gebhart/patrepeval huggingface dataset:
Transforming Growth Factor β-Induced Smad1/5 Phosphorylation in Epithelial Cells Is Mediated by Novel Receptor Complexes and Is Essential for Anchorage-Independent Growth (2008)

Transforming growth factor beta (TGF-beta) signals predominantly through a receptor complex comprising ALK5 and TbetaRII to activate receptor-regulated Smads (R-Smads) Smad2 and Smad3. In endothelial cells, however, TGF-beta can additionally activate Smad1 and Smad5. Here, we report that TGF-beta also strongly induces phosphorylation of Smad1/5 in many different normal epithelial cells, epithelium-derived tumor cells, and fibroblasts. We demonstrate that TbetaRII and ALK5, as well as ALK2 and/or ALK3, are required for TGF-beta-induced Smad1/5 phosphorylation. We show that the simultaneous activation of the R-Smads Smad2/3 and Smad1/5 by TGF-beta results in the formation of mixed R-Smad complexes, containing, for example, phosphorylated Smad1 and Smad2. The prevalence of these mixed R-Smad complexes explains why TGF-beta-induced Smad1/5 phosphorylation does not result in transcriptional activation via bone morphogenetic protein (BMP)-responsive elements, which bind activated Smad1/5-Smad4 complexes that are induced by BMP stimulation. Thus, TGF-beta induces two parallel pathways: one signaling via Smad2-Smad4 or Smad3-Smad4 complexes and the other signaling via mixed R-Smad complexes. Finally, we assess the function of the novel arm of TGF-beta signaling and show that TGF-beta-induced Smad1/5 activation is not required for the growth-inhibitory effects of TGF-beta but is specifically required for TGF-beta-induced anchorage-independent growth.
Range of sensory gating values and test–retest reliability in normal subjects (2007)

This article characterizes gating in normal subjects using P50, N100, and P200 components in a paired-click paradigm and compares the test-retest reliabilities of the three components. Sixty-seven normal subjects had gating data from a standard paired-click paradigm; 30 had test-retest data. The test-retest reliability of the amplitudes, latencies, and sensory gating indices derived from the P50, N100, and P200 responses were compared. Measured gating ratios showed either normal or positively skewed distributions. Test-retest reliability of the P50 gating ratio did not reach significance, but N100 and P200 ratios showed better reliability (.50 and .64). The P50 difference score was more reliable (.61), and the N100 and P200 test-retest reliabilities of difference scores were high (.83 and .81, respectively). N100 and P200 attenuation is reliable; further work is needed to develop more reliable P50 gating measures.
Structure and mechanical properties of thin films deposited from 1,3,5-trimethyl-1,3,5-trivinylcyclotrisiloxane and water (2003)

Pulsed-plasma chemical vapor deposition of 1,3,5-trimethyl-1,3,5-trivinylcyclotrisiloxane (V3D3) and water produced thin films with significant Si–OH content. Subsequent annealing of the films resulted in condensation of proximal Si–OH groups, further generating a Si–O–Si network and strengthening the film. Fourier-transform infrared spectroscopy analysis showed increasing OH content with increasing plasma duty cycle, and nanoindentation results confirmed increasing hardness with duty cycle, with the 10–40 duty cycle annealed sample having a hardness value of 0.527 GPa. These results were explained within the context of the continuous random network theory and percolation of rigidity arguments. Thermal stability was excellent, with a best-case thickness retention of 99.25% after a 2 h anneal at 400 °C under N2. Dielectric constants for the annealed films ranged between 2.55 and 2.9. The moderate power involved (200 W peak) is amenable to inclusion of a porogen species, opening the possibility of using this methodology to generate a porous thin film with adequate mechanical properties via chemical vapor deposition.
Specific absorbed fractions of energy at various ages from internal photon sources: 6, Newborn (1987)

Specific absorbed fraction (PHI's) in various organs of the body (target organs) from sources of monoenergetic photons in various other organs (source organs) are tabulated. In this volume PHI-values are tabulated for a newborn or 3.4-kg person. These PHI-values can be used in calculating the photon component of the dose-equivalent rate in a given target from a given radionuclide that is present in a given source organ. The International Commission on Radiological Protection recognizes that the endosteal, or bone surface, cells are the tissue at risk for bone cancer. We have applied the dosimetry methods that Spiers and co-workers developed for beta-emitting radionuclides deposited in bone to follow the transport of secondary electrons that were freed by photon interactions through the microscopic structure of the skeleton. With these methods we can estimate PHI in the endosteal cells and can better estimate PHI in the active marrow; the latter is overestimated with other methods at photon energies below 200 keV. 12 refs., 2 tabs.
Thrombin Receptor Activating Mutations (1996)

Constitutively active thrombin receptors were generated while constructing chimeric receptors to identify the structural basis for thrombin receptor agonist specificity. Substitution of eight amino acids from the Xenopus receptor's second extracellular loop (XECL2B) for the cognate sequence in the human thrombin receptor was sufficient to confer robust constitutive activity. Smaller substitutions within the XECL2B site yielded less constitutive activation, and substitution of several unrelated sequences at this site caused no activation. Expression of the XECL2B receptor caused high basal 45Ca efflux in Xenopus oocytes and high basal phosphoinositide hydrolysis and reporter gene induction in COS cells. Of note, a mutant receptor in which all four of the Xenopus thrombin receptor's extracellular segments replaced the cognate human sequences showed much less constitutive activity than XECL2B and preserved responsiveness to agonist. This partial complementation of the XECL2B phenotype by addition of other Xenopus extracellular structures suggests that the XECL2B mutation causes constitutive activation by altering interactions among the human receptor's extracellular domains. Thus, a change in an extracellular loop of a G protein-coupled receptor can transmit information across the cell membrane to cause signaling, perhaps via a conformational change similar to that caused by agonist binding. Indeed, the site of the activating mutation in XECL2B coincides with a putative agonist-docking site, supporting the hypothesis that agonist interactions with the thrombin receptor's extracellular loops contribute to receptor activation.
Capture and rendering of spatial sound over headphones (2006)

A theory for capturing an audio scene and then rendering it remotely over headphones is developed. The method relies on capture of a sound field up to a certain order in terms of spherical wave functions. Then, the captured sound field is convolved with the head-related transfer function and rendered to provide presence in the auditory scene. The sound-field representation is then transmitted to a remote location for immediate rendering or stored for later use. A system that implements the capture using a spherical array is developed and tested. Head-related transfer functions are measured using the system described in [D.N. Zotkin et al., J. Acoustic. Soc. Am. (to appear)]. The sound renderer, coupled with the head tracker, reconstructs the acoustic field using individualized head-related transfer functions to preserve the perceptual spatial structure of the audio scene. [Work partially supported by VA.]
Cannabinoid receptor systems: therapeutic targets for tumour intervention (2003)

The past decade has witnessed a rapid expansion of our understanding of the biological roles of cannabinoids and their cognate receptors. It is now certain that Delta9-tetrahydrocannabinol, the principle psychoactive component of the Cannabis sativa plant, binds and activates membrane receptors of the 7-transmembrane domain, G-protein-coupled superfamily. Several putative endocannabinoids have since been identified, including anandamide, 2-arachidonyl glycerol and noladin ether. Synthesis of numerous cannabinomimetics has also greatly expanded the repertoire of cannabinoid receptor ligands with the pharmacodynamic properties of agonists, antagonists and inverse agonists. Collectively, these ligands have proven to be powerful tools both for the molecular characterisation of cannabinoid receptors and the delineation of their intrinsic signalling pathways. Much of our understanding of the signalling mechanisms activated by cannabinoids is derived from studies of receptors expressed by tumour cells; hence, this review provides a succinct summary of the molecular pharmacology of cannabinoid receptors and their roles in tumour cell biology. Moreover, there is now a genuine expectation that the manipulation of cannabinoid receptor systems may have therapeutic potential for a diverse range of human diseases. Thus, this review also summarises the demonstrated antitumour actions of cannabinoids and indicates possible avenues for the future development of cannabinoids as antitumour agents.
The Hepatocyte Growth Factor Regulatory Factors in Human Breast Cancer (2004)

This study shows that there are aberrant levels of HGF, c-Met, HGFA, HAI-1, and HAI-2 expressed in breast cancer tissues compared with background breast tissue. HAI-1 and HAI-2 are expressed to a significantly lower level in poorly differentiated breast tumors, and HAI-2 is also inversely correlated with nodal involvement and tumor spread. Overall a low level of HAI-2 in the breast cancer tissues was associated with an overall poor outlook. Therefore, the HGF regulatory system may have an important role in the progression of breast cancer.
Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study (2013)

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with 4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1-2 prior therapies and 33% were refractory to the last treatment. The response ratepartial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.
Potassium channel dysfunction in hypothalamic glucose‐receptive neurones of obese Zucker rats. (1996)

1. We have shown, using intracellular and cell-attached recordings, that glucose-receptive (GR) neurones of obese Zucker rats exhibit abnormal electrophysiological responses to changes in extracellular glucose concentration, whereas GR neurones of lean Zucker and control rats respond normally. 2. In inside-out recordings from obese rat GR neurones it was shown that the 150 pS ATP-sensitive K+ (KATP) and the 160 pS calcium-activated K+ (KCa) channels were absent, whereas both were present in GR neurones of lean Zucker and control rats. 3. The potassium channel most frequently observed in inside-out patches from obese GR neurones was characterized by a conductance of 213 pS, was activated by raising internal calcium and inhibited by application of internal ATP. This channel (which we have termed Kfa) was not observed in lean or control rat GR neurones. 4. Tolbutamide (100 microM) was found to induce no effect or to elicit a small depolarization of obese rat GR neurones in the absence of glucose, in contrast to its clear excitatory actions on control or lean Zucker GR neurones. 5. Intracellular, cell-attached and inside-out recordings from obese rat non-GR neurones showed that there was no alteration in their membrane properties or firing characteristics or in the characteristics of the large-conductance calcium-activated K+ channel (KCa) present in these neurones as compared with lean and control rats. 6. It is concluded that the Kfa channel is specific to GR neurones of obese Zucker rats and that the presence of this channel coupled with the absence of KATP and KCa channels results in the abnormal glucose-sensing response of these neurones.
A framework for workflow management systems based on objects, rules and roles (2000)

article Free Access Share on A framework for workflow management systems based on objects, rules and roles Authors: Gerti Kappel Univ. of Linz, Linz, Austria Univ. of Linz, Linz, AustriaView Profile , Stefan Rausch-Schott Univ. of Linz, Linz, Austria Univ. of Linz, Linz, AustriaView Profile , Werner Retschitzegger Univ. of Linz, Linz, Austria Univ. of Linz, Linz, AustriaView Profile Authors Info & Claims ACM Computing SurveysVolume 32Issue 1esMarch 2000 pp 27–eshttps://doi.org/10.1145/351936.351963Published:01 March 2000Publication History 31citation2,806DownloadsMetricsTotal Citations31Total Downloads2,806Last 12 Months351Last 6 weeks58 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 SiteView all FormatsPDF
Induction of vascular endothelial growth factor expression in endothelial cells by platelet-derived growth factor through the activation of phosphatidylinositol 3-kinase. (1999)

Increased numbers of platelet-derived growth factor beta receptors betaPPDGFRs) on neovascular endothelial cells is a common occurrence in several pathological conditions including wound healing, inflammation, and glioma tumorigenesis. Here we sought to test the biological significance of this by determining whether expression of wild-type betaPDGFR by normal aortic endothelial cells affected the expression of the vascular endothelial growth factor (VEGF), a critical angiogenesis regulator and mitogen for such cells. The results showed that PDGF could increase transcription and secretion of VEGF by betaPDGFR-expressing endothelial cells. Moreover, we further demonstrated a requirement for the activation of phosphatidylinositol 3-kinase (PI3K) in this response by using chemical inhibitors of PI3K, mutant PDGFR, and dominant-negative PI3K. These studies suggest a novel mechanism by which PDGF induces VEGF expression in endothelial cells, define VEGF as a downstream target for PI3K, and invoke a role for PI3K in angiogenesis.
Oncolytic Virus Therapy for Glioblastoma Multiforme (2012)

Twenty years of oncolytic virus development have created a field that is driven by the potential promise of lasting impact on our cancer treatment repertoire. With the field constantly expanding-more than 20 viruses have been recognized as potential oncolytic viruses-new virus candidates continue to emerge even as established viruses reach clinical trials. They all share the defining commonalities of selective replication in tumors, subsequent tumor cell lysis, and dispersion within the tumor. Members from diverse virus classes with distinctly different biologies and host species have been identified. Of these viruses, 15 have been tested on human glioblastoma multiforme. So far, 20 clinical trials have been conducted or initiated using attenuated strains of 7 different oncolytic viruses against glioblastoma multiforme. In this review, we present an overview of viruses that have been developed or considered for glioblastoma multiforme treatment. We outline the principles of tumor targeting and selective viral replication, which include mechanisms of tumor-selective binding, and molecular elements usurping cellular biosynthetic machinery in transformed cells. Results from clinical trials have clearly established the proof of concept and have confirmed the general safety of oncolytic virus application in the brain. The moderate clinical efficacy has not yet matched the promising preclinical lab results; next-generation oncolytic viruses that are either "armed" with therapeutic genes or embedded in a multimodality treatment regimen should enhance the clinical results.
Granulocyte Colony-stimulating Factor Induces Erk5 Activation, Which Is Differentially Regulated by Protein-tyrosine Kinases and Protein Kinase C (2001)

Granulocyte colony-stimulating factor (G-CSF) plays a major role in the regulation of granulopoiesis. Treatment of cells with G-CSF has been shown to activate multiple signal transduction pathways. We show here that Erk5, a novel member of the MAPK family, and its specific upstream activator MEK5 were activated in response to incubation of cells with G-CSF. Different from other members of the MAPK family including Erk1/2, JNK, and p38, maximal activation of Erk5 by G-CSF required the C-terminal region of the G-CSF receptor. Genistein, a specific inhibitor of protein-tyrosine kinases, blocked G-CSF-induced Erk5 activation. In contrast, inhibition of protein kinase C activity increased G-CSF-mediated activation of Erk5 and MEK5, whereas stimulation of protein kinase C activity inhibited activation of the two kinases by G-CSF. The proliferation of BAF3 cells in response to G-CSF was inhibited by expression of a dominant-negative MEK5 but potentiated by expression of a constitutively active MEK5. Expression of the constitutively active MEK5 also increased the survival of BAF3 cells cultured in the absence of or in low concentrations of G-CSF. Together, these data implicate Erk5 as an important signaling component in the biological actions of G-CSF.
Vaginal Estrogen for Genitourinary Syndrome of Menopause (2014)

PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42013006656.
Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis (2002)

Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.
Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles (1994)

L-692,585 is a 2-hydroxypropyl derivative of L-692,429, both novel non-peptidyl growth hormone (GH) secretagogues. The effects of single and repeated intravenous administration of L-692,585 on serum or plasma GH and other hormones in beagles were evaluated. In a balanced 8-dog dose-ranging study, compared to the saline control with a mean (+/- S.E.M.) after-dose serum GH peak of 6.1 +/- 1.3 ng/ml, L-692,585 significantly increased (P < 0.05) peak GH concentrations 4.3-fold (32.5 +/- 7.0 ng/ml) at a dose of 0.005 mg/kg, 7-fold (49.4 +/- 10.6 ng/ml) at a dose of 0.02 mg/kg, and 21-fold (134.3 +/- 29.0 ng/ml) at a dose of 0.10 mg/kg. Total GH release, expressed as area under the curve, showed a similar dose-dependent increase. Peak GH levels were recorded at 5 or 15 min after dosing with the levels returning to near baseline by 90 min. Serum cortisol levels were increased above saline control levels in a dose-dependent manner; however, the increases were modest compared to the GH increases. Based on peak responses and total GH release, L-692,585 was 10- to 20-fold and 2- to 2.5-fold more potent than L-692,429 and the growth hormone releasing peptide, GHRP-6, respectively. When L-692,585 was administered once daily for 14 consecutive days at 0, 0.01 or 0.10 mg/kg to each of 6 dogs, peak plasma GH levels and total GH release on days 1, 8 and 15 significantly increased in a dose-dependent manner, and no desensitization was evident.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors (2004)

Elevated interstitial fluid pressure, a hallmark of solid tumors, can compromise the delivery of therapeutics to tumors. Here we show that blocking vascular endothelial growth factor (VEGF) signaling by DC101 (a VEGF-receptor-2 antibody) decreases interstitial fluid pressure, not by restoring lymphatic function, but by producing a morphologically and functionally "normalized" vascular network. We demonstrate that the normalization process prunes immature vessels and improves the integrity and function of the remaining vasculature by enhancing the perivascular cell and basement membrane coverage. We also show that DC101 induces a hydrostatic pressure gradient across the vascular wall, which leads to a deeper penetration of molecules into tumors. Thus, vascular normalization may contribute to the improved survival rates in tumor-bearing animals and in colorectal carcinoma patients treated with an anti-VEGF antibody in combination with cytotoxic therapies.
STHoles (2001)

Attributes of a relation are not typically independent. Multidimensional histograms can be an effective tool for accurate multiattribute query selectivity estimation. In this paper, we introduce STHoles , a “workload-aware” histogram that allows bucket nesting to capture data regions with reasonably uniform tuple density. STHoles histograms are built without examining the data sets, but rather by just analyzing query results. Buckets are allocated where needed the most as indicated by the workload, which leads to accurate query selectivity estimations. Our extensive experiments demonstrate that STHoles histograms consistently produce good selectivity estimates across synthetic and real-world data sets and across query workloads, and, in many cases, outperform the best multidimensional histogram techniques that require access to and processing of the full data sets during histogram construction.
Chemoenzymatic Synthesis of Phosphatidyl-L-serine Hydroperoxide (1994)

1-Stearoyl-2–[15′-(S)-hydroperoxyicosatetraenoyl]-phospho-serine was synthesized for the first time by utilizing lipoxygenase-catalyzed hydroperoxidation, protection of the hydroperoxy group, DCC-mediated esterification and phospholipase D-catalyzed transphosphatidylation. A hydroxy form of this hydroperoxide was prepared by reducing the hydroperoxy group with triphenylphos-phine. Unoxidized phosphatidylserine was also prepared as a reference compound.