma protein (Rb) was characterized. The cDNA fragment was isolated by using the yeast two-hybrid system and Rb as bait. The open reading frame of the longest cDNA codes for a protein with substantial sequence homology to members of the hsp90 family. Antibodies prepared against fusions between glutathione S-transferase and portions of this new heat shock protein specifically recognized a 75-kDa cellular protein, hereafter designated hsp75, which is expressed ubiquitously and located in the cytoplasm. A unique LxCxE motif in hsp75, but not in other hsp90 family members, appears to be important for binding to the simian virus 40 T-antigen-binding domain of hypophosphorylated Rb, since a single mutation changing the cysteine to methionine abolishes the binding. In mammalian cells, Rb formed complexes with hsp75 under two special physiological conditions: (i) during M phase, when the envelope that separates the nuclear and cytoplasmic compartments broke down, and (ii) after heat shock, when hsp75 moved from its normal cytoplasmic location into the nucleus. In vitro, hsp75 had a biochemical activity to refold denatured Rb into its native conformation. Taken together, these results suggest that Rb may be a physiological substrate for the hsp75 chaperone molecule. The discovery of a heat shock protein that chaperones Rb identifies a mechanism, in addition to phosphorylation, by which Rb is regulated in response to progression of the cell cycle and to external stimuli.
Considerations in perioperative assessment of valproic acid coagulopathy (2014)

Valproic acid (VPA) is one of the widely prescribed antiepileptic drugs in children with multiple indications. VPA-induced coagulopathy may occur and constitute a pharmacological and practical challenge affecting pre-operative evaluation and management of patients receiving VPA therapy. This review summarizes the different studies documenting the incidence, severity and available recommendations related to this adverse effect.
De novo generation of HSCs from somatic and pluripotent stem cell sources (2015)

Generating human hematopoietic stem cells (HSCs) from autologous tissues, when coupled with genome editing technologies, is a promising approach for cellular transplantation therapy and for in vitro disease modeling, drug discovery, and toxicology studies. Human pluripotent stem cells (hPSCs) represent a potentially inexhaustible supply of autologous tissue; however, to date, directed differentiation from hPSCs has yielded hematopoietic cells that lack robust and sustained multilineage potential. Cellular reprogramming technologies represent an alternative platform for the de novo generation of HSCs via direct conversion from heterologous cell types. In this review, we discuss the latest advancements in HSC generation by directed differentiation from hPSCs or direct conversion from somatic cells, and highlight their applications in research and prospects for therapy.
Functional gene expression analysis of clonal plasma cells identifies a unique molecular profile for light chain amyloidosis (2004)

Immunoglobulin light chain amyloidosis (AL) is characterized by a clonal expansion of plasma cells within the bone marrow. Gene expression analysis was used to identify a unique molecular profile for AL using enriched plasma cells (CD138+) from the bone marrow of 24 patients with AL and 28 patients with multiple myeloma (MM) and 6 healthy controls. Class prediction analysis (PAM) revealed a subset of 12 genes, which included TNFRSF7 (CD27), SDF-1, and PSMA2, that distinguished between these 2 groups with an estimated and observed accuracy of classification of 92%. This model was validated with an independent dataset of 11 patients with AL and 12 patients with MM with 87% accuracy. Differential expression for the most discriminant genes in the 12-gene subset was validated using quantitative real-time polymerase chain reaction and protein expression analysis, which upheld the observations from the micro-array expression data. Functional analyses using a novel network mapping software revealed a number of potentially significant pathways that were dysregulated in patients with AL, with those regulating proliferation, apoptosis, cell signaling, chemotaxis, and migration being substantially represented. This study provides new insight into the molecular profile of clonal plasma cells and its functional relevance in the pathogenesis of light chain amyloidosis.
Modulation of floral development by a gibberellin-regulated microRNA (2004)

Floral initiation and floral organ development are both regulated by the phytohormone gibberellin (GA). For example, in short-day photoperiods, the Arabidopsis floral transition is strongly promoted by GA-mediated activation of the floral meristem-identity gene LEAFY. In addition, anther development and pollen microsporogenesis depend on GA-mediated opposition of the function of specific members of the DELLA family of GA-response repressors. We describe the role of a microRNA (miR159) in the regulation of short-day photoperiod flowering time and of anther development. MiR159 directs the cleavage of mRNA encoding GAMYB-related proteins. These proteins are transcription factors that are thought to be involved in the GA-promoted activation of LEAFY, and in the regulation of anther development. We show that miR159 levels are regulated by GA via opposition of DELLA function, and that both the sequence of miR159 and the regulation of miR159 levels by DELLA are evolutionarily conserved. Finally, we describe the phenotypic consequences of transgenic over-expression of miR159. Increased levels of miR159 cause a reduction in LEAFY transcript levels, delay flowering in short-day photoperiods, and perturb anther development. We propose that miR159 is a phytohormonally regulated homeostatic modulator of GAMYB activity, and hence of GAMYB-dependent developmental processes.
Knockdown of SMYD3 by RNA interference inhibits cervical carcinoma cell growth and invasion in vitro (2008)

Elevated expression of SMYD3 is a frequent genetic abnormality in several malignancies. Few studies knocking down SMYD3 expression in cervical carcinoma cells have been performed to date. In this paper, we established an inducible short hairpin RNA expression system to examine its role in maintaining the malignant phenotype of HeLa cells. After being induced by doxycycline, SMYD3 mRNA and protein expression were both reduced, and significant reductions in cell proliferation, colony formation and migration/invasion activity were observed in the SMYD3-silenced HeLa cells. The percentage of cells in sub-G1 was elevated and DNA ladder formation could be detected, indicating potent induction of apoptosis by SMYD3 knockdown. These findings imply that SMYD3 plays crucial roles in HeLa cell proliferation and migration/invasion, and that it may be a useful therapeutic target in human cervical carcinomas.
Eventual Entrainment of the Human Circadian Pacemaker by Melatonin is Independent of the Circadian Phase of Treatment Initiation: Clinical Implications (2004)

About 15% of the legally blind completely lack light perception. Most of these individuals have abnormally phased circadian rhythms and many free-run. Light treatment is not an option for them. However, melatonin treatment can be highly effective. A daily dose of 0.5 mg of melatonin usually results in entrainment. It has been suggested that treatment in individuals with circadian periods > 24 h should be initiated on the advance zone of the melatonin phase response curve, which was based on findings in which melatonin initiated on the delay zone were less likely to result in entrainment, even though treatment continued across all circadian phases. In the present study, 7 totally blind people started low-dose melatonin treatment (0.5 mg; 1 person was given 0.05 mg) on the delay zone. All entrained as circadian phase free-ran and the advance zone of the melatonin phase response curve coincided with the time of melatonin administration. These results are consistent with studies in other mammals. It does not appear that low-dose melatonin treatment needs to be initiated on the advance zone to induce eventual entrainment in blind people with free-running rhythms > 24 h. Therefore, it is not essential that circadian phase be ascertained before starting low-dose melatonin treatment of blind people.