gebhart/patrepeval huggingface dataset:
Probing the structure of long single-stranded DNA fragments with neocarzinostatin chromophore. Extension of the base-catalyzed bulge-specific reaction (1995)

The base-catalyzed (bc) thiol-independent cleavage reaction of neocarzinostatin chromophore (NCS chrom) has been characterized with long single-stranded (ss) DNA in order to use this reaction as a selective probe for the tertiary structure of naturally occurring ss nucleic acids. The ss circular phi chi 174 phage and M13mp18 phage DNAs (approximately 5000 and 7500 bases, respectively) were shown to be bc NCS chrom reaction substrates, exhibiting the expected pH dependence. The ss DNA fragments (150-450 bases) were cleaved at six major sites; the lesions occurred at T-rich non-double-stranded sequences, as predicted from comparison with the minimal energy secondary structures. These sites exhibited the expected pH and drug: DNA ratio dependence shown to be required for this reaction. Optimization of the shortest sequence, which gave the highest cleavage yield, identified the minimal sequence requirements for the site (19-mer of the sequence 3'TACTGAGTCTCCTTTTGTA5', attacked residue in bold). Folding pattern analysis predicted that the oligonucleotide contained a two-base bulge at the cleavage site; this result was consistent with the observation that removing features which destabilize the bulged structure increased the cleavage yield. Furthermore, the derived 19-mer was shown to generate maximal amounts of the final drug product of the bc DNA cleavage reaction. Reaction of an RNA 339-mer containing the same sequence as one of the long ss DNA fragments showed it not to be a substrate for the bc reaction, while similar results were obtained for the RNA analog of shorter oligodeoxyribonucleotides identified in this and earlier studies. Through a combination of thermodynamic and kinetic assays, the observed difference in reactivity was shown to be the result of the low binding of the cleaving species to RNA.
Survival for colon and rectal cancer in Estonia: Role of staging and treatment (2011)

The 5-year RSR was 51% for colon cancer and 38% for rectal cancer; the corresponding 10-year RSR was 50% and 39%. We observed no excess mortality for early disease. For stages II and III, the survival was markedly higher in colon cancer (5-year RSR 79% and 66%, respectively) compared to rectal cancer (66% and 30%, respectively). Around 30% of cases were diagnosed with distant disease. Among radically operated colon and rectal cancer patients, the 10-year RSR was 90% and 70%, respectively. Most patients with available pathological information had one to four lymph nodes examined. Survival has notably improved for colon cancer, but not for rectal cancer in Estonia. High proportion of cases with distant metastasis at first diagnosis along with inadequate staging and low proportion of patients treated with curatively intended surgery and appropriate chemotherapy and radiotherapy may have contributed to this outcome. Progress could be achieved by earlier diagnosis and implementing higher standards for staging and treatment. These conclusions are likely to be relevant also for other Eastern European countries.
Practice patterns in sildenafil prescribing. (2006)

Sildenafil is being prescribed at a significant number of visits without documentation of a reason for visit or diagnosis consistent with psychosexual or erectile dysfunction.
PathProx-a runway incursion alerting system (2002)

This paper describes a Runway Incursion Advisory and Alerting System (RIAAS), intended to help minimize the number of runway incursions and provide conflict alerts for all aircraft and vehicles on the airport surface. PathProx is an RIAAS avionics system designed to provide timely alerts directly to the pilot. Airport surface incursions have been identified as one of the most significant safety hazards in civil aviation, and yet thus far, there is no operational system to alert pilots automatically at the onset of such conflicts. PathProx is designed to monitor aircraft that are either on the airport surface area, or are still within the airport's arrival and departure zones. The prototype design specifies that the system is activated whenever an aircraft enters an arrival or departure zone associated with a runway. ADS-B and/or TIS traffic data from other aircraft and ground vehicles within the proximity of this zone are processed by the system, which tracks their movement. Decision rules are set up to issue alerts based on the states and proximity of the aircraft. The goal of the system when implemented is a reduction in the number of runway incursions and also an improvement in the reaction time by pilots to avoid such conflicts.
A calcineurin- and NFAT-dependent pathway regulates Myf5 gene expression in skeletal muscle reserve cells (2001)

Myf5 is a member of the muscle regulatory factor family of transcription factors and plays an important role in the determination, development, and differentiation of skeletal muscle. However, factors that regulate the expression and activity of Myf5 itself are not well understood. Recently, a role for the calcium-dependent phosphatase calcineurin was suggested in three distinct pathways in skeletal muscle: differentiation, hypertrophy, and fiber-type determination. We propose that one downstream target of calcineurin and the calcineurin substrate NFAT in skeletal muscle is regulation of Myf5 gene expression. For these studies, we used myotube cultures that contain both multinucleated myotubes and quiescent, mononucleated cells termed 'reserve' cells, which share many characteristics with satellite cells. Treatment of such myotube cultures with the calcium ionophore ionomycin results in an approximately 4-fold increase in Myf5 mRNA levels, but similar effects are not observed in proliferating myoblast cultures indicating that Myf5 is regulated by different pathways in different cell populations. The increase in Myf5 mRNA levels in myotube cultures requires the activity of calcineurin and NFAT, and can be specifically enhanced by overexpressing the NFATc isoform. We used immunohistochemical analyses and fractionation of the cell populations to demonstrate that the calcium regulated expression of Myf5 occurs in the mononucleated reserve cells. We conclude that Myf5 gene expression is regulated by a calcineurin- and NFAT-dependent pathway in the reserve cell population of myotube cultures. These results may provide important insights into the molecular mechanisms responsible for satellite cell activation and/or the renewal of the satellite cell pool following activation and proliferation.
Quantifying single gene copy number by measuring fluorescent probe lengths on combed genomic DNA (2000)

An approach was developed for the quantification of subtle gains and losses of genomic DNA. The approach relies on a process called molecular combing. Molecular combing consists of the extension and alignment of purified molecules of genomic DNA on a glass coverslip. It has the advantage that a large number of genomes can be combed per coverslip, which allows for a statistically adequate number of measurements to be made on the combed DNA. Consequently, a high-resolution approach to mapping and quantifying genomic alterations is possible. The approach consists of applying fluorescence hybridization to the combed DNA by using probes to identify the amplified region. Measurements then are made on the linear hybridization signals to ascertain the region's exact size. The reliability of the approach first was tested for low copy number amplifications by determining the copy number of chromosome 21 in a normal and trisomy 21 cell line. It then was tested for high copy number amplifications by quantifying the copy number of an oncogene amplified in the tumor cell line GTL-16. These results demonstrate that a wide range of amplifications can be accurately and reliably quantified. The sensitivity and resolution of the approach likewise was assessed by determining the copy number of a single allele (160 kb) alteration.
Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice (1996)

Intranasal or intramuscular (i.m.) immunization of mice and i.m. immunization of rabbits with formalinized staphylococcal enterotoxin B (SEB) toxoid in saline elicited higher anti-SEB serum immunoglobulin G (IgG) titers when the toxoid was formulated with proteosomes. In addition, intranasal immunization of mice with this proteosome-toxoid vaccine elicited high levels of anti-SEB IgA in lung and intestinal secretions, whereas the toxoid without proteosomes did not. Two i.m. immunizations with proteosome-toxoid plus alum also induced higher murine serum responses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with either saline or alum afforded significant protection against lethal SEB challenge in two D-galactosamine-sensitized murine models of SEB intoxication, i.e., the previously described i.m. challenge model and a new respiratory challenge model of mucosal SEB exposure. Efficacy correlated with the induction of high serum levels of anti-SEB IgG. In contrast, intranasal or i.m. immunization with toxoid in saline without proteosomes was not significantly protective in either challenge model. Proteosome-toxoid plus alum given i.m. also elicited more significant protection against respiratory challenge than the alum-adjuvanted toxoid alone. The capacity of proteosomes to enhance both i.m. and intranasal immunogenicity and efficacy of SEB toxoid indicates that testing such proteosome-SEB toxoid vaccines in the nonhuman primate aerosol challenge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mucosal vaccine delivery system to protein toxoids and suggest that respiratory delivery of proteosome vaccines may be practical for enhancement of both mucosal and systemic immunity against toxic or infectious diseases.
Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. (2003)

Survivin functions as a novel upstream regulator of mitochondrial-dependent apoptosis, and molecular targeting of this pathway results in anticancer activity via a dual mechanism of induction of tumor cell apoptosis and suppression of angiogenesis.
Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro (1979)

Binding of the two photosensitizers, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), to serum proteins and to epidermis was measured. 8-MOP binds to serum proteins with an apparent dissociation constant (Kd) of 4 x 10(-5) M. Under conditions of oral therapy, serum concentrations of the photosensitizer 2 h after administration are usually in the range of 100-1000 ng per ml serum. In this concentration range, 75-80% of the drug was found to be reversibly bound to serum proteins. 5-MOP shows a higher binding affinity to serum proteins and 98-99% of the drug is protein bound. The binding of both psoralen derivatives appears to take place mainly to serum albumin. 5-MOP and 8-MOP bind to different and non-interacting sites on serum proteins and the binding of the one has no effect on the binding of the other methoxypsoralen. Both photosensitizers bind reversibly to human epidermis. 8-MOP concentration in the epidermis is increased by ten to twenty fold compared with the equilibrium buffer. 5-MOP shows a higher binding affinity, resulting in a higher tissue concentration of the photosensitizer. As in serum, the two drugs appear to be bound in the epidermis to independent and non-interacting sites. No binding competition was found between the two methoxypsoralens and hydrocortisone, fluocinonide and acetyl salicylic acid, either in serum or in epidermis, using up to 1000 fold higher concentrations as compared with those of 5-MOP and 8-MOP.
Relating STDP to BCM (2003)

We demonstrate that the BCM learning rule follows directly from STDP when pre- and postsynaptic neurons fire uncorrelated or weakly correlated Poisson spike trains, and only nearest-neighbor spike interactions are taken into account.
Comparison of relevant biological assays for the determination of biological active erythropoietin. (1988)

Human recombinant erythropoietin (rh EPO), a glycoprotein hormone which is an obligatory growth factor for the proliferation and differentiation of committed erythroid progenitor cells, has been purified to homogeneity and compared to human urinary erythropoietin (EPO). Erythropoietin levels will be determined and standardized by in vivo bioassays in which endogenous erythropoietin production has been reduced by hypertransfusion or hyperbaric atmosphere. The effect of EPO on the rate of red cell production or Fe59 incorporation is used as measure of its erythropoietin content. Both in vivo assay systems will be compared with respect to standardization for routine laboratory use. For in vitro characterization of EPO the classical assay for Fe59 incorporation in in vitro rat bone marrow cells will be compared to the proliferation and H3 Thd uptake by treatment with phenylhydrazin enriched erythroid progenitors from mouse spleens. (The direct physiological effect of EPO on stem cells will be shown by differences in BFUe progenitor levels). Rh EPO is jointly developed by Integrated Genetics (Boston) and Behringwerke AG (Marburg).
Induced formation of chelating agents by Pseudomonas aeruginosa grown in presence of thorium and uranium. Technical report no. 2, 1984-1985 (1985)

The aim of this program is to (1) identify microorganisms that bioaccumulate strategically important metals such as chromium, cobalt, niobium, tin, and platinum; (2) learn about the mechanisms that govern the bioaccumulation processes at the molecular level, including the chemical characterization of naturally occurring chelating agents; (3) immobilize isolated reactive centers, either cellular or molecular onto an inert carrier so that specific metals can be selectively recovered, and (4) suitably scale up the process developed from the information obtained in (1) - (3). If advisable in the future phases of the program, the most-successful organisms will be subjected to genetic-engineering manipulation. The selected microorganisms are part of a Brookhaven National Laboratory collection which includes strains of metal-resistant organisms such as Pseudomonas aeruginosa CSU, P. aeruginosa PAO-1, Saccharomyces cerevisiae, Aspergillus niger, P. fluorescens, Escherichlia coli, and Thiobacillus ferroxidans. Interaction of these microorganisms with salts of chromium, tin, manganese, cobalt, platinum, uranium and thorium was investigated.
Dendritic cells are specialized accessory cells along with TGF-β for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3− precursors (2007)

Foxp3(+)CD25(+)CD4(+) regulatory T cells are produced in the thymus (natural T regs) but can also differentiate from peripheral Foxp3(-)CD4(+) precursors (induced or adaptive T regs). We assessed antigen presenting cell (APC) requirements for the latter differentiation. With added transforming growth factor (TGF)-beta, both immature and mature populations of dendritic cells (DCs) induced antigen-specific Foxp3(+) T regs from Foxp3(-) precursors. Using endogenous TGF-beta, DCs from gut-associated mesenteric lymph nodes were capable of differentiating Foxp3(+)T regs. Spleen DCs were 100-fold more potent than DC-depleted APCs for the induction of T regs and required 10-fold lower doses of peptide antigen. Interleukin-2 (IL-2) was essential, but could be provided endogenously by T cells stimulated by DCs, but not other APCs. The required IL-2 was induced by DCs that expressed CD80/CD86 costimulatory molecules. The DC-induced Foxp3(+)T regs divided up to 6 times in 6 days and were comprised of CD62L and CD103 positive and negative forms. The induced Foxp3(+)T regs exerted suppression in vitro and blocked tumor immunity in vivo. These results indicate that DCs are specialized to differentiate functional peripheral Foxp3(+)T regs and help set the stage to use DCs to actively suppress the immune response in an antigen-specific manner.
Inhibitors of Bacterial Efflux Pumps as Adjuvants in Antibiotic Treatments and Diagnostic Tools for Detection of Resistance by Efflux (2006)

Active efflux is a widespread mechanism for bacterial resistance to antibiotics, which contributes to poor intrinsic susceptibility, cross-resistance to structurally diverse classes of drugs, or selection of other mechanisms of resistance. Thus, inhibition of efflux pumps appears to be (i) a promising strategy for restoring the activity of existing antibiotics, and (ii) a useful method to detect the presence of efflux determinants in clinical isolates. Structurally dissimilar classes of inhibitors have been patented in the last decade, some are analogs of antibiotic substrates [tetracyclines, quinolones or aminoglycosides] and others, new chemical entities [including substituted indoles, ureas, aromatic amides, piperidinecarboxylic acids, alkylamino- or alkoxyquinolines, peptidomimetics, and pyridopyrimidines]. Their spectrum of activity, in terms of antibiotics and bacteria, differ significantly. Narrow spectrum inhibitors are of prime interest as diagnostic tools, while broad spectrum inhibitors are expected for adjuvant therapies. Apart from (i) a peptidomimetic inhibitor of Mex pumps in Pseudomonas aeruginosa (MC-04,124), for which efficacy was evaluated in animal models, and (ii) a piperidinecarboxylic acid inhibitor of fluoroquinolone efflux in Gram-positive (VX-710), which was safely administered to humans, most of these products have only demonstrated their activity in vitro, so further investigations are needed to evaluate their clinical potential.
In vitro anthelmintic activity of Allium sativum, Ferula asafoetida, Syzygium aromaticum and their active components against Fasciola gigantica (2014)

The effect of dried clove powder of Allium sativum, dried latex powder of Ferula asafoetida and dried flower bud powder of Syzygium aromaticum in in vitro treatment against liver fluke Fasciola gigantica were studied. The anthelmintic activities of all the three plants were time and concentration dependent. A. sativum bulb powder 8h LC50 against F. gigantica was 5.48 mg/ml. Among different organic extracts, ethanol extract was more toxic than other organic extract. The ethanol extract of S. aromaticum (2h LC50 2.95 mg/ml) was more toxic against F. gigantica than A. sativum (2h LC50 3.48 mg/ml) and F. asafoetida (2h LC50 3.94 mg/ml). The 8h LC50 of column purified fraction of dried flower bud powder of S. aromaticum was 1.02 mg/ml whereas dried clove powder of A. sativum and latex powder of F. asafoetida were 1.87 and 2.75 mg/ml, respectively. The product of A. sativum, F. asafoetida and S. aromaticum may be used as anthelmintic.
Insights into Src kinase functions: structural comparisons (1998)

Recent structures of Src tyrosine kinases reveal complex mechanisms for regulation of enzymatic activity. The regulatory SH3 and SH2 domains bind to the back of the catalytic kinase domain via a linker region that joins the SH2 domain to the catalytic domain. Members of a subgroup of the Src kinase family show distinct features in this linker and in the loops that interact with it. Hydrophobicity of key residues in this region is important for intramolecular regulation. The kinases Abl, Btk and Csk seem to have the same molecular architecture as Src. Structural comparisons between serine/threonine and tyrosine kinases indicate a specific twisting mechanism involving the N- and C-terminal lobes of the catalytic domain. This motion could provide insights into the various mechanisms used to regulate kinase activity.
<scp>UK NHS</scp> pilot study on cell‐free <scp>DNA</scp> testing in screening for fetal trisomies: factors affecting uptake (2014)

This study has identified factors that can influence the decision of women undergoing combined screening in favor of or against CVS and in favor of or against cfDNA testing.
Chemokines and their receptors as potential targets for the treatment of asthma (2007)

Asthma is a chronic and sometimes fatal disease, which affects people of all ages throughout the world. Important hallmarks of asthma are airway inflammation and remodelling, with associated bronchial hyperresponsiveness and variable airflow obstruction. These features are orchestrated by cells of both the innate (eosinophils, neutrophils and mast cells) and the adaptive (T(H)2 T cells) immune system, in concert with structural airway cells. Chemokines are important for the recruitment of both immune and structural cells to the lung, and also for their microlocalisation within the lung tissue. Specific blockade of the responses elicited by chemokines and chemokine receptors responsible for the pathological migration of airway cells could therefore be of great therapeutic interest for the treatment of asthma.
Purine Receptors in Mammalian Tissues: Pharmacology and Functional Significance (1987)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Characterization of cDNA for human tripeptidyl peptidase II: the N-terminal part of the enzyme is similar to subtilisin (1991)

Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library and a cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open reading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilization of two different polyadenylation sites. Furthermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved.