gebhart/patrepeval huggingface dataset:
Genetic and Hormonal Regulation of Tryptophan–Kynurenine Metabolism (2007)

Impairment of cognition that is caused by (or associated with) vascular factors has been termed vascular cognitive impairment (VCI). The hallmark of VCI is an impairment of brain executive, or planning, functions caused by inflammatory changes of brain microvessels. VCI is characterized by impairment of the executive function and is distinct from Alzheimer's-type and multi-infarct dementias, although VCI might overlap with Alzheimer's disease. This review focuses on the possible contribution of the kynurenine pathway of tryptophan (Try) catabolism to the inflammatory changes in brain microvessels. One mechanism of brain microvessel inflammation is activation of the inducible nitric oxide synthase (iNOS) by the proinflammatory cytokine interferon gamma (IFN-gamma). The effect of IFN-gamma on iNOS might be mediated by kynurenine derivatives of tryptophan because (1) IFN-gamma stimulates the rate-determining enzyme of the Try-kynurenine pathway, indoleamine-2,3-dioxygenase (IDO) and (2) some kynurenines (e.g., quinolinic and picolinic acids) can stimulate iNOS. IFN-gamma production is controlled by (IFN-gamma) + 874(T/A) genotypes, suggesting the association of a high promoter T allele with the high rate of IFN-gamma production and, consequently, with activated IDO and enhanced production of kynurenines. Although IDO is strictly an IFN-gamma-induced gene product, tumor necrosis factor alpha (TNF-alpha) can synergistically increase the transcriptional activation of the IDO gene in response to IFN-gamma. The combination of high promoter T of (IFN-gamma) + 874(T/A) with high promoter A of (TNF-alpha) -308(G/A) might "superinduce" IDO and cause (or contribute to) inflammation of brain microvessels detected as white matter hyperintensities and leading to VCI development. Hormonal induction of tryptophan dioxygenase and the ability of hormones to potentiate IFN-gamma-induced activation of IDO might contribute to the development of inflammatory changes in major depressive disorder and in aging. The IFN-gamma-IDO-iNOS hypothesis of VCI suggests new ways of preventing (identifying population at risk by analysis of IFN-gamma and TNF-alpha genetic polymorphism) and treating VCI (using IDO inhibitors and melatonin and bupropion [Wellbutrin] as agents suppressing IFN-gamma and TNF-alpha production).
Endogenous Elevation of Homocysteine Induces Retinal Neuron Death in the Cystathionine-β-Synthase Mutant Mouse (2009)

This study provides the first analysis of morphologic and molecular effects of endogenous elevations of retinal homocysteine in an in vivo model. Increased retinal homocysteine alters inner and outer retinal layers in cbs homozygous mice and older cbs heterozygous mice, and it primarily affects the cells of the GCL in younger heterozygous mice. Elevated retinal homocysteine alters expression of genes involved in endoplasmic reticular stress, N-methyl-d-aspartate (NMDA) receptor activation, cell cycle, and apoptosis.
Coordinated 3D interaction in tablet- and HMD-based hybrid virtual environments (2014)

Traditional 3D User Interfaces (3DUI) in immersive virtual reality can be inefficient in tasks that involve diversities in scale, perspective, reference frame, and dimension. This paper proposes a solution to this problem using a coordinated, tablet- and HMD-based, hybrid virtual environment system. Wearing a non-occlusive HMD, the user is able to view and interact with a tablet mounted on the non-dominant forearm, which provides a multi-touch interaction surface, as well as an exocentric God view of the virtual world. To reduce transition gaps across 3D interaction tasks and interfaces, four coordination mechanisms are proposed, two of which were implemented, and one was evaluated in a user study featuring complex level-editing tasks. Based on subjective ratings, task performance, interview feedback, and video analysis, we found that having multiple Interaction Contexts (ICs) with complementary benefits can lead to good performance and user experience, despite the complexity of learning and using the hybrid system. The results also suggest keeping 3DUI tasks synchronized across the ICs, as this can help users understand their relationships, smoothen within- and between-task IC transitions, and inspire more creative use of different interfaces.
Zalutumumab in head and neck cancer (2011)

Zalutumumab has demonstrated acceptable toxicity in head and neck cancer patients, with rash being the most common adverse event. The toxicity profile makes zalutumumab an attractive option for patients who are heavily pretreated and/or have poor performance status due to concurrent co-morbidities. As the molecule is fully human, the likelihood of hypersensitivity to the drug is low. Zalutumumab may be effective at low concentrations through antibody-dependent cellular cytotoxicity. Current data from Phase I and II trials identify zalutumumab as a promising drug for the treatment of locally advanced head and neck cancer and recent data from a Phase III randomized trial showed encouraging survival results compared with best supportive care. Results from other ongoing Phase III trials will provide clarification on zalutumumab as a treatment option. The clinical development of this compound has been suspended from June 2011 until a development and commercialization partner is found.
The Evolutionarily Conserved Longevity Determinants HCF-1 and SIR-2.1/SIRT1 Collaborate to Regulate DAF-16/FOXO (2011)

The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.
Inhibition of Anaplastic Lymphoma Kinase (ALK) Activity Provides a Therapeutic Approach for CLTC-ALK-Positive Human Diffuse Large B Cell Lymphomas (2011)

ALK positive diffuse large B-cell lymphomas (DLBCL) are a distinct lymphoma subtype associated with a poor outcome. Most of them feature a t(2;17) encoding a clathrin (CLTC)-ALK fusion protein. The contribution of deregulated ALK-activity in the pathogenesis and maintenance of these DLBCLs is not yet known. We established and characterized the first CLTC-ALK positive DLBCL cell line (LM1). LM1 formed tumors in NOD-SCID mice. The selective ALK inhibitor NVP-TAE684 inhibited growth of LM1 cells in vitro at nanomolar concentrations. NVP-TAE684 repressed ALK-activated signalling pathways and induced apoptosis of LM1 DLBCL cells. Inhibition of ALK-activity resulted in sustained tumor regression in the xenotransplant tumor model. These data indicate a role of CLTC-ALK in the maintenance of the malignant phenotype thereby providing a rationale therapeutic target for these otherwise refractory tumors.
EBV-Induced Molecule 1 Ligand Chemokine (ELC/CCL19) Promotes IFN-γ-Dependent Antitumor Responses in a Lung Cancer Model (2003)

The antitumor efficacy of EBV-induced molecule 1 ligand CC chemokine (ELC/CCL19) was evaluated in a murine lung cancer model. The ability of ELC/CCL19 to chemoattract both dendritic cells and T lymphocytes formed the rationale for this study. Compared with diluent-treated tumor-bearing mice, intratumoral injection of recombinant ELC/CCL19 led to significant systemic reduction in tumor volumes (p < 0.01). ELC/CCL19-treated mice exhibited an increased influx of CD4 and CD8 T cell subsets as well as dendritic cells at the tumor sites. These cell infiltrates were accompanied by increases in IFN-gamma, MIG/CXCL9, IP-10/CXCL10, GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules PGE(2) and TGFbeta. Transfer of T lymphocytes from ELC/CCL19 treated tumor-bearing mice conferred the antitumor therapeutic efficacy of ELC/CCL19 to naive mice. ELC/CCL19 treated tumor-bearing mice showed enhanced frequency of tumor specific T lymphocytes secreting IFN-gamma. In vivo depletion of IFN-gamma, MIG/CXCL9, or IP-10/CXCL10 significantly reduced the antitumor efficacy of ELC/CCL19. These findings provide a strong rationale for further evaluation of ELC/CCL19 in tumor immunity and its use in cancer immunotherapy.
Directed in Vitro Evolution and Crystallographic Analysis of a Peptide-binding Single Chain Antibody Fragment (scFv) with Low Picomolar Affinity (2004)

We generated a single chain Fv fragment of an antibody (scFv) with a binding affinity of about 5 pm to a short peptide by applying rigorous directed evolution. Starting from a high affinity peptide binder, originally obtained by ribosome display from a murine library, we generated libraries of mutants with error-prone PCR and DNA shuffling and applied off-rate selection by using ribosome display. Crystallographic analysis of the scFv in its antigen-bound and free state showed that only few mutations, which do not make direct contact to the antigen, lead to a 500-fold affinity improvement over its potential germ line precursor. These results suggest that the affinity optimization of very high affinity binders is achieved by modulating existing interactions via subtle changes in the framework rather than by introducing new contacts. Off-rate selection in combination with ribosome display can evolve binders to the low picomolar affinity range even for peptide targets.
Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. (2001)

The expression of the activated mitogen-activated kinases/extracellular signal-regulated kinases (ERKs) ERK1 and ERK2 was characterized in 101 humanhead and neck squamous carcinoma specimens. Activated ERK1/2were detected at different levels in the majority of these tumors, as assayed by immunostaining with an antibody specific for the dually phosphorylated and activated ERK1 and ERK2. ERK1/2 activation levels were higher in tumors with advanced regional lymph node metastasis (P = 0.048) and in relapsed tumors (P = 0.021). The expression of epidermal growth factor (EGF) receptor (P = 0.037), transforming growth factor alpha (TGF-alpha; P < 0.001), and HER2 (P = 0.066; positive trend) correlated with activation of ERK1/2. In a multivariate analysis, both TGF-alpha (P < 0.0001) and HER2 (P = 0.045) were independently correlated with ERK1/2 activation. In turn, activation of ERK1/2 was associated with a higher Ki-67 proliferative index (P = 0.002). In EGF receptor-dependent model cells (A431 and DiFi), a specific EGF receptor tyrosine kinase inhibitor ("Iressa"; ZD1839) and a chimeric anti-EGF receptor antibody ("Cetuximab"; C225) inhibited ERK 1/2 activation at concentrations that inhibited autocrine cell proliferation. In patients on treatment with C225, the activation of ERK1/2 in skin, an EGF receptor-dependent tissue, was lower compared with control skin. Parallel changes were seen in keratinocyte Ki67 proliferation indexes in skin from C225-treated patients. Taken together, these studies provide support for a role of activation of ERK1/2 in head and neck squamous carcinoma and a correlation with EGF receptor/TGF-alpha expression. The inhibition of ERK1/2 activation in vitro and in vivo by compounds targeting the EGF receptor points to the interest of ERK1/2 as potential surrogate markers of EGF-receptor signaling in clinical therapeutic studies.
Molecular cloning and primary structure of myelin-associated glycoprotein. (1987)

Myelin-associated glycoprotein (MAG) may play a role in the cellular interactions leading to myelination. Using monoclonal antibodies and conventional antisera against MAG, we have isolated a cDNA clone from an expression library prepared from rat brain mRNA. The identity of the clone was confirmed by the exact match between its nucleotide sequence and two peptide sequences of 13 and 9 amino acids that we obtained by Edman degradation of two CNBr fragments of MAG. The cDNA clone hybridized to two size species of mRNA in rat approximately 3.5 kilobases in length. These mRNAs were present in brain but not liver and were expressed most abundantly at the time of active myelination (day 14). The mRNA for MAG was present at barely detectable levels in hypomyelinating jimpy mice compared to normal littermate controls. Therefore the MAG cDNA clone is both brain and myelin specific. DNA sequence analysis revealed that our MAG cDNA was derived from the same mRNA as clone p1B236, a randomly selected, brain-specific, partial cDNA isolated by Sutcliffe et al. [Sutcliffe, J. G., Milner, R. J., Shinnick, T. M. & Bloom, F. E. (1983) Cell 33, 671-682]. Analysis of the predicted protein sequence suggests that MAG has a long extracellular domain (499 amino acids), followed by a short transmembrane segment (20 amino acids) and an intracellular carboxyl-terminal domain (90 amino acids). The molecule has several glycosylation sites, three internal repeats homologous to a repeat in the neural cell adhesion molecule (N-CAM), and sites for phosphorylation near the carboxyl terminus. The primary structure reported here provides a molecular framework for further investigations into the function of the MAG molecule.
Detection, Diagnosing, Monitoring and Logical Treatment of Occlusal Caries in Relation to Lesion Activity and Severity: An in vivo Examination with Histological Validation (1998)

The aims of the present study were to investigate the ability of 3 experienced clinicians to detect occlusal carious lesions, assess their depth, diagnose their activity and define a logical management for each lesion. The material consisted of 35 third molars scheduled for extraction or surgical removal making it possible to validate the accuracy of the clinical recordings histologically. Examinations were carried out at baseline and after 4 months in order to monitor lesion progression. At the first visit a radiograph was taken; the number of filled surfaces was counted and the oral hygiene assessed generally and by disclosing occlusal plaque of the tooth under examination. After cleaning the occlusal surface caries was recorded in a selected investigation site using a visual ranked caries scoring system, as well as an electrical conductance recording (ECM). Apart from counting fillings and taking new radiographs the same procedure was performed at the second visit, which then was followed by extraction of the tooth. After sectioning the tooth lesion depth was recorded, and lesion activity, based on acid production, was assessed using methyl red dye. Lesion activity was also judged by means of polarized light microscopic examinations of the sections. Results showed strong relationships between the visual, ECM and radiographic assessments and both lesion depth and lesion activity. In contrast, all other parameters were poorly related to lesion activity. Changes in visual assessments and in conductance readings from first to second examination were poorly associated with lesion activity. In conclusion, clinicians are able to detect lesions, predict activity and severity and define a logical management of occlusal caries on the basis of a single examination.
Structure and Reactivity of the Oxyanions of Transition Metals. (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and Reactivity of the Oxyanions of Transition Metals.Alan Carrington and M. C. R. SymonsCite this: Chem. Rev. 1963, 63, 5, 443–460Publication Date (Print):October 1, 1963Publication History Published online1 May 2002Published inissue 1 October 1963https://pubs.acs.org/doi/10.1021/cr60225a001https://doi.org/10.1021/cr60225a001research-articleACS PublicationsRequest reuse permissionsArticle Views624Altmetric-Citations102LEARN 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
FBG sensor devices for spatial shape detection of intelligent colonoscope (2004)

Two novel kinds of slim FBG (fiber Bragg grating) sensor devices and their application are presented, which can show the three-dimensional image of colonoscope shape on a video screen. One of the two kinds of sensor device is for gradual detection; the other is for real-time dynamic reconstruction. The sensing network device comprises a plurality of FBG sensors mounted on the body of a flexible wire. After the colonoscope is advanced in the body, the wire is pushed through the biopsy channel of the colonoscope. It bends with the curvature of the colonoscope. The FBG sensors capture deformation of the sensor wire, and reconstruct the shape of colonoscope. Experiments in the colon of a live swine have been done. Configuration of experimental system and experimental result are also given.
An introduction to the proper orthogonal decomposition (2000)

A tutorial is presented on the Proper Orthogonal Decomposition (POD), which finds applications in computationally processing large amounts of high-dimensio nal data with the aim of obtaining low-dimensional descriptions that capture much of the phenomena of interest. The discrete version of the POD, which is the singular value decomposition (SVD) of matrices, is described in some detail. The continuous version of the POD is outlined. Low-rank approximations to data using the SVD are discussed. The SVD and the eigenvalue decomposition are compared. Two geometric interpretations of the SVD/POD are given. Computational strategies (using standard software) are mentioned. Two numerical examples are provided: one shows low-rank approximations of a surface, and the other demonstrates simple a posteriori analysis of data from a simulated vibroimpact system. Some relevant computer code is supplied.
Potent Immunosuppressive Activities of Cytomegalovirus- Encoded Interleukin-10 (2002)

Cytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.
Imaging with Phase-Sensitive Light (2007)

We show that almost all the characteristics of quantum optical coherence tomography and quantum ghost imaging are due to phase-sensitive cross correlations, and hence are obtainable with classical phase-sensitive sources.
Neuroprotectin D1 attenuates laser-induced choroidal neovascularization in mouse. (2010)

NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-kappaB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be effective after treatment is concluded, suggesting sustained protection and highlighting the potential applicability of this lipid mediator in preventing or ameliorating endothelial cell growth in pathoangiogenesis.
Marked Effects of Alloying on the Thermal Conductivity of Nanoporous Materials (2010)

We show that porous alloys can display thermal conductivity reductions at considerably larger pore sizes than nonalloyed porous materials of the same nominal porosity. The thermal conductivity of Si0.5Ge0.5 alloy with 0.1 porosity becomes half the nonporous value at 1000 nm pore sizes, whereas pores smaller than 100 nm are required to achieve the same relative reduction in pure Si or Ge. Using Monte Carlo simulations, we also show that previous models had overestimated the thermal conductivity in the small pore limit. Our results imply that nanoporous alloys should be advantageous with respect to nanoporous nonalloys, for applications requiring a low thermal conductivity, such as novel thermoelectrics.
Frontal Lobe Dysfunction in Progressive Supranuclear Palsy (2000)

Recent data from our laboratory have shown a regionally specific increase in lipid peroxidation in postmortem progressive supranuclear palsy (PSP) brain. To extend this finding, we measured activities of mitochondrial enzymes as well as tissue malondialdehyde (MDA) levels in postmortem superior frontal cortex (Brodmann's area 9; SFC) from 14 pathologically confirmed cases of PSP and 13 age-matched control brains. Significant decreases (-39%) in alpha-ketoglutarate dehydrogenase complex/glutamate dehydrogenase ratio and significant increases (+36%) in tissue MDA levels were observed in the SFC in PSP; no differences in complex I or complex IV activities were detected. Together, these results suggest that mitochondrial dysfunction and lipid peroxidation may underlie the frontal metabolic and functional deficits observed in PSP.