gebhart/patrepeval huggingface dataset:
Inhibition of Calcium Currents in Rat Colon Sensory Neurons by K- But Not μ- or δ-Opioids (1998)

Inhibition of calcium currents in rat colon sensory neurons by kappa- but not mu- or delta-opioids. J. Neurophysiol. 80: 3112-3119, 1998. We previously reported that kappa-, but not mu- or delta-opioid receptor agonists (ORAs) have selective, potentially useful peripheral analgesic effects in visceral pain. To evaluate one potential site and mechanism by which these effects are produced, we studied opioid effects on high-voltage activated (HVA) Ca2+ currents in identified (Di-I) pelvic nerve sensory neurons from the S1 dorsal root ganglion (DRG). Results were compared with opioid effects on cutaneous neurons from L5 or L6 DRG. Di-I-labeled DRG cells were voltage clamped (perforated whole cell patch clamp), and HVA Ca2+ currents were evoked by depolarizing 240-ms test pulses to +10 mV from a holding potential of -60 mV. Neither mu-ORAs (morphine, 10(-6 )M, n = 16; [D-Ala2, N-Me-Phe4, Gly-ol5] enkephalin, 10(-6 )M, n = 12) nor delta-ORAs ([D-Pen2, D-Pen5] enkephalin, 10(-7 )M, n = 16; SNC-80, 10(-7 )M, n = 7) affected HVA Ca2+ currents in colon sensory neurons. In contrast, the kappa-ORAs U50, 488 (10(-6 )M), bremazocine (10(-6)M), and nalBzoH (10(-6 )M) significantly attenuated HVA Ca2+ currents in colon sensory neurons; effects on cutaneous sensory neurons were variable. A nonreceptor selective concentration of naloxone (10(-5 )M) and nor-BNI (10(-6 )M), a selective kappa-opioid receptor antagonist, reversed the inhibitory effect of kappa-ORAs. In the presence of N-, P-, or Q-, but not L-type Ca2+ channel antagonists, the effect of U50,488 on HVA Ca2+ currents was significantly reduced. Pretreatment with pertussis toxin (PTX) prevented the inhibition by U50,488. These results suggest that kappa-opioid receptors are coupled to multiple HVA Ca2+ channels in colon sensory neurons by a PTX-sensitive G protein pathway. We conclude that inhibition of Ca2+ channel function likely contributes in part to the peripheral analgesic action of kappa-ORAs in visceral nociception.
Potent and Broad Anti-HIV-1 Activity Exhibited by a Glycosyl-Phosphatidylinositol-Anchored Peptide Derived from the CDR H3 of Broadly Neutralizing Antibody PG16 (2011)

PG9 and PG16 are two recently isolated quaternary-specific human monoclonal antibodies that neutralize 70 to 80% of circulating HIV-1 isolates. The crystal structure of PG16 shows that it contains an exceptionally long CDR H3 that forms a unique stable subdomain that towers above the antibody surface to confer fine specificity. To determine whether this unique architecture of CDR H3 itself is sufficient for epitope recognition and neutralization, we cloned CDR H3 subdomains derived from human monoclonal antibodies PG16, PG9, b12, E51, and AVF and genetically linked them to a glycosyl-phosphatidylinositol (GPI) attachment signal. Each fusion gene construct is expressed and targeted to lipid rafts of plasma membranes through a GPI anchor. Moreover, GPI-CDR H3(PG16, PG9, and E51), but not GPI-CDR H3(b12 and AVF), specifically neutralized multiple clades of HIV-1 isolates with a great degree of potency when expressed on the surface of transduced TZM-bl cells. Furthermore, GPI-anchored CDR H3(PG16), but not GPI-anchored CDR H3(AVF), specifically confers resistance to HIV-1 infection when expressed on the surface of transduced human CD4(+) T cells. Finally, the CDR H3 mutations (Y100HF, D100IA, and G7) that were previously shown to compromise the neutralization activity of antibody PG16 also abolished the neutralization activity of GPI-CDR H3(PG16). Thus, we conclude that the CDR H3 subdomain of PG16 neutralizes HIV-1 when targeted to the lipid raft of the plasma membrane of HIV-1-susceptible cells and that GPI-CDR H3 can be an alternative approach for determining whether the CDR H3 of certain antibodies alone can exert epitope recognition and neutralization.
Glypican-3 Targeted Human Heavy Chain Antibody as a Drug Carrier for Hepatocellular Carcinoma Therapy (2015)

Glypican-3 (GPC3) represents an attractive target for hepatocellular carcinoma (HCC) therapy because it is highly expressed in HCC but not in adult normal tissue. Recently, high affinity anti-GPC3 antibodies have been developed; however, full antibodies may not penetrate evenly into tumor parenchyma, reducing their effectiveness. In this study, we compared a whole IgG antibody, anti-GPC3 YP7, with an anti-GPC3 human heavy chain antibody, HN3, with regard to their relative therapeutic effects. Both YP7 and HN3 bound to GPC3-positive A431/G1 cells and were internalized by the cells by in vitro evaluation with (125)I- and (111)In-radiolabeling antibodies. In vivo biodistribution and tumor accumulation was performed with (111)In-labeled antibodies, and intratumoral microdistribution was evaluated using fluorescently labeled antibodies (IR700). HN3 showed similar high tumor accumulation but superior homogeneity within the tumor compared with YP7. Using the same IR700 conjugated antibodies photoimmunotherapy (PIT) was performed in vitro and in a tumor-bearing mouse model in vivo. PIT with IR700-HN3 and IR700-YP7 demonstrated that comparable results could be achieved despite of low reaccumulation 24 h after the first NIR light exposure. These results indicated that a heavy-chain antibody, HN3, showed more favorable characteristics than YP7, a conventional IgG, as a therapeutic antibody platform for designing molecularly targeted agents against HCC.
Music playlist prediction via detecting song moods (2013)

Modern internet technologies make people easily access millions of songs. However it also forms a huge barrier between customers and those songs people truely want, due to the difficulty to explore this large collections. In this paper, we propose a novel music playlist prediction algorithm to facilitate this process for users. This method captures the moods expressed by songs in playlist context and also models the nature of composing a playlist. With the help of captured moods, personalized predictions can be achieved. We offer two ways to represent these hidden song moods and the transitions between them. The empirical evaluations show that our method outperforms other state-of-the-art methods in terms of perplexity.
Fis activates the RpoS-dependent stationary-phase expression of proP in Escherichia coli (1995)

Fis is a general nucleoid-associated protein in Escherichia coli whose expression is highly regulated with respect to growth conditions. A random collection of transposon-induced lac fusions was screened for those which give increased expression in the presence of Fis in order to isolate a ProP-LacZ protein fusion. We find that proP, which encodes a low-affinity transporter of the important osmoprotectants proline and glycine betaine, is transcribed from two promoters. proP1 is transiently induced upon subculture and is upregulated by increases in medium osmolarity. As cells enter stationary phase, a second promoter, proP2, is strongly induced. This promoter can also be induced by high medium osmolarity in exponential phase. The activity of proP2 depends on Fis and the stationary-phase sigma factor sigmas. In the presence of Fis, proP2 expression is increased over 50-fold, as judged by the LacZ activity of cells carrying the proP-lacZ fusion as well as by direct RNA analysis, making this the most strongly activated promoter by Fis that has been described. Two Fis binding sites centered at positions -41 (site I) and -81 (site II) with respect to the transcription initiation site of P2 have been defined by DNase I footprinting. Mutations in site I largely abolish stationary-phase activation, while mutations at site II have a minor effect, suggesting that direct binding of Fis to site I is important for Fis-mediated activation of this promoter. In addition to Fis and sigmas, sequences located over 108 bp upstream of the proP2 transcription initiation site are required for efficient expression.
A transgene with repeated DNA causes high frequency, post‐transcriptional suppression of ACC‐oxidase gene expression in tomato (1998)

Gene silencing with sense genes is an important method for down-regulating the expression of endogenous plant genes, but the frequency of silencing is unpredictable. Fifteen per cent of tomato plants transformed with a 35S-ACC-oxidase ( ACO 1) sense gene had reduced ACC-oxidase activity. However, 96% of plants transformed with an ACC-oxidase sense gene, containing two additional upstream inverted copies of its 5' untranslated region, exhibited reduced ACC-oxidase activity compared to wild-type plants. In the three plants chosen for analysis, there were substantially reduced amounts of both endogenous and transgenic ACO RNA, indicating that this was an example of co-suppression. Ribonuclease protection assays using probes spanning intron-exon borders showed that the reduced accumulation of endogenous ACO mRNA occurred post-transcriptionally since the abundance of unprocessed transcripts was not affected. The ACO1 transgene with the repeated 5'UTR also strongly inhibited the accumulation of RNA from the related ACO 2 gene in flowers, although there is little homology between the 5'UTRs of ACO 1 and ACO 2. These results indicate that although repeated DNA in a transgene greatly enhances the probability of gene silencing of an endogenous gene, it also involves generation of a trans -acting silencing signal produced, at least partly, from sequences external to the repeat.
Drug Treatment in Urology (2006)

List of contributors. Preface. Part 1 Functional Disorders. 1 Urinary Incontinence (Stephen J. Griffin & William H. Turner). 2 Medical Therapy for Benign Prostatic Hyperplasia (Simon R. J. Bott, Charlotte L. Foley & Roger S. Kirby). 3 Drugs Used in the Treatment of Erectile Dysfunction (Ian Eardley). 4 Drugs Used in the Treatment of Interstitial Cystitis (Mary Garthwaite & Ian Eardley). Part 2 Urinary Tract Infection. 5 Treatment of Simple Urinary Tract Infection (Dana Stieber & Kalpana Gupta). 6 New Concepts in Antimicrobial Treatment for Complicated Urinary Tract Infections: Single Daily Aminoglycoside Dosing and 'Switch' Therapy (Richard A. Santucci & John N. Krieger). 7 Prostatitis (Martin Ludwig & Wolfgang Weidner). 8 Perioperative Antimicrobial Prophylaxis in Urological Interventions of the Urinary and Male Genital Tract (Kurt G. Naber). 9 Candiduria (Jack D. Sobel). Part 3 Urological Oncology. 10 Pharmacotherapy in the Management of Prostate Cancer (Jeetesh Bhardwa & Roger S. Kirby). 11 Drugs in Superficial Bladder Cancer (Peter Whelan). 12 Systemic Therapy for Bladder Cancer (J. D. Chester & M. G. Leahy). 13 Testicular Cancer (Jourik A. Gietema & Dirk Th. Sleijfer). 14 Renal Cancer (Naveen S. Vasudev & Poulam M. Patel). Part 4 Analgesia. 15 Postoperative Analgesia (Patrick McHugh). 16 Treatment of Pain in Urology (Adrian D. Joyce & William R. Cross). Index.
Defect Scattering in Graphene (2009)

Irradiation of graphene on SiO2 by 500 eV Ne and He ions creates defects that cause intervalley scattering as is evident from a significant Raman D band intensity. The defect scattering gives a conductivity proportional to charge carrier density, with mobility decreasing as the inverse of the ion dose. The mobility decrease is 4 times larger than for a similar concentration of singly charged impurities. The minimum conductivity decreases proportional to the mobility to values lower than 4e(2)/pih, the minimum theoretical value for graphene free of intervalley scattering. Defected graphene shows a diverging resistivity at low temperature, indicating insulating behavior. The results are best explained by ion-induced formation of lattice defects that result in midgap states.
Combining Single Class Features for Improving Performance of a Two Stage Classifier (2010)

We propose a feature selection--based approach for improving classification performance of a two stage classification system in contexts where a high number of features is involved. A problem with a set of $N$ classes is subdivided into a set of $N$ two class problems. In each problem, a GA--based feature selection algorithm is used for finding the best subset of features. These subsets are then used for training $N$ classifiers. In the classification phase, unknown samples are given in input to each of the trained classifiers by using the corresponding subspace. In case of conflicting responses, the sample is sent to a suitably trained supplementary classifier. The proposed approach has been tested on a real world dataset containing hyper--spectral image data. The results favourably compare with those obtained by other methods on the same data.
Liposomal vincristine preparations which exhibit decreased drug toxicity and increased activity against murine L1210 and P388 tumors. (1990)

The toxicity and antitumor activity of liposomal vincristine preparations have been examined. Vincristine was encapsulated inside egg phosphatidylcholine (EPC)/cholesterol (55/45, mol/mol) and distearoylphosphatidylcholine (DSPC)/cholesterol (55/45, mol/mol) vesicles utilizing transmembrane pH gradient (inside acidic) drug uptake processes. Trapping efficiencies approaching 100% were achieved for this procedure using drug:lipid ratios as high as 0.2:1 (w/w). Although both EPC/cholesterol and DSPC/cholesterol liposomal systems yielded high trapping efficiencies, DSPC/cholesterol vesicles exhibited superior drug retention properties. This ability to retain entrapped vincristine was related to maintenance of the transmembrane pH gradient as well as the membrane permeability properties. Thirty-day dose-response survival studies in mice indicated that vincristine encapsulated in DSPC/cholesterol liposomes was less toxic than free drug. The 50% lethal dose of 1.9 mg/kg in CD-1 mice observed for free vincristine increased to 4.8 mg/kg upon administration of the drug in liposomal form. Liposome encapsulation of vincristine also enhanced the antitumor activity against murine P388 and L1210 lymphocytic leukemia models. This resulted from increased efficacy for liposomal vincristine at doses equal to free drug (liposomal/free drug median survival times greater than 1.0) as well as the ability to administer increased doses of liposomal vincristine. The combined effects of decreased toxicity and increased antitumor efficacy of liposomal vincristine over free drug suggest significant clinical utility of appropriate liposomal vincristine systems.
In vivo detection of exercised-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography (2006)

Skeletal muscle fibers are a known source of form birefringence in biological tissue. The birefringence present in skeletal muscle is associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Certain structural proteins that prevent damage and maintain the structural and functional health of the muscle fiber preserve the organization of the Abands in skeletal muscle. Therefore, the level of birefringence detected can estimate the health of the muscle as well as the damage incurred during exercise. Murine skeletal muscle from both genetically-altered (mdx) and normal (wild-type) specimens were imaged in vivo with a fiber-based PSOCT imaging system to quantitatively determine the level of birefringence present in the tissue before and after exercise. The mdx muscle lacks dystrophin, a structural protein that is mutated in Duchenne muscular dystrophy in humans. Muscle from these mdx mice exhibited a marked decrease in birefringence after exercise, whereas the wild-type muscle was highly birefringent before and after exercise. The quantitative results from this tissue optics study suggest for the first time that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.
Improving Glaucoma Diagnosis by the Combination of Perimetry and HRT Measurements (2006)

The combination of optic disc measurements and VF data could not only improve glaucoma diagnosis in future, but could also help to find an objective way to diagnose glaucomatous optic atrophy. The limitation of the topographic relationship between structure and function is the individual variability of the optic disc morphology and the subjective variability of VF testing.
Viscosupplementation for Osteoarthritis of the Knee (2012)

Arco Foundation.
The Effect of Femoral Cutting Guide Design Improvements for Patient-Specific Instruments (2015)

Although the application of patient-specific instruments (PSI) for total knee arthroplasty (TKA) increases the cost of the surgical procedure, PSI may reduce operative time and improve implant alignment, which could reduce the number of revision surgeries. We report our experience with TKA using PSI techniques in 120 patients from March to December 2014. PSI for TKA were created from data provided by computed tomography (CT) scans or magnetic resonance imaging (MRI); which imaging technology is more reliable for the PSI technique remains unclear. In the first 20 patients, the accuracy of bone resection and PSI stability were compared between CT and MRI scans with presurgical results as a reference; MRI produced better results. In the second and third groups, each with 50 patients, the results of bone resection and stability were compared in MRI scans with respect to the quality of scanning due to motion artifacts and experienced know-how in PSI design, respectively. The optimized femoral cutting guide design for PSI showed the closest outcomes in bone resection and PSI stability with presurgical data. It is expected that this design could be a reasonable guideline in PSI.
Calibration of stereo cameras using a non-linear distortion model (CCD sensory) (2002)

A camera model is presented which accounts for major sources of camera distortion: radial, decentering, and thin-prism distortions. The proposed calibration procedure consists of two steps. In the first step, calibration parameters are estimated using a closed-form solution based on a distortion-free camera model. In the second step, the parameters estimated in the first step are improved iteratively through nonlinear optimization, taking into account camera distortions. According to minimum-variance estimation, the objective function to be minimized is the mean-square discrepancy between the observed image points and their inferred image projections computed with the estimated calibration parameters. A type of measure is introduced which can be used to directly evaluate the performance of the calibration and compare calibrations among different systems. The validity and the performance of the calibration procedure are tested on real images taken by wide-angle lenses. Results consistently show significant improvements over less complete camera models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Human vision fails to distinguish widespread sexual dichromatism among sexually “monochromatic” birds (2005)

Historical scenarios of evolution of avian plumage coloration have been called into question with the discoveries that most birds can see UV light (which normal humans cannot), and that UV-reflecting plumages are widespread in birds. Several examples of sexual dichromatism not detectable with human visual capabilities suggest that our categorizations of plumages as sexually mono- or dichromatic might often be incorrect. Nonetheless, given the limited taxonomic scope of those examples, the vast majority of sexually monochromatic birds are still treated as such without question in avian research. Herein, I show that >90% of 139 species, in a broad sampling of presumed sexually monochromatic passerine birds, were actually sexually dichromatic from an avian visual perspective, based on comparisons of plumage reflectance data using a visual model of color discrimination thresholds. The taxonomic ubiquity of this result suggests that many existing interpretations of evolutionary patterns of sexual dichromatism in birds are erroneous. The visual model used herein provides a method for quantifying sexual dichromatism, revealing that most (58.7%) feather patches sampled lie along a continuum of dichromatism between avian and human discriminatory abilities and could represent unrecognized sexually selected signals. Sexual dichromatism in this study rarely resulted from intersexual differences in UV coloration alone, emphasizing the need for analysis of bird coloration in relation to the full extent of avian visual discriminatory abilities, including, but not limited to, UV-visual capabilities.
A Coumermycin/Novobiocin-Regulated Gene Expression System (2003)

Regulated expression of transgenes in mammals is an important technique in both functional genomic studies and clinical applications. Here we describe a regulated gene expression system for mammals, based on coumarin-switched dimerization of the bacterial DNA gyrase B subunit (GyrB). The transactivator was constructed by fusing the GyrB activator to the bacterial lambda repressor-binding domain. The antibiotic coumermycin in nanomolar concentrations activated the transgene through binding of the homodimerized chimeric transactivator to the lambda operator located upstream of a minipromoter. More significantly, addition of novobiocin, an antagonist of coumermycin, promptly switched off expression of the gene by abolishing coumermycin-induced dimerization of the transactivator. Site-directed mutagenesis of the lambda repressor-binding domain resulted in significant reduction of basal expression levels and an induction reaching four orders of magnitude in stably transfected 293A cells in response to coumermycin. The capability of this inducible system for tightly regulated gene expression was demonstrated by the ready generation of stable cell lines inducibly expressing the proapoptotic bax gene in mammalian cells. Hence, this novel coumarin switch-on/switch-off system should broaden the utility of regulated gene expression, particularly when rapid on/off interchange is required.
Human renal tubular cells as a cytokine source: PDGF-B, GM-CSF and IL-6 mRNA expression in vitro. (1994)

The pathogenesis of renal interstitial fibrosis is not fully understood at present. As renal interstitial fibrosis occurs mainly in association with interstitial cell infiltrates, several cytokines, e.g. PDGF, TGF-beta, IL-6, are thought to play a major role in the induction and progression of renal interstitial fibrosis. In order to prove whether renal tubular epithelial cells produce cytokines which are known to modulate renal interstitial fibroblasts, RNA was isolated from human renal tubular epithelial cells and from human renal fibroblasts. The expression of specific cytokines and growth factors was analysed by Northern blot analysis using cDNA probes for IL-1 alpha, IL-1 beta, IL-6, INF-gamma, TNF-alpha, a-FGF, b-FGF, GM-CSF, PDGF-B and oligonucleotides for IL-2 and TGF-beta 1. In renal tubular epithelial cells from normal and diseased kidneys, mRNA transcripts for PDGF-B, IL-6 and GM-CSF could be detected. Quantitative analysis of the mRNA transcripts of the cytokines expressed revealed consistently higher amounts of GM-CSF and PDGF-B mRNA in tubular epithelial cells from diseased in comparison to normal kidneys. Furthermore, higher amounts of GM-CSF and PDGF-B mRNA transcripts were detected in tubular epithelial cells derived from kidneys with interstitial fibrosis as compared to tubular epithelial cells from diseased but nonfibrotic kidneys. Renal fibroblasts from normal and fibrotic kidneys showed a weak signal for IL-6, but PDGF-B and GM-CSF were not expressed in these cells. By means of colony assays, using human bone marrow cells in the presence or absence of neutralizing antibodies, the release of biologically active colony-stimulating factors GM-CSF and M-CSF by renal tubular epithelial cells from normal and diseased kidneys could be demonstrated. The present results probably indicate interactions between renal tubular epithelial cells and renal fibroblasts in the progression of renal diseases.