gebhart/patrepeval huggingface dataset:
Overexpression of the D-alanine racemase gene confers resistance to D-cycloserine in Mycobacterium smegmatis (1997)

D-Cycloserine is an effective second-line drug against Mycobacterium avium and Mycobacterium tuberculosis. To analyze the genetic determinants of D-cycloserine resistance in mycobacteria, a library of a resistant Mycobacterium smegmatis mutant was constructed. A resistant clone harboring a recombinant plasmid with a 3.1-kb insert that contained the glutamate decarboxylase (gadA) and D-alanine racemase (alrA) genes was identified. Subcloning experiments demonstrated that alrA was necessary and sufficient to confer a D-cycloserine resistance phenotype. The D-alanine racemase activities of wild-type and recombinant M. smegmatis strains were inhibited by D-cycloserine in a concentration-dependent manner. The D-cycloserine resistance phenotype in the recombinant clone was due to the overexpression of the wild-type alrA gene in a multicopy vector. Analysis of a spontaneous resistant mutant also demonstrated overproduction of wild-type AlrA enzyme. Nucleotide sequence analysis of the overproducing mutant revealed a single transversion (G-->T) at the alrA promoter, which resulted in elevated beta-galactosidase reporter gene expression. Furthermore, transformants of Mycobacterium intracellulare and Mycobacterium bovis BCG carrying the M. smegmatis wild-type alrA gene in a multicopy vector were resistant to D-cycloserine, suggesting that AlrA overproduction is a potential mechanism of D-cycloserine resistance in clinical isolates of M. tuberculosis and other pathogenic mycobacteria. In conclusion, these results show that one of the mechanisms of D-cycloserine resistance in M. smegmatis involves the overexpression of the alrA gene due to a promoter-up mutation.
Self-Assembly of a Virus-Mimicking Nanostructure System for Efficient Tumor-Targeted Gene Delivery (2002)

Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system.
Adaptive playout control for intra-/inter-client synchronization in multicast media streaming (2003)

Recently we have proposed a multicast media streaming framework that enhances the media synchronization by employing a server-client coordinated adaptive playout and error control. Focusing on the adaptive playout with time-scale modification, we adopt the adaptive playout to help both intra-client and inter-client synchronization in a multicast streaming environment. However, only the usability of adaptive playout in assisting the synchronized multicast streaming is demonstrated while leaving several detailed issues untouched. As an effort to enhance the proposed framework, in this paper, we concentrate on refining the adaptive playout between two (i.e., intra/inter) synchronization modes. We attempt to enhance each synchronization mode and enable appropriate switching between them. More specifically, we zoom into the tradeoff of adaptive playout for buffer control and playout time control by adopting a dynamic playback factor adjustment. To evaluate the proposed scheme, network simulation and analysis (performed in NS2 simulator over the PIM-SSM multicast network) are conducted. Results show that the proposed scheme can enhance the performance of intra-client as well as inter-client synchronization.
A novel method for the determination of posttranscriptional modification in RNA by mass spectrometry (1993)

A method is described for the detection, chemical characterization and sequence placement of post-transcriptionally modified nucleotides in RNA. Molecular masses of oligonucleotides produced by RNase T1 hydrolysis can be measured by electrospray mass spectrometry with errors of less than 1 Da, which provides exact base composition, and recognition of modifications resulting from incremental increases in mass. Used in conjunction with combined liquid chromatography-mass spectrometry and gene sequence data, modified residues can be completely characterized at the nucleoside level, and assigned to sequence sites within oligonucleotides defined by selective RNase cleavage. The procedures are demonstrated using E.coli 5S rRNA, in which all RNase T1 fragments predicted from the rDNA sequence are identified solely on the basis of their molecular masses, and using E.coli 16S rRNA for analysis of post-transcriptional modification, including placement of 3-methyluridine at position 1498. The principles described are generally applicable to other covalent structural modifications of RNA which produce a change in mass, such as those resulting from editing, photochemical cross-linking, or xenobiotic modification.
Inhaled atrial natriuretic peptide and asthmatic airways. (1992)

of > 15 IU/ml the fetus could be severely anaemic and therefore cordocentesis should be considered.
Separation of the SOS-dependent and SOS-independent components of alkylating-agent mutagenesis (1989)

Escherichia coli plasmids containing the rpsL+ gene (Strs phenotype) as the target for mutation were treated in vitro with N-methyl-N-nitrosourea. Following fixation of mutations in E. coli MM294A cells (recA+ Strs), an unselected population of mutant and wild-type plasmids was isolated and transferred into a second host, E. coli 6451 (recA Strr). Strains carrying plasmid-encoded forward mutations were then selected as Strr isolates, while rpsL+ plasmids conferred the dominant Strs phenotype in the second host. Mutation induction and reduced survival of N-methyl-N-nitrosourea-treated plasmids were shown to be dose dependent. Because this system permitted analysis and manipulation of the levels of certain methylated bases produced in vitro by N-methyl-N-nitrosourea, it afforded the opportunity to assess directly the relative roles of these bases and of SOS functions in mutagenesis. The methylated plasmid DNA gave a mutation frequency of 6 X 10(-5) (a 40-fold increase over background) in physiologically normal cells. When the same methylated plasmid was repaired in vitro by using purified O6-methylguanine DNA methyltransferase (to correct O6-methylguanine and O4-methylthymine), no mutations were detected above background levels. In contrast, when the methylated plasmid DNA was introduced into host cells induced by UV light for the SOS functions, rpsL mutagenesis was enhanced eightfold over the level seen without SOS induction. This enhancement of mutagenesis by SOS was unaffected by prior treatment of the DNA with O6-methylguanine DNA methyltransferase. These results demonstrate a predominant mutagenic role for alkylation lesions other than O6-methylguanine or O4-methylthymine when SOS functions are induced. The mutation spectrum of N-methyl-N-nitrosourea under conditions of induced SOS functions revealed a majority of mutagenic events at A . T base pairs.
One-Step Competitive Immunoassay for Cadmium Ions:  Development and Validation for Environmental Water Samples (2001)

A rapid, simple, and reliable competitive immunoassay was developed and validated for measurement of Cd(II) in environmental water samples. This assay employed a monoclonal antibody that recognizes Cd(II)-EDTA complexes as capture reagent and a Cd(II)-EDTA conjugate of horseradish peroxidase as an enzyme label. The assay depended on a competitive binding reaction between the enzyme conjugate and Cd(II)-EDTA complexes, derived from the environmental water sample, for the binding sites of the immobilized antibody. The concentration of Cd(II) in the sample was quantified by the ability of its EDTA complexes to inhibit the binding of the enzyme conjugate to the antibody and, subsequently, color formation in the assay. The assay was specific to Cd(II), with a limit of detection of 0.3 ppb. Ca(II), Mg(II), and Fe(III), the metal ions commonly found in ambient water at relatively high concentrations, did not interfere with the assay. Mean analytical recovery of added Cd(II) was 100.29 +/- 3.60. The precision of the assay was satisfactory; coefficients of variation were 3.6-10.9 and 4.81-10.21% for intra- and interassay precision, respectively. The assay compared favorably with graphite furnace atomic absorption spectroscopy in its ability to accurately measure Cd(II) spiked into water samples from a Louisiana bayou.
Cross-Domain Facial Expression Recognition Using Supervised Kernel Mean Matching (2012)

Even though facial expressions have universal meaning in communications, their appearances show a large amount of variation due to many factors, such as different image acquisition setups, different ages, genders, and cultural backgrounds etc. Collecting enough amounts of annotated samples for each target domain is impractical, this paper investigates the problem of facial expression recognition in the more challenging situation, where the training and testing samples are taken from different domains. To address this problem, after observing the fact of unsatisfactory performance of the Kernel Mean Matching (KMM) algorithm, we propose a supervised extension that matches the distributions in a class-to-class manner, called Supervised Kernel Mean Matching (SKMM). The new approach stands out by taking into consideration both matching the distributions and preserving the discriminative information between classes at the same time. The extensive experimental studies on four cross-dataset facial expression recognition tasks show promising improvements of the proposed method, in which a small number of labeled samples guide the matching process.
Laxative abuse. (1974)

Amongst the patients of every gastroenterologist there is probably one, a woman, with a long history of abdominal discomfort and diarrhoea, perhaps with vomiting, weight loss, weakness, thirst, and a psychiatric illness. There may be a past history of an ill defined metabolic disorder or renal disease. Numerous investigations will have proved fruitless although a low serum potassium, a rather distensible, featureless colon on radiographs and non-specific inflammatory changes on rectal biopsy may not have been fully explained. The latest medication is of only temporary benefit and the notes become progressively thicker. This is the picture of a patient who is taking laxatives to excess and probably concealing the fact from her doctor.
Hypoandrogenism in association with diminished functional ovarian reserve (2013)

This research was supported by the Foundation for Reproductive Medicine, a not-for-profit medical research foundation and intramural funds from the Center for Human Reproduction. N.G. and D.H.B are members of the Board of the Foundation for Reproductive Medicine. N.G., A.W. and D.H.B. received research support, lecture fees and travel support from a variety of pharmaceutical and medical device companies, none in any way related to the issues discussed in this manuscript. N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents, claiming diagnostic and therapeutic benefits from the determination of CGG repeats on the FMR1 gene. N.G. is the owner of the Center for Human Reproduction, where this research was performed.
Forks and combs and DNA: the synthesis of branched oligodeoxyribonucleotides (1989)

Nucleoside phosphoramidite derivatives containing two protected primary hydroxyl functions have been incorporated into synthetic oligonucleotides as 'branching monomers'. With selective deprotection, multiple identical copies of an additional oligonucleotide can be incorporated to form fork- or comb-like structures for use as signal amplification materials in nucleic acid hybridization assays.
Water excretion and plasma vasopressin in psychotic disorders (1989)

To investigate the pathogenesis of water intoxication in psychotic disorders, a standard water load test was given to 23 unmedicated patients with schizophrenic or schizoaffective disorders. Levels of plasma arginine vasopressin were measured concurrently. Compared with 28 healthy volunteers, the psychotic patients had significantly smaller cumulative urine output and higher minimum urine osmolalities. Patients whose current illness had lasted less than 24 weeks exhibited the most severe antidiuretic state and also had the highest plasma arginine vasopressin levels. Water intoxication in acute exacerbations of psychosis may develop as a result of impaired excretory mechanisms.
Dynamics of Vaginal Bacterial Communities in Women Developing Bacterial Vaginosis, Candidiasis, or No Infection, Analyzed by PCR-Denaturing Gradient Gel Electrophoresis and Real-Time PCR (2007)

The microbial flora of the vagina plays a major role in preventing genital infections, including bacterial vaginosis (BV) and candidiasis (CA). An integrated approach based on PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and real-time PCR was used to study the structure and dynamics of bacterial communities in vaginal fluids of healthy women and patients developing BV and CA. Universal eubacterial primers and Lactobacillus genus-specific primers, both targeted at 16S rRNA genes, were used in DGGE and real-time PCR analysis, respectively. The DGGE profiles revealed that the vaginal flora was dominated by Lactobacillus species under healthy conditions, whereas several potentially pathogenic bacteria were present in the flora of women with BV. Lactobacilli were the predominant bacterial population in the vagina for patients affected by CA, but changes in the composition of Lactobacillus species were observed. Real-time PCR analysis allowed the quantitative estimation of variations in lactobacilli associated with BV and CA diseases. A statistically significant decrease in the relative abundance of lactobacilli was found in vaginal fluids of patients with BV compared to the relative abundance of lactobacilli in the vaginal fluids of healthy women and patients with CA.
Trace elements in hemodialysis patients: a systematic review and meta-analysis (2009)

Average blood levels of biologically important trace elements were substantially different in hemodialysis patients, compared with healthy controls. Since both deficiency and excess of trace elements are potentially harmful yet amenable to therapy, the hypothesis that trace element status influences the risk of adverse clinical outcomes is worthy of investigation.
Immunohistochemical and ELISA Assays for Biomarkers of Oxidative Stress in Aging and Diseasea (1998)

Oxidative stress is apparent in pathology associated with aging and many age-related, chronic diseases, including atherosclerosis, diabetes mellitus, rheumatoid arthritis, and neurodegenerative diseases. Although it cannot be measured directly in biological systems, several biomarkers have been identified that provide a measure of oxidative damage to biomolecules. These include amino acid oxidation products (methionine sulfoxide, ortho-tyrosine (o-tyr) and dityrosine, chlorotyrosine and nitrotyrosine), as well as chemical modifications of protein following carbohydrate or lipid oxidation, such as N epsilon-(carboxymethyl)lysine and N epsilon-(carboxyethyl)lysine, and malondialdehyde and 4-hydroxynonenal adducts to amino acids. Other biomarkers include the amino acid cross-link pentosidine, the imidazolone adducts formed by reaction of 3-deoxyglucosone or methylglyoxal with arginine, and the imidazolium cross-links formed by the reaction of glyoxal and methylglyoxal with lysine residues in protein. These compounds have been measured in short-lived intracellular proteins, plasma proteins, long-lived extracellular proteins, and in urine, making them valuable tools for monitoring tissue-specific and systemic chemical and oxidative damage to proteins in biological systems. They are normally measured by sensitive high-performance liquid chromatography or gas chromatography-mass spectrometry methods, requiring both complex analytical instrumentation and derivatization procedures. However, sensitive immunohistochemical and ELISA assays are now available for many of these biomarkers. Immunochemical assays should facilitate studies on the role of oxidative stress in aging and chronic disease and simplify the evaluation of therapeutic approaches for limiting oxidative damage in tissues and treating pathologies associated with aging and disease. In this article we summarize recent data and conclusions based on immunohistochemical and ELISA assays, emphasizing the strengths and limitations of the techniques.
Opioid Analgesics and the Risk of Serious Infections Among Patients With Rheumatoid Arthritis: A Self‐Controlled Case Series Study (2015)

In within-person comparisons of patients with RA, opioid use was associated with an increased risk of hospitalization for serious infection.
Functional characterization of NTRK1 mutations identified in melanoma (2014)

Cutaneous melanoma is the most aggressive form of skin cancer, with a complex and heterogeneous aetiology. Deregulation of the mitogen activated protein kinase cascade is common in melanoma, due to activating mutations in the BRAF and NRAS genes. Genetic studies and high-throughput screening technologies have recently identified several somatic mutations affecting different receptor tyrosine kinase (RTK) genes. For the majority of these, however, the contribution to the complexity of melanoma biology has not been assessed. Among these, two novel missense somatic mutations (M379I and R577G) have recently been identified in the gene encoding the neurotrophic RTK NTRK1. The NTRK1 melanoma-associated point mutations were introduced in a NTRK1 expression plasmid. Functional characterization of mutants was assessed after transient and stable transfection in HeLa and NIH3T3 cells, respectively. We showed that M379I and R577G NTRK1 receptors do not display the kinase as constitutively activated and are functionally indistinguishable from the wild-type NTRK1 receptor. Our results indicate that a causative role for M379I and R577G NTRK1 mutations in melanoma development is highly unlikely. This supports the issue that, in parallel to systematic large scale cancer genome screening, functional studies are required to distinguish between mutations that play a causative role in tumor development and others that may only be passenger changes.
Polyreactive anti-DNA monoclonal antibodies and a derived peptide as vectors for the intracytoplasmic and intranuclear translocation of macromolecules (1998)

Naturally occurring polyreactive anti-DNA mAbs derived from a nonimmunized (NZB x NZW)F1 mouse with spontaneous lupus erythematosus penetrated and accumulated in the nuclei of a variety of cultured cells. These mAbs and their F(ab')2 and Fab' fragments, covalently coupled to fluorescein, peroxidase, or a 15-mer polynucleotide, also translocated to the cell nuclei. A 30-amino acid peptide corresponding to the combined sequences of the complementary-determining regions 2 and 3 of the heavy chain variable region of one mAb was able to penetrate into the cytoplasm and nucleus of cells of several lines. This peptide recognized DNA and was strongly polyreactive. Streptavidin-peroxidase conjugates complexed with the N-biotinylated peptide were rapidly translocated into cells. Similarly, peroxidase or anti-peroxidase polyclonal antibodies covalently coupled to the N-cysteinylated peptide through an heterobifunctional maleimide cross-linker were also rapidly internalized and frequently accumulated in nuclei. The peptide carrying 19 lysine residues at its N-terminal was highly effective in transfecting 3T3 cells with a plasmid containing the luciferase gene. Thus, penetrating mAbs and derived peptides are versatile vectors for the intracellular delivery of proteins and genes.
Predicting DNA duplex stability from the base sequence. (1986)

We report the complete thermodynamic library of all 10 Watson-Crick DNA nearest-neighbor interactions. We obtained the relevant thermodynamic data from calorimetric studies on 19 DNA oligomers and 9 DNA polymers. We show how these thermodynamic data can be used to calculate the stability and predict the temperature-dependent behavior of any DNA duplex structure from knowledge of its base sequence. We illustrate our method of calculation by using the nearest-neighbor data to predict transition enthalpies and free energies for a series of DNA oligomers. These predicted values are in excellent agreement with the corresponding values determined experimentally. This agreement demonstrates that a DNA duplex structure thermodynamically can be considered to be the sum of its nearest-neighbor interactions. Armed with this knowledge and the nearest-neighbor thermodynamic data reported here, scientists now will be able to predict the stability (delta G degree) and the melting behavior (delta H degree) of any DNA duplex structure from inspection of its primary sequence. This capability should prove valuable in numerous applications, such as predicting the stability of a probe-gene complex; selecting optimal conditions for a hybridization experiment; deciding on the minimum length of a probe; predicting the influence of a specific transversion or transition on the stability of an affected DNA region; and predicting the relative stabilities of local domains within a DNA duplex.