gebhart/patrepeval huggingface dataset:
Drug block of the hERG potassium channel: Insight from modeling (2007)

Many commonly used, structurally diverse, drugs block the human ether-a-go-go-related gene (hERG) K(+) channel to cause acquired long QT syndrome, which can lead to sudden death via lethal cardiac arrhythmias. This undesirable side effect is a major hurdle in the development of safe drugs. To gain insight about the structure of hERG and the nature of drug block we have produced structural models of the channel pore domain, into each of which we have docked a set of 20 hERG blockers. In the absence of an experimentally determined three-dimensional structure of hERG, each of the models was validated against site-directed mutagenesis data. First, hERG models were produced of the open and closed channel states, based on homology with the prokaryotic K(+) channel crystal structures. The modeled complexes were in partial agreement with the mutagenesis data. To improve agreement with mutagenesis data, a KcsA-based model was refined by rotating the four copies of the S6 transmembrane helix half a residue position toward the C-terminus, so as to place all residues known to be involved in drug binding in positions lining the central cavity. This model produces complexes that are consistent with mutagenesis data for smaller, but not larger, ligands. Larger ligands could be accommodated following refinement of this model by enlarging the cavity using the inherent flexibility about the glycine hinge (Gly648) in S6, to produce results consistent with the experimental data for the majority of ligands tested.
Chromosomal deletions and inversions mediated by TALENs and CRISPR/Cas in zebrafish (2013)

Customized TALENs and Cas9/gRNAs have been used for targeted mutagenesis in zebrafish to induce indels into protein-coding genes. However, indels are usually not sufficient to disrupt the function of non-coding genes, gene clusters or regulatory sequences, whereas large genomic deletions or inversions are more desirable for this purpose. By injecting two pairs of TALEN mRNAs or two gRNAs together with Cas9 mRNA targeting distal DNA sites of the same chromosome, we obtained predictable genomic deletions or inversions with sizes ranging from several hundred bases to nearly 1 Mb. We have successfully achieved this type of modifications for 11 chromosomal loci by TALENs and 2 by Cas9/gRNAs with different combinations of gRNA pairs, including clusters of miRNA and protein-coding genes. Seven of eight TALEN-targeted lines transmitted the deletions and one transmitted the inversion through germ line. Our findings indicate that both TALENs and Cas9/gRNAs can be used as an efficient tool to engineer genomes to achieve large deletions or inversions, including fragments covering multiple genes and non-coding sequences. To facilitate the analyses and application of existing ZFN, TALEN and CRISPR/Cas data, we have updated our EENdb database to provide a chromosomal view of all reported engineered endonucleases targeting human and zebrafish genomes.
Degeneration and regeneration of the peripheral nervous system: From Augustus Waller's observations to neuroinflammation (2002)

This review article on the degeneration and regeneration of peripheral nerve fibers was presented as a Plenary Lecture at the 2001 meeting of the Peripheral Nerve Society. It is accompanied by a reprint of Augustus Waller's 1850 article, which gave rise to the pathologic process termed Wallerian degeneration. This review is focused on the role of neuroinflammation in Wallerian degeneration and how immune mediators contribute to both axonal degeneration and regeneration. Similarities and differences between the PNS and CNS in terms of inflammation and microglial activation after nerve injury are discussed, and point towards progress in understanding the failure of nerve fiber regeneration in the CNS.
Improved Genome Editing Efficiency and Flexibility Using Modified Oligonucleotides with TALEN and CRISPR-Cas9 Nucleases (2016)

Genome editing has now been reported in many systems using TALEN and CRISPR-Cas9 nucleases. Precise mutations can be introduced during homology-directed repair with donor DNA carrying the wanted sequence edit, but efficiency is usually lower than for gene knockout and optimal strategies have not been extensively investigated. Here, we show that using phosphorothioate-modified oligonucleotides strongly enhances genome editing efficiency of single-stranded oligonucleotide donors in cultured cells. In addition, it provides better design flexibility, allowing insertions more than 100 bp long. Despite previous reports of phosphorothioate-modified oligonucleotide toxicity, clones of edited cells are readily isolated and targeted sequence insertions are achieved in rats and mice with very high frequency, allowing for homozygous loxP site insertion at the mouse ROSA locus in particular. Finally, when detected, imprecise knockin events exhibit indels that are asymmetrically positioned, consistent with genome editing taking place by two steps of single-strand annealing.
Tn5 transposase‐assisted transformation of indica rice (2011)

Here, we describe experiments on Tn5 transposase-assisted transformation of indica rice. Transposomes were formed in vitro as a result of hyperactive Tn5 transposase complexing with a transposon that contained a 19-bp tetracycline operator (tetO) sequence. To form modified projectiles for transformation, the Tn10-derived prokaryotic tetracycline repressor (TetR) proteins, which can bind transposomes via the high affinity of TetR for tetO, were immobilized onto the surface of bare gold microscopic particles. These projectiles were introduced into cells of the indica rice cultivar Zhuxian B by particle bombardment. Once projectiles were inside the cell, tetracycline induced an allosteric conformational change in TetR that resulted in the dissociation of TetR from tetO, and thus generated free transposomes. Molecular evidence of transposition was obtained by the cloning of insertion sites from many transgenic plants. We also demonstrated that the introduced foreign DNA was inherited stably over several generations. This technique is a promising transformation method for other plant species as it is species independent.
Ideas previas del alumnado de un curso de 4º de ESO acerca del ruido (2001)

espanolEl conocimiento de las ideas previas del alumnado sobre cualquier tema a trabajar es uno de los puntos fundamentales del proceso de ensenanza-aprendizaje. En este trabajo se ponen de manifiesto las ideas previas del alumnado de un curso de 4o de ESO (Educacion Secundaria Obligatoria) acerca del ruido. El analisis de los resultados revelo una serie de aspectos significativos que podran servir de reflexion ante la mejora de la practica educativa. EnglishThe knowledge of the previous ideas of the pupil on any topic to work is one of the fundamental points of the teaching-learning process. In this work they show the previous ideas of the pupil of a course of 4o of E.S.O (Secondary Education) about the noise. The analysis of the results revealed a series of significant aspects that will be able to serve as reflection in the face of the improvement of the educational practice.
Mutations in POL1 increase the mitotic instability of tandem inverted repeats in Saccharomyces cerevisiae. (1993)

Tandem inverted repeats (TIRs or hairpins) of 30 and 80 base-pair unit lengths are unstable mitotically in yeast (Saccharomyces cerevisiae). TIR instability results from deletions that remove part or all of the presumed hairpin structure from the chromosome. At least one deletion endpoint is always at or near the base of the hairpin, and almost all of the repaired junctions occur within short direct sequence repeats of 4 to 9 base pairs. The frequency of this event, which we call "hairpin excision," is influenced by chromosomal position, length of the inverted repeats, and the distance separating the repeat units; increasing the distance between the inverted repeats as little as 25 base pairs increases their chromosomal stability. The frequency of excision is not affected by representative rad mutations, but is influenced by mutations in certain genes affecting DNA synthesis. In particular, mutations in POL1/CDC17, the gene that encodes the large subunit of DNA polymerase I, increase the frequency of hairpin deletions significantly, implicating this protein in the normal maintainance of genomic TIRs.
Preorganization of DNA:  Design Principles for Improving Nucleic Acid Recognition by Synthetic Oligonucleotides (1997)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreorganization of DNA: Design Principles for Improving Nucleic Acid Recognition by Synthetic OligonucleotidesEric T. KoolView Author Information Department of Chemistry and Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York 14627 Cite this: Chem. Rev. 1997, 97, 5, 1473–1488Publication Date (Web):August 5, 1997Publication History Received2 October 1996Revised13 January 1997Published online5 August 1997Published inissue 1 August 1997https://pubs.acs.org/doi/10.1021/cr9603791https://doi.org/10.1021/cr9603791research-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views2150Altmetric-Citations248LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biopolymers,Genetics,Molecules,Nucleic acids,Selectivity Get e-Alerts
Warts are not merely blemishes on the skin: A study on the morbidity associated with having viral cutaneous warts (2003)

Eighty-five people aged 2-76 years with 250 common and plantar warts were followed prospectively for 9 months. The majority (57; 67%) had one to two warts. Of the 54 subjects who had a past history of warts, 41 (75.9%) had sought treatment for them. Twenty-four (58.5%) said that treatment had been unsuccessful; 22 (53.7%) experienced pain during their treatment; 14 (34.1%) said that treatment had been inconvenient; nine (22%) required multiple treatments; and eight (19.5%) said the treatment resulted in the development of scars. The quality-of-life assessment related to their current warts revealed that 81.2% were moderately to extremely embarrassed by them; 70.5% were moderately to extremely concerned about negative appraisal by others for having them; 24.7% said that it was moderately to extremely difficult to play sport because of their warts. Moderate to severe discomfort from their warts occurred in 51.7% of people and 35.4% said they had moderate to severe pain. During the 9-month study period, 27 (31.8%) of the participants had at least one wart regress spontaneously with 49 (19.6%) of the 254 warts regressing during that time. These data confirm the impression that a wart is not merely a blemish on the skin. Warts have the potential to cause considerable morbidity at times; this should be taken into account when a patient asks for treatment.
Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer (2017)

Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration-approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors. We also review recent clinical trials of immunotherapy in breast cancer and provide a number of interesting questions that will need to be answered for successful breast cancer immunotherapy.
A Dynamic-SOA Home Control Gateway (2006)

The convergence of smart field devices and business services stands to profoundly change the way we interact with our environment. This is especially true in the home context. In this paper, we present an open architecture and a dynamic service-oriented gateway running home services. The gateway is based on the OSGi standard and provides mechanisms to integrate different service technologies
The Native Rat Olfactory Cyclic Nucleotide-Gated Channel Is Composed of Three Distinct Subunits (1999)

Cyclic nucleotide-gated (CNG) channels play central roles in visual and olfactory signal transduction. In the retina, rod photoreceptors express the subunits CNCalpha1 and CNCbeta1a. In cone photoreceptors, only CNCalpha2 expression has been demonstrated so far. Rat olfactory sensory neurons (OSNs) express two homologous subunits, here designated CNCalpha3 and CNCalpha4. This paper describes the characterization of CNCbeta1b, a third subunit expressed in OSNs and establishes it as a component of the native channel. CNCbeta1b is an alternate splice form of the rod photoreceptor CNCbeta1a subunit. Analysis of mRNA and protein expression together suggest co-expression of all three subunits in sensory cilia of OSNs. From single-channel analyses of native rat olfactory channels and of channels expressed heterologously from all possible combinations of the CNCalpha3, -alpha4, and -beta1b subunits, we conclude that the native CNG channel in OSNs is composed of all three subunits. Thus, CNG channels in both rod photoreceptors and olfactory sensory neurons result from coassembly of specific alpha subunits with various forms of an alternatively spliced beta subunit.
Nogo signaling and non‐physical injury‐induced nervous system pathology (2004)

The Nogo gene products were described first as myelin-associated inhibitors that prevent neuronal regeneration upon injury. Recent findings have also implicated Nogo in several neuronal pathologies that are not induced by physical injury. Nogo-A may be an important determinant of autoimmune demyelinating diseases, as active immunization with Nogo-A fragments attenuates the symptoms of experimental autoimmune encephalomyelitis (EAE). Nogo-A levels are elevated markedly in hippocampal neurons of patients with temporal lobe epilepsy (TLE), in brain and muscle of patients with amyotrophic lateral sclerosis (ALS), and in schizophrenic patients. Concrete evidence for a direct role of Nogo-A in the latter neuropathies is not yet available, but such a role is logically in line with new findings associated with localization of Nogo-A and Nogo-Nogo-66 receptor (NgR)-mediated signaling. We speculate on possible linkages between the effect of aberrant elevation of Nogo levels and the signaling consequences that could lead to nervous system pathology.
Increased Resistance to Oxidative Stress in Transgenic Plants by Targeting Mannitol Biosynthesis to Chloroplasts (1997)

To investigate the potential role of a polyol, mannitol, in oxidative stress protection, a bacterial mannitol-1-phosphate dehydrogenase gene was targeted to chloroplasts by the addition of an amino-terminal transit peptide. Transgenic tobacco (Nicotiana tabacum) lines accumulate mannitol at concentrations ranging from 2.5 to 7 mumol/g fresh weight. Line BS1-31 accumulated approximately 100 mM mannitol in chloroplasts and was identical to the wild type in phenotype and photosynthetic performance. The presence of mannitol in chloroplasts resulted in an increased resistance to methyl viologen (MV)-induced oxidative stress, documented by the increased retention of chlorophyll in transgenic leaf tissue following MV treatment. In the presence of MV, isolated mesophyll cells of BS1-31 exhibited higher CO2 fixation than the wild type. When the hydroxyl radical probe dimethyl sulfoxide was introduced into cells, the initial formation rate of methane sulfinic acid was significantly lower in cells containing mannitol in the chloroplast compartment than in wild-type cells, indicating an increased hydroxyl radical-scavenging capacity in BS1-31 tobacco. We suggest that the chloroplast location of mannitol can supplement endogenous radical-scavenging mechanisms and reduce oxidative damage of cells by hydroxyl radicals.
Outlier Detection Techniques for Wireless Sensor Networks: A Survey (2010)

In the field of wireless sensor networks, those measurements that significantly deviate from the normal pattern of sensed data are considered as outliers. The potential sources of outliers include noise and errors, events, and malicious attacks on the network. Traditional outlier detection techniques are not directly applicable to wireless sensor networks due to the nature of sensor data and specific requirements and limitations of the wireless sensor networks. This survey provides a comprehensive overview of existing outlier detection techniques specifically developed for the wireless sensor networks. Additionally, it presents a technique-based taxonomy and a comparative table to be used as a guideline to select a technique suitable for the application at hand based on characteristics such as data type, outlier type, outlier identity, and outlier degree.
miR-146a controls the resolution of T cell responses in mice (2012)

T cell responses in mammals must be tightly regulated to both provide effective immune protection and avoid inflammation-induced pathology. NF-κB activation is a key signaling event induced by T cell receptor (TCR) stimulation. Dysregulation of NF-κB is associated with T cell-mediated inflammatory diseases and malignancies, highlighting the importance of negative feedback control of TCR-induced NF-κB activity. In this study we show that in mice, T cells lacking miR-146a are hyperactive in both acute antigenic responses and chronic inflammatory autoimmune responses. TCR-driven NF-κB activation up-regulates the expression of miR-146a, which in turn down-regulates NF-κB activity, at least partly through repressing the NF-κB signaling transducers TRAF6 and IRAK1. Thus, our results identify miR-146a as an important new member of the negative feedback loop that controls TCR signaling to NF-κB. Our findings also add microRNA to the list of regulators that control the resolution of T cell responses.
The Structure-Function Relationship of GLP-1 Related Peptides in the Endocrine Function of the Canine Pancreas. (1991)

In order to clarify the relationship between the structure and function of glucagon-like peptide (GLP) 1 in the endocrine function of the pancreas, the response of insulin and glucagon to various synthetic GLP-1-related peptides was investigated in anesthetized dogs. GLP-1-related peptides were administered in a dosage of 400 pmol within 10 min into the pancreatic artery during glucose or arginine infusion and the changes in plasma insulin and glucagon in the pancreatic vein were studied. GLP-1 (7-36) and (7-37), as well as glucagon enhanced insulin release during glucose infusion, whereas neither GLP-1 (1-37), (7-20), (6-37) nor (8-37) stimulated insulin release. The administration of GLP-1 (1-37), (7-36) and (7-37) reduced glucagon release during glucose infusion. When arginine was infused, GLP-1 (7-20), (7-36), (7-37), and glucagon enhanced insulin release. In contrast, glucagon release was increased by the administration of GLP-1 (7-20), (8-37), and (7-37). The present study indicates that histidine at the 7th position of GLP-1 is important in eliciting biological action and that only truncated GLP-1 (7-36), (7-37), and (7-20) showed an insulinotropic action as strong as glucagon in dogs. Furthermore, it is suggested that the response of insulin and glucagon to GLP-1-related peptides is dependent on a background condition.
Molecular Distortion and Exciton Coupling Effects in β Metal-Free Phthalocyanine (1999)

As pointed out in titanylphthalocyanine, molecular distortion (reduction in molecular symmetry) upon crystallization exerts a significant influence on the optical absorption in the near-IR region. The electronic spectra of β metal-free phthalocyanine (MfPc) has been investigated from the standpoint of molecular distortion and exciton coupling effects. Close examination of the crystal structure of MfPc revealed that the molecular symmetry is reduced from D2h to Ci on going from solution to the solid state. Molecular distortion is found to enhance the band splitting in such a way that the longer-wavelength band is more displaced toward longer wavelengths while the shorter-wavelength band is more shifted toward shorter wavelengths. The electronic spectra of MfPc can mostly be interpreted in terms of the distortion of molecular framework. However, some exciton coupling effect is also observed, as shown by polarized reflection spectra on single crystals as well as the temperature dependence of absorption spectra.
Simplifying Polynomial Expressions in a Proof Assistant (2005)

This paper presents a simple way of performing polynomial simplifications in a proof assistant. This method has been implemented and tested within the Coq prover.
Stereocontrolled Synthesis of C1−C17 Fragment of Narasin via a Free Radical-Based Approach (2009)

An efficient synthesis of the C1-C17 western unit of narasin was achieved from (S)-Roche ester. Highlights in our synthesis include the successful exploitation of three stereoselective sequences of Lewis acid mediated reaction followed by free-radical-based hydrogen transfer.
Differential responses of regional sympathetic activity and blood flow to visceral afferent stimulation (2001)

The sympathetic nervous system is essential for the cardiovascular responses to stimulation of visceral afferents. It remains unclear how the reflex-evoked sympathetic output is distributed to different vascular beds to initiate the hemodynamic changes. In the present study, we examined changes in regional sympathetic nerve activity and blood flows in anesthetized cats. Cardiovascular reflexes were induced by either electrical stimulation of the right splanchnic nerve or application of 10 microg/ml of bradykinin to the gallbladder. Blood flows were measured using colored microspheres or the Transonic flow meter system. Sympathetic efferent activity was recorded from the left splanchnic, inferior cardiac, and tibial nerves. Stimulation of visceral afferents decreased significantly blood flows in the celiac (from 49 +/- 4 to 25 +/- 3 ml/min) and superior mesenteric (from 35 +/- 4 to 23 +/- 2 ml/min) arteries, and the vascular resistance in the splanchnic bed was profoundly increased. Consistently, stimulation of visceral afferents decreased tissue blood flows in the splanchnic organs. By contrast, activation of visceral afferents increased significantly blood flows in the coronary artery and portal vein but did not alter the vascular resistance of the femoral artery. Furthermore, stimulation of visceral afferents increased significantly sympathetic efferent activity in the splanchnic (182 +/- 44%) but not in the inferior cardiac and tibial nerves. Therefore, this study provides substantial new evidence that stimulation of abdominal visceral afferents differentially induces sympathetic outflow to the splanchnic vascular bed.