gebhart/patrepeval huggingface dataset:
Rho Kinase–Mediated Vasoconstriction Is Important in Severe Occlusive Pulmonary Arterial Hypertension in Rats (2007)

Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined whether Rho kinase–mediated vasoconstriction was also important in a rat model of severe occlusive PAH. Adult rats were exposed to chronic hypoxia (≈10% O 2 ) after subcutaneous injection of the vascular endothelial growth factor receptor inhibitor SUGEN 5416. Hemodynamic measurements were made in anesthetized rats after 2 weeks of hypoxia (early group) and 3 weeks of hypoxia plus 2 weeks of normoxia (late group). Both groups developed PAH, with greater severity in the late group. In the early group, intravenous fasudil was more effective than intravenous bradykinin, inhaled NO, or intravenous iloprost in reducing right ventricular systolic pressure. Despite more occlusive vascular lesions, fasudil also markedly reduced right ventricular systolic pressure in late-stage rats. Blood-perfused lungs from late-stage rats showed spontaneous vasoconstriction, which was reversed partially by the endothelin A receptor blocker BQ123 and completely by fasudil or Y-27632. Phosphorylation of MYPT1, a downstream target of Rho kinase, was increased in lungs from both groups of rats, and fasudil (intravenous) reversed the increased phosphorylation in the late group. Thus, in addition to structural occlusion, Rho kinase–mediated vasoconstriction is an important component of severe PAH in SUGEN 5416/hypoxia-exposed rats, and PAH can be significantly reduced in the setting of a severely remodeled lung circulation if an unconventional vasodilator is used.
Human adipose tissue as a source of Flk-1 cells: new method of differentiation and expansion (2004)

This report describes the first isolation and culture of Flk-1+ cells from human adipose tissue. The feasibility of the extraction and culture of these cells in increased numbers suggests that such autologous cells will be useful for applications ranging from basic research to cell-based therapies.
Mammalian mitogen-activated protein kinase kinase kinase (MEKK) can function in a yeast mitogen-activated protein kinase pathway downstream of protein kinase C. (1994)

Mitogen-activated protein kinase cascades are conserved in fungal, plant, and metazoan species. We expressed murine MAP kinase kinase kinase (MEKK) in the yeast Saccharomyces cerevisiae to determine whether this kinase functions as a general or specific activator of genetically and physiologically distinct MAP-kinase-dependent signaling pathways and to investigate how MEKK is regulated. Expression of MEKK failed to correct the mating deficiency of a ste11 delta mutant that lacks an MEKK homolog required for mating. MEKK expression also failed to induce expression of a reporter gene controlled by the HOG1 gene product (Hog1p), a yeast MAP kinase homolog involved in response to osmotic stress. Expression of MEKK did correct the cell lysis defect of a bck1 delta mutant that lacks an MEKK homolog required for cell-wall assembly. MEKK required the downstream MAP kinase homolog in the BCK1-dependent pathway, demonstrating that it functionally replaces the BCK1 gene product (Bck1p) rather than bypassing the pathway. MEKK therefore selectively activates one of three distinct MAP-kinase-dependent pathways. Possible explanations for this selectivity are discussed. Expression of the MEKK catalytic domain, but not the full-length molecule, corrected the cell-lysis defect of a pkc1 delta mutant that lacks a protein kinase C homolog that functions upstream of Bck1p. MEKK therefore functions downstream of the PKC1 gene product (Pkc1p). The N-terminal noncatalytic domain of MEKK, which contains several consensus protein kinase C phosphorylation sites, may, therefore, function as a negative regulatory domain. Protein kinase C phosphorylation may provide one mechanism for activating MEKK.
Crosslinking of an iodo-uridine-RNA hairpin to a single site on the human U1A N-terminal RNA binding domain. (1995)

The N-terminal RNA binding domain (RBD) of the human U1A snRNP protein binds tightly and specifically to an RNA hairpin that contains a 10-nucleotide loop. The protein is one of a class of RNA binding proteins that adopts a beta alpha beta beta alpha beta global fold, which in turn forms a four-stranded antiparallel beta-sheet. This sheet forms the primary binding surface for the RNA, as shown by the crosslinking results described here, and in more detail by a recently described co-crystal of this RBD with an RNA hairpin (Oubridge C, et al., 1994, Nature 372:432-438). The RNA hairpin sequence used in the crosslinking experiments, containing 5-iodo-uridine, is a variant of the normal U1 snRNA sequence which is able to form a crosslink with the protein, in contrast to the wild-type sequence, which does not. This single uridine substitution in the 10-nucleotide loop is the site of cross-linking to one tyrosine (Tyr 13) in the beta 1 strand of the U1A N-terminal RBD. This same uridine is also crosslinked to a mutant Tyr 13 Phe RBD, at this Phe 13 substitution.
Combining Anthrax Vaccine and Therapy: a Dominant-Negative Inhibitor of Anthrax Toxin Is Also a Potent and Safe Immunogen for Vaccines (2005)

Anthrax is caused by the unimpeded growth of Bacillus anthracis in the host and the secretion of toxins. The currently available vaccine is based on protective antigen (PA), a central component of anthrax toxin. Vaccination with PA raises no direct immune response against the bacilli and, being a natural toxin component, PA might be hazardous when used immediately following exposure to B. anthracis. Thus, we have sought to develop a vaccine or therapeutic agent that is safe and eliminates both secreted toxins and bacilli. To that end, we have previously developed a dually active vaccine by conjugating the capsular poly-gamma-d-glutamate (PGA) with PA to elicit the production of antibodies specific for both bacilli and toxins. In the present report, we describe the improved potency of anthrax vaccines through the use of a dominant-negative inhibitory (DNI) mutant to replace PA in PA or PA-PGA vaccines. When tested in mice, DNI alone is more immunogenic than PA, and DNI-PGA conjugate elicits significantly higher levels of antibodies against PA and PGA than PA-PGA conjugate. To explain the enhanced immunogenicity of DNI, we propose that the two point mutations in DNI may have improved epitopes of PA allowing better antigen presentation to helper T cells. Alternatively, these mutations may enhance the immunological processing of PA by altering endosomal trafficking of the toxin in antigen-presenting cells. Because DNI has previously been demonstrated to inhibit anthrax toxin, postexposure use of DNI-based vaccines, including conjugate vaccines, may provide improved immunogenicity and therapeutic activity simultaneously.
Solid Phase Synthesis of 5'-Methylenephosphonate DNA (1995)

Abstract A new approach to the solid phase synthesis of 5′-methylenephosphonate DNA is described. It makes use of intramolecular catalysis which ensures rapid and high-yielding condensations and thus provides a convenient entry to ionic, achiral analogs of thymidylic acids up to 20 nucleotides in length.
Zika Virus and the Guillain–Barré Syndrome — Case Series from Seven Countries (2016)

During the past year and a half, Zika virus has been spreading rapidly throughout Latin America. In this letter, evidence for the Guillain–Barre syndrome being temporally associated with Zika virus transmission is presented.
Effect of ethoxy‐ and methoxysilane donors in propene/1‐hexene copolymerization with high‐yield supported Ziegler‐Natta catalysts (1994)

Abstract The effects of two alkoxysilane donors, triethoxyphenylsilane (PTES) and dimethoxydi‐ tert ‐butylsilane (DTBDMS), on the propene/1‐hexene copolymerization with MgCl 2 /DIBP/TiCl 4 (DIBP: diisobutyl phthalate) are compared. Two series of copolymers of different compositions were produced and the copolymers with the lowest hexene content, were fractionated. An analogous series, produced with the same catalyst without the use of an external donor, is the point of reference. All the fractions were characterized by 13 C NMR. The data reported show that there is a noticeable difference in the behaviour of ethoxy‐and methoxysilanes in the copolymerization. The copolymers prepared with ethoxysilanes can be separated into fractions characterized by increasing isotacticity and decreasing comonomer content as long as the fractionation temperature increases. The copolymer obtained with DTBDMS is nearly completely isospecific while the comonomer content distribution is even wider than with ethoxysilanes. The sum of these data provides a deeper insight into the alkoxysilane activation mechanism.
The redox protein HMGB1 regulates cell death and survival in cancer treatment (2010)

Metabolic and therapeutic stress activates several signal transduction pathways and releases damageassociated molecular pattern molecules (DAMPs) that regulate cell death and cell survival. The prototypical DAMP, high-mobility group box 1 protein (HMGB1) is released with sustained autophagy, late apoptosis and necrosis. Our recent findings reveal that the HMGB1 protein triggers autophagy or apoptosis in cancer cells, depending on its redox status. Reducible HMGB1 binds to the receptor for advanced glycation end products (RAGE), induces Beclin 1-dependent autophagy and promotes pancreatic or colon tumor cell line resistance to chemotherapeutic agents or ionizing radiation. In contrast, oxidized HMGB1 increases the cytotoxicity of these agents and induces apoptosis via the mitochondrial pathway. This suggests a new function for HMGB1 within the tumor microenvironment, regulating cell death and survival and suggests that it plays an important functional role in cross-regulating apoptosis and autophagy.
The design and evaluation of an end-user-deployable, whole house, contactless power consumption sensor (2010)

We present the design, development, and evaluation of an end-user installable, whole house power consumption sensing system capable of gathering accurate real-time power use that does not require installing a current transformer around the electrical feeds in a home. Rather, our sensor system offers contactless operation by simply placing it on the outside of the breaker panel in a home. Although there are a number of existing commercial systems for gathering energy use in a home, almost none can easily and safely be installed by a homeowner (especially for homes in the U.S.). Our approach leverages advances in magnetoresistive materials and circuit design to allow contactless operation by reliably sensing the magnetic field induced by the 60 Hz current and a closed loop circuit allows us to precisely infer the power consumption in real-time. The contribution of this work is an enabling technology for researchers in the fields of Ubiquitous Computing and Human-Computer Interaction wanting to conduct practical large-scale deployments of end-user-deployable energy monitoring applications. We discuss the technical details, the iterative design, and end-user evaluations of our sensing approach.
Correction of depth-dependent aberrations in 3D single-molecule localization and super-resolution microscopy (2014)

Single-molecule switching based super-resolution microscopy techniques have been extended into three dimensions through various 3D single-molecule localization methods. However, the localization accuracy in z can be severely degraded by the presence of aberrations, particularly the spherical aberration introduced by the refractive index mismatch when imaging into an aqueous sample with an oil immersion objective. This aberration confines the imaging depth in most experiments to regions close to the coverslip. Here we show a method to obtain accurate, depth-dependent z calibrations by measuring the point spread function (PSF) at the coverslip surface, calculating the microscope pupil function through phase retrieval, and then computing the depth-dependent PSF with the addition of spherical aberrations. We demonstrate experimentally that this method can maintain z localization accuracy over a large range of imaging depths. Our super-resolution images of a mammalian cell nucleus acquired between 0 and 2.5 μm past the coverslip show that this method produces accurate z localizations even in the deepest focal plane.
T Cell–specific Ablation of Fas Leads to Fas Ligand–mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis (2004)

To study the role of Fas-Fas ligand (FasL) interaction-mediated apoptosis in lymphocyte homeostasis, we generated a mutant fas allele allowing conditional inactivation of the fas gene through Cre-mediated recombination. Experiments in which Fas was ablated in T cells, B cells, T and B cells, or in a more generalized manner demonstrated that the development of lymphoproliferative disease as seen in Fas-deficient mice requires Fas ablation in lymphoid and nonlymphoid tissues. Selective inactivation of Fas in T cells led to a severe lymphopenia over time, accompanied by up-regulation of FasL on activated T cells and apoptosis of peripheral lymphocytes. In addition, the mutant animals developed a fatal wasting syndrome caused by massive leukocyte infiltration in the lungs together with increased inflammatory cytokine production and pulmonary fibrosis. Inhibition of Fas-FasL interaction in vivo completely prevented the loss of lymphocytes and initial lymphocyte infiltration in the lungs. Thus, FasL-mediated interaction of activated, Fas-deficient T cells with Fas-expressing cells in their environment leads to break down of lymphocyte homeostasis and development of a lung disease strikingly resembling idiopathic pulmonary fibrosis in humans, a common and severe disease for which the mutant mice may serve as a first animal model.
Nanostructure and optical transparency of silica aerogels (1993)

No abstract available
RPM and flow modulation for a continuous flow left ventricular assist device to increase vascular pulsatility : a computer simulation, mock circulation, and in-vivo animal study. (2011)

Purpose: Continuous flow (CF) left ventricular assist devices (LVAD) support diminishes vascular pressure pulsatility. Despite its recent clinical success and reliability, CF LVAD support has been associated with adverse events including gastrointestinal bleeding, aortic valve insufficiency, and hemorrhagic strokes. To overcome these limitations, we have developed flow/RPM modulation algorithms to provide vascular pulsatility using a CF LVAD. Methods: The effects of timing and synchronizing the CF LVAD flow/RPM modulation to the native ventricle, modulation amplitude, and modulation widths were studied on the native ventricle and vasculature using computer simulation, mock loop, and animal model studies. A total of over 100 combinations of flow modulation algorithms to modulate CF LVAD flow/RPM were tested for partial and full LVAD support modes. Results: Modulation of CF LVAD flow/RPM resulted in an increased arterial pressure pulsatility of up to 50 mmHg during asynchronous modulation and 20 mmHg during synchronous modulation. Synchronous CF LVAD RPM modulation allowed for a range of reduced left ventricular external work (LVEW) as compared to un-modulated CF LVAD support conditions. Full support co-pulsation (high RPM during systole, low RPM during diastole) created greater pulse pressures as compared to counter pulsation (high RPM during diastole, low RPM during systole). However, all full support modulation timings yielded higher pulse pressure than normal full support CF LVAD flow at low ventricular contractilities. Importantly, reduction in LVEW and increase in pulsatility may be adjusted to user-defined values while maintaining the same average CF LVAD flow rate. Conclusions: These LVAD flow/RPM modulations may reduce the incidence of adverse events associated with the CF LVAD therapy by increasing vascular pulsatility and reducing vascular impedance. Further, these methods of CF LVAD flow/RPM modulation may enable tailored unloading of the native ventricle to provide rest and rehabilitation (maximal unloading to rest followed by gradual reloading to wean), which may promote sustainable myocardial recovery.
Structure of Flow Fields in Low Pressure Impactor (1998)

In order to clarify the detailed flow fields of impinging jets in a low pressure impactor, nitrogen and argon flow fields are investigated experimentally and numerically at a relatively small range of P down/P up, where P down is the downstream stagnation pressure and P up the upstream stagnation pressure. The pressure at the center of collection plate, P c, is measured in addition to the flow visualization by Laser Induced Fluorescence (LIF) technique, which is used in previous study. Furthermore, the flow fields in a low pressure impactor have been simulated by solving the axisymmetric Euler equation through Harten-Yee TVD method. The effects of P down/P up and H/D on flow fields are examined in detail, where H is the jet-to-plate distance and D the nozzle diameter. The calculated shock wave position on jet axis and the pressure at the center of collection plate are in reasonable agreement with the experimental results. It is found that the structure of flow fields changes drastically at a certain value of P down/P up and there exist hysteresis phenomena in the relationship between the value of P c/P up and that of P dowb/P up for both gases. The formation of the separation bubble at a certain value of H/D is discussed.
Enabling Resiliency Operations Across Multiple Microgrids With Grid Friendly Appliance Controllers (2017)

Changes in economic, technological, and environmental policies are resulting in a re-evaluation of the dependence on large central generation facilities and their associated transmission networks. Emerging concepts of smart communities/cities are examining the potential to leverage cleaner sources of generation, as well as integrating electricity generation with other municipal functions. When grid connected, these generation assets can supplement the existing interconnections with the bulk transmission system, and in the event of an extreme event, they can provide power via a collection of microgrids. To achieve the highest level of resiliency, it may be necessary to conduct switching operations to interconnect individual microgrids. While the interconnection of multiple microgrids can increase the resiliency of the system, the associated switching operations can cause large transients in low inertia microgrids. The combination of low system inertia and IEEE 1547 and 1547a-compliant inverters can prevent multiple microgrids from being interconnected during extreme weather events. This paper will present a method of using end-use loads equipped with grid friendly appliance controllers to facilitate the switching operations between multiple microgrids; operations that are necessary for optimal operations when islanded for resiliency.
On the propagation of errors in the size of join results (1991)

article On the propagation of errors in the size of join results Share on Authors: Yannis E. Ioannidis Computer Sciences Department, University of Wisconsin, Madison, WI Computer Sciences Department, University of Wisconsin, Madison, WIView Profile , Stavros Christodoulakis Electronic and Computer Eng. Department, Technical University of Crete, 73100 Chania, Crete, Greece Electronic and Computer Eng. Department, Technical University of Crete, 73100 Chania, Crete, GreeceView Profile Authors Info & Claims ACM SIGMOD RecordVolume 20Issue 2June 1991 pp 268–277https://doi.org/10.1145/119995.115835Online:01 April 1991Publication History 196citation867DownloadsMetricsTotal Citations196Total Downloads867Last 12 Months47Last 6 weeks0 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 SiteGet Access
Progress in Gene Therapy for Chronic Granulomatous Disease (1999)

Progress in development of gene therapy for chronic granulomatous disease (CGD), an inherited defect in leukocyte oxidase deficiency, is reviewed. The use of retrovirus vectors to transfer oxidase enzyme subunit cDNA sequence into hematopoietic progenitors results in correction of oxidase activity in neutrophils differentiating from transduced progenitors. In CGD mouse knockouts (X-linked gp91phox-deficient CGD and autosomal recessive p47phox-deficient CGD), gene therapy correction of the CGD defect resulted in appearance of oxidase-normal neutrophils in the peripheral blood and increased host resistance to challenge with fungi or bacteria. In a phase I clinical trial of ex vivo gene therapy of p47phox-deficient CGD, prolonged production (2-6 months) of a low number (1:5000) of oxidase-normal neutrophils was achieved. This therapy might prove beneficial in a setting of prolonged infection in CGD patients, in which even transient production of autologous gene-corrected neutrophils might augment host defense.
A phase II trial of cetuximab as therapy for recurrent non-small cell lung cancer (NSCLC) (2004)

7084 Background: The addition of cetuximab (Erbitux™), an IgG1 monoclonal antibody, to chemotherapy has produced encouraging results in advanced non-small cell lung cancer (NSCLC) in doublet (ASCO 2002: A1168; ASCO 2003: 2581) as well as triplet therapy (ASCO 2003: A2587; ASCO 2003: A2582). Since single agent activity of cetuximab in NSCLC is not known, a phase II trial was undertaken. Methods: Eligible pts with stage IIIB/IV NSCLC who have recurrent or metastatic disease following ≥ 1 prior regimen, including a prior platinum, are eligible to participate in the study. Patients must have an ECOG PS of 0 or 1, and tumors can be EGFR positive or negative. Patients receive an initial cetuximab dose of 400 mg/m2 on Day 1 of Cycle 1, followed by weekly cetuximab doses of 250 mg/m2. One cycle equals four weeks. Weekly treatment with cetuximab continues until disease progression or unacceptable toxicity develops. The response rate with cetuximab will be determined for EGFR (+) positive pts, EGFR (-) negative pts, and for the total study population. Patients will also be assessed for time to disease progression, survival, and toxicity. Results: At a planned interim analysis of the first 29 EGFR + patients, there were 2 confirmed partial responses and 5 pts with stable disease. Preliminary demographic and safety data includes: 29 EGFR + pts, M/F 20/10, 23 pts with stage IV, 6 pts who never smoked and a mean age of 64 years (range 40–78). The mean number of cycles received was 3 (range 1–6). Reported grade 3/4 adverse events deemed possibly related to cetuximab included rash, cellulitis, fatigue, nausea and vomiting (1 pt each). Conclusions: The study is currently ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline AstraZeneca; Aventis; Bristol-Myers Squibb Bristol-Myers Squibb Aventis
Phase I Study of Recombinant Human CD40 Ligand in Cancer Patients (2001)

The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases. Encouraging antitumor activity, including a long-term complete remission, was observed. Phase II studies are warranted.