gebhart/patrepeval huggingface dataset:
Is The Cerebral Cortex Hyperexcitable or Hyperresponsive in Migraine? (2007)

Although migraineurs appear in general to be hypersensitive to external stimuli, they maybe also have increased daytime sleepiness and complain of fatigue. Neurophysiological studies between attacks have shown that for a number of different sensory modalities the migrainous brain is characterised by a lack of habituation of evoked responses. Whether this is due to increased cortical hyperexcitability, possibly due to decreased inhibition, or to an abnormal responsivity of the cortex due a decreased preactivation level remains disputed. Studies using transcranial magnetic stimulation in particular have yielded contradictory results. We will review here the available data on cortical excitability obtained with different methodological approaches in patients over the migraine cycle. We will show that these data congruently indicate that the sensory cortices of migraineurs react excessively to repetitive, but not to single, stimuli and that the controversy above hyper- versus hypo-excitability is merely a semantic misunderstanding. Describing the migrainous brain as 'hyperresponsive' would fit most of the available data. Deciphering the precise cellular and molecular underpinnings of this hyperresponsivity remains a challenge for future research. We propose, as a working hypothesis, that a thalamo-cortical dysrhythmia might be the culprit.
The effect of thymidine kinase transduction and ganciclovir therapy on tumor vasculature and growth of 9L gliomas in rats (1994)

Eradication of malignant brain tumors by in situ intratumoral, retrovirally mediated transfer of the herpes simplex virus thymidine kinase (HSVtk) gene, which sensitizes the tumor cells to ganciclovir, has recently been demonstrated in animal models. The observation that tumors studied in vitro and in animals can be completely eliminated despite only partial transduction of the tumor suggests a bystander mechanism that affects nontransduced tumor cells. Such a bystander effect is not completely understood and may represent a combination of several factors that lead to tumor eradication. Endothelial cells of the tumor blood vessels were shown to occasionally integrate the retroviral vector and thus become sensitized to ganciclovir. In the presence of vector-producer cells, which continuously release infectious viral particles, diffuse multifocal hemorrhages occurred during ganciclovir administration. When the tumor was composed of cells that had been transduced with the thymidine kinase gene before inoculation, no infectious viral particles were present within the tumor, no transduction of endothelial cells occurred, and no hemorrhages were observed during ganciclovir therapy. These observations suggest that tumor regression may be due, in part, to destruction of in vivo HSVtk-transduced endothelial cells after exposure to ganciclovir, resulting in tumor ischemia as one possible bystander mechanism. The authors investigated this hypothesis using the subcutaneous 9L gliosarcoma tumor model in Fischer rats. The tumors were evaluated with Doppler color-flow and ultrasound imaging during the various phases of the study. Twenty rats received intratumoral injections of HSVtk retroviral vector-producer cells (6 x 10(7) cells/ml) 21 days after bilateral flank tumor inoculation. Ten rats were subsequently treated with intraperitoneal ganciclovir (15 mg/kg/ml twice a day) for 14 days starting on Day 7 after producer cell injection; 10 control rats received intraperitoneal saline injections (1 ml twice a day) instead of ganciclovir. Ultrasound and flow images were obtained before cell injection, before and during ganciclovir or saline administration, and after cessation of treatment. The number, location, and ultrasonographic appearance of tumor vessels and the tumor volumes were recorded. The number of blood vessels in the tumors increased over time in both groups before treatment. Intratumoral cell injection without ganciclovir administration did not influence tumor growth or intratumoral vasculature. However, tumor vasculature decreased after initiation of ganciclovir therapy in the HSVtk-transduced tumors (p < 0.05). Early patchy or diffuse necrotic changes associated with ultrasonographic evidence of scattered intratumoral hemorrhage occurred in tumors treated with ganciclovir.(ABSTRACT TRUNCATED AT 400 WORDS)
Identifying patients with diabetes and the earliest date of diagnosis in real time: an electronic health record case-finding algorithm (2013)

A diabetes case-finding algorithm using data exclusively extracted from a comprehensive EHR can accurately identify patients with diabetes at the earliest possible date within a healthcare system. The real-time capability may enable proactive disease management.
Development of Methods for the Determination of pK a Values (2013)

The acid dissociation constant (pK a ) is among the most frequently used physicochemical parameters, and its determination is of interest to a wide range of research fields. We present a brief introduction on the conceptual development of pK a as a physical parameter and its relationship to the concept of the pH of a solution. This is followed by a general summary of the historical develop- ment and current state of the techniques of pKa determination and an attempt to develop insight into future developments. Fourteen methods of determining the acid dissociation constant are placed in context and are critically evaluated to make a fair comparison and to determine their applications in modern chemistry. Additionally, we have studied these techniques in light of present trends in science and technology and attempt to determine how these trends might affect future developments in the field.
A Significant Shift of Schottky Barrier Heights at Strongly Pinned Metal/Germanium Interface by Inserting an Ultra-Thin Insulating Film (2008)

At any metal/germanium (Ge) interfaces, Schottky junctions to n-Ge and ohmic ones to p-Ge are formed by the strong Fermi level pinning to the valence band edge of Ge. In this paper, we report that Schottky-ohmic characteristics are reversed by inserting an ultra-thin oxide film into the metal/Ge interface. A gradual change of Schottky barrier heights (SBHs) with increasing insulating film thickness has been found, which supports that the origin of Fermi level pinning at the metal/Ge junction is caused by the metal-induced gap states. Furthermore, the SBH change enables us to operate metal source/drain Ge n-channel metal–oxide–semiconductor field effect transistors (n-MOSFETs) without any impurity doping. We demonstrate the metal source/drain Ge n-MOSFET with a peak mobility of 270 cm2/(V·s).
Syngeneic stem cell transplant for spent‐phase polycythaemia vera: eradication of myelofibrosis and restoration of normal haematopoiesis (2002)

We report a patient with spent-phase polycythaemia vera (S-PV) and massive splenomegaly who failed to engraft after a syngeneic granulocyte colony-stimulating factor-primed peripheral blood stem cell transplant (SCT), but later engrafted after splenectomy. Bone marrow (BM) showed resolution of myelofibrosis (MF) and absent endogenous erythroid colonies. This case demonstrated that (1) normal haematopoiesis can be restored after syngeneic SCT despite extensive MF, and (2) fibrosis can regress following a total body irradiation-containing regimen and syngeneic SCT. As a graft-versus-BM stroma effect is non-existent in syngeneic transplants, there may be a role for autologous SCT to obliterate MF in S-PV.
Brain Redox Imaging Using Blood—Brain Barrier-Permeable Nitroxide MRI Contrast Agent (2008)

Reactive oxygen species (ROS) and compromised antioxidant defense may contribute to brain disorders such as stroke, amyotrophic lateral sclerosis, etc. Nitroxides are redox-sensitive paramagnetic contrast agents and antioxidants. The ability of a blood-brain barrier (BBB)-permeable nitroxide, methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-P), as a magnetic resonance-imaging (MRI) contrast agent for brain tissue redox imaging was tested. MC-P relaxation in rodent brain was quantified by MRI using a fast Look-Locker T(1)-mapping sequence. In the cerebral cortex and thalamus, the MRI signal intensity increased up to 50% after MC-P injection, but increased only by 2.7% when a BBB-impermeable nitroxide, 3CxP (3-carboxy-2,2,5,5,5-tetramethylpyrrolidine-1-oxyl) was used. The maximum concentrations in the thalamus and cerebral cortex after MC-P injection were calculated to be 1.9+/-0.35 and 3.0+/-0.50 mmol/L, respectively. These values were consistent with the ex vivo data of brain tissue and blood concentration obtained by electron paramagnetic resonance (EPR) spectroscopy. Also, reduction rates of MC-P were significantly decreased after reperfusion following transient MCAO (middle cerebral artery occlusion), a condition associated with changes in redox status resulting from oxidative damage. These results show the use of BBB-permeable nitroxides as MRI contrast agents and antioxidants to evaluate the role of ROS in neurologic diseases.
Network considerations for distributed multimedia object composition and communication (1990)

Terminology is defined, and issues related to providing temporal data integration in a distributed environment are identified. Current technological approaches to the issues are reviewed, and the state of the art is assessed. A unified model for synchronization at three levels, based on previously reviewed approaches, is presented. Directions for future efforts are indicated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations (2009)

Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1. We performed SOS1, RAF1, BRAF, MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11- and KRAS-negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1-positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations.
Circulating Autoantibodies to the 200,000-Dalton Protein of Neurofilaments in the Serum of Healthy Individuals (1985)

There is substantial evidence that human serum contains antibodies to many autoantigens. For example, all healthy people have autoantibodies (immunoglobulin M) to some undefined brain antigens. In this study immunoblots and immunohistochemical staining were used to detect antibodies to neural tissues in serum samples from 200 healthy people and 200 patients with various neurological diseases. Ninety-nine percent of the 400 subjects had serum immunoglobulin M and 95 percent had immunoglobulin G that bound to a 200-kilodalton protein in homogenates of neural tissues. In most cases there were no antibodies to anything else in the homogenates. The 200-kilodalton protein was the heaviest of the neurofilament triplet proteins. These observations do not support a role for antibodies to the 200-kilodalton protein of neurofilaments in the pathogenesis of neurological diseases.
Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens (2011)

Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711-19 peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E711-19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711-19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711-19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.
Abnormal Sodium Stimulation of Carnitine Transport in Primary Carnitine Deficiency (2000)

Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation characterized by hypoketotic hypoglycemia and skeletal and cardiac myopathy. It is caused by mutations in the sodium-dependent carnitine cotransporter OCTN2. The majority of natural mutations identified in this and other Na(+)/solute symporters introduce premature termination codons or impair insertion of the mutant transporter on the plasma membrane. Here we report that a missense mutation (E452K) identified in one patient with primary carnitine deficiency did not affect membrane targeting, as assessed with confocal microscopy of transporters tagged with the green fluorescent protein, but reduced carnitine transport by impairing sodium stimulation of carnitine transport. The natural mutation increased the concentration of sodium required to half-maximally stimulate carnitine transport (K(Na)) from the physiological value of 11.6 to 187 mm. Substitution of Glu(452) with glutamine (E452Q), aspartate (E452D), or alanine (E452A) caused intermediate increases in the K(Na). Carnitine transport decreased exponentially with increased K(Na). The E452K mutation is the first natural mutation in a mammalian cotransporter affecting sodium-coupled solute transfer and identifies a novel domain of the OCTN2 cotransporter involved in transmembrane sodium/solute transfer.
A Study on the Temperature Variation of Rise Velocity for Large Clean Bubbles (2000)

A series of microphysical laboratory experiments studying the hydrodynamics of single bubbles were conducted to measure the variation of rise velocity, VB, with temperature, T, and radius, r. Bubbles with an equivalent spherical radius between 377 and 4500 μm were studied for T varying between 0° and 40°C. While for nonoscillating bubbles VB increases with T; due to the significance of oscillations, VB decreases with T for oscillating bubbles, in conjunction with an increase in trajectory oscillations with T. Using observations from this study and data from other researchers, a three-part parameterization of VB(r, T) is proposed with transitions at Re = 1 and the onset of oscillations, where Re is the Reynolds number. The T for the transition to oscillatory behavior was found to vary linearly with r. An empirical parameterization of VB(r, T) for oscillatory and nonoscillatory bubbles that correctly incorporates the effect of T is presented.
9‐Cis‐retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic protein (2008)

Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H(2)O(2) or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia-induced injury, and these effects involve BMPs.
Orientable textures for image-based pen-and-ink illustration (1997)

Article Free Access Share on Orientable textures for image-based pen-and-ink illustration Authors: Michael P. Salisbury University of Washington, Box 352350, Seattle, WA University of Washington, Box 352350, Seattle, WAView Profile , Michael T. Wong University of Washington, Box 352350, Seattle, WA University of Washington, Box 352350, Seattle, WAView Profile , John F. Hughes NSF STC for Computer Graphics and Scientific Visualization, Brown University Site, PO Box 1910, Providence, RI NSF STC for Computer Graphics and Scientific Visualization, Brown University Site, PO Box 1910, Providence, RIView Profile , David H. Salesin University of Washington, Box 352350, Seattle, WA University of Washington, Box 352350, Seattle, WAView Profile Authors Info & Claims SIGGRAPH '97: Proceedings of the 24th annual conference on Computer graphics and interactive techniquesAugust 1997 Pages 401–406https://doi.org/10.1145/258734.258890Published:03 August 1997Publication History 203citation1,795DownloadsMetricsTotal Citations203Total Downloads1,795Last 12 Months106Last 6 weeks10 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Long-range pseudoknot interactions dictate the regulatory response in the tetrahydrofolate riboswitch (2011)

Tetrahydrofolate (THF), a biologically active form of the vitamin folate (B(9)), is an essential cofactor in one-carbon transfer reactions. In bacteria, expression of folate-related genes is controlled by feedback modulation in response to specific binding of THF and related compounds to a riboswitch. Here, we present the X-ray structures of the THF-sensing domain from the Eubacterium siraeum riboswitch in the ligand-bound and unbound states. The structure reveals an "inverted" three-way junctional architecture, most unusual for riboswitches, with the junction located far from the regulatory helix P1 and not directly participating in helix P1 formation. Instead, the three-way junction, stabilized by binding to the ligand, aligns the riboswitch stems for long-range tertiary pseudoknot interactions that contribute to the organization of helix P1 and therefore stipulate the regulatory response of the riboswitch. The pterin moiety of the ligand docks in a semiopen pocket adjacent to the junction, where it forms specific hydrogen bonds with two moderately conserved pyrimidines. The aminobenzoate moiety stacks on a guanine base, whereas the glutamate moiety does not appear to make strong interactions with the RNA. In contrast to other riboswitches, these findings demonstrate that the THF riboswitch uses a limited number of available determinants for ligand recognition. Given that modern antibiotics target folate metabolism, the THF riboswitch structure provides insights on mechanistic aspects of riboswitch function and may help in manipulating THF levels in pathogenic bacteria.
Functional group convergency in a binuclear dephosphorylation reagent (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFunctional group convergency in a binuclear dephosphorylation reagentDavid H. Vance and Anthony W. CzarnikCite this: J. Am. Chem. Soc. 1993, 115, 25, 12165–12166Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/ja00078a065https://doi.org/10.1021/ja00078a065research-articleACS PublicationsRequest reuse permissionsArticle Views325Altmetric-Citations123LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Maintenance of Intratumoral Androgens in Metastatic Prostate Cancer: A Mechanism for Castration-Resistant Tumor Growth (2008)

Therapy for advanced prostate cancer centers on suppressing systemic androgens and blocking activation of the androgen receptor (AR). Despite anorchid serum androgen levels, nearly all patients develop castration-resistant disease. We hypothesized that ongoing steroidogenesis within prostate tumors and the maintenance of intratumoral androgens may contribute to castration-resistant growth. Using mass spectrometry and quantitative reverse transcription-PCR, we evaluated androgen levels and transcripts encoding steroidogenic enzymes in benign prostate tissue, untreated primary prostate cancer, metastases from patients with castration-resistant prostate cancer, and xenografts derived from castration-resistant metastases. Testosterone levels within metastases from anorchid men [0.74 ng/g; 95% confidence interval (95% CI), 0.59-0.89] were significantly higher than levels within primary prostate cancers from untreated eugonadal men (0.23 ng/g; 95% CI, 0.03-0.44; P < 0.0001). Compared with primary prostate tumors, castration-resistant metastases displayed alterations in genes encoding steroidogenic enzymes, including up-regulated expression of FASN, CYP17A1, HSD3B1, HSD17B3, CYP19A1, and UGT2B17 and down-regulated expression of SRD5A2 (P < 0.001 for all). Prostate cancer xenografts derived from castration-resistant tumors maintained similar intratumoral androgen levels when passaged in castrate compared with eugonadal animals. Metastatic prostate cancers from anorchid men express transcripts encoding androgen-synthesizing enzymes and maintain intratumoral androgens at concentrations capable of activating AR target genes and maintaining tumor cell survival. We conclude that intracrine steroidogenesis may permit tumors to circumvent low levels of circulating androgens. Maximal therapeutic efficacy in the treatment of castration-resistant prostate cancer will require novel agents capable of inhibiting intracrine steroidogenic pathways within the prostate tumor microenvironment.