gebhart/patrepeval huggingface dataset:
An analysis of target preferences of Escherichia coli outer‐membrane endoprotease OmpT for use in therapeutic peptide production: efficient cleavage of substrates with basic amino acids at the P4 and P6 positions (2002)

The Escherichia coli outer-membrane endoprotease OmpT mainly cleaves peptide bonds between consecutive basic amino acids. The effect of adjacent residues on cleavage efficiency is currently unknown, except at positions P2 and P2'. Therefore we investigated the effects of amino acid residues upstream of the cleavage site on the ability of OmpT to cleave efficiently a fusion protein carrying human glucagon-like peptide-1 (7-37) in 4 M urea. The P1-P10 residues were replaced by Ala and each substrate was subjected to OmpT digestion. The replacement of Arg residue at P1 blocked the cleavage due to the loss of the cleavage site, and the replacement of Arg residue at P4 maximally reduced the cleavage rate. Conversely, cleavage efficiency increased on replacing Glu at P6. Substitution of the residues at P4 and P6 with several different amino acids showed that OmpT preferred basic residues at these positions, whereas acidic residues had a negative effect. This was also shown to be true with synthetic decapeptide substrates in the absence of urea. The k(cat)/ K(m) ratio increased with basic residues at P4 or P6, mainly due to a lower K(m) rather than an increase in k(cat). On the basis of these findings, we prepared a fusion protein carrying human atrial natriuretic peptide (ANP), a drug for acute congestive heart failure. OmpT released mature ANP from the E. coli-expressed fusion protein. As expected, the introduction of an Arg residue at P4 and P6 enhanced the release of ANP.
Endothelin: 20 years from discovery to therapyThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin. (2008)

Since its identification as an endothelial cell-derived vasoconstrictor peptide in 1988, endothelin-1, the predominant member of the endothelin peptide family, has received considerable interest in basic medical science and in clinical medicine, which is reflected by more than 20 000 scientific publications on endothelin research in the past 20 years. The story of endothelin is unique as the gene sequences of endothelin receptors and the first receptor antagonists became available within only 4 years of the identification of the peptide sequence. The first clinical study in patients with congestive heart failure was published only 3 years thereafter. Yet, despite convincing experimental evidence of a pathogenetic role for endothelin in development, cell function, and disease, many initial clinical studies on endothelin antagonism were negative. In many of these studies, study designs or patient selection were inadequate. Today, for diseases such as pulmonary hypertension, endothelin antagonist treatment has become reality in clinical medicine, and ongoing clinical studies are evaluating additional indications, such as renal disease and cancer. Twenty years after the discovery of endothelin, its inhibitors have finally arrived in the clinical arena and are now providing us with new options to treat disease and prolong the lives of patients. Possible future indications include resistant arterial hypertension, proteinuric renal disease, cancer, and connective tissue diseases.
Home-Diagnosis of Deep Venous Thrombosis with Impedance Plethysmography (1982)

In order to assess the value of I.P.G. for the diagnosis of D.V.T. in general practice, an I.P.G. was carried out by a skilled technician in 255 consecutive patients with suspected D.V.T. at home. Ascending venography was carried out in 185 of these patients. In addition, blood for assay of AT III, platelet count, fibrinogen, a2-antiplasmin, ethanol gelation test and spontaneous platelet aggregation was collected at the time the I.P.G. was performed. In 61 patients (33%) venography showed the presence of D.V.T., and was negative in the remaining 124 patients. I.P.G. was positive in 51 of the 61 patients with D.V.T., a sensitivity of 84%. I.P.G. was normal in 115 of the 124 patients with a negative venogram, a specificity of 93%. The sensitivity of the I.P.G. for proximal vein thrombosis was 92% and for calf vein thrombosis 68%. Mean a2-antiplasmin concentration was significant (p less than 0.05) lower (101 +/- 15%, mean +/- SD) in patients with D.V.T. compared with patients with a normal venogram (107 +/- 11%, mean +/- SD). No differences between the two groups were observed in the other coagulation parameters assayed, and none was of diagnostic value, either alone or in combination with I.P.G. This study shows that I.P.G. is of potential value for the home diagnosis of D.V.T., in particular proximal vein thrombosis. This is potentially clinically useful, because these thrombi are thought to carry a high risk for pulmonary embolism.
Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes (2005)

The c-Jun NH(2)-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes. However, a potential role for the JNK2 protein kinase in diabetes has not been established. Here, we demonstrate that JNK2 may play an important role in type 1 (insulin-dependent) diabetes that is caused by autoimmune destruction of beta cells. Studies of nonobese diabetic mice demonstrated that disruption of the Mapk9 gene (which encodes the JNK2 protein kinase) decreased destructive insulitis and reduced disease progression to diabetes. CD4(+) T cells from JNK2-deficient nonobese diabetic mice produced less IFN-gamma but significantly increased amounts of IL-4 and IL-5, indicating polarization toward the Th2 phenotype. This role of JNK2 to control the Th1/Th2 balance of the immune response represents a mechanism of protection against autoimmune diabetes. We conclude that JNK protein kinases may have important roles in diabetes, including functions of JNK1 in type 2 diabetes and JNK2 in type 1 diabetes.
Optimal feedback control formulation of the active noise cancellation problem : pointwise and distributed (1994)

Unwanted noise is a by-product of many industrial processes and systems. In active noise cancellation (ANC), one introduces a secondary noise source to generate an acoustic field that interferes destructively with the unwanted noise, and thereby attenuates it. Noise reduction is important to protect listeners in high noise environments from hearing damage, to enhance speech communication, and to reduce noise-induced fatigue. These adverse effects of noise can cause accidents and reduce the productivity of workers.
Lupus antibodies to the HMGB1 chromosomal protein: epitope mapping and association with disease activity (2009)

The high mobility group box 1 (HMGB1) protein is a non-histone chromosomal protein that acts as a potent proinflammatory cytokine when actively secreted from LPS- or TNF-activated macrophages, monocytes, and other cells. Anti-HMGB1/2 antibodies have been previously identified in sera from a high proportion of patients with autoimmune diseases. In this study, we examined anti-HMGB1 antibody titers in sera of patients with systemic rheumatic diseases and the correlations between the presence of anti-HMGB1 antibodies and disease activity in systemic lupus erythematosus (SLE) patients by enzyme-linked immunosorbent assay and western blotting. We detected increases in both the levels and the frequency of anti-HMGB1 antibodies in sera from SLE and polymyositis/dermatomyositis (PM/DM) patients, and observed that the presence of anti-HMGB1 antibodies positively correlates with SLE disease activity index. Through epitope mapping, we found that multiple HMGB1 epitopes were recognised in SLE sera, with the major epitope mapping to box A. Another epitope, the joiner region of HMGB1, was preferentially recognized by SLE sera, but not by PM/DM sera. Collectively, these observations suggest that the presence of anti-HMGB1 antibodies correlates with disease activity in SLE patients.
Analysis of the variations of follicular fluid composition during follicular growth and maturation in the mare using proton nuclear magnetic resonance (1H NMR) (2002)

Follicular development and ovulatory processes in mammals involve local biochemical changes as a result of substantial modifications in cellular metabolism, the most well known of which is steroid variation. In the present study, the intrafollicular variation of several other components was studied using proton nuclear magnetic resonance ((1)H NMR). This approach made it possible to demonstrate that the intrafollicular biochemical content changes during follicular growth and maturation. Follicular fluid was aspirated by ovarian puncture of the dominant follicle at various physiological stages of its development: early dominant, late dominant and preovulatory. Serum samples were collected during each puncture session. (1)H NMR was used to evaluate intrafollicular and circulating glycoconjugates (sugar chains and N-acetyl groups), lipoproteins (CH(3) and CH(2) groups), glucose metabolites (trimethylamines, acetate and lactate), amino acids (glutamine/glutamate and alanine), creatine/creatinine and polyamines. Follicular fluids were assayed by radioimmunoassay for oestradiol and progesterone contents. The intrafollicular contents of alanine and lipoproteins (CH(3) groups) decreased in the dominant follicle during growth, whereas concentrations of progesterone and oestradiol increased significantly. After injection of gonadotrophin to induce ovulation, follicular maturation was characterized by a decrease in glycoconjugates (sugar chains), trimethylamines and acetate, a decrease in oestradiol concentration, and a further increase in CH(3) groups of lipoproteins and progesterone. The results from the present study showed a clear correlation between the intrafollicular content of alanine and that of oestradiol. A correlation between progesterone and glycoconjugates (sugar chains) was also observed. Therefore, (1)H NMR was shown to be effective for studying specific changes in the biochemical composition of the follicular fluid that occur during follicular development. For the first time, the variation of several compounds (glycoconjugates, lipoproteins, glucose metabolites, amino acids and polyamines) in relation to growth and maturation was demonstrated. Some of these changes could be of crucial importance for follicular maturation and ovulation as well as for oocyte maturation and further fertilization.
Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus (1997)

The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p &lt; 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p &lt; 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.
[Vasopressin effect and pathophysiological analysis on postprandial hypotension]. (1990)

In order to clarify the effect of arginine vasopressin (AVP) on postprandial hypotension (PPH) in patients with multiple system atrophy, a loading test of 75 g glucose in 225 ml water was performed during infusion of AVP (0.3 U/min). AVP (0.3 U/min) infusion prior to the loading was significantly effective for PPH in all patients: PPH following to oral intake of glucose was completely prevented. We conclude that infusion of AVP maintained circulating systemic blood volumes by reduced portal venous flow (after a reduction of portal venous inflow) as a result of vasoconstrictive effect of AVP on the splanchnic vessels in patients with PPH.
A growth hormone-based phylogenetic analysis of euteleostean fishes including a representative species of the Atheriniformes Order, Odontesthes argentinensis (2003)

The GH (growth hormone) cDNA sequence of the marine silverside fish Odontesthes argentinensis was obtained using the RACE protocol (Rapid Amplification of cDNA Ends). The marine silverside GH cDNA sequence is 928 nucleotides long and was found to encode a polypeptide of 204 amino acids, including a signal peptide of 17 amino acids. The 5' and 3' untranslated regions of the messenger are 109 and 204 nucleotides long, respectively. The deduced GH amino acid sequence was used to infer a phylogenetic tree with GH amino acid sequences from representative species belonging to the Euteleostei Subdivision using the maximum parsimony method. The topology found is according to the major phylogenetic grouping of euteleosts. The results corroborate the hypothesis that atherinids are not related to paracanthopterygians as previously suggested, and show a lack of solid synapomorphies among most of the Acanthopterygii Orders analysed indicating a complex assemblage of fishes in which the phylogenetic tree remains indeterminable.
Detection of Breast Cancer Microcalcifications Using a Dual-modality SPECT/NIR Fluorescent Probe (2008)

Efficient chemical synthesis of a trifunctional, hydroxyapatite-binding molecule, which provides simultaneous in vivo imaging by NIR fluorescence and SPECT/CT has been described. Quantitation by SPECT provides the "gold standard" by which NIR fluorescence tomography of breast cancer microcalcifications can now be compared and optimized.
Nitrogen fixation by Klebsiella pneumoniae is inhibited by certain multicopy hybrid nif plasmids (1983)

In our studies of nif gene regulation, we have observed that certain hybrid nif plasmids drastically inhibit the expression of the chromosomal nif genes of Klebsiella pneumonia. Wild-type (Nif+) K. pneumoniae strains that acquire certain hybrid nif plasmids also acquire the Nif- phenotype; these strains lose 90 to 99% of all detectable nitrogen fixation activity and grow poorly (or not at all) on solid media with N2 as the sole nitrogen source. We describe experiments which defined this inhibition of the Nif+ phenotype by hybrid nif plasmids and identify and characterize four nif DNA regions associated with this inhibition. We show that plasmids carrying these nif regions could recombine with, but not complement, nif chromosomal mutations. Our results suggest that inhibition of the Nif+ phenotype will provide a useful bioassay for some of the factors that mediate nif gene expression.
Translational Efficiency of EMCV IRES in Bicistronic Vectors is Dependent Upon IRES Sequence and Gene Location (2006)

The internal ribosomal entry site (IRES)from encephalomyocarditis virus (EMCV) is a popular RNA element used widely in experimental and pharmaceutical applications to express proteins in eukaryotic cells or cell-free extracts. Inclusion of the wild-type element in monocistronic or bicistronic messenger RNAs (mRNAs) confers a high level of cap-independent translation activity to appropriately configured cistrons. The history of this element and the experimental consequences of sequence derivations inherent to commercial IRES vectors are less well known. Compared head-to-head with dual-luciferase reporter constructs, a native EMCV IRES in a bicistronic configuration directed 8- to 10-fold more protein than a similarly configured pIRES vector. It also produced nearly twice as much protein as pCITE-1, an early monocistronic iteration, harboring a suboptimal A7 sequence in a crucial structural motif The results indicate that investigators should be aware of and carefully report the sequence of their IRES in any comparative study. The preferred IRES (viral bases 273-845) and the minimum IRES (viral bases 400-836) for optimum activity are illustrated.
Virtual proxy servers for WWW and intelligent agents on the Internet (2002)

The World Wide Web (WWW) has become extremely popular in recent years. However, there still exist many fundamental problems not yet solved in a satisfactory way, such as information search, distribution, caching, filtering problems, etc. Users still often suffer from long retrieval latency, and the lack of search function which can conduct localized search or hierarchical search. We propose a framework for solving the above mentioned fundamental problems by introducing a new model of WWW proxy servers. In our model, a proxy is not just an add-in to existing Web servers to provide cache and security functions, but works as a middle layer between browsers and Web servers, which can be plugged in a variety of functions for WWW applications, such as search engine, resource index, information filtering, robot, profile, intelligent agents, etc. It's a framework for implementing hierarchical information servers and it's the right place to plug in various intelligent agents. To illustrate the usefulness of our model, we have implemented two fundamental functions into this middle layer: the object lookup scheme (collaborative caching) and the searchable proxy. We call this extensible proxy server "Virtual Proxy". Since search and retrieval are the most fundamental problems in the World Wide Web, we explain how these two problems can be solved in a better way using the Virtual Proxy servers.
Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors (2005)

Reactive oxygen species (ROS) signal cascades involved in cell growth, cell death, mitogenesis, angiogenesis and carcinogenesis. ROS are produced as a byproduct of oxidative phosphorylation (OXPHOS) in the mitochondria. It is estimated that 2-4% of the oxygen consumed during OXPHOS is converted to ROS. Besides mitochondria, NADPH-oxidase 1 (Nox1) also generates a significant amount of ROS in the cell. In this paper, we tested the hypothesis that mitochondria control Nox 1 redox signaling and the loss of control of this signaling contributes to tumorigenesis. We analyzed Nox1 expression in a mitochondrial gene knockout (rho(0)) cell line and in the isogenic cybrid cell line in which mitochondrial genes were restored by transfer of wild type mitochondria into rho(0) cells. Our study revealed, for the first time, that the inactivation of mitochondrial genes leads to down-regulation of Nox1 and that the transfer of wild type mitochondrial genes restored the Nox1 expression to a level comparable to that in the parental cell line. Consistent with Nox1 down-regulation, we found that rho(0) cells contained low levels of superoxide anion and that superoxide levels reversed to parental levels in cybrid cells when Nox1 expression was restored by transfer of wild type mitochondria. Increasing mitochondrial superoxide levels also increased the expression of Nox1 in parental cells. Confocal microscopy studies revealed that Nox1 localizes in the mitochondria. Nox1 was highly expressed in breast (86%) and ovarian (71%) tumors and that its expression positively correlated with expression of cytochrome C oxidase encoded by mtDNA. Our study, described in this paper demonstrates the existence of cross talk between the mitochondria and NADPH oxidase. Furthermore, our studies suggest that mitochondria control Nox1 redox signaling and the loss of control of this signaling contributes to breast and ovarian tumorigenesis.
Excess Mortality or Institutionalization After Hip Fracture: Men Are at Greater Risk Than Women (2002)

For both men and women who incur a hip fracture, the risks of dying or being institutionalized within 2 years are higher than for their peers. The independent effect of hip fracture on this outcome was significantly greater for men than women. The marked influences of prefracture health status, physical limitations, and gender on outcome have important implications for preventative strategies.
An idea of the application of fuzzy neural networks to medical decision support systems (2002)

The paper presents a methodology for medical decision support systems design which combines a fuzzy-set approach with artificial neural networks. The proposed methodology can deal with two types of medical knowledge which usually contribute to medical diagnosis: fuzzy knowledge (linguistic rules provided by human experts); and nonfuzzy knowledge (numerical data obtained from medical tests). The proposed approach has been successfully applied in medical diagnosis as a support system in the treatment of duodenal ulcers with the use of highly selective vagotomy.
Soluble Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor Carries Multiple High Molecular Weight Forms of Insulin-like Growth Factor II in Fetal Bovine Serum (1995)

We have characterized a soluble form of the insulin-like growth factor II/mannose 6-phosphate receptor (sIGF-II/MPR) and bound ligands from bovine serum. Fetal serum contained 2-8 mg/liter sIGF-II/MPR. Affinity-purified receptor isolated by adsorption to phosphomannan-agarose and elution with mannose 6-phosphate contained nearly stoichiometric amounts of bound 7.5-kDa IGF-II. In addition, at least 12 distinct 12-20-kDa proteins immunologically related to IGF-II also copurified with receptor. Receptor was separated from its associated ligands by acidification and gel filtration chromatography. Sequence analysis revealed that the 12-20-kDa proteins have the same amino termini as mature 7.5-kDa IGF-II. Protease and glycosidase treatments revealed that the different high molecular weight IGF-II species contain an identical COOH-terminal extension that is differentially glycosylated with O-linked sugars. Radiolabeled tracer experiments demonstrated that the sIGF-II/MPR carries approximately 1/4 of the IGF-II in fetal bovine serum. These results support a significant role for sIGF-II/MPR in the transport of circulating IGF-II isoforms during development.
Mimotopes: realization of an unlikely concept (2000)

Theoretically it seems highly unlikely that relatively small peptides could mimic functionally discontinuous epitopes of antigens. Nevertheless various recent reports show this to be the case. Peptide mimics of protein-, polysaccharide- and DNA-epitopes have been shown to be able to replace the native epitope. Moreover, some of them are able to induce, when used in a vaccine, antibodies with the same activity as that of the antibody used as a template. These mimics, called mimotopes, can be used in vaccines and diagnostics and can be developed more or less systematically using solely antibodies and random, semi-random and dedicated peptide arrays or libraries. Furthermore, the mimotope concept which seems to have proven itself for antibody and antigen interaction can be applied equally well to many receptor ligand interactions and thus may form a new generic approach to the development of drugs. Ltd.