gebhart/patrepeval huggingface dataset:
Mutational Evidence for a Common κ Antagonist Binding Pocket in the Wild-Type κ and Mutant μ[K303E] Opioid Receptors (1998)

ADVERTISEMENT RETURN TO ISSUELetterNEXTMutational Evidence for a Common κ Antagonist Binding Pocket in the Wild-Type κ and Mutant μ[K303E] Opioid Receptors†Robert M. Jones, Siv A. Hjorth, Thue W. Schwartz, and Philip S. PortogheseView Author Information Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, and Laboratory for Molecular Pharmacology, Department of Pharmacology, Panum Institute, DK-2200 Copenhagen, Denmark Cite this: J. Med. Chem. 1998, 41, 25, 4911–4914Publication Date (Web):November 13, 1998Publication History Received11 September 1998Published online13 November 1998Published inissue 1 December 1998https://pubs.acs.org/doi/10.1021/jm9805182https://doi.org/10.1021/jm9805182rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views468Altmetric-Citations80LEARN 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:Antagonists,Monomers,Peptides and proteins,Receptors,Selectivity Get e-Alerts
Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer (2012)

Ubiquitin-binding histone deacetylase 6 (HDAC6) is uniquely endowed with tubulin deacetylase activity and plays an important role in the clearance of misfolded protein by autophagy. In cancer, HDAC6 has become a target for drug development due to its major contribution to oncogenic cell transformation. In the present study we show that HDAC6 expression was down-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that low expression of HDAC6 was significantly associated with poor prognosis of HCC patients in 5-year overall, disease-free, and recurrence-free survival. Notably, we observed that ectopic overexpression of HDAC6 suppressed tumor cell growth and proliferation in various liver cancer cells, and elicited increased LC3B-II conversion and autophagic vacuole formation without causing apoptotic cell death or cell cycle inhibition. In addition, the sustained overexpression of HDAC6 reduced the in vivo tumor growth rate in a mouse xenograft model. It was also found that HDAC6 mediated autophagic cell death by way of Beclin 1 and activation of the LC3-II pathway in liver cancer cells, and that HDAC6 overexpression activated c-Jun NH2-terminal kinase (JNK) and increased the phosphorylation of c-Jun. In contrast, the induction of Beclin 1 expression was blocked by SP600125 (a specific inhibitor of JNK) or by small interfering RNA directed against HDAC6. Conclusion: Our findings suggest that loss of HDAC6 expression in human HCCs and tumor suppression by HDAC6 occur by way of activation of caspase-independent autophagic cell death through the JNK/Beclin 1 pathway in liver cancer and, thus, that a novel tumor suppressor function mechanism involving HDAC6 may be amenable to nonepigenetic regulation. (HEPATOLOGY 2012)
Aneuploid and unbalanced sperm in two translocation carriers: evaluation of the genetic risk (2002)

Translocation carriers have an increased risk of reproductive failure or affected offspring, because of the production of unbalanced gametes by meiotic segregation or the possible presence of interchromosomal effects (ICE). We therefore performed an analysis of meiotic segregation using the human-hamster IVF technique, and an aneuploidy assay for chromosomes 6, 18, 21, X and Y, using dual and triple-colour fluorescence in-situ hybridization, in two translocation carriers, t(1;13)(q41;q22) and t(3;19)(p21;p13.3). Sperm chromosome complements were analysed by whole chromosome painting. The frequencies observed for alternate, adjacent I, adjacent II and 3:1 segregations were, for t(1;13), 41.6, 41.6, 14.5 and 2.3% respectively, and for t(3;19), the frequencies were 39.1, 35.9, 21.8 and 3.2% respectively. More than 20,000 sperm per subject were analysed in the aneuploidy assay. Disomy 21 was found to be higher than other autosome disomies. Evidence for a possible ICE was found only in t(3;19). This study has shown that unbalanced sperm are more frequent than aneuploid sperm in the total sperm population. However, data in the literature suggest that the importance of each aberrant population seems to be more significant for embryo viability than would be expected from the increases in the percentages of abnormal sperm.
A new ultrafast superionic Li-conductor: ion dynamics in Li11Si2PS12and comparison with other tetragonal LGPS-type electrolytes (2014)

We report on a new ultrafast solid electrolyte of the composition Li11Si2PS12, which exhibits a higher room-temperature Li ion diffusivity than the present record holder Li10GeP2S12. We discuss the high-pressure synthesis and ion dynamics of tetragonal Li11Si2PS12, and comparison is made with our investigations of related members of the LMePS family, i.e. electrolytes of the general formula Li11-xMe2-xP1+xS12 with Me = Ge, Sn : Li10GeP2S12, Li7GePS8, Li10SnP2S12. The structure and dynamics were studied with multiple complementary techniques and the macroscopic diffusion could be traced back to fast Li ion hopping in the crystalline lattice. A clear correlation between the diffusivity and the unit cell volume of the LGPS-type electrolytes was observed.
A simple assay for agonist-regulated Cl and K conductances in salt-secreting epithelial cells (1990)

We developed a convenient flux assay that permits simultaneous measurement of Cl and K conductance pathways in Cl-secreting epithelial cells. Monolayers of the colonic tumor cell line T84 were preloaded with 125I and 86Rb, and isotope effluxes were monitored by a sample-replace procedure. The adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agonists forskolin and prostaglandin E2 increased I efflux with little effect on Rb efflux, whereas the Ca-mediated agonists ionomycin, A23187, and carbachol increased both I and Rb effluxes. Simultaneous determinations of I and Cl or Rb and K effluxes indicated that I and Rb provide good measures of the effluxes of Cl and K, respectively. Forskolin- and ionomycin-stimulated I effluxes were inhibited by the Cl-channel blockers diphenylamine-2-dicarboxylate (DPC), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), and 2-[cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H- inden-5-yl)oxy]acetic acid (IAA-94) and by high external K. The Rb efflux evoked by ionomycin was inhibited by the K-channel blockers Ba and charybdotoxin. These findings suggest that I and Rb effluxes provide qualitative estimates of agonist-stimulated Cl and K conductance pathways. Thus this method can provide a simple and relatively inexpensive screening assay for Cl and K conductances in cultured cells to assess the effects of agonist, blockers, or genetic manipulations.
Inflammatory Cytokines in the Herniated Disc of the Lumbar Spine (1996)

The results demonstrate that at the site of lumbar disc herniation, inflammatory cytokines such as interleukin-1 alpha are produced, which increases prostaglandin E2 production. Further studies are required to elucidate the role of inflammatory cytokines in causing sciatic pain.
Acarbose Treatment and the Risk of Cardiovascular Disease and Hypertension in Patients With Impaired Glucose Tolerance (2003)

This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.
Fibroblast Activation Protein, a Dual Specificity Serine Protease Expressed in Reactive Human Tumor Stromal Fibroblasts (1999)

Proteolytic degradation of extracellular matrix (ECM) components during tissue remodeling plays a pivotal role in normal and pathological processes including wound healing, inflammation, tumor invasion, and metastasis. Proteolytic enzymes in tumors may activate or release growth factors from the ECM or act directly on the ECM itself, thereby facilitating angiogenesis or tumor cell migration. Fibroblast activation protein (FAP) is a cell surface antigen of reactive tumor stromal fibroblasts found in epithelial cancers and in granulation tissue during wound healing. It is absent from most normal adult human tissues. FAP is conserved throughout chordate evolution, with homologues in mouse and Xenopus laevis, whose expression correlates with tissue remodeling events. Using recombinant and purified natural FAP, we show that FAP has both dipeptidyl peptidase activity and a collagenolytic activity capable of degrading gelatin and type I collagen; by sequence, FAP belongs to the serine protease family rather than the matrix metalloprotease family. Mutation of the putative catalytic serine residue of FAP to alanine abolishes both enzymatic activities. Consistent with its in vivo expression pattern determined by immunohistochemistry, FAP enzyme activity was detected by an immunocapture assay in human cancerous tissues but not in matched normal tissues. This study demonstrates that FAP is present as an active cell surface-bound collagenase in epithelial tumor stroma and opens up investigation into physiological substrates of its novel, tumor-associated dipeptidyl peptidase activity.
Computational approach for depth from defocus (2005)

Active depth from defocus (DFD) eliminates the main limitation faced by passive DFD, namely its inability to recover depth when dealing with scenes defined by weakly textured (or textureless) objects. This is achieved by projecting a dense illumination pattern onto the scene and depth can be recovered by measuring the local blurring of the projected pattern. Since the illumination pattern forces a strong dominant texture on imaged surfaces, the level of blurring is determined by applying a local operator (tuned on the frequency derived from the illumination pattern) as opposed to the case of window-based passive DFD where a large range of band pass operators are required. The choice of the local operator is a key issue in achieving precise and dense depth estimation. Consequently, in this paper we introduce a new focus operator and we propose refinements to compensate for the problems associated with a suboptimal local operator and a nonoptimized illumination pattern. The developed range sensor has been tested on real images and the results demonstrate that the performance of our range sensor compares well with those achieved by other implementations, where precise and computationally expensive optimization techniques are employed.
Computing homography with RANSAC algorithm: a novel method of registration (2005)

An AR (Augmented Reality) system can integrate computer-generated objects with the image sequences of real world scenes in either an off-line or a real-time way. Registration, or camera pose estimation, is one of the key techniques to determine its performance. The registration methods can be classified as model-based and move-matching. The former approach can accomplish relatively accurate registration results, but it requires the precise model of the scene, which is hard to be obtained. The latter approach carries out registration by computing the ego-motion of the camera. Because it does not require the prior-knowledge of the scene, its registration results sometimes turn out to be less accurate. When the model defined is as simple as a plane, a mixed method is introduced to take advantages of the virtues of the two methods mentioned above. Although unexpected objects often occlude this plane in an AR system, one can still try to detect corresponding points with a contract-expand method, while this will import erroneous correspondences. Computing homography with RANSAC algorithm is used to overcome such shortcomings. Using the robustly estimated homography resulted from RANSAC, the camera projective matrix can be recovered and thus registration is accomplished even when the markers are lost in the scene.
CD19, the earliest differentiation antigen of the B cell lineage, bears three extracellular immunoglobulin-like domains and an Epstein-Barr virus-related cytoplasmic tail. (1988)

The isolation and expression of a full-length cDNA clone encoding the B cell-specific glycoprotein CD19 is reported. The sequence of the cDNA predicts a glycosylated integral membrane protein with a precursor molecular weight of 51.8 x 10(3) and an extracellular domain organized into three contiguous Ig-like sub-domains. The cytoplasmic domain bears significant relatedness to two proteins encoded by the Epstein-Barr virus and the int-1 oncogene. CD19 transcripts are restricted to members of the B cell lineage, being most abundant in pre-B cell lines and least abundant in plasmacytomas.
<title>Software tools and test data for research and testing of page-reading OCR systems</title> (2005)

We announce the availability of the UNLV/ISRI Analytic Tools for OCR Evaluation together with a large and diverse collection of scanned document images with the associated ground-truth text. This combination of tools and test data will allow anyone to conduct a meaningful test comparing the performance of competing page-reading algorithms. The value of this collection of software tools and test data is enhanced by knowledge of the past performance of several systems using exactly these tools and this data. These performance comparisons were published in previous ISRI Test Reports and are also provided. Another value is that the tools can be used to test the character accuracy of any page-reading OCR system for any language included in the Unicode standard. The paper concludes with a summary of the programs, test data, and documentation that is available and gives the URL where they can be located.
Brain Drug Targeting: The Future of Brain Drug Development (2001)

The thesis of this innovative and challenging book, first published in 2001, is that brain drug development has been restricted by the failure of adequate brain drug targeting, and that this is an increasingly urgent problem as developments in genomics lead to new generations of therapeutic macromolecules. The author, a world leader in the study of the blood-brain barrier and its clinical implications, reviews the field of neurotherapeutics from the point of view of drug targeting. He surveys the scientific and clinical basis of drug delivery across biological membranes, including topics such as genetically engineered trojan horses for drug targeting, antisense neurotherapeutics, and gene therapy of brain disorders. At a time when there are few significant new drug treatments in prospect for common neurological diseases, this authoritative review will encourage a wide range of clinicians and neuroscientists to reexamine the development and use of drugs in treating disorders of the central nervous system
Breakdown voltage in LDMOS transistors using internal field rings (1991)

The optimization of the floating-ring parameters and the breakdown voltage of a lateral DMOS (LDMOS) transistor using a single floating ring is presented. A first-order analytical approach is presented, showing the upper limit of the position of the ring, with respect to the channel, and the doping concentration within the ring to increase the breakdown voltage. A 2D numerical calculation of the breakdown voltage and on-resistance of the LDMOS transistor is also presented. The results, which support the analytical approach, allow the use of simple design rules for the implementation of high-voltage LDMOS transistors on a thick epitaxial layer. It is shown that improvements of breakdown voltage is obtained if the distance between the channel and the field ring is equal to the field plate length and the doping concentration in the ring satisfies a specific relationship. With a single ring, the breakdown voltage increases from 170 to 280 V for the same device area and to over 480 V if the area is allowed to increase by 25%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Members of the zinc finger protein gene family sharing a conserved N-terminal module (1991)

We report the isolation of human members of a sub-family of structurally related finger protein genes. These potentially encode polypeptides containing finger motifs of the Krüppel type at the C-terminus, and a conserved amino acid module at the N-terminus; because of its invariant location the latter is referred to as finger preceding box (FPB). The FPB, detected also in previously described finger proteins from human, mouse and Xenopus, extends over approximately 65 amino acids and appears to be composed of two contiguous modules: FPB-A (residues 1-42) and FPB-B (residues 43-65). The latter is absent in some of the members analyzed. Elements A and B and the zinc finger domain are encoded by separate exons in the ZNF2 gene, a human member of this sub-family. The positioning of introns within this gene is remarkable. One intron flanks and a second interrupts the first codon of the FPB-A and FPB-B modules, respectively. A third intron occurs a few nucleotides downstream of FPB-B marking its separation from the remainder of the coding sequences. This organization, together with the absence of FPB-B in some cDNAs, supports the hypothesis that mRNAs encoding polypeptides that include one, both or none of the FPB-A and FPB-B modules may be assembled through alternative splicing pathways. Northern analyses showed that members of this sub-family are expressed as multiple transcripts in several cell lines. The sequences of distinct cDNAs homologous to the ZNF2 gene indicate that alternative splicing events adjoin either coding or non coding exons to the FPB sequences.
Distributive Dynamic Spectrum Access Through Deep Reinforcement Learning: A Reservoir Computing-Based Approach (2018)

Dynamic spectrum access (DSA) is regarded as an effective and efficient technology to share radio spectrum among different networks. As a secondary user (SU), a DSA device will face two critical problems: 1) avoiding causing harmful interference to primary users (PUs) and 2) conducting effective interference coordination with other SUs. These two problems become even more challenging for a distributed DSA network where there is no centralized controllers for SUs. In this paper, we investigate communication strategies of a distributive DSA network under the presence of spectrum sensing errors. To be specific, we apply the powerful machine learning tool, deep reinforcement learning (DRL), for SUs to learn “appropriate” spectrum access strategies in a distributed fashion assuming NO knowledge of the underlying system statistics. Furthermore, a special type of recurrent neural network, called the reservoir computing (RC), is utilized to realize DRL by taking advantage of the underlying temporal correlation of the DSA network. Using the introduced machine learning-based strategy, SUs could make spectrum access decisions distributedly relying only on their own current and past spectrum sensing outcomes. Through extensive experiments, our results suggest that the RC-based spectrum access strategy can help the SU to significantly reduce the chances of collision with PUs and other SUs. We also show that our scheme outperforms the myopic method which assumes the knowledge of system statistics, and converges faster than the Q-learning method when the number of channels is large.
How do hotel firms obtain a competitive advantage? (2004)

Hotel managers need to understand how their firm can achieve a competitive advantage (CA) over their competitors. Three conceptual frameworks: Porter’s five, forces approach, the resource‐based approach, and the relational approach, have assisted managers in identifying the sources of CA. Although these three approaches pursue similar goals such as customer value creation and high firm performance, hotel managers have focused on only one of these approaches, limiting their understanding of the sources of CA. Why these three approaches need to be integrated to understand the sources of CA is discussed and a more comprehensive approach to strategic management in the lodging industry is proposed. Implications for research and practice are also offered.
Audio bandwidth detection in the EVS codec (2015)

Speech and audio codecs are usually designed such that they encode all the frequency bands of the input signal spectrum. If the higher bands do not contain any perceptually meaningful content, these codecs often do not work optimally as they assign part of the available bit budget to encode these bands. In this paper we describe a bandwidth detection algorithm that determines the effective audio bandwidth of the input signal. This information is used to set the codec to its optimal configuration and consequently increase the coding efficiency for band-limited signals by allocating bits to encode only the useful bandwidth. The presented algorithm has been used in the new codec for Enhanced Voice Services (EVS), recently standardized by 3GPP, but it can be employed in other codecs as well.
Intranasal delivery of growth differentiation factor 5 to the central nervous system (2012)

This study is the first to show that GDF5 can be formulated at neutral pH and can be directly delivered to the CNS via IN administration, with biologically relevant concentrations in the midbrain where it may be used to treat Parkinson's disease.
Dam Safety Controls under Present New Zealand Legislation (1987)

The paper briefly canvasses the legislative controls on dam construction, operation and maintenance in New Zealand. The general requirements of a duty of care and professional responsibility are described firstly. Land use planning controls are identified and then the more specific provisions of building permits, water rights and bylaws regulating dams are described. All are limited in application and effectiveness leading to the conclusion that at present there are no effective and specific legislative controls.
New recombinant linear DNA-elements derived fromKluyveromyces lactiskiller plasmids (1989)

The cytoplasmically localized linear killer plasmids pGKL1 and 2 from Iltuyveromyces lactis carry terminal inverted repeats (TIRs) and 5' covalently linked proteins. pGKLI (8.8 kb) encodes the killer toxin, whereas pGKL2 (13.4 kb) is responsible for the maintenanceof both linear plasmids (1). After integration of a