gebhart/patrepeval huggingface dataset:
Renal Therapeutic Angiogenesis Using a Bioengineered Polymer-Stabilized Vascular Endothelial Growth Factor Construct (2015)

Renovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD. We measured single-kidney blood flow (RBF) and GFR and established the degree of renal damage after 6 weeks of RVD. Pigs then received a single stenotic kidney infusion of ELP-VEGF (100 μg/kg), a matching concentration of unconjugated VEGF (18.65 μg/kg), ELP alone (100 μg/kg), or placebo. Analysis of organ distribution showed high renal binding of ELP-VEGF 4 hours after stenotic kidney infusion. Therapeutic efficacy was determined 4 weeks after infusion. ELP-VEGF therapy improved renal protein expression attenuated in RVD, restoring expression levels of VEGF, VEGF receptor Flk-1, and downstream angiogenic mediators, including phosphorylated Akt and angiopoietin-1 and -2. This effect was accompanied by restored MV density, attenuated fibrogenic activity, and improvements in RBF and GFR greater than those observed with placebo, ELP alone, or unconjugated VEGF. In summary, we demonstrated the feasibility of a novel therapy to curtail renal injury. Recovery of the stenotic kidney in RVD after ELP-VEGF therapy may be driven by restoration of renal angiogenic signaling and attenuated fibrogenic activity, which ameliorates MV rarefaction and improves renal function.
Stimulation of prostate cancer growth by androgens and estrogens through the intermediacy of sex hormone-binding globulin. (1996)

Sex hormone-binding globulin (SHBG) not only regulates the free concentration of certain steroid sex hormones in plasma, but is involved in a nongenomic mechanism of steroid hormone action. It binds to a receptor on prostatic cell membranes and is activated by an appropriate steroid to initiate the generation of intracellular cAMP. Using the human prostate cancer cell line ALVA-41, we show that in serum-free medium, both dihydrotestosterone and estradiol increase growth in the presence, but not the absence, of SHBG. The increase in growth also follows the addition of cAMP to the cells and is enhanced by inhibiting protein dephosphorylation with the protein phosphatase inhibitor, okadaic acid. We conclude that cAMP causes increased growth in this prostate cancer cell line, and that both SHBG-dihydrotestosterone and SHBG-estradiol can regulate intracellular cAMP, and hence growth, in these cells.
Targeting Btk in Lymphoma: PCI-32765 Inhibits Tumor Growth in Mouse Lymphoma Models and a Fluorescent Analog of PCI-32765 Is an Active-Site Probe That Enables Assessment of Btk Inhibition In Vivo. (2007)

Abstract There is increasing evidence indicating that B-cell-receptor (BCR) signaling is required for survival of non-Hodgkin’s lymphoma (NHL) cells. Bruton’s tyrosine kinase (Btk) is required for BCR signaling and mutations that inactivate human Btk cause X-linked-agammaglobulinemia, a B-cell immunodeficiency. Although Btk functions selectively in B cells, the Btk active site is structurally similar to the active site in several Src and Abl kinases and as a result, there have been few highly selective small molecule inhibitors of Btk. We have developed a series of covalent Btk inhibitors that target Cys-481 in Btk and this approach results in increased potency and selectivity over related kinases that lack a Cys residue at this position (ChemMedChem 15:58). PCI-32765 is a Cys-481 targeting Btk inhibitor that has been optimized for potency, selectivity and pharmacokinetics. In cellular assays, PCI-32765 inhibits BCR-stimulus induced phosphorylation of Phospholipase-C-gamma, a Btk substrate, as well as downstream phosphorylation of Erk (IC50 &lt; 100 nM). In addition, PCI-32765 induces apoptosis and inhibits proliferation in a subset of NHL cell lines including DHL-4, DHL-6, WSU-DLCL2, OCI-Ly10 and DOHH2 (IC50s = 0.6–1.6uM). We have used RNAi knockdown in DOHH2 cells as an independent method to confirm that Btk is required for lymphoma cell proliferation. In vivo, orally dosed PCI-32765 (50mg/kg) inhibits growth of DOHH2 and WSU-DLCL2 xenografts. PCI-32765 also prevents disease progression in a mouse collagen-induced arthritis model (12.5mg/kg PO), indicating that other B cell lineage diseases are sensitive to Btk inhibition. In order to further characterize the selectivity and in vivo potency of PCI-32765, we have developed PCI-33380, an active-site probe consisting of a covalent Btk inhibitor linked to the fluorophore Bodipy-FL. PCI-33380 binds to Btk and can be detected by flow cytometry or by denaturing gel electrophoresis of cell lysates. In cell lysates, the probe labels a single predominant band of the same molecular weight as Btk and this band is absent in cells from xid mice. Labeling of this band is inhibited (IC50=10nM) by a brief pre-treatment of cells with PCI-32765, indicating that the probe can be used to assess occupancy of Btk by a covalent inhibitor. We have used the probe to quantitate the inhibition of Btk by PCI-32765 in vivo. A single oral dose of PCI-32765 (10mg/kg) delivered to mice leads to rapid and complete inhibition of Btk in spleen. In addition, a single oral dose of PCI-32765 fully inhibits Btk in xenograft tumors and peripheral blood cells and this inhibition is maintained for up to 24hr. The Btk probe provides pharmacodynamic measurements that may allow optimization of dosing and schedule for in vivo studies and we are currently adapting the probe assays for use in monitoring the inhibition of Btk in human clinical trials.
Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, tat. (1990)

Tat, the transactivation factor of human immunodeficiency virus type 1 (HIV-1), contains the highly conserved tripeptide sequence Arg-Gly-Asp (RGD) that characterizes sites for integrin-mediated cell adhesion. The tat protein was assayed for cell attachment activity by measuring the adhesion of monocytic, T lymphocytic, and skeletal muscle-derived cell lines to tat-coated substratum. All cell lines tested bound to tat in a dose-dependent manner and the tat cell adhesion required the RGD sequence because tat mutants constructed to contain an RGE or KGE tripeptide sequence did not mediate efficient cell adhesion. The tat-mediated cell attachment also required divalent cations and an intact cytoskeleton. In addition, cell adhesion to tat was inhibited in the presence of an RGD-containing peptide GRGDSPK or an anti-tat mAb that recognizes the RGD epitope. These results strongly suggest that cells are bound to tat through an integrin. Interestingly, myoblast cells bound to tat remained round, whereas the same cells attached through an integrin for a matrix protein typically flatten and spread. The role of this RGD-dependent cellular adhesion of tat in HIV-1 infection remains to be determined.
Cardiac and Respiratory Parameter Estimation Using Head-mounted Motion-sensitive Sensors (2015)

This work explores the feasibility of using motion-sensitive sensors embedded in Google Glass, a head-mounted wearable device, to robustly measure physiological signals of the wearer. In particular, we develop new methods to use Glass’s accelerometer, gyroscope, and camera to extract pulse and respiratory waves of 12 participants during a controlled experiment. We show it is possible to achieve a mean absolute error of 0.82 beats per minute (STD: 1.98) for heart rate and 0.6 breaths per minute (STD: 1.19) for respiration rate when considering different observation windows and combinations of sensors. Moreover, we show that a head-mounted gyroscope sensor shows improved performance versus more commonly explored sensors such as accelerometers and demonstrate that a head-mounted camera is a novel and promising method to capture the physiological responses of the wearer. These findings included testing across sitting, supine, and standing postures before and after physical exercise.
An Efficient Single-Cell RNA-Seq Approach to Identify Neoantigen-Specific T Cell Receptors (2017)

The adoptive transfer of neoantigen-reactive tumor-infiltrating lymphocytes (TILs) can result in tumor regression in patients with metastatic cancer. To improve the efficacy of adoptive T cell therapy targeting these tumor-specific mutations, we have proposed a new therapeutic strategy, which involves the genetic modification of autologous T cells with neoantigen-specific T cell receptors (TCRs) and the transfer of these modified T cells back to cancer patients. However, the current techniques to isolate neoantigen-specific TCRs are labor intensive, time consuming, and technically challenging, not suitable for clinical applications. To facilitate this process, a new approach was developed, which included the co-culture of TILs with tandem minigene (TMG)-transfected or peptide-pulsed autologous antigen-presenting cells (APCs) and the single-cell RNA sequencing (RNA-seq) analysis of T cells to identify paired TCR sequences associated with cells expressing high levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2). Following this new approach, multiple TCRs were identified, synthesized, cloned into a retroviral vector, and then transduced into donor T cells. These transduced T cells were shown to specifically recognize the neoantigens presented by autologous APCs. In conclusion, this approach provides an efficient procedure to isolate neoantigen-specific TCRs for clinical applications, as well as for basic and translational research.
A 1.4µA reset current phase change memory cell with integrated carbon nanotube electrodes for cross-point memory application (2011)

A cross-point phase change memory (PCM) cell working close to its ultimate scaling limit is demonstrated for the first time with an ultra low reset current of 1.4µA and set current of 0.5µA. This is the lowest value ever reported. Carbon nanotubes (CNTs) are utilized as the bottom electrode of the cell, which bring the lithography-independent critical dimension down to 1.2nm. Good electrical characteristics obtained demonstrate the functionality and potential viability of PCM for highly scaled ultra-dense memory at 2.5nm node.
Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. (1988)

We have found that the spontaneous migration of bovine aortic endothelial cells from the edge of a denuded area in a confluent monolayer is dependent upon the release of endogenous basic fibroblast growth factor (bFGF). Cell movement is blocked by purified polyclonal rabbit IgG to bFGF as well as affinity purified anti-bFGF IgG and anti-bFGF F(ab')2 fragments. The inhibitory effect of the immunoglobulins is dependent upon antibody concentration, is reversible, is overcome by the addition of recombinant bFGF, and is removed by affinity chromatography of the antiserum through a column of bFGF-Sepharose. Cell movement is also reversibly inhibited by the addition of protamine sulfate and suramin; two agents reported to block bFGF binding to its receptor. The addition of recombinant bFGF to wounded monolayers accelerates the movement of cells into the denuded area. Transforming growth factor beta which has been shown to antagonize several other effects of bFGF also inhibits cell movement. The anti-bFGF IgG prevents the movement of bovine capillary endothelial cells, BHK-21, NIH 3T3, and human skin fibroblasts into a denuded area. Antibodies to bFGF, as well as suramin and protamine sulfate also suppress the basal levels of plasminogen activator and DNA synthesis in bovine aortic endothelial cells.
Modulation Codes for Multi-amplitude Optical Recording (1994)

We consider the problem of coding for a recording channel. Traditional magnetic or optical channels employ saturation recording, where the input to the channel is a two-level waveform. A new optical recording channel has been developed that supports unsaturated, M-ary (M ≥ 3) signal levels. In this paper we introduce the new channel and discuss modulation codes for it. In particular, we consider the analysis and design of new partial response codes for these channels. Comparisons are made with M-ary run length limited codes. The partial response codes achieve the largest known storage density with coding gains of 3 - 5.5 dB above M-ary run length limited codes.
A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis (2009)

Our objective was to determine if chronic treatment with the non-competitive AMPA antagonist talampanel is efficacious and safe in subjects with ALS. A double-blind, placebo-controlled, multicenter, randomized clinical trial of nine months treatment duration was conducted in 59 subjects with ALS, with 40 subjects receiving talampanel 50 mg p.o. t.i.d, and 19 subjects receiving placebo. Primary outcome measure was rate of decline in isometric arm strength (as measured by change in arm strength megaslope of the Tufts Quantitative Neuromuscular Exam (TQNE)). Other efficacy endpoints included rate of decline in respiratory function, isometric leg strength, bulbar function, fine motor function, the ALS Functional Rating Scale (ALSFRS), and survival. Secondary safety outcome measures were frequency of adverse events, neurological status, plasma concentration of talampanel, vital signs, routine laboratory tests, and electrocardiograms. Decline in muscle strength was 15% less in talampanel treated subjects, and decline in ALSFRS was 30% slower in talampanel treated subjects. Talampanel was safe in subjects with ALS. Mortality rates (8% talampanel, 5% placebo) and drug discontinuation rates (25% talampanel, 16% placebo) were similar in active treatment and placebo groups. Dizziness and somnolence occurred significantly more often in talampanel treated subjects. Although no efficacy measure reached statistical significance, there was a repeated trend toward slower decline in ALSFRS and isometric muscle strength in talampanel treated subjects. Talampanel was well tolerated in subjects with ALS. Although certain adverse events occurred more frequently in the active treatment group, the rate of subject drop-out after nine months did not exceed that seen in other trials. These findings provide strong support for a phase III trial to determine the efficacy of talampanel in subjects with ALS.
Direct Detection of Multidrug-Resistant Mycobacterium tuberculosis in Clinical Specimens in Low- and High-Incidence Countries by Line Probe Assay (2003)

ABSTRACT The INNO-LiPA Rif.TB assay is designed for the detection of rpoΒ gene mutations causing rifampin resistance in isolates. We applied the method directly to 60 Lithuanian and Danish clinical specimens to detect rifampin resistance rapidly. Results were obtained in 78.3% of clinical specimens, and all were concordant with those obtained by BACTEC 460. The assay could have major impact on the management of multidrug-resistant tuberculosis.
Expectation and Housing Price Dynamics Following Deregulation in Korea (1999)

This paper offers an explanation for the existence of price control on new houses in Korea, which is deemed both inefficient and inequitable. This phenomenon cannot be explained by the conventional model of rent-seeking or the capture theory of regulation. Instead, it is attributable to the popular belief that the removal of the price regulation will lead to the increase in the overall housing price by increasing the demand for existing houses that are a perfect substitute for new houses. However, the paper, using a stock-adjustment model of the housing market, demonstrates that the claimed outcome cannot materialize under perfect foresight or adaptive expectation. The outcome is possible in the short run under a peculiar expectation scheme of a self-fulfilling nature. But even in this case, the price increase will be a one-time event and in the long-run overall housing prices will fall below the level that would prevail if the price regulations were maintained.
Characterizing the service usage of online video sharing system: Uploading vs. playback (2016)

Large online video sharing systems are becoming increasingly prevalent among the general public recently. A better understanding of their service usages is crucial for allocating the network resources and adjusting the service design. In this paper, we focus on a leading online video sharing system in China, namely Youku. We collected over 12 billion traffic traces from the network operator, and crawled the video meta-data for 30 consecutive days from Youku website. Based on those data, we present the first comparative characterization work on two key usages of online video sharing system: uploading and playback. We first check the different temporal patterns and intensities of uploaders' and viewers' activities. Then, the properties of the uploaded videos and watched videos are compared, to reveal the various user preferences behind those two service usages. Next, we study the dynamics of video popularity in video uploading and playback, in terms of view count distribution and active period. At last, we look through the followers of uploaders and the network formed by viewers, to analyze the relationships between different kinds of video service users. Our analysis results in this paper can be utilized by network operators, service providers, content creators and other interest parties of online video service, to adjust their service design and improve the user experience.
A Conformal FDTD Method With Accurate Waveport Excitation and S-Parameter Extraction (2016)

We demonstrate a conformal finite-difference time domain (CFDTD) technique with accurate waveport excitation and S-parameter extraction. We discuss, under the CFDTD framework, object modeling with effective subcell material, impedance calibration for the conformal modeled coaxial feed, waveport mode calculation with a newly developed conformal 2-D finite-difference frequency domain solver, waveport excitation with a modified total field scattered field method, and a modified S-parameter extraction scheme that is compatible with the CFDTD method. Lastly, we present two specific validation cases intended asWe demonstrate a conformal finite-difference time domain (CFDTD) technique with accurate waveport excitation and S-parameter extraction. We discuss, under the CFDTD framework, object modeling with effective subcell material, impedance calibration for the conformal modeled coaxial feed, waveport mode calculation with a newly developed conformal 2-D finite-difference frequency domain solver, waveport excitation with a modified total field scattered field method, and a modified S-parameter extraction scheme that is compatible with the CFDTD method. Lastly, we present two specific validation cases intended as relevant precursors to the inverse scattering application: modeling of the reflection coefficient of a tapered patch antenna and modeling of the transmission coefficient in a probe-fed rectangular waveguide. relevant precursors to the inverse scattering application: modeling of the reflection coefficient of a tapered patch antenna and modeling of the transmission coefficient in a probe-fed rectangular waveguide.
PC based multi-phase flow loop sensor calibration (2009)

A small multi-phase flow loop has been developed to calibrate oil & water mixture composition sensors under various conditions. The loop features two precision gear pumps, piping manifold with a cooler and a gravity based separator. The pumps are controlled by a Linux PC based data acquisition card. This allows for an automated and compact calibration process.
The “Metabolic Memory”: Is More Than Just Tight Glucose Control Necessary to Prevent Diabetic Complications? (2008)

The emergence of this metabolic memory suggests the need for early aggressive treatment aiming to "normalize" metabolic control together perhaps with the addition of agents which reduce cellular reactive species and glycation in order to minimize long-term diabetic complications.
Low-quality natural gas sulfur removal/recovery (1998)

A significant fraction of U.S. natural gas reserves are subquality due to the presence of acid gases and nitrogen; 13% of existing reserves (19 trillion cubic feed) may be contaminated with hydrogen sulfide. For natural gas to be useful as fuel and feedstock, this hydrogen sulfide has to be removed to the pipeline specification of 4 ppm. The technology used to achieve these specifications has been amine, or similar chemical or physical solvent, absorption. Although mature and widely used in the gas industry, absorption processes are capital and energy-intensive and require constant supervision for proper operation. This makes these processes unsuitable for treating gas at low throughput, in remote locations, or with a high concentration of acid gases. The U.S. Department of Energy, recognizes that exploitation of smaller, more sub-quality resources will be necessary to meet demand as the large gas fields in the U.S. are depleted. In response to this need, Membrane Technology and Research, Inc. (MTR) has developed membranes and a membrane process for removing hydrogen sulfide from natural gas. During this project, high-performance polymeric thin-film composite membranes were brought from the research stage to field testing. The membranes have hydrogen sulfide/methane selectivities in the range 35 to 60, depending on the feed conditions, and have been scaled up to commercial-scale production. A large number of spiral-wound modules were manufactured, tested and optimized during this project, which culminated in a field test at a Shell facility in East Texas. The short field test showed that membrane module performance on an actual natural gas stream was close to that observed in the laboratory tests with cleaner streams. An extensive technical and economic analysis was performed to determine the best applications for the membrane process. Two areas were identified: the low-flow-rate, high-hydrogen-sulfide-content region and the high-flow-rate, high-hydrogen-sulfide-content region. In both regions the MTR membrane process will be combined with another process to provide the necessary hydrogen sulfide removal from the natural gas. In the first region the membrane process will be combined with the SulfaTreat fixed-bed absorption process, and in the second region the membrane process will be combined with a conventional absorption process. Economic analyses indicate that these hybrid processes provide 20-40% cost savings over stand-alone absorption technologies.