gebhart/patrepeval huggingface dataset:
Free radical tissue damage: protective role of antioxidant nutrients 1 (1987)

Highly reactive molecules called free radicals can cause tissue damage by reacting with polyunsaturated fatty acids in cellular membranes, nucleotides in DNA, and critical sulfhydryl bonds in proteins. Free radicals can originate endogenously from normal metabolic reactions or exogenously as components of tobacco smoke and air pollutants and indirectly through the metabolism of certain solvents, drugs, and pesticides as well as through exposure to radiation. There is some evidence that free radical damage contributes to the etiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. Defenses against free radical damage include tocopherol (vitamin E), ascorbic acid (vitamin C), beta-carotene, glutathione, uric acid, bilirubin, and several metalloenzymes including glutathione peroxidase (selenium), catalase (iron), and superoxide dismutase (copper, zinc, manganese) and proteins such as ceruloplasmin (copper). The extent of tissue damage is the result of the balance between the free radicals generated and the antioxidant protective defense system. Several dietary micronutrients contribute greatly to the protective system. Based on the growing interest in free radical biology and the lack of effective therapies for many of the chronic diseases, the usefulness of essential, safe nutrients in protecting against the adverse effects of oxidative injury warrants further study.
Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. (1991)

We previously demonstrated that the gap junction protein connexin43 is translated as a 42-kD protein (connexin43-NP) that is efficiently phosphorylated to a 46,000-Mr species (connexin43-P2) in gap junctional communication-competent, but not in communication-deficient, cells. In this study, we used a combination of metabolic radiolabeling and immunoprecipitation to investigate the assembly of connexin43 into gap junctions and the relationship of this event to phosphorylation of connexin43. Examination of the detergent solubility of connexin43 in communication-competent NRK cells revealed that processing of connexin43 to the P2 form was accompanied by acquisition of resistance to solubilization in 1% Triton X-100. Immunohistochemical localization of connexin43 in Triton-extracted NRK cells demonstrated that connexin43-P2 (Triton-insoluble) was concentrated in gap junctional plaques, whereas connexin43-NP (Triton-soluble) was predominantly intracellular. Using either a 20 degrees C intracellular transport block or cell-surface protein biotinylation, we determined that connexin43 was transported to the plasma membrane in the Triton-soluble connexin43-NP form. Cell-surface biotinylated connexin43-NP was processed to Triton-insoluble connexin43-P2 at 37 degrees C. Connexin43-NP was also transported to the plasma membrane in communication defective, gap junction-deficient S180 and L929 cells but was not processed to Triton-insoluble connexin43-P2. Taken together, these results demonstrate that gap junction assembly is regulated after arrival of connexin43 at the plasma membrane and is temporally associated with acquisition of insolubility in Triton X-100 and phosphorylation to the connexin43-P2 form.
Use of defined TLR ligands as adjuvants within human vaccines (2010)

Our improved understanding of how innate immune responses can be initiated and how they can shape adaptive B- and T-cell responses is having a significant impact on vaccine development by directing the development of defined adjuvants. Experience with first generation vaccines, as well as rapid advances in developing defined vaccines containing Toll-like receptor ligands (TLRLs), indicate that an expanded number of safe and effective vaccines containing such molecules will be available in the future. In this review, we outline current knowledge regarding TLRs, detailing the different cell types that express TLRs, the various signaling pathways TLRs utilize, and the currently known TLRLs. We then discuss the current status of TLRLs within vaccine development programs, including the importance of appropriate formulation, and how recent developments can be used to better define the mechanisms of action of vaccines. Finally, we introduce the possibility of using TLRLs, either in combination or with non-TLRLs, to synergistically potentiate vaccine-induced responses to provide not only prophylactic, but therapeutic protection against infectious diseases and cancer.
Effect of serum dilution on apparent unbound bilirubin concentration as measured by the peroxidase method. (1981)

I studied the effects of serum dilution and oxidation of albumin-bound bilirubin on the accuracy of results by the peroxidase method for assessing bilirubin-albumin binding. The apparent concentration of unbound bilirubin decreases with dilution of bilirubin-enriched serum or defatted-albumin solutions, the effect being more marked with serum. The decrease in apparent unbound bilirubin does not appear to be due to slow oxidation of albumin-bound bilirubin. Instead, the bilirubin-albumin complex has a much lower apparent dissociation rate constant (K-1) in serum (0.0033 [SD 0.0002] s-1) than in solutions of defatted-albumin (0.017 [SD 0.006] s-1), causing the dissociation of the complex to be rate-limiting when serum is analyzed at the currently recommended 40-fold dilution and peroxidase concentration (0.11 mu mol/L). In addition, dilution appears to enhance bilirubin binding by serum but not by defatted-albumin solutions. Decreasing the serum dilution and peroxidase concentration may significantly improve the accuracy of the peroxidase test. The actual correlation between clinical bilirubin toxicity and specific unbound bilirubin concentrations, however, remains to be determined.
Basic design and construction of the Vienna FES implants: existing solutions and prospects for new generations of implants (2001)

We can distinguish 3 generations of FES implants for activation of neural structures: 1. RF-powered implants with antenna displacement dependent stimulation amplitude; 2. RF-powered implants with stabilised stimulation amplitude; and 3. battery powered implants. In Vienna an 8-channel version of the second generation type has been applied clinically to mobilisation of paraplegics and phrenic pacing. A 20-channel implant of the second generation type for mobilisation of paraplegics and an 8-channel implant of the third generation type for cardiac assist have been tested in animal studies. A device of completely new design for direct stimulation of denervated muscles is being tested in animal studies. There is a limited choice of technologically suitable biocompatible and bioresistant materials for implants. The physical design has to be anatomically shaped without corners or edges. Electrical conductors carrying direct current (D.C.) have to be placed inside a hermetic metal case. The established sealing materials, silicone rubber and epoxy resin, do not provide hermeticity and should only embed DC-free components. For electrical connections outside the hermetic metal case welding is preferable to soldering; conductive adhesives should be avoided. It is advisable to use a hydrophobic oxide ceramic core for telemetry antenna coils embedded in sealing polymer. Cleaning of all components before sealing in resin is of the utmost importance as well as avoidance of rapid temperature changes during the curing process.
The mRNA expression of inhibitors of DNA binding-1 and -2 is associated with advanced tumour stage and adverse clinical outcome in human breast cancer. (2013)

Our findings are suggestive of a role for ID1 and ID2 in human breast cancer as possible prognostic markers and therapeutic targets meriting further validating investigations, by immunohistochemistry and mechanistic studies.
Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. (1987)

The effect of four dose levels of piroxicam administered during different stages of colon tumor development was studied in male F344 rats to obtain a data base on the efficacy of piroxicam as an inhibitor of colon carcinogenesis. Piroxicam was added at levels of 25, 50, 75, and 150 ppm to the NIH-07 open-formula diet and fed to male F344 rats starting 1, 13, and 23 wk after the carcinogen administration. At 7 wk of age, while the animals were consuming the control diet, all animals except the vehicle-treated controls were given s.c. injection of azoxymethane (CAS:25843-45-2; 29.6 mg/kg body weight, once) to induce intestinal tumors. Forty wk after AOM injection, all animals were necropsied, and tumor incidences were compared among the various dietary groups. Colon tumor incidence (percentage of animals with tumors) was inhibited in a dose-dependent manner in rats fed the diets containing 25, 50, 75, and 150 ppm piroxicam starting 1 and 13 wk after carcinogen treatment. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm of piroxicam starting at 1 wk after carcinogen treatment were 89, 61, 58, 50, and 39%, respectively. When the diets containing 0, 25, 50, 75, and 150 ppm were fed 13 wk after carcinogen treatment, the colon tumor incidences were 89, 69, 69, 44, and 33%, respectively. Colon tumor multiplicity (tumors/animal; tumors/tumor-bearing animal) was also significantly inhibited in animals fed the diets containing 25 to 150 ppm piroxicam starting 1 and 13 wk after carcinogen administration. The number of colon tumors/animal was inhibited by about 80 to 84% in animals fed the 150 ppm piroxicam diet. When the diets containing different levels of piroxicam were fed 23 wk after carcinogen treatment, the colon tumor incidence was significantly inhibited in animals fed the 75 and 150 ppm piroxicam diets. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm were 89, 78, 67, 64, and 64%, respectively. The colon tumor multiplicity (colon tumors/animal) was slightly but significantly inhibited in animals fed the diets containing 25 to 150 ppm piroxicam. The results of this study demonstrate that increasing levels of piroxicam in the diet, when fed 1 or 13 wk after carcinogen insult, inhibit colon tumor incidence in a dose-dependent manner.
Evolutionary conservation of sequence and secondary structures in CRISPR repeats (2007)

We show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification, including specific relationships between CRISPR and CAS subtypes.
Detection of CDKN2 deletions in tumor cell lines and primary glioma by interphase fluorescence in situ hybridization. (1995)

Deletions of chromosomal band 9p21 have been detected in various tumor types including melanoma, glioma, lung cancer, mesothelioma, and bladder cancer. Recently, the CDKN2 gene (p16INK4A, MTS I, CDK41) has been proposed as a candidate tumor suppressor gene because it is frequently deleted in cell lines derived from multiple tumor types. We performed fluorescence in situ hybridization (FISH) with interphase cells using yeast artificial chromosome clones and a cosmid contig of the CDKN2 region. In 10 cell lines (4 glioma, 2 melanoma, 2 non-small cell lung cancer, 2 bladder cancer) with 9p alterations detected by molecular or cytogenetic analysis, interphase FISH with the CDKN2 cosmid contig detected all 9p deletions previously identified by molecular analysis. Using this probe, FISH analysis of primary glioblastoma tumors revealed homozygous deletions of the CDKN2 region in 6 of 9 tumors (67%) whereas a yeast artificial chromosome probe containing the interferon type I (IFN) gene cluster was deleted in only 4 cases (44%). Thus, it is likely that the CDKN2 region is the target of 9p deletions in gliomas. Interphase FISH will play an important role in defining the clinical significance of 9p deletions in primary tumors because it is especially applicable to clinical samples which may be contaminated by normal cells.
Three novel F8 mutations in sporadic haemophilia A cases (2012)

Hemophilia A (HA) due to defective F8 is an X-linked hereditary disorder characterized by bleeding of variable severity through mild, moderate to severe owing to large range of mutations [1]. All kind of mutations, except repeats have been reported for HA, in total up to 2370 [2]. A preliminary study was conducted in our lab for identification of mutations in F8 gene in HA patients with an emphasis on study of molecular pathology of Pakistani HA patients and their correlation with clinical manifestations. For this study, all exons of F8 gene were selected. Samples were collected from 62 HA patients from all over the Pakistan and their clinical history was recorded (only patients frequently visiting medical centers for frequent treatment of F8 were selected for the study). Their genomic DNA was separated by standard procedures. Specific primers (Figure-1) were designed using Primer3 (http://biotools.umassmed.edu/bioapps/primer 3_www.cgi) to amplify the selected portions of the gene; amplification products were sequenced by ABI 310 and ABI 3100 sequencer (Applied Biosystems). The sequencing results were visualized using Chromas2.33 software (Applied Biosystem) and mutations were detected using BLAST software available on the NCBI website (http:balst.ncbi.nlm.nih.gov/Blast.cgi? PROGRAM=blastnB 2 point mutations) were detected in four sporadic patients, all from different ethnic backgrounds. Single T deletion at Exon 7 within the A1 domain clearly represents a frame-shift change disrupting protein structure and function resulting in severe manifestation of the disease. A missense point mutation in the A3 domain occurs at codon 1907 at nucleotide number 5720 replacing Serine with Isoleucine and confers a moderate type of severity, although both amino-acids have different properties: serine being polar and acidic and Isoleucine a nonpolar and basic compound. A nonsense point-mutation was available in two unrelated patients in the C3 domain in exon 26 manifesting moderate hemophilic conditions. Beside these mutations, 27 common SNPs were also detected among exons of F8 for all the patients (Table-2). Their allelic data and accession numbers were collected from Ensembl Genome Browser [3]. The results will not only form the basis of an enlarged study but also will be useful in the genetic and molecular analysis/diagnosis and genetic counseling of classical hemophilia in Pakistan.
Gene expression in hypothalamus and brown adipose tissue of mice divergently selected for heat loss (2000)

Gene expression was evaluated in mice divergently selected for 16 generations for heat loss, measured by direct calorimetry. The high (MH) heat loss line has approximately 50% greater heat loss, approximately 35% less body fat, approximately 20% greater feed intake, and twofold greater activity levels than the low (ML) heat loss line. At 11 wk, inbred males (developed from MH and ML) were euthanized 3 h after dark for dissection of tissues and extraction of RNA. Differential display PCR (DD-PCR) was used to evaluate transcriptional differences between lines in hypothalamus and brown adipose tissue (BAT). Evaluation was replicated within and across lines, using family pools of mRNA. Two genes were confirmed by competitive RT-PCR and/or Northern analysis to have greater levels of mRNA present in ML relative to MH mice. In both hypothalamus and BAT, the ribosomal protein L3 (RPL3) gene was expressed at higher levels in ML, whereas an unknown expressed sequence tag (EST) was also found at higher levels in the hypothalamus of ML mice. These results implicate RPL3 in regulation of energy balance and extend the genetic dissection of response to selection to the transcriptional level.
Amplification and disruption of the phenylacetyl-CoA ligase gene of Penicillium chrysogenum encoding an aryl-capping enzyme that supplies phenylacetic acid to the isopenicillin N-acyltransferase (2006)

A gene, phl, encoding a phenylacetyl-CoA ligase was cloned from a phage library of Penicillium chrysogenum AS-P-78. The presence of five introns in the phl gene was confirmed by reverse transcriptase-PCR. The phl gene encoded an aryl-CoA ligase closely related to Arabidopsis thaliana 4-coumaroyl-CoA ligase. The Phl protein contained most of the amino acids defining the aryl-CoA (4-coumaroyl-CoA) ligase substrate-specificity code and differed from acetyl-CoA ligase and other acyl-CoA ligases. The phl gene was not linked to the penicillin gene cluster. Amplification of phl in an autonomous replicating plasmid led to an 8-fold increase in phenylacetyl-CoA ligase activity and a 35% increase in penicillin production. Transformants containing the amplified phl gene were resistant to high concentrations of phenylacetic acid (more than 2.5 g/l). Disruption of the phl gene resulted in a 40% decrease in penicillin production and a similar reduction of phenylacetyl-CoA ligase activity. The disrupted mutants were highly susceptible to phenylacetic acid. Complementation of the disrupted mutants with the phl gene restored normal levels of penicillin production and resistance to phenylacetic acid. The phenylacetyl-CoA ligase encoded by the phl gene is therefore involved in penicillin production, although a second aryl-CoA ligase appears to contribute partially to phenylacetic acid activation. The Phl protein lacks a peptide-carrier-protein domain and behaves as an aryl-capping enzyme that activates phenylacetic acid and transfers it to the isopenicillin N acyltransferase. The Phl protein contains the peroxisome-targeting sequence that is also present in the isopenicillin N acyltransferase. The peroxisomal co-localization of these two proteins indicates that the last two enzymes of the penicillin pathway form a peroxisomal functional complex.
Pharmaceutical Applications of Cyclodextrins. 1. Drug Solubilization and Stabilization (1996)

Cyclodextrins are cyclic oligosaccharides which have recently been recognized as useful pharmaceutical excipients. The molecular structure of these glucose derivatives, which approximates a truncated cone or torus, generates a hydrophilic exterior surface and a nonpolar cavity interior. As such, cyclodextrins can interact with appropriately sized molecules to result in the formation of inclusion complexes. These noncovalent complexes offer a variety of physicochemical advantages over the unmanipulated drugs including the possibility for increased water solubility and solution stability. Further, chemical modification to the parent cyclodextrin can result in an increase in the extent of drug complexation and interaction. In this short review, the effects of substitution on various cyclodextrin properties and the forces involved in the drug-cyclodextrin complex formation are discussed. Some general observations are made predicting drug solubilization by cyclodextrins. In addition, methods which are useful in the optimization of complexation efficacy are reviewed. Finally, the stabilizing/destabilizing effects of cyclodextrins on chemically labile drugs are evaluated.
On the use of one-way chain based authentication protocols in secure control systems (2007)

The use of one-way chains in authentication protocols is a technique of great importance which has many applications. Employing cryptographic techniques in the area of industrial control systems has gained significant interest in the last few years. This paper proposes the use of a one-way chain based authentication protocol in a robust control system. Some enhancements of a generic one-way chain based authentication protocol are required by the scenario of secure robust and they are intended for achieving lower authentication delays and computational costs while preserving the control robust in the presence of potential attackers. We also underline that the techniques described in this paper are not restricted to the subject of authentication in robust control systems since the presented protocols may be useful for other applications as well
International Collaborative Study To Compare Reverse Transcriptase PCR Assays for Detection and Genotyping of Noroviruses (2003)

To allow more rapid and internationally standardized assessment of the spread of noroviruses (previously called Norwalk-like viruses [NLVs]) as important food-borne pathogens, harmonization of methods for their detection is needed. Diagnosis of NLVs in clinical diagnostic laboratories is usually performed by reverse transciptase PCR (RT-PCR) assays. In the present study, the performance of five different RT-PCR assays for the detection of NLVs was evaluated in an international collaborative study by five laboratories in five countries with a coded panel of 91 fecal specimens. The assays were tested for their sensitivity, detection limit, and ease of standardization. In total, NLVs could be detected by at least one RT-PCR assay in 69 (84%) of the samples that originally tested positive. Sensitivity ranged from 52 to 73% overall and from 54 to 100% and 58 to 85% for genogroup I and II viruses, respectively. In all, 64% of the false-negative results were obtained with a set of diluted stools (n = 20) that may have lost quality upon storage. Sensitivity was improved when these samples were excluded from analysis. No one single assay stood out as the best, although the p1 assay demonstrated the most satisfactory overall performance. To promote comparability of data, this assay will be recommended for newly starting groups in future collaborative studies.
TACI:Fc scavenging B cell activating factor (BAFF) alleviates ovalbumin-induced bronchial asthma in mice (2007)

Asthma was induced by the sensitization and challenge with ovalbumin (OVA) in mice. B-cell activating factor (BAFF) plays a role in mature B cell generation and maintenance. Here, we investigated whether, BAFF expression was changed in OVA-induced mice and whether the control of BAFF expression level alleviates the symptom of bronchial asthma. BAFF expression was detected in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues. BAFF protein was also increased in OVA-induced mouse serum. The increased BAFF transcripts was detected in OVA-induced mouse splenocytes. OVA-induced asthma was associated with the increased number of eosinophils in bronchoalveolar lavage fluid (BALF). When TACI:Fc scavenging soluble BAFF was injected to OVA-induced mice, a significant inhibition was detected in the thickness of airway smooth muscle and glycol-containing cellular elements in airway that were visualized by hematoxylin/eosin Y and periodic acid-Schiff staining, respectively. In addition, when mice were treated with TACI:Fc protein, BAFF protein level was decreased in alveolar-associated cells surrounding bronchi of OVA-induced mouse lung tissues compared to control mice. When compared to OVA-induced control, TACI:Fc treatment reduced the percentage of non-lymphoid cells and no changes were detected in lymphoid cell population. Hypodiploid cell formation in BALF was decreased by OVA-challenge but it was recovered by TACI:Fc treatment. Collectively, data suggest that asthmatic symptom could be alleviated by scavenging BAFF and then BAFF could be a novel target for the development of anti-asthmatic agents.
Missed Insulin Meal Boluses and Elevated Hemoglobin A1c Levels in Children Receiving Insulin Pump Therapy (2004)

Missed mealtime insulin boluses seem to be the major cause of suboptimal glycemic control in youths with diabetes receiving continuous subcutaneous insulin infusion therapy.