gebhart/patrepeval huggingface dataset:
Mass Spectrometry of Nucleic Acids: The Promise of Matrix-Assisted Laser Desorption-Ionization (MALDI) Mass Spectrometry (1995)

In the past several years, significant progress has been made in the application of matrix-assisted laser desorption-ionization (MALDI) mass spectrometry to the analysis of large biopolymers, including nucleic acids. By isolating analyte molecules in an appropriate matrix and irradiating the sample with a high-intensity, pulsed laser beam, MALDI can generate intact, gas-phase ions of these analytes. Primarily used with time-of-flight mass spectrometers, this relatively new, soft ionization technique has allowed for the routine analysis of oligonucleotides up to 60 or so nucleotides in length. Recent results have also shown that base specific, matrix-dependent fragmentation is an important factor in the MALDI analysis of oligonucleotides. Further extension of the technique to longer oligonucleotides will rely on both the continued search for new matrix materials and an increased understanding of the desorption and ionization process in MALDI.
The Transcription Factors GATA4 and GATA6 Regulate Cardiomyocyte Hypertrophy in Vitro and in Vivo (2001)

The zinc finger-containing transcription factors GATA4 and GATA6 are important regulators of basal and inducible gene expression in cardiac and smooth muscle cell types. Here we demonstrate a direct functional role for GATA4 and GATA6 as regulators of cardiomyocyte hypertrophic growth and gene expression. To model the increase in endogenous GATA4 and GATA6 transcriptional activity that occurs in response to hypertrophic stimulation, each factor was overexpressed in cardiomyocytes using recombinant adenovirus. Overexpression of either GATA4 or GATA6 was sufficient to induce cardiomyocyte hypertrophy characterized by enhanced sarcomeric organization, a greater than 2-fold increase in cell surface area, and a significant increase in total protein accumulation. In vivo, transgenic mice with 2.5-fold overexpression of GATA4 within the adult heart demonstrated a slowly progressing increase in heart to body weight ratio, histological features of cardiomyopathy, and activation of hypertrophy-associated genes, suggesting that GATA factors are sufficient regulators of cardiomyocyte hypertrophy in vitro and in vivo. To evaluate the requirement of GATA factors as downstream transcriptional mediators of hypertrophy, a dominant negative GATA4-engrailed repressor fusion-encoding adenovirus was generated. Expression of GATA4-engrailed blocked GATA4- and GATA6-directed transcriptional responses and agonist-induced cardiomyocyte hypertrophy, demonstrating that cardiac-expressed GATA factors are necessary mediators of this process.
Anonymous credit cards and their collusion analysis (1996)

Communications networks are traditionally used to bring information together. They can also be used to keep information apart in order to protect personal privacy. A cryptographic protocol specifies a process by which some information is transferred among some users and hidden from others. We show how to implement anonymous credit cards using simple cryptographic protocols. We pose, and solve, a collusion problem which determines whether it is possible for a subset of users to discover information that is designed to be hidden from them during or after execution of the anonymous credit card protocol.
Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin (1994)

Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic development, but functional interactions between the proteins are unknown. We have examined Wnt-1 function in mammalian cells in which armadillo (beta-catenin and plakoglobin) is known to bind to and regulate cadherin cell adhesion proteins. We show that Wnt-1 expression results in the accumulation of beta-catenin and plakoglobin. In addition, binding of beta-catenin to the cell adhesion protein, cadherin, is stabilized, resulting in a concomitant increase in the strength of calcium-dependent cell-cell adhesion. Thus, a consequence of the functional interaction between Wnt-1 and armadillo family members is the strengthening of cell-cell adhesion, which may lead to the specification of cellular boundaries.
Anodic Protection of Mild Steel in Nitric Acid (1983)

The applicability and efficiency of anodic protection technique for controlling corrosion of mild steel in nitric acid of different concentrations at different temperatures are studied in this paper. The relevant polarization curves were obtained by potentiodynamic technique and the safe passive zone, and the protection potentials to be applied were established by analyzing these curves. The mild steel specimens were held at these potentials and the corrosion currents were monitored over a 10 hour period. The weight loss of the anodically protected sample was compared with the weight loss it suffered under similar conditions in the absence of anodic protection. The results revealed that corrosion could be controlled to an acceptable degree by the application of anodic protection. For example, a sample with a high corrosion rate of the order of 105 mpy in 40% HNO3 was found to corrode at less than 20 mpy when anodically protected.
Monolithic magnetic Hall sensor using dynamic quadrature offset cancellation (1997)

The offset voltage and its temperature drift and production spread, which generally degrades the zero-level stability and reproducibility of magnetic Hall sensors, can be reduced using a single Hall plate and switching means for periodic permutation of the supply and output contact pairs. The present work describes a chopper-based 5-V monolithic linear Hall sensor with a /spl plusmn/0.1 T full scale where this dynamic plate offset cancellation technique has been employed together with a cost-effective signal conditioner. The device was integrated using a 2-/spl mu/m conventional BiCMOS process and the final chip, measuring 15/spl times/1.5 mm/sup 2/, shows, after packaging in a 3-pin plastic package, a residual offset with a production spread and a temperature-induced drift five to ten times smaller than in currently used multiplate dc quadrature cancellation approaches. The device does not require external components and provides an output free of HF residues.
Induction of human tumor-loaded dendritic cells (2001)

A preferred anti-cancer vaccine would be tumor-specific, simple to rapidly construct and safe to administer. It would permit immunization against a spectrum of the tumor's distinctive antigens, without requiring their prior identification. Toward these goals, we describe a modification of standard extracorporeal photopheresis (ECP) which initiates, within a single day, both monocyte-to-dendritic cell (DC) differentiation and malignant cell apoptosis. The transition of monocytes to immature DCs was identified by the expression of cytoplasmic CD83 and membrane CD36 in the absence of membrane CD14 staining, as well as induction of membrane CD83 expression. Differentiating DCs were avidly phagocytic and engulfed apoptotic malignant T cells. Differentiating DCs were capable of stimulating significant proliferation of normal alloreactive lymphocyte responders, indicting increased expression of membrane MHC class II molecules. This approach provides a clinically practical means of developing tumor-loaded cells that have initiated the transition to DCs without the requirement of exogenous cytokines, excessive cellular manipulation or isolation. Construction of DC vaccines using this methodology can be generalized to other diseases and may offer a novel approach for improved cancer immunotherapy.
Types as models (2002)

Abstraction and composition are the fundamental issues in making model checking viable for software. This paper proposes new techniques for automating abstraction and decomposition using source level type information provided by the programmer. Our system includes two novel components to achieve this end: (1) a behavioral type-and-effect system for the π-calculus, which extracts sound models as types, and (2) an assume-guarantee proof rule for carrying out compositional model checking on the types. Open simulation between CCS processes is used as both the subtyping relation in the type system and the abstraction relation for compositional model checking.We have implemented these ideas in a tool---PIPER. PIPER exploits type signatures provided by the programmer to partition the model checking problem, and emit model checking obligations that are discharged using the SPIN model checker. We present the details on applying PIPER on two examples: (1) the SIS standard for managing trouble tickets across multiple organizations and (2) a file reader from the pipelined implementation of a web server.
Recognition-Domain Focused Chemosensors: Versatile and Efficient Reporters of Protein Kinase Activity (2008)

Catalyzed by kinases, serine/threonine and tyrosine phosphorylation is a vital mechanism of intracellular regulation. Thus, assays that easily monitor kinase activity are critical in both academic and pharmaceutical settings. We previously developed sulfonamido-oxine (Sox)-based fluorescent peptides following a beta-turn focused (BTF) design for the continuous assay of kinase activity in vitro and in cell lysates. Upon phosphorylation of the Sox-containing peptide, the chromophore binds Mg (2+) and undergoes chelation-enhanced fluorescence (CHEF). Although the design was applied successfully to the development of several kinase sensors, an intrinsic limitation was that only residues C- or N-terminal to the phosphorylated residue could be used to derive specificity for the target kinase. To address this limitation, a new, recognition-domain focused (RDF) strategy was developed that also relies on CHEF. In this approach, the requirement for the constrained beta-turn motif is obviated by alkylation of a cysteine residue with a Sox-based derivative to afford an amino acid termed C-Sox. The RDF design allows inclusion of extended binding determinants to maximize recognition by the cognate kinase, which has now permitted the construction of chemosensors for a variety of representative Ser/Thr (PKC alpha, PKC betaIota, PKC delta, Pim2, Akt1, MK2, and PKA) as well as receptor (IRK) and nonreceptor (Src, Abl) Tyr kinases with greatly enhanced selectivity. The new sensors have up to 28-fold improved catalytic efficiency and up to 66-fold lower K M when compared to the corresponding BTF probes. The improved generality of the strategy is exemplified with the synthesis and analysis of Sox-based probes for PKC betaIota and PKC delta, which were previously unattainable using the BTF approach.
Notch Ligand Delta-Like 1 Is Essential for Postnatal Arteriogenesis (2007)

Growth of functional arteries is essential for the restoration of blood flow to ischemic organs. Notch signaling regulates arterial differentiation upstream of ephrin-B2 during embryonic development, but its role during postnatal arteriogenesis is unknown. Here, we identify the Notch ligand Delta-like 1 (Dll1) as an essential regulator of postnatal arteriogenesis. Dll1 expression was specifically detected in arterial endothelial cells, but not in venous endothelial cells or capillaries. During ischemia-induced arteriogenesis endothelial Dll1 expression was strongly induced, Notch signaling activated and ephrin-B2 upregulated, whereas perivascular cells expressed proangiogenic vascular endothelial growth factor, and the ephrin-B2 activator EphB4. In heterozygous Dll1 mutant mice endothelial Notch activation and ephrin-B2 induction after hindlimb ischemia were absent, arterial collateral growth was abrogated and recovery of blood flow was severely impaired, but perivascular vascular endothelial growth factor and EphB4 expression was unaltered. In vitro, angiogenic growth factors synergistically activated Notch signaling by induction of Dll1, which was necessary and sufficient to regulate ephrin-B2 expression and to induce ephrin-B2 and EphB4-dependent branching morphogenesis in human arterial EC. Thus, Dll1-mediated Notch activation regulates ephrin-B2 expression and postnatal arteriogenesis.
Spliced early mRNAs of simian virus 40 (1978)

Biochemical methods are presented for determining the structure of spliced RNAs present in cells at low concentrations. Two cytoplasmic spliced viral RNAs were detected in CV-1 cells during the early phase of simian virus 40 (SV40) infection. One is 2200 nucleotides in length and is composed of two parts, 330 and 1900 nucleotides, mapping from approximately 0.67 to approximately 0.60 and from approximately 0.54 to approximately 0.14, respectively, on the standard viral map. The other is 2500 nucleotides long and also is composed of two parts, 630 and 1900 nucleotides mapping from approximately 0.67 to approximately 0.54 and from approximately 0.54 to approximately 0.14, respectively. Correlation of the structure of these mRNAs with the structure of the early SV40 proteins, small T antigen (17,000 daltons) and large T antigen (90,000 daltons), determined by others suggests that: (i) translation of the 2500-nucleotide mRNA yields small T antigen; (ii) translation of the 2200-nucleotide mRNA proceeds through the splice point in the RNA to produce large T antigen (and thus large T antigen is encoded in two separate regions of the viral genome); and (iii) the DNA sequences between approximately 0.67 and approximately 0.60 present in both mRNAs are translated in the same reading frame in both mRNAs to yield two separate gene products that have the same NH(2)-terminal sequence. Therefore, expression of the early SV40 genes is partially controlled at the level of splicing of RNAs.
The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. (1990)

The general applicability of the "cysteine-switch" activation mechanism to the members of the matrix metalloproteinase (MMP) gene family is examined here. All currently known members of the MMP gene family share the characteristic that they are synthesized in a latent, inactive, form. Recent evidence suggests that this latency in human fibroblast collagenase (HFC) is the result of formation of an intramolecular complex between the single cysteine residue in its propeptide domain and the essential zinc atom in the catalytic domain, a complex that blocks the active site. Latent HFC can be activated by multiple means, all of which effect the dissociation of the cysteine residue from the complex. This is referred to as the "cysteine-switch" mechanism of activation. The propeptide domain that contains the critical cysteine residue and the catalytic domain that contains the zinc-binding site are the only two domains common to all of the MMPs. The amino acid sequences surrounding both the critical cysteine residue and a region of the protein chains containing two of the putative histidine zinc-binding ligands are highly conserved in all of the MMPs. A survey of the literature shows that many of the individual MMPs can be activated by the multiple means observed for latent HFC. These observations support the view that the cysteine-switch mechanism is applicable to all members of this gene family. This mechanism is unprecedented in enzymology as far as we know and offers the opportunity for multiple modes of physiological activation of these important enzymes. Since conditions in different cells and tissues may match those necessary to effect one of these activation modes for a given MMP, this may offer metabolic flexibility in the control of MMP activation.
Epithelium-Mesenchyme Interactions Control the Activity of Peroxisome Proliferator-Activated Receptor β/δ during Hair Follicle Development (2005)

Hair follicle morphogenesis depends on a delicate balance between cell proliferation and apoptosis, which involves epithelium-mesenchyme interactions. We show that peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) and Akt1 are highly expressed in follicular keratinocytes throughout hair follicle development. Interestingly, PPARbeta/delta- and Akt1-deficient mice exhibit similar retardation of postnatal hair follicle morphogenesis, particularly at the hair peg stage, revealing a new important function for both factors in the growth of early hair follicles. We demonstrate that a time-regulated activation of the PPARbeta/delta protein in follicular keratinocytes involves the up-regulation of the cyclooxygenase 2 enzyme by a mesenchymal paracrine factor, the hepatocyte growth factor. Subsequent PPARbeta/delta-mediated temporal activation of the antiapoptotic Akt1 pathway in vivo protects keratinocytes from hair pegs against apoptosis, which is required for normal hair follicle development. Together, these results demonstrate that epithelium-mesenchyme interactions in the skin regulate the activity of PPARbeta/delta during hair follicle development via the control of ligand production and provide important new insights into the molecular biology of hair growth.
Rapid and bacteria-dependent in vitro hydrolysis of iodothyronine-conjugates by intestinal contents of humans and rats. (1986)

Faecal suspensions from healthy humans, conventional (CV), germ-free (GF) and intestine-decontaminated (ID) rats were tested for the in vitro hydrolysis of 125I-labelled iodothyronine sulphates and 3,3',5-triiodothyronine glucuronide (T3G). Whereas 20-fold diluted human and CV rat faecal suspensions hydrolyzed up to 90% of the sulphates, no hydrolysis was observed in 5 times diluted faecal suspensions of GF and ID rats. These results add further weight to the assumption that intestinal iodothyronine sulphatase activity is of bacterial origin. Twenty times diluted human and CV rat faecal suspensions hydrolyzed approximately 80% of the T3G. In the 5 times diluted faecal suspensions of GF and ID rats up to 15% hydrolysis of T3G was still observed. It was concluded that the major part of the gastrointestinal iodothyronine glucuronidase activity is produced by bacteria. The remaining activity presumably originates from gastrointestinal mucosal cells.
Migration Inhibitory Factor Mediates Angiogenesis via Mitogen-Activated Protein Kinase and Phosphatidylinositol Kinase (2003)

In this study, we investigated the effects of migration inhibitory factor (rhMIF) on angiogenesis-related signaling cascades and apoptosis in human endothelial cells (ECs). We show that in vitro rhMIF induces migration and tube formation in Matrigel of human dermal microvascular endothelial cells (HMVECs), with potency comparable to that of basic fibroblast growth factor. In vivo, rhMIF induces angiogenesis in Matrigel plugs and in the corneal bioassay. Using panels of relatively specific kinase inhibitors, antisense oligonucleotides, and dominant-negative mutants, we show that mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) are critical for MIF-dependent HMVEC migration, whereas Src and p38 kinases are nonessential. Moreover, we demonstrate that rhMIF induces time-dependent increases in phosphorylation levels of MEK1/2, Erk1/2, and Elk-1, as well as PI3K, and its effector kinase, Akt, in HMVECs. Studies with dominant-negative mutants and antisense oligonucleotides corroborate these effects in HMVECs. Furthermore, we demonstrate that rhMIF-induced angiogenesis in the rat cornea in vivo and in the ex vivo endothelial cell morphogenesis assay is also MAPK- and PI3K-dependent. Our findings support a role for MIF as an angiogenic factor and provide a rationale for the use of MIF as a therapeutic inducer of neovascularization in the development of collateral circulation in coronary artery disease.
Does Omeprazole Improve Antimicrobial Therapy Directed Towards Gastric Campylobacter Pylori in Patients with Antral Gastritis?: A Pilot Study (1989)

This double-blind pilot study has been undertaken in order to investigate the effect of amoxicillin and pronounced suppression of gastric acid secretion on mucosal colonisation with Campylobacter pylori (CP). Twenty four CP-positive patients were included in the study and assigned to 14 days of treatment in either one of the following three therapy groups: Group 1: Omeprazole 40 mg o.m. + Amoxicillin 750 mg b.i.d (9 pat); Group 2: Omeprazole 40 mg o.m. (8 pat); Group 3: Amoxicillin 750 mg b.i.d (7 pat). Gastroscopy with biopsy for culture and histology was performed pre-entry, at cessation of therapy and four weeks later. In the group receiving omeprazole and amoxicillin in combination 5 out of 8 patients were negative for CP four weeks after stopping treatment, while in the amoxicillin and the omeprazole groups respectively one (1/7) and none (0/8) were negative. Except for one patient who was withdrawn because of severe diarrhoea, only minor adverse effects occurred.
POCS-enhanced correction of motion artifacts in parallel MRI (2010)

A new method for correction of MRI motion artifacts induced by corrupted k-space data, acquired by multiple receiver coils such as phased arrays, is presented. In our approach, a projections onto convex sets (POCS)-based method for reconstruction of sensitivity encoded MRI data (POCSENSE) is employed to identify corrupted k-space samples. After the erroneous data are discarded from the dataset, the artifact-free images are restored from the remaining data using coil sensitivity profiles. The error detection and data restoration are based on informational redundancy of phased-array data and may be applied to full and reduced datasets. An important advantage of the new POCS-based method is that, in addition to multicoil data redundancy, it can use a priori known properties about the imaged object for improved MR image artifact correction. The use of such information was shown to improve significantly k-space error detection and image artifact correction. The method was validated on data corrupted by simulated and real motion such as head motion and pulsatile flow.
Advance in Photosensitizers and Light Delivery for Photodynamic Therapy (2013)

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo.