gebhart/patrepeval huggingface dataset:
Phosphorylation of Serine 256 Suppresses Transactivation by FKHR (FOXO1) by Multiple Mechanisms (2002)

FKHR is a member of the FOXO subfamily of Forkhead transcription factors, which are important targets for insulin and growth factor signaling. FKHR contains three predicted protein kinase B phosphorylation sites (Thr-24, Ser-256, and Ser-319) that are conserved in other FOXO proteins. We have reported that phosphorylation of Ser-256 is critical for the ability of insulin and insulin-like growth factors to suppress transactivation by FKHR (Guo, S., Rena, G., Cichy, S., He, X., Cohen, P., and Unterman, T. (1999) J. Biol. Chem. 274, 17184-17192) and for its exclusion from the nucleus (Rena, G., Prescott, A. R., Guo, S., Cohen, P., and Unterman, T. G. (2001) Biochem. J. 354, 605-612). Ser-256 is located in a basic region of the FKHR DNA binding domain where phosphorylation may have direct effects on DNA binding and/or nuclear targeting. Phosphorylation of Ser-256 may also be required for the phosphorylation of Thr-24 and Ser-319. Here, we provide the first direct evidence that basic residues in the FKHR DNA binding domain are critical for DNA binding and that Ser-256 phosphorylation alters binding activity. Ser-256 phosphorylation also is critical for regulating nuclear/cytoplasmic trafficking; however, this effect requires Thr-24/Ser-319 phosphorylation. Transient transfection studies with reporter gene constructs in 293 cells reveal that the phosphorylation of Ser-256 can inhibit the function of FKHR independent of Thr-24/Ser-319 phosphorylation. Studies with GFP(1) fusion proteins indicate that Ser-256 phosphorylation is critical for nuclear exclusion of FKHR. However, this effect is disrupted when Thr-24 and Ser-319 are replaced by alanine, indicating that nuclear exclusion of FKHR also requires Thr-24/Ser-319 phosphorylation. Gel shift and fluorescence anisotropy studies reveal that basic residues at the C-terminal end of the FKHR DBD are important for DNA binding, and the introduction of a negative charge at the site of Ser-256 limits binding activity. Binding is rapid and reversible, providing an opportunity for the phosphorylation of Ser-256 and subsequent phosphorylation of Thr-24 and Ser-319 and nuclear exclusion of FKHR.
Molecular cloning of a potential proteinase activated receptor. (1994)

A DNA sequence encoding a G-protein-coupled receptor was isolated from a mouse genomic library. The predicted protein is similar in structure to the thrombin receptor and has a similar activation mechanism. When expressed in Xenopus laevis oocytes, the receptor was activated by low concentrations of trypsin (EC 3.4.21.4) and by a peptide (SLIGRL) derived from the receptor sequence, but was not activated by thrombin (EC 3.4.21.5). Trypsin failed to activate a mutant receptor in which the presumed cleavage site Arg-34-Ser-35 was changed to an Arg-Pro sequence. The agonist peptide (SLIGRL) activated equally well mutant and wild-type receptors. Northern blot analysis demonstrated receptor transcripts in highly vascularized tissues such as kidney, small intestine, and stomach. Because this, to our knowledge, is the second example, besides the thrombin receptor, of a proteolytically activated seven-transmembrane G-protein-coupled receptor, we have provisionally named it proteinase activated receptor 2.
Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC-1] and Byler syndrome): Evidence for heterogeneity (1997)

Byler disease (ByD) is an autosomal recessive disorder in which cholestasis of onset in infancy leads to hepatic fibrosis and death. Children who have a clinically similar disorder, but are not members of the Amish kindred in which ByD was described, are said to have Byler syndrome (ByS). Controversy exists as to whether ByD and ByS (subtypes of progressive familial intrahepatic cholestasis [PFIC]) represent one clinicopathological entity. The gene for ByD has been mapped to a 19-cM region of 18q21-q22. PFIC caused by a lesion in this region, including ByD, can be designated PFIC-1. Examination of haplotypes in siblings with ByS in two unrelated non-Amish families showed that the gene(s) responsible for their disorder(s) did not lie in the PFIC-1 candidate region. On light microscopy and transmission electron microscopy (TEM), liver tissue differed between Amish children with PFIC-1, who had coarsely granular bile and at presentation had bland intracanalicular cholestasis, and the children with ByS in the two non-Amish families, who had amorphous or finely filamentous bile and at presentation had neonatal hepatitis. Bile acid composition of bile also differed: In the Amish children with PFIC-1 and in one ByS family, the proportional concentration of chenodeoxycholic acid (CDCA) in bile was low compared with normal bile; in the other ByS family, it was only slightly reduced. Genetic analysis and light microscopy and TEM of liver may help distinguish PFIC-1 from other forms of ByS.
Metabolic capacity of Bacillus subtilis for the production of purine nucleosides, riboflavin, and folic acid (1998)

We developed a stoichiometric model of Bacillus subtilis metabolism for quantitative analysis of theoretical growth and biochemicals production capacity. This work concentrated on biochemicals that are derived from the purine biosynthesis pathway; inosine, guanosine, riboflavin, and folic acid. These are examples of commercially relevant biochemicals for which Bacillus species are commonly used production hosts. Two previously unrecognized, but highly desirable properties of good producers of purine pathway-related biochemicals have been identified for optimally engineered product biosynthesis; high capacity for reoxidation of NADPH and high bioenergetic efficiency. Reoxidation of NADPH, through the transhydrogenase or otherwise, appears to be particularly important for growth on glucose, as deduced from the corresponding optimal carbon flux distribution. The importance of cellular energetics on optimal performance was quantitatively assessed by including a bioenergetic efficiency parameter as an unrestricted, ATP dissipating flux in the simulations. An estimate for the bioenergetic efficiency was generated by fitting the model to experimentally determined growth yields. The results show that the maximum theoretical yields of all products studied are limited by pathway stoichiometry at high bioenergetic efficiencies. Simulations with the estimated bioenergetic efficiency of B. subtilis, growing under glucose-limiting conditions, indicate that the yield of these biochemicals is primarily limited by energy and thus is very sensitive to the process conditions. The maximum yields that can reasonably be expected with B. subtilis on glucose were estimated to be 0.343, 0.160, and 0.161 (mol product/mol glucose) for purine nucleosides, riboflavin, and folic acid, respectively. Potential strategies for improving these maximum yields are discussed. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59: 227–238, 1998.
Amino Acid Sequences Common to Rapidly Degraded Proteins: The PEST Hypothesis (1986)

The amino acid sequences of ten proteins with intracellular half-lives less than 2 hours contain one or more regions rich in proline (P), glutamic acid (E), serine (S), and threonine (T). These PEST regions are generally, but not always, flanked by clusters containing several positively charged amino acids. Similar inspection of 35 proteins with intracellular half-lives between 20 and 220 hours revealed that only three contain a PEST region. On the basis of this information, it was anticipated that caseins, which contain several PEST sequences, would be rapidly degraded within eukaryotic cells. This expectation was confirmed by red blood cell-mediated microinjection of 125I-labeled caseins into HeLa cells where they exhibited half-lives of less than 2 hours. The rapid degradation of injected alpha- and beta-casein as well as the inverse correlation of PEST regions with intracellular stability indicate that the presence of these regions can result in the rapid intracellular degradation of the proteins containing them.
Virtual Worlds as Proxy for Multi-Object Tracking Analysis (2016)

Modern computer vision algorithms typically require expensive data acquisition and accurate manual labeling. In this work, we instead leverage the recent progress in computer graphics to generate fully labeled, dynamic, and photo-realistic proxy virtual worlds. We propose an efficient real-to-virtual world cloning method, and validate our approach by building and publicly releasing a new video dataset, called Virtual KITTI (see http://www.xrce.xerox.com/Research-Development/Computer-Vision/Proxy-Virtual-Worlds), automatically labeled with accurate ground truth for object detection, tracking, scene and instance segmentation, depth, and optical flow. We provide quantitative experimental evidence suggesting that (i) modern deep learning algorithms pre-trained on real data behave similarly in real and virtual worlds, and (ii) pre-training on virtual data improves performance. As the gap between real and virtual worlds is small, virtual worlds enable measuring the impact of various weather and imaging conditions on recognition performance, all other things being equal. We show these factors may affect drastically otherwise high-performing deep models for tracking.
Structural Characterization of Phospholipids by Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (1995)

Matrix-assisted laser desorption/ionization (MALDI) Fourier transform ion cyclotron resonance mass spectrometry provides for structural analysis of the principal biological phospholipids: glycerophosphatidylcholine, -ethanolamine, -serine, and -inositol. Both positive and negative molecular or quasimolecular ions are generated in high abundance. Isolated molecular ions may be collisionally activated in the source side of a dual trap mass analyzer, yielding fragments serving to identify the polar head group (positive ion mode) and fatty acid side chains (negative ion mode). Azimuthal quadrupolar excitation following collisionally activated dissociation refocuses productions close to the solenoid axis; subsequent transfer of product ions to the analyzer ion trap allows for high-resolution mass analysis. Cyro-cooling of the sample probe with liquid nitrogen greatly reduces matrix adduction encountered in the negative ion mode.
Vision-Based Bridge Deformation Monitoring (2017)

Optics-based tracking of civil structures is not new, due to historical application in surveying, but automated applications capable of tracking at rates that capture dynamic effects are now a hot research topic in structural health monitoring. Recent innovations show promise of true non-contacting monitoring capability avoiding the need for physically attached sensor arrays. The paper reviews recent experience using the Imetrum Dynamic Station (DMS) commercial optics-based tracking system on Humber Bridge and Tamar Bridge, aiming to show both the potential and limitations. In particular the paper focuses on the challenges to field application of such a system resulting from camera instability, nature of the target (artificial or structural feature) and illumination. The paper ends with evaluation of a non-proprietary system using a consumer grade camera for cable vibration monitoring to emphasise the potential for lower cost systems where if performance specifications can be relaxed.
Phase III Study of Gemcitabine in Combination With Fluorouracil Versus Gemcitabine Alone in Patients With Advanced Pancreatic Carcinoma: Eastern Cooperative Oncology Group Trial E2297 (2002)

5-FU, administered in conjunction with gemcitabine, did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine. Further studies with other combinations of gemcitabine and 5-FU are not compelling, and clinical trial resources should address other combinations and novel agents.
Complete genomic sequence analysis of infectious bronchitis virus Ark DPI strain and its evolution by recombination (2008)

An infectious bronchitis virus Arkansas DPI (Ark DPI) virulent strain was sequenced, analyzed and compared with many different IBV strains and coronaviruses. The genome of Ark DPI consists of 27,620 nucleotides, excluding poly (A) tail, and comprises ten open reading frames. Comparative sequence analysis of Ark DPI with other IBV strains shows striking similarity to the Conn, Gray, JMK, and Ark 99, which were circulating during that time period. Furthermore, comparison of the Ark genome with other coronaviruses demonstrates a close relationship to turkey coronavirus. Among non-structural genes, the 5'untranslated region (UTR), 3C-like proteinase (3CLpro) and the polymerase (RdRp) sequences are 100% identical to the Gray strain. Among structural genes, S1 has 97% identity with Ark 99; S2 has 100% identity with JMK and 96% to Conn; 3b 99%, and 3C to N is 100% identical to Conn strain. Possible recombination sites were found at the intergenic region of spike gene, 3'end of S1 and 3a gene. Independent recombination events may have occurred in the entire genome of Ark DPI, involving four different IBV strains, suggesting that genomic RNA recombination may occur in any part of the genome at number of sites. Hence, we speculate that the Ark DPI strain originated from the Conn strain, but diverged and evolved independently by point mutations and recombination between field strains.
BTK as a Mediator of Radiation-Induced Apoptosis in DT-40 Lymphoma B Cells (1996)

Bruton's tyrosine kinase (BTK) is a member of the SRC-related TEC family of protein tyrosine kinases (PTKs). DT-40 lymphoma B cells, rendered BTK-deficient through targeted disruption of the btk gene by homologous recombination knockout, did not undergo radiation-induced apoptosis, but cells with disrupted lyn or syk genes did. Introduction of the wild-type, or a SRC homology 2 domain or a plecstrin homology domain mutant (but not a kinase domain mutant), human btk gene into BTK-deficient cells restored the apoptotic response to radiation. Thus, BTK is the PTK responsible for triggering radiation-induced apoptosis of lymphoma B cells, and its kinase domain is indispensable for the apoptotic response.
Lipid Nanoparticles Enabling Gene Therapies: From Concepts to Clinical Utility (2018)

Genetic drugs based on RNA or DNA have remarkable therapeutic potential as virtually any disease can be treated by silencing a pathological gene, expressing a beneficial protein, or by editing defective genes. However, therapies based on nucleic acid polymers require sophisticated delivery systems to deliver these macromolecules to the interior of target cells. In this study, we review progress in developing nonviral lipid nanoparticle (LNP) delivery systems that have attractive properties, including ease of manufacture, reduced immune responses, multidosing capabilities, larger payloads, and flexibility of design. LNP systems represent the most advanced delivery systems for genetic drugs as it is expected that an LNP-short interfering RNA (siRNA) formulation will receive clinical approval from the Food and Drug Administration (FDA) in 2018 for treatment of the hereditary condition transthyretin-mediated amyloidosis, a fatal condition for which there is currently no treatment. This achievement is largely due to the development of optimized ionizable cationic lipids, arguably the most important factor in the clinical success of LNP-siRNA. In addition, we highlight potential LNP applications, including targeting tissues beyond the liver and therapeutic approaches based on messenger RNA or Clustered Regularly Interspaced Short Palindromic Repeats/Cas.
Syntheses of the stereoisomers of the sex pheromones of the southern corn rootworm and lesser tea tortrix (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSyntheses of the stereoisomers of the sex pheromones of the southern corn rootworm and lesser tea tortrixPhilip E. SonnetCite this: J. Org. Chem. 1982, 47, 19, 3793–3796Publication Date (Print):September 1, 1982Publication History Published online1 May 2002Published inissue 1 September 1982https://pubs.acs.org/doi/10.1021/jo00140a049https://doi.org/10.1021/jo00140a049research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations35LEARN 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 Get e-Alerts
Splicy: a web-based tool for the prediction of possible alternative splicing events from Affymetrix probeset data (2007)

Splicy generates probeset annotations and images describing the relation between the single probes and intron/exon structure of the target transcript in all its known variants. We think that Splicy will be useful for giving to the researcher a clearer picture of the possible transcript variants linked with a given gene and an additional view on the interpretation of microarray experiment data. Splicy is publicly available and has been realized in the framework of a bioinformatics grant from the Italian Cancer Research Association.
A divergent synthesis of 2-acyl derivatives of PUGNAc yields selective inhibitors of O-GlcNAcase (2006)

A divergent route facilitating the rapid synthesis of a series of O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc)-based inhibitors, bearing different N-acyl groups has been developed. All compounds of this series are inhibitors of both human O-GlcNAcase and human beta-hexosaminidase, yet some effectively exploit differences between the active site architectures of these two human enzymes which render them selective for O-GlcNAcase. Such inhibitors may be valuable tools in dissecting the role of the O-GlcNAc post-translational modification at the cellular and organismal level since these compounds may have different pharmacokinetic properties when compared to other inhibitors of beta-N-acetyl-glucosaminidases.
An attenuated variant of Coxsackievirus B3 preferentially induces immunoregulatory T cells in vivo (1991)

BALB/c mice infected with the Woodruff variant of coxsackievirus group B type 3 (CVB3W) develop myocarditis mediated by autoimmune cytolytic T lymphocytes. A variant of CVB3W (designated H3-10A1) which infects the myocardium but induces minimal mortality of myocarditis compared to the parental virus was selected. Although H3-10A1 infections stimulate normal CTL responses to CVB3-infected myocytes, the autoimmune response to myocardial antigens is absent. Treatment of H3-10A1-infected mice with 50 mg of cyclophosphamide per kg of body weight, a treatment which preferentially eliminates suppressor cells, allows both the development of the autoimmune cytotoxic T-lymphocyte response and the expression of myocarditis. Similar treatment of CVB3W-infected mice had no effect on the disease. The presence of the immunoregulatory cells was confirmed by adoptive transfer of T lymphocytes from either H3-10A1 or CVB3W-infected donor mice into syngeneic CVB3W-infected recipients. Animals given H3-10A1-immune cells had minimal myocardial inflammation, while animals given CVB3W-immune lymphocytes developed enhanced cardiac disease. Elimination of the T-lymphocyte population from the donor cells prior to transfer abrogated suppression with the H3-10A1-immune population, showing that immunoregulation depended upon T lymphocytes. Both H3-10A1 and CVB3W have cross-reactive epitopes between the adenine translocator protein and the virion which are indicative of antigenic mimicry and may be the basis for the autoimmunity to cardiac antigens. These results suggest that immunoregulatory T cells may be primarily responsible for the nonpathogenicity of the H3-10A1 variant.
Development of a lightweight, underactuated exoskeleton for load-carrying augmentation (2006)

Metabolic studies have shown that there is a metabolic cost associated with carrying load. Several leg exoskeletons have been developed by various groups in an attempt to augment the load carrying capability of the human. Previous research efforts have not fully exploited the passive dynamics of walking and have largely focused on fully actuated exoskeletons that are heavy with large energy requirements. In this paper, a lightweight, underactuated exoskeleton design is presented that runs in parallel to the human and supports the weight of a payload. Two exoskeleton architectures are pursued based on examining human walking data. A first architecture consists of springs at the hip, a variable impedance device at the knee, and springs at the ankle. A second architecture replaces the springs at the hip with a non-conservative actuator to examine the effect of adding power at desired instances throughout the gait cycle. Preliminary studies show that an efficient, underactuated leg exoskeleton can effectively transmit payload forces to the ground during the walking cycle
Fast LIDAR localization using multiresolution Gaussian mixture maps (2015)

This paper reports on a fast multiresolution scan matcher for vehicle localization in urban environments for self-driving cars. State-of-the-art approaches to vehicle localization rely on observing road surface reflectivity with a three-dimensional (3D) light detection and ranging (LIDAR) scanner to achieve centimeter-level accuracy. However, these approaches can often fail when faced with adverse weather conditions that obscure the view of the road paint (e.g., puddles and snowdrifts) or poor road surface texture. We propose a new scan matching algorithm that leverages Gaussian mixture maps to exploit the structure in the environment; these maps are a collection of Gaussian mixtures over the z-height distribution. We achieve real-time performance by developing a novel branch-and-bound, multiresolution approach that makes use of rasterized lookup tables of these Gaussian mixtures. Results are shown on two datasets that are 3.0 km: a standard trajectory and another under adverse weather conditions.
Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Extended-Release Tolterodine: Results From the Overactive Bladder Innovative Therapy Trial (2009)

This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.