gebhart/patrepeval huggingface dataset:
Learning Tags from Unsegmented Videos of Multiple Human Actions (2011)

Providing methods to support semantic interaction with growing volumes of video data is an increasingly important challenge for data mining. To this end, there has been some success in recognition of simple objects and actions in video, however most of this work requires strongly supervised training data. The supervision cost of these approaches therefore renders them economically non-scalable for real world applications. In this paper we address the problem of learning to annotate and retrieve semantic tags of human actions in realistic video data with sparsely provided tags of semantically salient activities. This is challenging because of (1) the multi-label nature of the learning problem and (2) realistic videos are often dominated by (semantically uninteresting) background activity un-supported by any tags of interest, leading to a strong irrelevant data problem. To address these challenges, we introduce a new topic model based approach to video tag annotation. Our model simultaneously learns a low dimensional representation of the video data, which dimensions are semantically relevant (supported by tags), and how to annotate videos with tags. Experimental evaluation on three different video action/activity datasets demonstrate the challenge of this problem, and value of our contribution.
Systemically administered neuregulin‐1β1 rescues nigral dopaminergic neurons via the ErbB4 receptor tyrosine kinase in MPTP mouse models of Parkinson's disease (2015)

Previously, we demonstrated that systemically injected extracellular domain of neuregulin-1β1 (Nrg1β1), a nerve growth and differentiation factor, passes the blood-brain barrier and rescues dopaminergic neurons of substantia nigra in the 6-hydroxydopamine-mouse model of Parkinson's disease (PD). Here, we studied the effects of peripherally administered Nrg1β1 in another toxin-based mouse model of PD. For this purpose, (i) nigrostriatal pathway injury was induced by treatment of adult wild-type mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in acute and subchronic paradigms; and (ii) Nrg1β1 or saline (control) were administered 1 h before each MPTP injection. We found that Nrg1β1 significantly reduced the loss of nigral dopaminergic neurons in both intoxication paradigms (7 days post-injection). However, Nrg1β1 did not reverse MPTP-induced decrease in dopamine levels and dopaminergic fibers in the striatum. We also show that MPTP conversion to its toxic metabolite 1-methyl-4-phenylpyridinium as well as levels of dopamine transporter, mediating intracellular uptake of 1-methyl-4-phenylpyridinium, are unaffected by Nrg1β1. Finally, neuroprotective properties of Nrg1β1 on nigral dopaminergic neurons are specifically mediated by ErbB4 as revealed through the study of ErbB4 knockout mice. In conclusion, systemically administered Nrg1β1 protects midbrain dopaminergic neurons against this PD-related toxic insult. Thus, Nrg1β1 may have a benefit in the treatment of PD patients. Previously, we demonstrated that systemically administered neuregulin-1β1 (Nrg1β1) passes the blood-brain barrier, phosphorylates ErbB4 receptors and elevates dopamine (DA) levels in the nigrostriatal system of healthy mice. Nrg1β1 protects nigral DAergic neurons in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD). Here, we show that Nrg1β1 rescues nigral DAergic neurons also against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cell death. ErbB4 expression is essential for the neuroprotective effect of Nrg1β1 on midbrain DAergic neurons. Nrg1β1 might be beneficial in PD treatment.
Sequence-specific DNA-binding proteins are components of a nuclear matrix-attachment site. (1992)

We have identified a nuclear matrix-attachment region within an upstream element of a human H4 histone gene promoter. Nuclear matrix proteins, isolated and solubilized from HeLa S3 cells, were found to interact with sequence specificity at this matrix-attachment region. Several types of assays for protein-DNA interaction showed that the minimal sequence for the nuclear matrix protein-DNA interaction was 5'-TGACGTCCATG-3'; the underlined region corresponds to the core consensus sequence for ATF transcription factor binding. Two proteins with molecular masses of 43 and 54 kDa were identified by UV-crosslinking analysis as integral components of this protein-DNA complex. The molecular masses of these proteins and the ATF-binding site consensus sequence suggest that these proteins are members of the ATF family. Our results provide direct evidence for nuclear matrix localization of sequence-specific DNA-binding factors for an actively transcribed gene. The proximity of a strong positive transcriptional regulatory element to the matrix-attachment region of this gene suggests that the nuclear matrix may serve to localize and concentrate trans-acting factors that facilitate regulation of gene expression.
Human Embryonic Stem Cell-Derived Cardiomyocytes for Heart Therapies (2007)

Cardiovascular diseases remain the leading cause of mortality and morbidity worldwide. Despite substantial improvements in acute management, survivors of myocardial infarction often progress to heart failure. Since adult cardiomyocytes (CMs) do not regenerate, their loss permanently compromises myocardial contractile function. Heart transplantation is currently the last resort for end-stage heart failure, but is hampered by a severe shortage of donor organs and rejection. Cell-based therapies are a promising alternative: Various cell types such as human fetal CMs, skeletal muscle myoblasts and smooth muscle cells have been tested but these approaches are also limited by cell availability or side effects (e.g. due to their non-cardiac identity). In recent years, clinical studies exploiting adult bone marrow mesenchymal stem cells for transplantation in patients with coronary artery disease have reported favorable outcomes but their cardiomyogenic ability is limited. By contrast, human embryonic stem cells (hESCs), derived from the inner cell mass of blastocyst-stage embryos, are pluripotent and can self-renew and differentiate into all cell types including CMs. Furthermore, hESC-derived CMs (hESC-CMs) are viable human heart cells that can functionally integrate with the recipient organ after transplantation. This article reviews the current state and hurdles of hESC-CM research, as well as their therapeutic potentials and limitations.
Induction of antigen-specific antibodies in vaginal secretions by using a nontoxic mutant of heat-labile enterotoxin as a mucosal adjuvant (1996)

Immunization of the female reproductive tract is important for protection against sexually transmitted diseases and other pathogens of the reproductive tract. However, intravaginal immunization with soluble antigens generally does not induce high levels of secretory immunoglobulin A (IgA). We recently developed safe mucosal adjuvants by genetically detoxifying Escherichia coli heat-labile enterotoxin, a molecule with a strong mucosal adjuvant activity, and here we describe the use of the nontoxic mutant LTK63 to induce a response in the mouse vagina against ovalbumin (Ova). We compared intravaginal and intranasal routes of immunization for induction of systemic and vaginal responses against LTK63 and Ova. We found that LTK63 is a potent mucosal immunogen when given by either the intravaginal or intranasal route. It induces a strong systemic antibody response and IgG and long-lasting IgA in the vagina. The appearance of vaginal IgA is delayed in the intranasally immunized mice, but the levels of vaginal anti-LTK63 IgA after repeated immunizations are higher in the intranasally immunized mice than in the intravaginally immunized mice. LTK63 also acts as a mucosal adjuvant, inducing a serum response against Ova, when given by both the intravaginal and intranasal routes. However, vaginal IgA against Ova is stimulated more efficiently when LTK63 and antigen are given intranasally. In conclusion, our results demonstrate that LTK63 can be used as a mucosal adjuvant to induce antigen-specific antibodies in vaginal secretions and show that the intranasal route of immunization is the most effective for this purpose.
Photoprocesses in dimers of thiacarbocyanines (1999)

The properties of monomeric and dimeric thiacarbocyanine (1) and three derivatives with methyl (2) and ethyl (3 and 4) meso-substituents were studied in aqueous solution by time-resolved and steady-state spectroscopic methods. Dimerization is characterized by a blue-shifted band at 512–536 nm, a high association constant, e.g. KD=3.8×104 and 2.8×105 d mol-1 for 1 and 3, respectively and a negative enthalpy and enthropy, e.g. ΔHD=-72 kJ mol-1 and ΔSD=-142 J mol-1 K-1 for 3. Dimers are composed from the all-trans isomers for 1 and from mono-cis isomers for 2–4 with face-to-face alignment. They are non-fluorescent and the observed weak fluorescence originates essentially from the all-trans monomers. The triplet state of the monomer/dimer composition was observed upon naphthalene-sensitized and direct excitation. The triplet yield is largest for 3 and is due only to the dimer, whereas for 2 both monomer and dimer contribute to the overall T-T absorption spectrum. The amounts of T-T absorption and bleaching as a function of temperature resemble that of the ratio of monomer to dimer concentrations. Reasons for the lack of trans→cis photoisomerization in the cases of 2–4 are discussed.
Modeling Ring-Chain Equilibria in Ring-Opening Polymerization of Cycloolefins (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModeling Ring-Chain Equilibria in Ring-Opening Polymerization of CycloolefinsZhong-Ren Chen, Jerome P. Claverie, Robert H. Grubbs, and Julia A. KornfieldCite this: Macromolecules 1995, 28, 7, 2147–2154Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://doi.org/10.1021/ma00111a007RIGHTS & PERMISSIONSArticle Views968Altmetric-Citations73LEARN 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 (882 KB) Get e-Alertsclose Get e-Alerts
Molecular mechanisms of allosteric probe dependence in μ opioid receptor (2017)

Allostery is one of the most important features of proteins. It greatly contributes to the complexity of life, since it enables possibility of precise tuning of protein function, as well as performing more than one function per protein. Probe dependence is one of the unique features of allostery. It allows a protein to respond differently to the same allosteric modulator when different drugs or transmitters are bound. Unfortunately, allosteric mechanisms are difficult to investigate experimentally. Instead, they can be reproduced artificially in simulations. We simulated in silico a native-like cell membrane fragment with an active-state human μ opioid receptor (MOR) in order to investigate diverse effects of a receptor's positive allosteric modulator on various agonists. Particular emphasis on native-likeness of the environment was put. We managed to reproduce the experimentally observed effects, which allowed us to take deeper insight into their underlying mechanisms. We found an allosteric pathway in the receptor, leading from the ligand binding site to the intracellular, effector site. We observed that the modulator affected the pathway, inducing different resultant responses for full and partial agonists.
Arachidonic Acid Cascade and Signal Transduction (1990)

Since a review on this topic in this Journal appeared (Wolfe, 1982), the CNS has proved to be a major focus in eicosanoid research. Although our knowledge is limited at the moment, the research in this field is rapidly growing. In this short review, we summarize recent progress of research (1982-1989) in this field with special attention directed to eicosanoid metabolism, functions of eicosanoids in the neuroendocrine system and synaptic transmission, current information on eicosanoid receptors, and the link between eicosanoids and cerebral circulation. Knowledge of the eicosanoids has paved the way to a better understanding of intercellular signal transduction systems, including neuronal functions.
Preventive strategies in chronic liver disease: part II. Cirrhosis. (2001)

Cirrhosis is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. The modified Child-Pugh score, which ranks the severity of cirrhosis based on signs and liver function test results, has been shown to predict survival. Strategies have been established to prevent complications in patients with cirrhosis. Esophageal varices can be identified by endoscopy; if large varices are present, prophylactic nonselective beta blocker therapy should be administered. Alpha-fetoprotein testing and ultrasonography can be effective in screening for hepatocellular carcinoma. Vaccines should be administered to prevent secondary infections. The use of nonsteroidal anti-inflammatory drugs should be avoided, and patients should maintain a balanced diet containing 1 to 1.5 g of protein per kg per day. An extensive assessment should be performed before patients with cirrhosis undergo elective surgery. Before advanced liver decompensation occurs, patients should be referred for liver transplantation evaluation. If advanced cirrhosis is present and transplantation is not feasible, survival is between one and two years.
Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension (2020)

This study examined the dose-response characteristics of aprocitentan, a dual endothelin A/endothelin B receptor antagonist, in patients with essential hypertension. In a randomized, double-blind, parallel study design, eligible patients with a sitting diastolic blood pressure (BP) of 90-109 mm Hg received aprocitentan 5, 10, 25, or 50 mg, placebo, or lisinopril 20 mg as a positive control once daily for 8 weeks. Multiple automated office BP readings were obtained with patients resting unattended (unattended automated office BP) at baseline, weeks 2, 4, and 8. Ambulatory BP was monitored for 24 hours at baseline and week 8. After a single-blind placebo run-in period, 490 eligible patients were randomized to the double-blind phase, with 409 patients completing 8 weeks of therapy per protocol. Aprocitentan 10, 25, and 50 mg decreased sitting systolic/diastolic unattended automated office BP from baseline to week 8 (placebo-corrected decreases: 7.05/4.93, 9.90/6.99, and 7.58/4.95 mm Hg, respectively, <i>P</i>≤0.014 versus placebo), compared with an unattended automated office BP reduction of 4.84/3.81 mm Hg with lisinopril 20 mg. For patients with valid ambulatory BP, aprocitentan 10, 25, and 50 mg significantly decreased placebo-corrected 24-hour BP by 3.99/4.04, 4.83/5.89, and 3.67/4.45 mm Hg, respectively. Incidence of adverse events was similar in the aprocitentan groups (22.0%-40.2%) and the placebo group (36.6%). Aprocitentan produced dose-dependent decreases in hemoglobin, hematocrit, albumin, and uric acid, an increase in estimated plasma volume, but no change in weight versus placebo. These findings support further investigation of aprocitentan at doses of 10 to 25 mg in hypertension. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02603809.
Interactive Virtual Relighting and Remodeling of Real Scenes (1999)

Lighting design is often tedious due to the required physical manipulation of real light sources and objects. As an alternative, we present an interactive system to virtually modify the lighting and geometry of scenes with both real and synthetic objects, including mixed real/virtual lighting and shadows. In our method, real scene geometry is first approximately reconstructed from photographs. Additional images are taken from a single viewpoint with a real light in different positions to estimate reflectance. A filtering process is used to compensate for inaccuracies, and per image reflectances are averaged to generate an approximate reflectance image for the given viewpoint, removing shadows in the process. This estimate is used to initialise a global illumination hierarchical radiosity system, representing real-world secondary illumination; the system is optimized for interactive updates. Direct illumination from lights is calculated separately using ray-casting and a table for efficient reuse of data where appropriate. Our system allows interactive modification of light emission and object positions, all with mixed real/virtual illumination effects. Real objects can also be virtually removed using texture-filling algorithms for reflectance estimation.
Flow and myocardial interaction: an imaging perspective (2007)

Heart failure due to coronary artery disease has considerable morbidity and poor prognosis. An understanding of the underlying mechanics governing myocardial contraction is a prerequisite for interpreting and predicting changes induced by heart disease. Gross changes in contractile behaviour of the myocardium are readily detected with existing techniques. For more subtle changes during early stages of cardiac dysfunction, however, a sensitive method for measuring, as well as a precise criterion for quantifying, normal and impaired myocardial function is required. The purpose of this paper is to outline the role of imaging, particularly cardiovascular magnetic resonance (CMR), for investigating the fundamental relationships between cardiac morphology, function and flow. CMR is emerging as an important clinical tool owing to its safety, versatility and the high-quality images it produces that allow accurate and reproducible quantification of cardiac structure and function. We demonstrate how morphological and functional assessment of the heart can be achieved by CMR and illustrate how blood flow imaging can be used to study flow and structure interaction, particularly for elucidating the underlying haemodynamic significance of directional changes and asymmetries of the cardiac looping. Future outlook on combining imaging with engineering approaches in subject-specific biomechanical simulation is also provided.
Effect of natural polymorphism at residue 86 of the HLA-DR beta chain on peptide binding (1991)

Class I and class II MHC glycoproteins are highly polymorphic molecules that bind antigenic peptides and present them on cell surfaces for recognition by T lymphocytes. Even though MHC polymorphism has long been known to affect both peptide binding and recognition by the TCR, the role of individual amino acids of MHC proteins in these interactions is poorly understood. To examine the effect of a small number of amino acid residues on T cell stimulation, B lymphoblastoid cell lines homozygous for the closely related DR1 subtypes, Dw1 and Dw20, and the DR4 subtypes, Dw4 and Dw14, were compared for their ability to present an immunogenic influenza hemagglutinin peptide (HA307-319) to an Ag-specific, DR1,4-restricted T cell clone. B cell lines expressing DR1 Dw20 and DR4 Dw14 presented HA307-319 much less efficiently than DR1 Dw1 and DR4 Dw4 and bound a biotinylated analogue of the same peptide less well. Analysis of DRB1 gene sequences suggested that polymorphism at residue 86 had a major effect on peptide binding. Differences in binding of a set of HA307-319 analogues biotinylated at each residue to cells expressing DR1 Dw1 and DR1 Dw20 suggested that the polymorphism affected the interactions of many peptide residues with the class II molecule. In inhibition assays, DR1 Dw1 and DR4 Dw4 were shown to differ from DR1 Dw20 and DR4 Dw14 in their length requirements for peptide binding. Using a larger panel of homozygous B cell lines expressing many class II haplotypes, a Ser-309 substituted HA307-319 analogue was shown to bind to most B cell lines expressing Val-86 containing alleles (including DR1 Dw20 and DR4 Dw14) but failed to bind most B cell lines expressing Gly-86 alleles (including DR1 Dw1 and DR4 Dw4). The results indicated that polymorphism at residue 86 influenced the specificity and affinity of peptide binding and affected the conformation of peptide-DR protein complexes without completely eliminating T cell recognition.
Transcription Factors: Structural Families and Principles of DNA Recognition (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A pilot study of N‐acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease (2000)

GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric-release preparations are required to confirm its efficacy and establish indications for use.
Mechanical stretch induces hair regeneration through the alternative activation of macrophages (2019)

Tissues and cells in organism are continuously exposed to complex mechanical cues from the environment. Mechanical stimulations affect cell proliferation, differentiation, and migration, as well as determining tissue homeostasis and repair. By using a specially designed skin-stretching device, we discover that hair stem cells proliferate in response to stretch and hair regeneration occurs only when applying proper strain for an appropriate duration. A counterbalance between WNT and BMP-2 and the subsequent two-step mechanism are identified through molecular and genetic analyses. Macrophages are first recruited by chemokines produced by stretch and polarized to M2 phenotype. Growth factors such as HGF and IGF-1, released by M2 macrophages, then activate stem cells and facilitate hair regeneration. A hierarchical control system is revealed, from mechanical and chemical signals to cell behaviors and tissue responses, elucidating avenues of regenerative medicine and disease control by demonstrating the potential to manipulate cellular processes through simple mechanical stimulation.