gebhart/patrepeval huggingface dataset:
Chaotropic Agents and Increased Matrix Volume Enhance Binding of Mitochondrial Cyclophilin to the Inner Mitochondrial Membrane and Sensitize the Mitochondrial Permeability Transition to [Ca2+] (1996)

Binding of mitochondrial cyclophilin (CyP) to the inner mitochondrial membrane is induced by treatment of mitochondria with thiol reagents or oxidative stress and correlates with a sensitization to [Ca2+] of the cyclosporin A-sensitive mitochondrial permeability transition pore (MTP) [Connern, C. P., & Halestrap, A. P. (1994) Biochem. J. 303, 321-324]. Here we show that detection of the bound CyP by Western blotting is greatly enhanced by fixing the CyP to the blotting membrane with glutaraldehyde. CyP binding was only observed when mitochondria were incubated and then frozen in KSCN medium before preparation of the membrane fraction, but not when KCl medium was used. However, incubation of mitochondria (energized or deenergized) in KCl medium followed by KSCN addition immediately prior to freezing did allow CyP binding to be detected. The action of KSCN could be mimicked by guanidinium chloride, implying that the chaotropic action of these agents stabilized the bound complex. The sensitivity to [Ca2+] of the MTP in deenergized mitochondria was greatly enhanced in KSCN medium as compared to KCl medium. Binding of CyP to the mitochondrial membrane was increased by treatment with tert-butylhydroperoxide, phenylarsine oxide, and diamide and by hypoosmotic KCl medium. These conditions all increased the sensitivity of the MTP to [Ca2+]. Conditions known to increase the mitochondrial NADH/NAD+ ratio decreased CyP binding. In contrast, the effects of mitochondrial membrane potential, matrix pH, and adenine nucleotide translocase conformation on the sensitivity of the MTP to [Ca2+] were not associated with a change in CyP binding. Our data imply that there may be two independent mechanisms of altering the Ca2+ sensitivity of the MTP, one brought about by CyP binding which is stabilized by chaotropic agents and another involving additional regulatory sites on the pore complex.
5-Aminosalicylic acid derivatives. Clinical and pharmaceutical evaluation. (1989)

Several new 5-aminosalicylic acid (5-ASA) derivatives have been introduced for the treatment of chronic inflammatory bowel disease (CIBD). In azo-bond preparations, 5-ASA is linked to an inert carrier (Balsalazide) or to another 5-ASA molecule (Dipentum). The pharmacokinetic profile is similar to salazosulphapyridine (SASP) and the preparations are as effective as SASP in treatment of ulcerative colitis (UC) and with fewer side effects. In controlled release preparations (Asacol, Pentasa, Salofalk), 5-ASA is coated with compounds resistant to low pH, but which deliver 5-ASA to the intestines at various rates at higher pH values. The drugs are as effective as SASP in maintenance of remission and in the treatment of mild to moderate flare ups in UC. A larger systemic absorption is found for the three preparations compared to SASP. The controlled release preparations seem promising in the treatment of Crohn's disease, but further studies are needed. The controlled release preparations should be the drugs of choice in patients with UC allergic to or intolerant of SASP and to males who wish to have children.
Characterization of the Domain of Fibronectin-Binding Protein I ofStreptococcus pyogenesResponsible for Elicitation of a Protective Immune Response (2001)

Fibronectin-binding protein I (SfbI) represents a major adhesin of Streptococcus pyogenes. Mice were intranasally immunized with recombinant proteins spanning different portions of SfbI to identify the minimal fragment able to elicit a protective response against a lethal challenge with S. pyogenes. The strongest cellular responses and the highest levels of antigen-specific secretory immunoglobulin A (IgA) were detected in mice immunized with the fibronectin-binding region of SfbI. In contrast, animals vaccinated with a polypeptide spanning the aromatic and proline-rich regions showed the highest titers and fastest IgG response in serum. Vaccination with either SfbI without a membrane anchor and signal peptide or a polypeptide encompassing its fibronectin-binding regions resulted in efficient protection against heterologous challenge (60% and 80%, respectively), whereas the use of a polypeptide lacking this region conferred marginal protection (10%) with respect to the control group (0%). These results demonstrate that the fibronectin-binding region of SfbI is a promising candidate antigen for developing anti-S. pyogenes vaccines.
Efficient computation of quasi-periodic circuit operating conditions via a mixed frequency/time approach (1999)

Design of communications circuits often requires computing steady-state responses to multiple periodic inputs of differing frequencies. Mixed frequency-time (MFT) approaches are orders of magnitude more efficient than transient circuit simulation, and perform better on highly nonlinear problems than traditional algorithms such as harmonic balance. We present algorithms for solving the huge nonlinear equation systems the MFT approach generates from practical circuits.
Near-Infrared Spectrophotometric Methods Development with a Limited Number of Samples: Application to Carbonate in Geological Samples (1985)

In the present study, an approach is described which can be used to create a near-infrared spectrophotometric calibration in a situation where only a limited number of training samples are available. The particular application studied is the determination of carbonate concentration in a series of 23 powdered geological samples. Because of the small size of the data set, unusual techniques were used to create the analytical calibration. The number of analytical wavelengths was determined by factor analysis. The analytical wavelengths and weighting coefficients were determined by means of a previously described algorithm. Finally, the calibration was confirmed by a cross-validation procedure and by the reconstruction of the spectrum of pure “carbonate” from the near-infrared reflectance spectra of the samples.
Quercetin and allopurinol reduce liver thioredoxin‐interacting protein to alleviate inflammation and lipid accumulation in diabetic rats (2013)

Inhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes-associated NAFLD.
T cell–mediated suppression of angiogenesis results in tumor protective immunity (2005)

Antiangiogenic intervention is known to inhibit tumor growth and dissemination by attacking the tumor's vascular supply. Here, we report that this was achieved for the first time using an oral DNA minigene vaccine against murine vascular endothelial growth factor receptor 2 (FLK-1), a self-antigen overexpressed on proliferating endothelial cells in the tumor vasculature. Moreover, we identified the first H-2Db-restricted epitope, FLK400 (VILT-NPISM), specifically recognized by cytotoxic T lymphocytes (CTLs). Such CTLs were capable of killing FLK-1+ endothelial cells, resulting in suppression of angiogenesis and long-lived tumor protection. The specificity of this immune response was indicated because the DNA vaccine encoding the entire FLK-1 gene also induced a FLK400-specific CTL response. This minigene vaccine strategy provides a more flexible alternative to whole-gene vaccination and facilitates in-depth mechanism studies to tailor DNA vaccines for optimal T-cell activation and tumor protection.
Complete microcrystalline p-i-n solar cell—Crystalline or amorphous cell behavior? (1994)

Complete μc-Si:H p-i-n solar cells have been prepared by the very high frequency glow discharge method. Up to now, intrinsic μc-Si:H has never attracted much attention as a photovoltaic active material. However, an efficiency of 4.6% and remarkably high short circuit current densities of up to 21.9 mA/cm2 due to an enhanced absorption in the near-infrared could be obtained. First light-soaking experiments indicate no degradation for the entirely μc-Si:H cells. Voltage-dependent spectral response measurements suggest that the carrier transport in complete μc-Si:H p-i-n cells may possibly be cosupported by diffusion (in addition to drift).
Structure of the O-Glycosidically Linked Carbohydrate Units of Fetuin (1974)

Fetuin isolated from fetal calf serum was shown to contam 3 carbohydrate units which are attached to serine and threonine residues on the peptide chain and are distinct from the 3 asparagine-linked heteropolysaccharides previously reported to occur in this protein.The 0-glycosidically linked saccharide units were obtained as reduced oligosaccharides after alkaline borohydride treatment of fetuin and as glycopeptides subsequent to pronase digestion of this protein.Gel filtration and Dowex 1 chromatography of the oligosaccharides resulted in the isolation of a tri-and a tetrasaccharide which were made up of sialic acid, galactose, and N-acetylgalactosaminitol residues and could be converted after selective removal of the sialic acid to the same disaccharide (galactosyl-N-acetylgalactosaminitol).Studies employing periodate oxidation and glycosidase digestion indicated that the structure of the tetrasaccharide was N-acetylneuraminyl-(2 -+3) -P-D -galactopyranosyl-(l -+3)[N-acetylneuraminyl-(2 -+6)]-N-acetylgalactosaminiitol and that the trisaccharide differed only by the absence of the sialyl residue linked to the N-acetylgalactosaminitol.Glycopeptides containing the alkali-labile carbohydrate units were purified on Sephadex and diethylaminoethylcellulose columns.In this manner peptides distinguished by a high proline content and containing 1 tetrasaccharide, 1 trisaccharide, or 2 trisaccharides were obtained.Alkaline sulfite treatment of these glycopeptides indicated that 2 serine and 1 threonine residue in each fetuin molecule is involved in the attachment of carbohydrate units.The tetrasaccharide was found to be linked only to serine while attachment of trisaccharide units involved a serine and a threonine residue which were located in close proximity in the peptide chain.Smith periodate degradation of sialic acid-free glycopeptides resulted in removal of the galactose and yielded a product from which complete release of N-acetylgalactosamine
Protein phosphatases: structures and implications. (1997)

Protein phosphatases are signal transducing enzymes that dephosphorylate intracellular proteins phosphorylated on serine, threonine, and tyrosine residues. This brief review surveys recently determined structures of members of the protein tyrosine phosphatase and protein serine/threonine phosphatase families. In each family, characteristic and distinct structures confer different enzymatic mechanisms in catalyzing dephosphorylation reactions. Within each family, however, there exists remarkable similarity in active-site conformation and catalytic mechanism despite, in some cases, little or no sequence homology. The crystal structures also provide the basis for understanding the substrate binding specificity, inhibition by physiologically relevant compounds, and regulation of the protein phosphatases.
Analysis of Hoxd-13 and Hoxd-11 misexpression in chick limb buds reveals that Hox genes affect both bone condensation and growth (1997)

Hox genes are important regulators of limb pattern in vertebrate development. Misexpression of Hox genes in chicks using retroviral vectors provides an opportunity to analyze gain-of-function phenotypes and to assess their modes of action. Here we report the misexpression phenotype for Hoxd-13 and compare it to the misexpression phenotype of Hoxd-11. Hoxd-13 misexpression in the hindlimb results in a shortening of the long bones, including the femur, the tibia, the fibula and the tarsometatarsals. Mutations in an alanine repeat region in the N-terminus of Hoxd-13 have recently been implicated in human synpolydactyly (Muragaki, Y., Mundlos, S., Upton, J. and Olsen, B. R. (1996) Science 272, 548-551). N-terminal truncations of Hoxd-13 which lack this repeat were constructed and were found to produce a similar, although slightly milder, misexpression phenotype than the full-length Hoxd-13. The stage of bone development regulated by Hox genes has not previously been examined. The changes in bone lengths caused by Hoxd-13 misexpression are late phenotypes that first become apparent during the growth phase of the bones. Analysis of tritiated thymidine uptake by the tibia and fibula demonstrates that Hox genes can pattern the limb skeleton by regulating the rates of cell division in the proliferative zone of growing cartilage. Hoxd-11, in contrast to Hoxd-13, acts both at the initial cartilage condensation phase in the foot and during the later growth phase in the lower leg. Ectopic Hoxd-13 appears to act in a dominant negative manner in regions where it is not normally expressed. We propose a model in which all Hox genes are growth promoters, regulating the expression of the same target genes, with some Hox genes being more effective promoters of growth than other Hox genes. According to this model, the overall rate of growth in a given region is the result of the combined action of all of the Hox genes expressed in that region competing for the same target genes.
Triggered Sorting and Co‐Assembly of Genetically Engineered Protein Microdomains in the Cytoplasm (2013)

Elastin-like polypeptides (ELPs) are genetically encoded protein polymers that reversibly phase separate in response to stimuli. They respond sharply to small shifts in temperature and form dense microdomains in the living eukaryotic cytosol. For the first time, this communication illustrates how to tune the ELP sequence and architecture for either co-assembly or sorting of distinct proteins into microdomains within a living cell.
Perspectives on Immunoglobulins in Colostrum and Milk (2011)

Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk.
Incremental Construction of Minimal Acyclic Finite-State Automata (2000)

In this paper, we describe a new method for constructing minimal, deterministic, acyclic finite-state automata from a set of strings. Traditional methods consist of two phases: the first to construct a trie, the second one to minimize it. Our approach is to construct a minimal automaton in a single phase by adding new strings one by one and minimizing the resulting automaton on-the-fly. We present a general algorithm as well as a specialization that relies upon the lexicographical ordering of the input strings. Our method is fast and significantly lowers memory requirements in comparison to other methods.
Zeolitic Boron Imidazolate Frameworks (2009)

B-hive? A family of crystalline materials analogous to porous AlPO(4) but based on boron imidazolate frameworks (BIFs) can be formed by the crosslinking of various presynthesized boron imidazolates with monovalent cations (Li(+) and Cu(+), see picture). This synthetic method is capable of generating a large variety of open frameworks, ranging from the four-connected zeolitic sodalite type to the three-connected chiral (10,3)-a type.
Approaches to nonconventional control of plant virus diseases (1992)

Abstract Plant viruses cause significant losses to crops worldwide and the three basic approaches to controlling them have not been overly successful. The new concept of nonconventional resistance, which involves transforming plants with nucleic acid sequences that interfere with the viral infection cycle, is a promising new approach. The current nonconventional strategies, those of coat protein‐mediated protection, antisense nucleic acids, satellite sequences, defective interfering molecules, and nonstructural genes, are reviewed with their advantages and disadvantages being discussed. The question of what exactly is nonconventional resistance is raised and suggestions are made for defining resistance. A range of strategies that are likely to be developed in the future are outlined together with some guiding principles for selection and deployment of these forms of resistance.
Antihypertensive drugs decrease risk of Alzheimer disease (2013)

Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.
Inflammatory Bowel Disease (1992)

We have evaluated the economic costs to society for the two major types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, using a medical decision algorithm costing methodology augmented by examination of 1988-89 claims data from a major U.S. commercial insurer. The average annual medical cost per patient with Crohn's disease was estimated at $6,561 (1990 U.S. dollars). The total annual medical costs for U.S. Crohn's disease patients in 1990 was estimated at $1.0-1.2 billion. The average annual medical cost per patient with ulcerative colitis was estimated at $1,488. The total annual medical costs for U.S. patients with ulcerative colitis in 1990 was estimated at $0.4-0.6 billion. Adjusting for productivity losses, we estimated the annual economic cost for both diseases at $1.8 billion to $2.6 billion. Analysis of insurance claims data for inflammatory bowel disease patients showed that the distribution of annual medical expenses charged and paid is highly uneven by patient. The top 2% of Crohn's disease patients accounted for 28.9% of total charges and 34.3% of the total amount paid. The top 2% of ulcerative colitis patients accounted for 36.2% of total charges and 39.0% of the total amount paid. We used a multivariate regression model to examine potential cost-effectiveness tradeoffs between different types of medical services in treatment of inflammatory bowel disease.
Recombinant Thyroid Peroxidase-Specific Fab Converted to Immunoglobulin G (IgG) Molecules: Evidence for Thyroid Cell Damage by IgG1, but Not IgG4, Autoantibodies1 (1997)

A recombinant autoantibody Fab (SP1.4) to thyroid peroxidase (TPO), cloned from intrathyroidal B cell immunoglobulin genes, interacts with an epitope on TPO recognized by all patients with autoimmune thyroid disease. To compare the biological properties of IgG1 and IgG4 TPO autoantibodies, we converted Fab SP1.4 to full-length immunoglobulins. The SP1.4 heavy and kappa light chain variable region genes, spliced by overlap PCR to a mammalian signal peptide, were transferred to expression vectors for human IgG1, IgG4, and kappa L chains. Plasmids containing the IgG1 (or IgG4) heavy chain and the kappa L chain were cotransfected into SP2/0 mouse myeloma cells. Cells secreting TPO autoantibodies were cloned, and IgG1-SP and IgG4-SP were affinity purified from medium using protein G. Their subclass specificities were confirmed by enzyme-linked immunosorbent assay and fluorometry after binding to Chinese hamster ovary cells expressing cell surface TPO. Further confirmation of SP1.4 Fab conversion to full-length molecules was the ability of protein A to precipitate IgG1-SP and IgG4-SP complexed to [125I]TPO. IgG1-SP1.4, IgG4-SP1.4, and Fab SP1.4 had similar high affinities for TPO (Kd = approximately 2 x 10(-10) mol/L). Complexes of [125I]TPO and IgG1-SP (but not IgG4-SP) bound to peripheral blood mononuclear cells (PBMC), but not to a B cell line. Flow cytometry demonstrated Fc receptors Fc gamma RI, Fc gamma RII, and Fc gamma RIII on PBMC, but only Fc gamma RII on the B cell line. Together, these data indicate that IgG1-SP/TPO complexes bind to either Fc gamma RI on monocytes or RIII on natural killer cells. In assays for antibody-dependent cytotoxicity using PBMC, 51Cr release was higher for thyroid cells preincubated with IgG1-SP (13.4%) than with IgG4-SP (2.5%) or with culture medium alone (-0.7%). No specific 51Cr release was observed when either fibroblasts or Chinese hamster ovary cells expressing cell surface TPO were used as target cells. In conclusion, a human TPO-specific Fab converted to IgG1, but not IgG-4, can mediate cytotoxic effects on human thyroid cells in vitro. These observations support the clinical relevance of TPO autoantibody subclass distribution and emphasize the likelihood that, as opposed to being simple markers of thyroid damage, TPO autoantibodies may play a role in the induction of thyroid dysfunction in vivo.
Concentrations of Cefpirome in Cerebrospinal Fluid of Children with Bacterial Meningitis after a Single Intravenous Dose (1998)

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) microg/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.
Designing Large-Scale Web Sites: A Visual Design Methodology (1996)

Preliminary Design Preparation Designing the Organizational Framework Applying Visual Design for the Web Visual Design Workshop Bibliography Index.
Square-Cut: A Segmentation Algorithm on the Basis of a Rectangle Shape (2012)

We present a rectangle-based segmentation algorithm that sets up a graph and performs a graph cut to separate an object from the background. However, graph-based algorithms distribute the graph's nodes uniformly and equidistantly on the image. Then, a smoothness term is added to force the cut to prefer a particular shape. This strategy does not allow the cut to prefer a certain structure, especially when areas of the object are indistinguishable from the background. We solve this problem by referring to a rectangle shape of the object when sampling the graph nodes, i.e., the nodes are distributed non-uniformly and non-equidistantly on the image. This strategy can be useful, when areas of the object are indistinguishable from the background. For evaluation, we focus on vertebrae images from Magnetic Resonance Imaging (MRI) datasets to support the time consuming manual slice-by-slice segmentation performed by physicians. The ground truth of the vertebrae boundaries were manually extracted by two clinical experts (neurological surgeons) with several years of experience in spine surgery and afterwards compared with the automatic segmentation results of the proposed scheme yielding an average Dice Similarity Coefficient (DSC) of 90.97±2.2%.