gebhart/patrepeval huggingface dataset:
Quinoxaline Antibiotics Enhance Peptide Nucleic Acid Binding to Double-Stranded DNA (2000)

The effects of a wide range of DNA binding drugs on peptide nucleic acid (PNA) binding to double-stranded DNA by strand displacement have been investigated using a gel retardation assay. The bis-PNA [H-(Lys)-TTJTTJTTTT-(eg)(3)-TTTTCTTCTT-Lys-NH(2)] was used together with a 248 bp DNA fragment containing an appropriate target for the PNA. Most of the ligands that were studied, including DNA minor groove binders as well as intercalators and bis-intercalators, either have no effect or strongly inhibit PNA binding to DNA. By contrast, quinoxaline antibiotics facilitate PNA-DNA complex formation. The "PNA-helper" effect of echinomycin was studied in more detail using time and temperature dependence experiments to elucidate the mechanism. PNA binding to DNA follows pseudo-first-order kinetics, but the initial rate of binding is accelerated more than 10-fold in the presence of 10 microM echinomycin. The activation energy for PNA binding to dsDNA is lowered 2-fold by the antibiotic (45 vs 90 kJ/mol in the control). The reasons why quinoxalines promote the binding of PNA to DNA are not entirely clear but may well include distortions (opening) of the double helix that facilitate PNA invasion. This study establishes that the efficacy of DNA-targeted PNA antigene molecules could potentially be enhanced by judiciously adding certain DNA-interactive ligands.
Modeling, synthesis, and hybridization properties of (L)-ribonucleic acid (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModeling, synthesis, and hybridization properties of (L)-ribonucleic acidGary W. AshleyCite this: J. Am. Chem. Soc. 1992, 114, 25, 9731–9736Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://doi.org/10.1021/ja00051a001RIGHTS & PERMISSIONSArticle Views418Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (641 KB) Get e-Alertsclose Get e-Alerts
Oral apremilast in the treatment of active psoriatic arthritis: Results of a multicenter, randomized, double‐blind, placebo‐controlled study (2012)

Treatment with apremilast at a dosage of 20 mg twice per day or 40 mg once per day demonstrated efficacy in comparison with placebo and was generally well tolerated in patients with active PsA. The balance of efficacy, tolerability, and safety supports further study of apremilast in PsA.
Information Retrieval Based on p Norm Model (2000)

With more and more electronic texts available,more efficient retrieval tools are required.This article describes an extended Boolean retrieval model and its application in Chinese information retrieval systems.It also discusses retrieval improvement through relevance feedback.
Unsupervised clustering in Hough space for identification of partially occluded objects (1999)

An automated approach for template-free identification of partially occluded objects is presented. The contour of each relevant object in the analyzed scene is modeled with an approximating polygon whose edges are then projected into the Hough space. A structurally adaptive self-organizing map neural network generates clusters of collinear and/or parallel edges, which are used as the basis for identifying the partially occluded objects within each polygonal approximation. Results on a number of cases under different conditions are provided.
Assembled supported monolayers of synthetic lipids on gold electrodes via‘ion-exchange methods’ (1990)

N. Nakashima, Y. Takada, M. Kunitake and O. Manabe, J. Chem. Soc., Chem. Commun., 1990, 845 DOI: 10.1039/C39900000845
Engineering of glucose-stimulated insulin secretion and biosynthesis in non-islet cells. (1992)

The high-capacity glucose transporter known as GLUT-2 and the glucose phosphorylating enzyme glucokinase are thought to be key components of the "glucose-sensing apparatus" that regulates insulin release from the beta cells of the islets of Langerhans in response to changes in external glucose concentration. AtT-20ins cells are derived from anterior pituitary cells and are like beta cells in that they express glucokinase and have been engineered to secrete correctly processed insulin in response to analogs of cAMP, but, unlike beta cells, they fail to respond to glucose and lack GLUT-2 expression. Herein we demonstrate that stable transfection of AtT-20ins cells with the GLUT-2 cDNA confers glucose-stimulated insulin secretion and glucose regulation of insulin biosynthesis and also results in glucose potentiation of the secretory response to non-glucose secretagogues. This work represents a first step toward creation of a genetically engineered "artificial beta cell."
The female androgen deficiency syndrome (1993)

We evaluated the sexual functioning of 11 women who developed demonstrable androgen deficiencies after undergoing chemotherapy with cytotoxic agents and/or bilateral salpingo-oophorectomies for a variety of medical conditions. For comparison, we evaluated the sexual status of 11 subjects with comparable medical, menopausal, marital, and sexual histories, whose levels of circulating testosterone were within normal limits. The results of this clinical study confirm and extend the observations originally made by Waxenberg and his colleagues in 1959, that testosterone deficiency in women produces a marked decrease in libido and sexual responsiveness. Our findings further indicate that the female androgen deficiency syndrome is often indistinguishable from psychogenic desire disorders on clinical grounds alone.
A novel Snail-related transcription factor Smuc regulates basic helix-loop-helix transcription factor activities via specific E-box motifs (2000)

Snail family proteins are zinc finger transcriptional regulators first identified in Drosophila which play critical roles in cell fate determination. We identified a novel Snail -related gene from murine skeletalmusclecells designated Smuc. Northern blot analysis showed that Smuc was highly expressed in skeletal muscle and thymus. Smuc contains five putative DNA-binding zinc finger domains in its C-terminal half. In electrophoretic mobility shift assays, recombinant zinc finger domains of Smuc specifically bound to CAGGTG and CACCTG E-box motifs (CANNTG). Because basic helix-loop-helix transcription factors (bHLH) bind to the same E-box sequences, we examined whether Smuc competes with the myogenic bHLH factor MyoD for DNA binding. Smuc inhibited the binding of a MyoD-E12 complex to the CACCTG E-box sequence in a dose-dependent manner and suppressed the transcriptional activity of MyoD-E12. When heterologously targeted to the thymidine kinase promoter as fusion proteins with the GAL4 DNA-binding domain, the non-zinc finger domain of Smuc acted as a transcriptional repressor. Furthermore, overexpression of Smuc in myoblasts repressed transactivation of muscle differentiation marker Troponin T. Thus, Smuc might regulate bHLH transcription factors by zinc finger domains competing for E-box binding, and non-zinc finger repressor domains might also confer transcriptional repression to control differentiation processes.
Pedestrian Detection: An Evaluation of the State of the Art (2011)

Pedestrian detection is a key problem in computer vision, with several applications that have the potential to positively impact quality of life. In recent years, the number of approaches to detecting pedestrians in monocular images has grown steadily. However, multiple data sets and widely varying evaluation protocols are used, making direct comparisons difficult. To address these shortcomings, we perform an extensive evaluation of the state of the art in a unified framework. We make three primary contributions: 1) We put together a large, well-annotated, and realistic monocular pedestrian detection data set and study the statistics of the size, position, and occlusion patterns of pedestrians in urban scenes, 2) we propose a refined per-frame evaluation methodology that allows us to carry out probing and informative comparisons, including measuring performance in relation to scale and occlusion, and 3) we evaluate the performance of sixteen pretrained state-of-the-art detectors across six data sets. Our study allows us to assess the state of the art and provides a framework for gauging future efforts. Our experiments show that despite significant progress, performance still has much room for improvement. In particular, detection is disappointing at low resolutions and for partially occluded pedestrians.
Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes (2016)

Biologic treatment of T1D typically results in transient stabilization of C-peptide levels (a surrogate for endogenous insulin secretion) in some patients, followed by progression at the same rate as in untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody teplizumab. We identified a population of CD8 T cells that accumulated in subjects with the best response to treatment (responders) and showed that these cells phenotypically resembled exhausted T cells by expressing high levels of the transcription factor EOMES, effector molecules, and multiple inhibitory receptors (IRs), including TIGIT and KLRG1. These cells expanded after treatment, with levels peaking after 3-6 months. To functionally characterize these exhausted-like T cells, we isolated memory CD8 TIGIT+KLRG1+ T cells from responders and showed that they exhibited expanded TCR clonotypes, indicative of prior in vivo expansion; recognized a broad-based spectrum expressed of environmental and auto-antigens; and were hypo-proliferative during polyclonal stimulation, increasing expression of IR genes and decreasing cell cycle genes. Triggering these cells with a recombinant ligand for TIGIT during polyclonal stimulation further downregulated their activation, demonstrating their exhausted phenotype was not terminal. These findings identify and functionally characterize a partially exhausted cell type associated with response to teplizumab therapy and suggest that pathways regulating T cell exhaustion may play a role in successful immune interventions for T1D.
A high speed and high reliability MOSFET utilizing an auxiliary gate (1990)

For future submicron MOSFETs, the realization of both high speed and high reliability is becoming more and more difficult. A conventional LDD structure is not adequately reliable for future submicron MOSFETs due to the high electric field in the vicinity of the drain junction. To decrease the electric field, gate-overlap LDD (GOLDD) structures have been proposed. However, these structures have larger gate-drain and gate-source overlap capacitance which results in a slow circuit speed. This research demonstrates a novel auxiliary-gate lightly-doped-drain (AGLDD) structure which realizes high speed and high reliability simultaneously
Investigative Bronchoprovocation and Bronchoscopy in Airway Diseases (2005)

This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States.
Pulmonary fibrosis: cytokines in the balance (1998)

Pulmonary fibrosis can complicate diverse pulmonary and systemic pathologies. In many cases the underlying cause remains unidentified. Mortality from the disease is increasing steadily in the UK and USA. The clinical features are well-described, but patients frequently present at an advanced stage, and current treatments have not improved the poor prognosis. There is a compelling need to identify the fibrotic process earlier and to develop new therapeutic agents. Increased collagen deposition is central to the pathology and interest over the last decade has focused on the role of cytokines in this process. These polypeptide mediators are believed to be released from both circulating inflammatory and resident lung cells in response to endothelial and epithelial injury. Key cytokines currently implicated in the fibrotic process are transforming growth factor-beta, tumour necrosis factor-alpha and endothelin-1. This article outlines the evidence implicating these mediators in the pathogenesis of pulmonary fibrosis and also considers the possible role of cytokines with antifibrotic effects, such as interferon-gamma. The "balance" of positively and negatively regulating cytokines is discussed, and the potential for interaction with other factors including viruses, hormones and altered antioxidant status is also considered. Finally, potential novel therapeutic approaches are discussed, together with suggestions for future studies and clinical trials. As the outcomes of different avenues of research over the last ten years are brought together, it is clear that there is now a hitherto unrivalled opportunity to begin to tackle the treatment of this devastating disease.
Neurochemical Characterization of Traumatic Brain Injury in Humans (2001)

Trauma is the leading cause of death in individuals between the ages of 1 and 44 years. And, in the case of severe head injury mortality can reach as high as 35-70%. Despite this fact, there has been little progress in the development of effective pharmacological agents to protect brain injured patients. To date, there is little data on the mechanisms involved in neuronal cellular insult after severe head injury, especially in humans. Glutamate acts both as a primary excitatory neurotransmitter and a potential neurotoxin within the mammalian brain. Evidence indicates that hyperactivity of the glutamate system contributes to neuronal death in brain trauma. Also, in animal models of neurotrauma, this neural injury is followed by gliosis which has been linked to the severity of brain injury. To investigate the glutamate system in brain trauma, we carried out [3H]glutamate and [3H]MK801 (a noncompetitive NMDA-receptor antagonist) binding and [3H]glutamate uptake assays in human cerebral cortex preparations obtained from severely brain injured and control victims. Additionally, to investigate gliosis following brain injury, we performed GFAP immunohistochemistry. There were no significant differences in [3H]glutamate binding (affinity or density of sites) between the control and head injured groups. In contrast, cerebral cortical [3H]MK801 binding revealed both a significant increase in the density of sites (Bmax) and a decrease in the dissociation constant (Kd) in the head injured group when compared to controls. There were no significant differences in [3H]glutamate uptake between groups. The injured brains presented an increased number of GFAP-positive astrocytes and more intense GFAP reaction in comparison to control brains. In the context of traumatic brain injury, our results encourage further investigation into compounds capable of selective modulation of NMDA receptor subtype in humans while also therapeutically manipulating glial cell responses following brain trauma.
De novo deletion 17p13.1 chronic lymphocytic leukemia shows significant clinical heterogeneity: the M. D. Anderson and Mayo Clinic experience (2009)

To determine the clinical fate of patients with de novo deletion 17p13.1 (17p-) chronic lymphocytic leukemia (CLL), we retrospectively studied the outcome of 99 treatment-naive 17p- CLL patients from the M. D. Anderson Cancer Center (n = 64) and the Mayo Clinic (n = 35). Among 67 asymptomatic patients followed for progression, 53% developed CLL requiring treatment over 3 years. Patients who had not progressed by 18 months subsequently had stable disease, with 3 of 19 patients progressing after follow-up of up to 70 months. Risk factors for progressive disease were Rai stage of 1 or higher and unmutated immunoglobulin variable region heavy chain (IgVH). The overall survival rate was 65% at 3 years. Rai stage 1 or higher, unmutated IgVH, and 17p- in 25% or more of nuclei were adverse factors for survival. The 3-year survival rates of patients with 1 or fewer, 2, and 3 of these factors were 95%, 74%, and 22%, respectively (P < .001). Response rates to therapy with rituximab (n = 6); purine analogues and rituximab (n = 25); and purine analogues, rituximab, and alemtuzumab (n = 16) combinations were 50%, 72%, and 81%, respectively. Patients with 17p- CLL exhibit clinical heterogeneity, with some patients experiencing an indolent course. Survival can be predicted using clinical and biologic characteristics.
An HIV-1 integrase genotype assay for the detection of drug resistance mutations (2009)

This assay is suitable for routine drug resistance screening of plasma samples from HIV-infected patients receiving integrase inhibitor antiretroviral drugs and also serves as a useful research tool.
The Function of the Long Dorsal Sacroiliac Ligament (1996)

The long dorsal sacroiliac ligament has close anatomical relations with the erector spinae muscle, the posterior layer of the thoracolumbar fascia, and a specific part of the sacrotuberous ligament (tuberoiliac ligament). Functionally, it is an important link between legs, spine, and arms. The ligament is tensed when the sacroiliac joints are counternutated and slackened when nutated. The reverse holds for the sacrotuberous ligament. Slackening of the long dorsal sacroiliac ligament can be counterbalanced by both the sacrotuberous ligament and the erector muscle. Pain localized within the boundaries of the long ligament could indicate among other things a spinal condition with sustained counternutation of the sacroiliac joints. In diagnosing patients with aspecific low back pain or peripartum pelvic pain, the long dorsal sacroiliac ligament should not be neglected. Even in cases of arthrodesis of the sacroiliac joints, tension in the long ligament can still be altered by different structures.
Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? (2009)

Evaluation of: Segal BM, Constantinescu CS, Raychaudhuri A et al. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a Phase II, double-blind, placebo-controlled, randomized, dose-ranging study. Lancet Neurol. 7, 796-804 (2008). IL-12 and IL-23 are two cytokines that appear to play a key role in the pathogenesis of multiple sclerosis. Blocking these cytokines via a neutralizing antibody caused dramatic improvements in animal models of the disease, and Phase I trials found the antibody to be safe in humans. The paper under review is a Phase II clinical trial of ustekinumab, an anti-IL-12/23p40 antibody for treatment of multiple sclerosis. Investigators found no clinical or radiologic improvement in any treatment group compared with placebo controls. We consider the known mechanisms of action for IL-12/23 in multiple sclerosis and suggest that ustekinumab's lack of efficacy was partially due to the study's inclusion of patients with advanced disease. Studies of the antibody in a more limited subset of patients (those with very early disease) might show a treatment effect.
Peers in Pain: The Experiences of Student Athletic Trainers (1997)

Recent work has suggested that masculinist sport subcultures (e.g., Young &amp; White, 1995) and “conspiratorial” sports organizations (Nixon, 1992a) foster the acceptance of pain and injury by athletes. Using semistructured interviews, this study examined the experiences and beliefs of 22 student athletic trainers at a large university. The study found that student athletic trainers had conflicting alliances to student athletes and to staff trainers, held competing beliefs about athlete pain and injury , and struggled with athletes who did not properly use health care services and advice. It is recommended that future studies focus upon processes of negotiation and conflict, that more attention be directed to medical treatment of injured women athletes, and that recommendations to change medical services for athletes await further research.
Engineering of Stable Recombinant Bacteria for Production of Chiral Medium-Chain-Length Poly-3-Hydroxyalkanoates (1999)

In order to scale up medium-chain-length polyhydroxyalkanoate (mcl-PHA) production in recombinant microorganisms, we generated and investigated different recombinant bacteria containing a stable regulated expression system for phaC1, which encodes one of the mcl-PHA polymerases of Pseudomonas oleovorans. We used the mini-Tn5 system as a tool to construct Escherichia coli 193MC1 and P. oleovorans POMC1, which had stable antibiotic resistance and PHA production phenotypes when they were cultured in a bioreactor in the absence of antibiotic selection. The molecular weight and the polydispersity index of the polymer varied, depending on the inducer level. E. coli 193MC1 produced considerably shorter polyesters than P. oleovorans produced; the weight average molecular weight ranged from 67,000 to 70,000, and the polydispersity index was 2.7. Lower amounts of inducer added to the media shifted the molecular weight to a higher value and resulted in a broader molecular mass distribution. In addition, we found that E. coli 193MC1 incorporated exclusively the R configuration of the 3-hydroxyoctanoate monomer into the polymer, which corroborated the enantioselectivity of the PhaC1 polymerase enzyme.
Boosting Neural Networks (2000)

Boosting is a general method for improving the performance of learning algorithms. A recently proposed boosting algorithm, AdaBoost, has been applied with great success to several benchmark machine learning problems using mainly decision trees as base classifiers. In this article we investigate whether AdaBoost also works as well with neural networks, and we discuss the advantages and drawbacks of different versions of the AdaBoost algorithm. In particular, we compare training methods based on sampling the training set and weighting the cost function. The results suggest that random resampling of the training data is not the main explanation of the success of the improvements brought by AdaBoost. This is in contrast to bagging, which directly aims at reducing variance and for which random resampling is essential to obtain the reduction in generalization error. Our system achieves about 1.4% error on a data set of on-line handwritten digits from more than 200 writers. A boosted multilayer network achieved 1.5% error on the UCI letters and 8.1% error on the UCI satellite data set, which is significantly better than boosted decision trees.