gebhart/patrepeval huggingface dataset:
Photocleavable linker for the patterning of bioactive molecules (2015)

Herein, we report the use of a versatile photocleavable nitrobenzyl linker to micropattern a wide variety of bioactive molecules and photorelease them on demand. On one end, the linker has an NHS group that can be coupled with any amine, such as peptides, proteins or amine-linkers, and on the other end an alkyne for convenient attachment to materials with an azide functional group. This linker was conjugated with NTA-amine or the cell adhesion peptide cRGD to enable straightforward patterning of His6-tagged proteins or cells, respectively, on PEGylated glass surfaces. This approach provides a practical way to control the presentation of a wide variety of bioactive molecules with high spatial and temporal resolution. The extent of photocleavage can also be controlled to tune the biomolecule density and degree of cell attachment to the surface.
Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP. (1993)

The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.
Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Δ51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene (2007)

Multiple myeloma is a radiosensitive malignancy that is currently incurable. Here, we generated a novel recombinant vesicular stomatitis virus [VSV(Delta51)-NIS] that has a deletion of methionine 51 in the matrix protein and expresses the human sodium iodide symporter (NIS) gene. VSV(Delta51)-NIS showed specific oncolytic activity against myeloma cell lines and primary myeloma cells and was able to replicate to high titers in myeloma cells in vitro. Iodide uptake assays showed accumulation of radioactive iodide in VSV(Delta51)-NIS-infected myeloma cells that was specific to the function of the NIS transgene. In bg/nd/xid mice with established subcutaneous myeloma tumors, administration of VSV(Delta51)-NIS resulted in high intratumoral virus replication and tumor regression. VSV-associated neurotoxicity was not observed. Intratumoral spread of the infection was monitored noninvasively by serial gamma camera imaging of (123)I-iodide biodistribution. Dosimetry calculations based on these images pointed to the feasibility of combination radiovirotherapy with VSV(Delta51)-NIS plus (131)I. Immunocompetent mice with syngeneic 5TGM1 myeloma tumors (either subcutaneous or orthotopic) showed significant enhancements of tumor regression and survival when VSV(Delta51)-NIS was combined with (131)I. These results show that VSV(Delta51)-NIS is a safe oncolytic agent with significant therapeutic potential in multiple myeloma.
[The effect of a phorbol ester on the aortic wall]. (1996)

Changes in the muscle tissue stiffness are important and necessary signs of the contractile process. The work is devoted to the study of this parameter of the smooth muscle tissue reaction during the action of phorbol esters, (namely, phorbol 12-myristate 13-acetate (PMA)), synthetic imitators of diacylglycerole. The experiments were carried out on isolated native preparations of aorta thoracic area of guinea pig under isometric conditions. Contraction induced by PMA or by the temperature was not accompanied by the stiffness changes. Potassium contraction (its development, amplitude, relaxation) evoked on the plateau of the PMA-induced contraction was similar in all respects to that in control: the stiffness increased significantly. These findings prove independent development of these two types of contractile processes. At the same time, the stiffness invariability and similar ratios of optical density to mechanical strength changes in the contractions induced by PMA action or by temperature show the likeness of the force generation mechanisms in these mechano-chemical reactions. The results obtained cannot be explained in terms of the generally accepted hypothesis of actomyosin interaction. The conclusion is made that phorbolic esters during the action on the smooth muscle tissue activate the mechanical strength generation by the connective tissue matrix.
Molecular biology of the symbiotic-pathogenic bacteria Xenorhabdus spp. and Photorhabdus spp (1996)

Free access1 March 1996 Share on Molecular biology of the symbiotic-pathogenic bacteria Xenorhabdus spp. and Photorhabdus sppAuthors: S Forst, K NealsonAuthors Info & AffiliationsDOI: https://doi.org/10.1128/mr.60.1.21-43.1996 PDF/EPUB
DNA Packing in Filamentous Bacteriophages (1988)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
A neural network for tactile sensing: the Hertzian contact problem (1992)

A neural network has been developed for use in local closed-loop gripper control using a tactile sensor array. Backpropagation is used to train a network with a single hidden layer to recognize the angle of contact between a cylindrical finger with an embedded sensor array and a cylindrical rod. Simulation results are presented and discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Oncocin (VDKPPYLPRPRPPRRIYNR-NH2): A Novel Antibacterial Peptide Optimized against Gram-Negative Human Pathogens (2010)

Small proline-rich antimicrobial peptides (AMP) have attracted considerable interest, as they target specific intracellular bacterial components and do not act by lytic mechanisms. Here, a novel peptide, termed oncocin (VDKPPYLPRPRPPRRIYNR-NH(2)), is reported that was optimized for the treatment of Gram-negative pathogens. Its minimal inhibitory concentrations in tryptic soy broth medium ranged from 0.125 to 8 microg/mL for 34 different strains and clinical isolates of Enterobacteriaceae and nonfermenters, such as Escherichia coli , Pseudomonas aeruginosa , and Acinetobacter baumannii . Substitutions of two arginine residues by ornithine increased the half-lives in full mouse serum from about 20 min to greater than 180 min and the activity. Both optimized oncocin derivatives were neither toxic to human cell lines nor hemolytic to human erythrocytes. They could freely penetrate lipid membranes and were washed out completely without any sign of lytic activity, as assessed by quartz crystal microbalance. Fluorescence labeled peptides entered the periplasmic space within 20 min at room temperature and homogeneously stained E. coli within 50 min. In conclusion, the optimized oncocin represents a very promising candidate for future in vivo work and may serve as a novel lead compound for an antibacterial drug class.
Melanocortin-independent Effects of Leptin on Hepatic Glucose Fluxes (2004)

Leptin and insulin share some hypothalamic signaling molecules, but their central administration induces different effects on hepatic glucose fluxes. Acute insulin infusion in the third cerebral ventricle inhibits endogenous glucose production (GP), whereas acute leptin infusion stimulates gluconeogenesis but does not alter GP because of a compensatory decrease in glycogenolysis. Because melanocortin agonists also stimulate hepatic gluconeogenesis, here we examined whether central melanocortin blockade modifies the acute effects of leptin on GP, on gluconeogenesis, on glycogenolysis, and/or on the hepatic expression of the gluconeogenic enzymes glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Systemic or central administration of leptin alone did not alter GP, despite increasing both the rate of gluconeogenesis and the expression of Glc-6-Pase and PEPCK. When activation of the central melanocortin pathway was prevented, the effects of leptin on gluconeogenesis, Glc-6-Pase, and PEPCK were abolished, and a marked suppression of glycogenolysis resulted in decreased GP. We conclude that leptin regulates hepatic glucose fluxes through a melanocortin-dependent pathway leading to stimulation of gluconeogenesis and a melanocortin-independent pathway causing inhibition of GP and glycogenolysis.
THE SQUARE-FREE DIVISOR PROBLEM (1994)

Journal Article THE SQUARE-FREE DIVISOR PROBLEM Get access R. C. BAKER R. C. BAKER Department of Mathematics Brigham Young UniversityProvo, UT 84602 U.S.A. Search for other works by this author on: Oxford Academic Google Scholar The Quarterly Journal of Mathematics, Volume 45, Issue 3, September 1994, Pages 269–277, https://doi.org/10.1093/qmath/45.3.269 Published: 01 September 1994 Article history Received: 17 November 1992 Published: 01 September 1994
Serotyping of Clostridium difficile (1988)

A total of 246 live Clostridium difficile cultures were serotyped by a slide agglutination technique. Fifteen grouping antisera were produced which serotyped 98% of the cultures (241 of 246). Our results indicated that certain serogroups may have specific pathogenicity. Strains of serogroups A, G, H, K, S1, and S4 were cytotoxigenic and were isolated mainly from adult patients with pseudomembranous colitis or antibiotic-associated diarrhea. Nontoxigenic strains of serogroups D and Cd-5 were isolated mainly from asymptomatic neonates and small children. Some cross-reactions occurred among some strains of serogroups A, Cd-5, G, and K. These strains were further examined by analysis of protein profiles and restriction endonuclease patterns to elucidate their serology. Typing of C. difficile by using slide agglutination is a simple technique suitable for routine examination. Serogrouping may be a useful epidemiological marker and could help in elucidating the medical relevance of some C. difficile isolates.
2‘,6‘-Dimethylphenoxyacetyl:  A New Achiral High Affinity P3-P2Ligand for Peptidomimetic-Based HIV Protease Inhibitors (2000)

Starting from palinavir (1), our lead HIV protease inhibitor, we have discovered a new series of truncated analogues in which the P(3)-P(2) quinaldic-valine portion of 1 was replaced by 2', 6'-dimethylphenoxyacetyl. With EC(50)'s in the 1-2 nM range, some of these compounds are among the most potent inhibitors of HIV replication in vitro, reported to date. One of the most promising members in this series (compound 27, BILA 2185 BS) exhibited a favorable overall pharmacokinetic profile, with 61% apparent oral bioavailability in rat. X-ray crystal structures and molecular modeling were used to rationalize the high potency resulting from incorporation of this structurally simple, achiral ligand into the P(3)-P(2) position of hydroxyethylamine-based HIV protease inhibitors.
Intra-retinal layer segmentation of optical coherence tomography using diffusion map (2013)

Optical coherence tomography (OCT) is known to be one of the powerful and noninvasive methods in retinal imaging. OCT uses retroreflected light to provide micron-resolution, cross-sectional scans of biological tissues. In contrast to OCT technology development, which has been a field of active research since 1991, OCT image segmentation has only been fully explored during the last decade. In this paper, we introduce a fast segmentation method based on a new kind of spectral graph theory named diffusion maps. The research is performed on spectral domain OCT images depicting normal macular appearance. In contrast to our recent methods of graph based OCT image segmentation, the presented approach does not require edge-based image information and rather relies on regional image texture. Consequently, the proposed method demonstrates robustness in situations of low image contrast or poor layer-to-layer image gradients. This method is tested on thirteen 3D macular SD-OCT images obtained from eyes without pathologies with Topcon 3D OCT-1000 imaging system (with a size of 650 × 512 × 128 voxels and a voxel resolution of 4.81 × 13.67 × 24.41 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ). The mean unsigned and signed border positioning errors (mean ± SD) was 8.52±3.13 and -4.61±3.35 micrometers, respectively. The average computation time of the proposed algorithms (implemented with MATLAB) was 12 seconds per 2D slice.
Identification of the motifs within the tobacco mosaic virus 5′-leader responsible for enhancing translation (1992)

The leader (called omega) of tobacco mosaic virus RNA enhances translation in both eukaryotes and prokaryotes. Although little secondary structure is predicted to exist within omega, the primary sequence of the 68 base leader is highly organized. Three copies of an eight base direct repeat and a (CAA)n region represent the two motifs found in the leaders of many TMV strains, and together these comprise 72% of omega. In previous deletion studies, no mutants exhibited loss-of-function, suggesting that functional redundancy exists within omega. We report here that a more comprehensive deletion analysis identified the motifs involved in translational enhancement. In a separate approach, oligonucleotides containing the sequence of each motif were used to construct leaders that varied in the number and configuration of the motifs. beta-Glucuronidase mRNA constructs containing these mutant leaders were synthesized in vitro and their translational efficiency measured in vivo following mRNA delivery to carrot protoplasts via electroporation. A combination of one copy of the 8 base direct repeat and a 25 base (CAA)n region was identified as the core regulatory element, although the (CAA)n motif is more critical. Two copies of the (CAA)n region are sufficient to confer a high level of enhancement and a leader composed of multiple copies of the direct repeat is moderately enhancing. Thus, these two motifs are functionally redundant.
Crystallographic Studies of the Escherichia coli Quinol-Fumarate Reductase with Inhibitors Bound to the Quinol-binding Site (2002)

The quinol-fumarate reductase (QFR) respiratory complex of Escherichia coli is a four-subunit integral-membrane complex that catalyzes the final step of anaerobic respiration when fumarate is the terminal electron acceptor. The membrane-soluble redox-active molecule menaquinol (MQH(2)) transfers electrons to QFR by binding directly to the membrane-spanning region. The crystal structure of QFR contains two quinone species, presumably MQH(2), bound to the transmembrane-spanning region. The binding sites for the two quinone molecules are termed Q(P) and Q(D), indicating their positions proximal (Q(P)) or distal (Q(D)) to the site of fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein subunits. It has not been established whether both of these sites are mechanistically significant. Co-crystallization studies of the E. coli QFR with the known quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and 2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors block the binding of MQH(2) at the Q(P) site. In the structures with the inhibitor bound at Q(P), no density is observed at Q(D), which suggests that the occupancy of this site can vary and argues against a structurally obligatory role for quinol binding to Q(D). A comparison of the Q(P) site of the E. coli enzyme with quinone-binding sites in other respiratory enzymes shows that an acidic residue is structurally conserved. This acidic residue, Glu-C29, in the E. coli enzyme may act as a proton shuttle from the quinol during enzyme turnover.
Fluoxetine and Premature Ejaculation (1998)

The purpose of this study was to investigate the effect of fluoxetine on sexual function in men with premature ejaculation and/or erectile dysfunction and control subjects in a prospective, double-blind, placebo-controlled, crossover study. There were four groups: (1) premature ejaculation (PE, N = 9); (2) premature ejaculation and erectile dysfunction (PE/ED, N = 9); (3) erectile dysfunction (ED, N = 7); and (4) healthy, sexually functional control subjects (N = 15). The study consisted of three 4-week periods: fluoxetine, washout, and placebo (or vice versa). Fluoxetine began at 5 mg/day for 2 weeks, followed by 10 mg/day for 2 weeks. At weeks 0, 4, 8, and 12, subjects visited the laboratory for evaluation of sexual function and assessment of erectile response, ejaculation, and sexual arousal to visual erotic stimulation without and with concomitant vibrotactile stimulation to the penis. At home, daily logs for sexual activities and feelings of well-being were maintained, and nocturnal penile tumescence was measured. The latency to ejaculation increased significantly in the PE/ED group (p = 0.03) and in the PE and the PE/ED group taken together (p = 0.007) but not in the PE group alone. Fluoxetine stimulated objectively but not subjectively measured erectile response during laboratory assessment in all groups. No major side effects were reported. In conclusion, fluoxetine (5-10 mg/day) was effective in increasing latency to ejaculation in patients with PE (PE and PE/ED groups combined).
Fungicidal properties, sterol binding, and proteolytic resistance of the synthetic peptide D4E1 (1998)

The fungicidal properties of the synthetic peptide D4E1 were studied with nongerminated and germinating conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Fusarium moniliforme, and Fusarium oxysporum. The minimal lethal concentrations (MLC) needed to kill 100% of germinating conidia ofA. fumigatus, A. flavus, and A. niger were 12.5, 12.5, and 25 µM, respectively. The MLC value for nongerminated and germinating conidia of both Fusarium spp. was 3.0 µM. Except for A. fumigatus, D4E1 was inactive against the nongerminated conidia of the Aspergillus spp. Physicochemical studies showed D4E1 complexed with ergosterol, a sterol present in conidial walls. Cholesterol, present in nongerminated conidia of F. moniliforme, had a greater affinity for D4E1 than did ergosterol. D4E1 was more resistant to fungal and plant protease degradation than the natural peptide, cecropin A. These in vitro results suggest D4E1 is a candidate for transgenic expression in plants to enhance host resistance to fungal infection.Key words: peptides, fungicidal, Aspergillus spp., Fusarium spp., sterols.
The regulation of GH secretion by sex steroids (2004)

Gonadal sex steroids modulate GH synthesis and secretion with effects on both the hypothalamus and anterior pituitary. In the post-pubertal animal, androgens and oestrogens modulate hypothalamic somatostatin (SS) and GHRH synthesis respectively. These effects may be direct as SS neurons express the androgen receptor and many GHRH neurons are oestrogen receptor positive. The neonatal steroid environment modulates the number of GHRH neurons in the adult hypothalamus, as well as their responsivity to post-pubertal steroids. Furthermore, both neonatal and post-pubertal steroids modulate hypothalamic synaptic organisation affecting the number of synaptic inputs and the morphology of glial cells. This in turn has important effects on the ability of the hypothalamus to drive the secretory pulsatility of anterior pituitary hormone release. At the level of the somatotroph, androgens and oestrogens have been reported to stimulate, inhibit or have no effect on GH synthesis. In primary cultures, we found no effect of either androgens or oestrogens on GH mRNA levels. However, the sex steroid environment significantly modified the response of somatotrophs to SS. Furthermore, males have more somatotrophs compared with female rats and this partially depends on the neonatal sex steroid environment. In conclusion, sex steroids have both organisational and activational effects on the GH axis. These effects range from modulating the number of hypothalamic neurons controlling GH secretion, their responsiveness to later steroids, and the synaptic connectivity and neuropeptide production, to modulation of somatotroph numbers in the anterior pituitary and their responsiveness to inputs controlling GH synthesis and secretion.
Pharmacokinetics of recombinant interleukin 2 in humans. (1990)

This report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an i.v. bolus, i.v. or i.p. infusion, and i.m. or s.c. injection. Immediately after an i.v. bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units/ml for a dose of 10(6) units/m2. The level initially decreases with a half-life of 12.9 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus. The median steady state level during an i.v. infusion of 10(6) units/m2 over 6 h is 41 units/ml. A clearance rate of approximately 120 ml/min is obtained from either the i.v. bolus or infusion data and is consistent with the renal filtration being the major route of clearance. Serum levels remain fairly constant for about 8 h after s.c. or i.m. injection but are approximately 2% of the level seen immediately after an i.v. bolus. The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an i.m. injection to the blood. After i.p. infusion IL-2 is only slowly transported to the blood. The median serum IL-2 levels are 430-fold lower than levels in the i.p. fluid and decrease with a median half-life of 6.3 h.
Antigens recognized by two human monoclonal IgM anticolon cancer antibodies, 16.88 and C-OU1 (B9165) (1991)

We have compared by SDS-PAGE Western blotting the molecules detected by two human monoclonal antibodies, C-OU1 and 16.88. The antibodies have previously been shown to detect a cytoplasmatic antigen with an Mr of 43 kD present in colon adenocarcinoma cell lines and in colon cancer tissues. We now demonstrate that these antibodies differ significantly in their fine specificity, resulting in a quite dissimilar tumor selectivity. The antibody 16.88, in addition to reactivity with the 43-kD molecule, also recognizes a 190-kD molecule present both in melanoma cells and in cells previously reported as 16.88 antigen positive. The 16.88 antibody does not detect a 43-kD molecule in extracts of melanoma cells. The 190-kD component was not detectable in hepatoma or mamma carcinoma cells, both of which showed presence of the 43-kD molecule. The C-OU1 antibody shows no reactivity with the 190-kD molecule in any of the cells tested or with other proteins in melanoma cells. Radiolabeled 16.88 antibody shows better localization to melanoma cancer than to colon cancer xenograft transplanted onto nude mice. These findings indicate the presence of a tumor-associated antigen not previously described and have obvious implications for potential clinical uses of the antibodies.
Rapid growth in infancy and childhood and obesity in later life – a systematic review (2005)

The association between obesity and morbidity resulting from chronic diseases is well known. This systematic review addresses studies of the role of rapid growth in infancy and childhood as possible determinants of overweight and obesity later in the life course. We reviewed MEDLINE for studies reporting on growth in infancy and childhood, as well as measures of weight or adiposity in later childhood, adolescence or adulthood. The methodological quality of the papers was assessed using the criteria suggested by Downs and Black. Sixteen articles that fulfilled review criteria were located. There was wide variability in the indicators used for defining rapid growth as well as overweight or obesity. The age range in which weight or adiposity was measured ranged from 3 to 70 years. In spite of differences in definitions used, 13 articles that reported on early rapid growth found significant associations with later overweight or adiposity. Efforts should be made to standardize the definition of rapid growth, as well as that of overweight and obesity in children and adolescents. The most frequent definition for rapid growth in this review was a Z-score change greater than 0.67 in weight for age between two different ages in childhood. Regarding obesity, the definition proposed by the International Obesity Task Force also appears to be most appropriate. The present results indicate that early growth is indeed associated with the prevalence of obesity later in the life course.