gebhart/patrepeval huggingface dataset:
Rapid accurate point-of-care tests combining diagnostics and antimicrobial resistance prediction forNeisseria gonorrhoeaeandMycoplasma genitalium (2017)

In addition to inadequate access to early diagnosis and treatment with antimicrobial agents for patients and sexual contacts, management and control of STIs is significantly challenged by emergence and spread of antimicrobial resistance (AMR), particularly for STIs such as <i>Neisseria gonorrhoeae</i> and <i>Mycoplasma genitalium</i> This is further compounded by use of nucleic acid amplification techniques for diagnosis, resulting in reduced phenotypic AMR testing for <i>N. gonorrhoeae</i> and absence or suboptimal AMR surveillance for guiding treatment of both STIs in many settings. Rapid accurate point-of-care (POC) tests for diagnosis of all STIs would be valuable but to significantly impact treatment precision and management of <i>N. gonorrhoeae</i> and <i>M. genitalium</i> infections, combinations of rapid POC diagnostic and AMR testing (POC-AMR) will likely be required. This strategy would combat STI burden and AMR emergence and spread by enabling diagnosis and individualised treatment at the first healthcare visit, potentially reducing selection pressure on recommended antimicrobials, reducing transmission of resistant strains and providing means for AMR surveillance. Microfluidic and nanotechnology platforms under development for rapid detection of STIs provide a basis to also develop molecular rapid POC-AMR prediction. A number of prototypic devices are in the pipeline but none as yet approved for routine use. However, particularly for <i>N. gonorrhoeae</i>, more knowledge is required to assess which antimicrobials lend themselves to a genotypic POC-AMR approach, in relation to genotypic-phenotypic associations and potential impact clinically and epidemiologically. Key for successful deployment will include also understanding cost-effectiveness, cost-consequences and acceptability for key stakeholders.
NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health (2007)

Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), B-chronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.
Reduced androgen receptor gene expression with first exon CAG repeat expansion (1996)

The molecular basis for partial androgen insensitivity associated with adult onset spinal/bulbar muscular atrophy was investigated by transient transfection of human androgen receptor (AR) expression vectors containing increasing CAG repeat lengths in the first exon. An inverse relationship was observed between CAG repeat length and AR mRNA and protein levels. Trinucleotide repeat lengths of 43 and 65 associated with spinal/bulbar muscular atrophy decreased AR mRNA and protein levels but did not alter equilibrium binding affinity for [3H]R1881 or inherent transcriptional activity of AR, expressed as androgen-dependent fold induction of a mouse mammary tumor virus promoter-luciferase reporter vector. The findings indicate that glutamine expansion up to 66 residues in the NH2-terminal domain of AR does not alter AR functional activity. Rather, CAG repeat expansion in the region of the first exon reduces AR mRNA and protein expression. The study reveals a previously unrecognized effect of CAG repeat length on AR mRNA expression and a novel molecular mechanism for androgen resistance.
The BTB/POZ domain: a new protein-protein interaction motif common to DNA- and actin-binding proteins. (1995)

The BTB/POZ domain defines a newly characterized protein-protein interaction interface. It is highly conserved throughout metazoan evolution and generally found at the NH2 terminus of either actin-binding or, more commonly, nuclear DNA-binding proteins. By mediating protein binding in large aggregates, the BTB/POZ domain serves to organize higher order macromolecular complexes involved in ring canal formation or chromatin folding.
A new method for sequencing DNA. (1977)

DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave DNA preferentially at guanines, at adenines, at cytosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by electrophoresis on a polyacrylamide gel, the DNA sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of labeling.
Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts (2011)

The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species.
Knee pain and joint loading in subjects with osteoarthritis of the knee (2000)

Although treatments for osteoarthritis of the knee are often directed at relieving pain, pain may cause patients to alter how they perform activities to decrease the loads on the joints. The knee-adduction moment is a major determinant of the load distribution between the medial and lateral plateaus. Therefore, the interrelationship between pain and the external knee-adduction moment during walking may be especially important for understanding mechanical factors related to the progression of medial tibiofemoral osteoarthritis. Fifty-three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied. These subjects were a subset of those enrolled in a double-blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2-week washout of anti-inflammatory and analgesic treatment. The subjects then took a nonsteroidal anti-inflammatory drug, acetaminophen, or placebo for 2 weeks, and the gait and clinical evaluations were repeated. The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain (R = 0.48, p < 0.001) and was significantly different between those whose pain increased (n = 7), decreased (n = 18), or remained unchanged (n = 28) (p = 0.009). Those with increased pain had a significant decrease in the peak external adduction (p = 0.005) and flexion moments (p = 0.023). In contrast, the subjects with decreased pain tended to have an increase in the peak external adduction moment (p = 0.095) and had a significant increase in the peak external extension moment (p = 0.017). The subjects whose pain was unchanged had no significant change in the peak external adduction (p = 0.757), flexion (p = 0.234), or extension (p = 0.465) moments. Thus, decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints. Additional long-term prospective studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease.
Formation of a Molten Globule Intermediate Early in the Kinetic Folding Pathway of Apomyoglobin (1993)

Hydrogen exchange pulse labeling and stopped-flow circular dichroism were used to establish that the structure of the earliest detectable intermediate formed during refolding of apomyoglobin corresponds closely to that of a previously characterized equilibrium molten globule. This compact, cooperatively folded intermediate was formed in less than 5 milliseconds and contained stable, hydrogen-bonded secondary structure localized in the A, G, and H helices and part of the B helix. The remainder of the B helix folded on a much slower time scale, followed by the C and E helices and the CD loop. The data indicate that a molten globule intermediate was formed on the kinetic folding pathway.
Nanoscale 1,3,5,7-Tetrasubstituted Adamantanes and p-Substituted Tetraphenyl-methanes for AFM Applications (2002)

[structure: see text] Tetrahedrally shaped nanoscale molecules 18-20 were synthesized from the corresponding tetraiodide by a series of Sonogashira coupling reactions. Three of the sulfur-containing termini are intended for eventual binding to a gold-coated conventional AFM tip, while the fourth terminus scans the sample. AFM images of 19 demonstrate that the molecule is sufficiently large and rigid to be imaged by a conventional AFM tip.
Hypertext '87: keynote address (1988)

article Free AccessHypertext '87: keynote address Author: Andries van Dam Brown Univ. Providence, RI Brown Univ. Providence, RIView Profile Authors Info & Claims Communications of the ACMVolume 31Issue 7July 1988 pp 887–895https://doi.org/10.1145/48511.48519Published:01 July 1988Publication History 110citation652DownloadsMetricsTotal Citations110Total Downloads652Last 12 Months51Last 6 weeks22 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
COMPLEX TRANSCRIPTIONAL UNITS: DIVERSITY IN GENE EXPRESSION BY ALTERNATIVE RNA PROCESSING (1986)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Topoisomerase IV is a target of quinolones in Escherichia coli. (1995)

We have demonstrated that, in Escherichia coli, quinolone antimicrobial agents target topoisomerase IV (topo IV). The inhibition of topo IV becomes apparent only when gyrase is mutated to quinolone resistance. In such mutants, these antibiotics caused accumulation of replication catenanes, which is diagnostic of a loss of topo IV activity. Mutant forms of topo IV provided an additional 10-fold resistance to quinolones and prevented drug-induced catenane accumulation. Drug inhibition of topo IV differs from that of gyrase. (i) Wild-type topo IV is not dominant over the resistant allele. (ii) Inhibition of topo IV leads to only a slow stop in replication. (iii) Inhibition of topo IV is primarily bacteriostatic. These differences may result from topo IV acting behind the replication fork, allowing for repair of drug-induced lesions. We suggest that this and a slightly higher intrinsic resistance of topo IV make it secondary to gyrase as a quinolone target. Our results imply that the quinolone binding pockets of gyrase and topo IV are similar and that substantial levels of drug resistance require mutations in both enzymes.
Inhibition of CD73 stimulates the migration and invasion of B16F10 melanoma cells in vitro, but results in impaired angiogenesis and reduced melanoma growth in vivo (2013)

The role of ecto-5'-nucleotidase (CD73), an enzyme providing interstitial adenosine, was investigated in B16F10 melanoma progression. Chemical inhibition of CD73 decreased adherence of cells to extracellular matrix proteins in vitro and led to enhanced migration and invasion. Both processes were reversed by adenosine receptor agonists. In CD73‑deficient mice, tumor growth was decreased in comparison with that of wild-type animals. Additionally, the vasculature of CD73-inhibited tumors was impaired and neoangiogenesis in Matrigel plugs was reduced. It is, therefore, proposed that although CD73 shows anti-invasive and antimigratory function in B16F10 melanoma cells, its proangiogenic action is prevalent in vivo and may contribute to increased tumor growth.
Treatment of Chronic Nonhealing Leg Ulceration with Gaseous Nitric Oxide: A Case Study (2004)

This single case study demonstrated that gNO as a topical agent was well tolerated by the patient without any report of discomfort or side effect. The result of wound healing was very promising and warrants future exploration.
Capillary-Scale Refractive Index Detection by Interferometric Backscatter (1996)

We describe a novel approach for measuring fluid bulk properties such as refractive index (RI) and temperature changes in tubes of capillary dimensions based on a simple optical configuration which uses an unfocused He−Ne laser, a cylindrical tube, and a photodetector. Side illumination of a fused silica capillary produces a fan radiation in a 360° plane normal to the central axis of the capillary that is spatially well defined in the lateral direction. It is shown that, upon viewing a high-contrast interference pattern contained in the beam profile on a flat imaging plane in a direct backscattering configuration, the physical characteristics of the capillary and the bulk properties of the fluid contained within the tube can be determined. Position changes in the maxima and minima in the intensity-modulated profile (interference fringes) are directly related to the refractive index of the fluid in the tube. Measurement of the fringe shift by a slit-photodetector assembly facilitates the determination of dn/n at the level of 1.8 × 10-7, while temperature changes can be measured using the fringe centroid position at a level of 5.8 × 10-5 °C (DL = 3σ). Each determination can be made within a probe volume of 2.6 nL. Also, a wide range of tube diameters can be employed (75−775 μm i.d.) with no modification to the optical train or measurable degradation in system performance. We report results for an optical ray trace model for predicting fringe pattern energy distributions, optimization of the optical configuration, and general system performance predictions. Comparison of our four-beam interference model with experimental results illustrates the utility of the model.
Nucleosides and nucleotides. 112. 2-(1-Hexyn-1-yl)adenosine-5'-uronamides: a new entry of selective A2 adenosine receptor agonists with potent antihypertensive activity (1992)

Chemical modifications of the potent A2 adenosine receptor agonist 2-(1-hexyn-1-yl)adenosine (7, 2-HA) at the 5'-position have been carried out to find more potent and selective A2 agonists. These analogues were evaluated for adenosine A1 and A2 receptor binding affinity in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR). Among the series of compounds, 2-(1-hexyn-1-yl)adenosine-5'-N-cyclopropyluronamide (16d) had the most potent affinity to the A2 receptor with a Ki of 2.6 nM, which is essentially the same as that of the parent agonist, 2-HA. However, the most selective agonist for the A2 receptor was 2-(1-hexyn-1-yl)adenosine-5'-N-methyluronamide (16b) with a Ki of 11 nM and a 162-fold selectivity. The N-alkyl substituents of 5'-uronamide derivatives did not seem to potentiate the A2 binding affinity but drastically reduced the A1 affinity compared with the parent 2-HA. Therefore, the A1/A2 selectivity was consequently increased. Other 5'-deoxy-5'-substituted derivatives of 2-HA such as the chloro (20), carboxamide (27, 28), sulfonamide (29), urea (30), and thiourea (22) analogues were also prepared. Among these nucleosides, no active compounds with potent or selective affinities to both receptors were found except 20. Although glycosyl conformations and sugar-puckering of these nucleosides were studied by 1H NMR spectroscopy, there were no positive correlations between active and inactive agonists. 2-(1-Hexyn-1-yl)adenosine-5'-uronamide (16a) and 16d had a potent hypotensive effect at ED30 values of 0.18 and 0.17 micrograms/kg, respectively, upon iv administration to anesthetized SHR.
Diagnosis of Bearing Faults in Induction Machines by Vibration or Current Signals: A Critical Comparison (2010)

Mechanical imbalances and bearing faults account for a large majority of the faults in a machine, particularly for small-medium size machines. Therefore, their diagnosis is an intensively investigated field of research. Recently, many research activities were focused on the diagnosis of bearing faults by current signals. This paper compares the bearing fault detection capability obtained with the vibration and current signals. The paper contribution is the use of a simple and effective signal processing technique for both current and vibration signals, and a theoretical analysis of the physical link between faults, modeled as a torque disturbance, and current components. The focus of the paper is on the theoretical development of the correlation between torque disturbances and the amplitude of the current components, together with a review of fault models used in the literature. Another contribution is the re-creation of realistic incipient faults and their experimental validation. Radial effects are visible only in case of large failures that result in air-gap variations. Experiments are reported that confirm the proposed approach.
Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole (2001)

In epithelial cells, the intracellular pathogen Brucella abortus escapes from the endocytic pathway, exploits the autophagic machinery of the host cell and establishes a unique replication niche in the endoplasmic reticulum. The molecular mechanisms underlying these processes are still poorly understood. Recently, a B. abortus type IV-related secretion system encoded by the virB operon has been described as being involved in the intracellular trafficking of the bacteria. In this study, we have analysed the intracellular pathway of B. abortus virB10 mutant strains by confocal microscopy. We demonstrate that a functional virB operon is essential for the biogenesis of the Brucella-containing vacuole. Polar mutation preventing the transcription of virB10 and downstream sequences did not allow Brucella to bypass the endocytic pathway. Consequently, polar mutant-containing vacuoles fused with lysosomes in which bacteria underwent a degradation process. In contrast, virB10 non-polar mutants were capable of avoiding interactions with the endocytic pathway but, diverging to wild-type Brucella, were unable to reach the endoplasmic reticulum to establish their intracellular replication niche and seemed to be recycled to the cell surface. Based on the two particular phenotypes described in this work, a model of maturation of the Brucella-containing vacuole is proposed.
Similar molecular properties of granulocyte-macrophage colony-stimulating factors produced by different mouse organs in vitro and in vivo. (1979)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was partially purified from post-endotoxin serum and conditioned media produced by organs from both normal and endotoxin-injected C57BL mice. The organs used to condition medium were heart, thigh muscle, salivary gland, thymus, spleen, kidney, brain, and femur shaft. The charge properties, molecular weights, and concanavalin A binding profiles of these GM-CSFs were analyzed and compared to purified mouse lung GM-CSF. All the GM-CSFs examined were shown to be gycoproteins since a proportion of the activity (80 to 100%) bound to concanavalin A-Sepharose. The organ-conditioned medium GM-CSFs were purified (3- to 13-fold) by absorption to calcium phosphate gel and chromatography on DEAE-Sepharose (further 2- to 10-fold). Analysis of the DEAE-Sepharose elution profiles indicated that there were two major charge species of GM-CSF eluting at conductivities of 10 and 14 mmho. These partially purified GM-CSFs showed considerable differences in their apparent molecular weights on Sephacryl S-200 (37,000 to 200,000). However, these differences could be eliminated by treating the GM-CSFs with neuraminidase and performing molecular sizing experiments under dissociating conditions (Sepharose CL-6B, 6 M guanidine hydrochloride). Although some of the GM-CSFs showed anomalously high molecular weights (40,000) on gel filtration columns, even under dissociating conditions, this appeared to be due to properties of the sialic acid residues. After neuraminidase treatment all of the conditioned medium GM-CSFs eluted from DEAE-Sepharose as a single peak of biological activity at a conductivity of 10 mmho and from gel filtration columns in the presence of 6 M guanidine hydrochloride as a single molecular weight species of approximately 23,000. GM-CSF from post-endotoxin serum (produced in vivo) eluted from the gel filtration column with an apparent molecular weight of 39,000, but analysis using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that this GM-CSF also had an apparent molecular weight of 23,000.