gebhart/patrepeval huggingface dataset:
Evaluating antivascular effects and antitumoral activity in patients with hepatocellular carcinoma treated with JX-594, a targeted multimechanistic oncolytic poxvirus, prior to sorafenib therapy. (2010)

e14564 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus granulocyte macrophage, colony stimulating factor (GM-CSF) expression stimulates acute tumor vascular shutdown and antitumoral immunity. JX-594 has been shown to be well tolerated by intravenous (IV) infusion and intratumoral (IT) injection and JX-594 is being developed as a novel therapy for patients with refractory hepatocellular carcinoma (HCC). Sorafenib is an antiangiogenic agent approved for patients with advanced HCC. Complementary antitumor effects are predicted with these two agents due to acute vascular disrupting effects of JX-594 and chronic antiangiogenic effects of sorafenib. Methods: Patients with confirmed treatment-refractory HCC were treated with JX-594 followed by standard sorafenib therapy. A subset of patients had previously received and failed sorafenib therapy. Patients were treated with three doses of JX-594 (IV and/or IT) and subsequently initiated standard sorafenib therapy. Results: As of January 10, 2010, seven patients have been treated with JX-594 followed by sorafenib. The sequential treatment regimen was well tolerated. Due to the different toxicity profiles of JX-594 and sorafenib, as well as the sequential dosing regimen, no drug interactions were expected. To date, five patients were evaluable for tumor response. Five (5) of 5 (100%) patients treated with both agents exhibited significantly decreased tumor blood flow and Choi responses (defined as > 15% reduction in density of tumor; range 68% - 125%). Choi responses occurred as early as 10 days post sorafenib initiation and have not been reported with sorafenib therapy alone. Conclusions: JX-594 shows promise as a novel agent for the treatment of refractory HCC. The complementary anticancer effects observed with subsequent sorafenib therapy warrant a randomized, controlled study of JX-594 followed by sorafenib versus placebo followed by sorafenib which will be initiated in 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Green Cross, Jennerex Biotherapeutics Jennerex Biotherapeutics Jennerex Biotherapeutics, Sillajen Green Cross, Jennerex Biotherapeutics, Sillajen
The Pseudomonas aeruginosa Quorum-Sensing Signal Molecule N -(3-Oxododecanoyl)- l -Homoserine Lactone Has Immunomodulatory Activity (1998)

Diverse gram-negative bacterial cells communicate with each other by using diffusible N-acyl homoserine lactone (AHL) signal molecules to coordinate gene expression with cell population density. Accumulation of AHLs above a threshold concentration renders the population "quorate," and the appropriate target gene is activated. In pathogenic bacteria, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants. We therefore sought to determine whether the immune system is capable of responding to these bacterial signal molecules. Consequently the immunomodulatory properties of the AHLs N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-(3-oxohexanoyl)-L-homoserine lactone (OHHL) were evaluated in murine and human leukocyte immunoassays in vitro. OdDHL, but not OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alpha production by lipopolysaccharide-stimulated macrophages. Furthermore, OdDHL simultaneously and potently down-regulated the production of IL-12, a Th-1-supportive cytokine. At high concentrations (>7 x 10(-5) M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-stimulated spleen cells, but at lower concentrations (<7 x 10(-5) M), antibody production was stimulated, apparently by increasing the proportion of the immunoglobulin G1 (IgG1) isotype. OdDHL also promoted IgE production by interleukin-4-stimulated human peripheral blood mononuclear cells. These data indicate that OdDHL may influence the Th-1-Th-2 balance in the infected host and suggest that, in addition to regulating the expression of virulence determinants, OdDHL may contribute to the pathogenesis of P. aeruginosa infections by functioning as a virulence determinant per se.
Bidentate Iron(II) Dichloride Complexes Bearing Substituted 8-(Benzimidazol-2-yl)quinolines: Synthesis, Characterization, and Ethylene Polymerization Behavior (2011)

The series of N-benzimidazolyl-substituted 2-alkyl-8-(benzimidazol-2-yl)quinolines (L1–L10) and 2-phenyl-8-(benzimidazol-2-yl)quinolines (L11–L14) and their respective bidentate iron(II) dichloride complexes (C1–C14) were synthesized and fully characterized. The molecular structures of a representative ligand (L5) and iron complexes (C2, C7) were determined by X-ray crystal structure analyses, and the distorted tetrahedral coordination geometry was observed around the iron center in both complexes C2 and C7. After activation of the iron complexes with methylaluminoxane, the iron catalysts showed activities up to 106 g·mol–1·h–1 in ethylene polymerization at elevated temperature (100 °C), yielding linear polyethylenes. The reaction parameters of the polymerization reactions were optimized, and the effect of the substituents of the different ligands on the catalytic activity and on the obtained polyethylene was discussed.
Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. (1992)

PURPOSE To determine the effects of high-dose cyclosporine (CsA) infusion on the pharmacokinetics of etoposide in patients with cancer. PATIENTS AND METHODS Sixteen patients were administered 20 paired courses of etoposide and CsA/etoposide. Etoposide was administered daily for three days, alone or with CsA, which was delivered by a loading dose and 3-day infusion. Etoposide was measured by high-performance liquid chromatography (HPLC) and serum CsA by nonspecific immunoassay. Etoposide pharmacokinetics included area under the concentration-time curve (AUC), total and renal clearance (CL), half-life (T1/2), and volume of distribution at steady state (Vss). RESULTS CsA concentrations more than 2,000 ng/mL produced an increase in etoposide AUC of 80% (P less than .001), a 38% decrease in total CL (P &lt; .01), a &gt; twofold increase in T1/2 (P &lt; .01), and a 46% larger Vss (P = .01) compared with etoposide alone. CsA levels ranged from 297 to 5,073 ng/mL. Higher CsA levels (&lt; 2,000 ng/mL v &gt; 2,000 ng/mL) resulted in greater changes in etoposide kinetics: Vss (1.4% v 46%) and T1/2 (40% v 108%). CsA produced a 38% decrease in renal and a 52% decrease in nonrenal CL of etoposide. Etoposide with CsA levels &gt; 2,000 ng/mL produced a lower WBC count nadir (900/mm3 v 1,600/mm3) compared with baseline etoposide cycles. CONCLUSIONS High-dose CsA produces significant increases in etoposide systemic exposure and leukopenia. These pharmacokinetic changes are consistent with inhibition by CsA of the multidrug transporter P-glycoprotein in normal tissues. Etoposide doses should be reduced by 50% when used with high-dose CsA in patients with normal renal and liver function. Alterations in the disposition of other multidrug resistance (MDR)-related drugs should be expected to occur with modulation of P-glycoprotein function in clinical trials.
Some applications of optical networks in the architecture of electronic computers (1990)

The authors examine the basic characteristics of three different types of optical network in the context of important communications bottlenecks that may arise as the processing power of computers increases. They are more concerned with estimates of the ultimate performance of archetypal networks and computer architectures, e.g. optically connected parallel machines. >
Self‐Assembled Magnetic Bead Biosensor for Measuring Bacterial Growth and Antimicrobial Susceptibility Testing (2012)

Bacterial antibiotic resistance is one of the major concerns of modern healthcare worldwide, and the development of rapid, growth-based, antimicrobial susceptibility tests is key for addressing it. The cover image shows a self-assembled asynchronous magnetic bead rotation (AMBR) biosensor developed for rapid detection of bacterial growth. Using the biosensors, the minimum inhibitory concentration of a clinical E. coli isolate can be measured within two hours, where currently tests take 6-24 hours. A 16-well prototype is also constructed for simple and robust observation of the self-assembled AMBR biosensors.
Inhibitor of complement, Compstatin, prevents polymer‐mediated Mac‐1 up‐regulation of human neutrophils independent of biomaterial type tested (2003)

The inflammatory reaction after cell contact with polymer materials is primarily mediated by activated neutrophils and may, in some cases, lead to exhaustion of neutrophil cell function. A direct consequence of this can be impairment of local or even systemic host defense mechanisms, which in turn can result in foreign body infections. Neutrophil activation, as indicated by the up-regulation of the Mac-1 adhesion receptor, is a reliable parameter for estimating the inflammatory risk due to implanted biomaterials. Because at blood contact, biomaterials immediately acquire a material-specific layer of blood proteins on their surface, including fibrinogen, complement, and immunoglobulin G, it is generally believed that after biomaterial contact, neutrophil activation primarily occurs by interaction with this protein layer. In this study, using our recently established polymer bead in vitro assay, we investigated whether complement inhibition alone can reduce biomaterial-mediated neutrophil activation, independent of the type of polymer and, hence, also its surface chemistry. Complement inhibition was achieved by using Compstatin, a recently developed complement inhibitor that binds to the complement component C3 preventing C3 convertase formation. We revealed significantly reduced (p < or = 0.025) Mac-1 receptor expression levels after 45 min of blood contact with the following polymers (without and with Compstatin): 1. polyurethane, 98.3%, 13.6%; 2. polymethylmetacrylate, 88.5%, 11.0%; and poly-D,L-lactide, 71.8%, 8.4%. Although these three polymer types acquire material-specific protein layers because of their different surface chemistry, complement inhibition by Compstatin alone proved to be sufficient to reduce neutrophil activation after surface contact, thus reducing the risk of biomaterial-mediated inflammatory reaction.
ENZYME IMMOBILIZATION INTO POLYMERS AND COATINGS (2002)

In this study, we have developed strategies to immobilize enzymes into various polymer and coatings. Three categories of bioplastic matrices were investigated. The first type of bioplastics was prepared by irreversibly incorporating di-isopropylfluorophosphatase (DFPase) into polyurethane (PU) foams. The resulting bioplastic retained up to 67 % of the activity for native enzyme. The thermostability of DFPase was highly affected by the immobilization process. Unlike native enzyme, immobilized DFPase had biphasic deactivation kinetics. Our data demonstrated that the initial rapid deactivation of immobilized DFPase lead to the formation of a hyper-stable and still active form of enzyme. Spectroscopic studies enabled a structural analysis of the hyper-stable intermediate. Biopolymers were also prepared via atom transfer radical polymerization (ATRP) using acrylic and sulfonate-derived monomers. ATRP ensured the covalent and multi-point immobilization of enzyme within polymer matrices. However, this approach was only partially successful, as no activity retention was obtained after polymerizationEnzyme-containing PU- and Michael adduct (MA)-based coatings correspond to the last category of bioplastics that was investigated. DFPase was irreversibly incorporated into PU coatings. The distribution of immobilized DFPase as well as activity retention were homogeneous within the coating. The resulting enzyme-containing coating (ECC) film hydrolyzed DFP in buffered media at high rates retaining approximately 39% intrinsic activity. DFPase-ECC had a biphasic deactivation profile similar to that of bioplastic foams. The synthesis of enzyme-containing MA coatings was performed in a two-step process using carbonic anhydrase (CA, E.C. 4.2.1.1). CA was first covalently immobilized into NVF-based water-soluble polymer (EP). The resulting EP was further entrapped into the matrix of MA coating. The so-formed ECC's exhibited approximately 7% apparent activity. CA-ECC showed good stability under ambient conditions and retained 55% activity after 90 days of storage.
Xanthomonas oryzae pathovars: model pathogens of a model crop (2006)

SUMMARY Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola cause bacterial blight and bacterial leaf streak of rice (Oryza sativa), which constrain production of this staple crop in much of Asia and parts of Africa. Tremendous progress has been made in characterizing the diseases and breeding for resistance. X. oryzae pv. oryzae causes bacterial blight by invading the vascular tissue, while X. oryzae pv. oryzicola causes bacterial leaf streak by colonizing the parenchyma. In rice there are 29 major genes for resistance to bacterial blight, but so far only a few quantitative resistance loci for bacterial leaf streak. Over 30 races of X. oryzae pv. oryzae have been reported. Both pathogens exhibit genetic variation among isolates. Mechanisms of pathogenesis and resistance have begun to be elucidated. Members of the AvrBs3/PthA family of transcription activator-like effectors play a major role in the virulence of X. oryzae pv. oryzae and possibly X. oryzae pv. oryzicola. Cloning of six rice resistance genes for bacterial blight and one from maize effective against bacterial leaf streak has uncovered a diversity of structure and function, some shared by genes involved in defence in animals. This article reviews research that spans a century. It also presents a perspective on challenges for sustainable control, and opportunities that interactions of X. oryzae pathovars with rice present as models for understanding fundamental aspects of bacterial pathogenesis of plants and plant disease resistance, as well as other aspects of plant and microbial biology, with implications also for animal innate immunity.
Klotho gene polymorphisms are related to colorectal cancer susceptibility. (2015)

Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC.
Successful Culture of Rat Embryos on Human Serum: Use in the Detection of Teratogens (1980)

Growth of head-fold-stage rat embryos cultured with human serum for 48 hours was enhanced by supplementation with glucose. Embryo growth (protein and DNA contents) varied with the source of the serum. Serum from 16 of 19 untreated subjects produced normal embryos. Serum from five subjects undergoing cancer chemotherapy and six subjects receiving anticonvulsants was either lethal or teratogenic.
Fine-grained network time synchronization using reference broadcasts (2002)

Recent advances in miniaturization and low-cost, low-power design have led to active research in large-scale networks of small, wireless, low-power sensors and actuators. Time synchronization is critical in sensor networks for diverse purposes including sensor data fusion, coordinated actuation, and power-efficient duty cycling. Though the clock accuracy and precision requirements are often stricter than in traditional distributed systems, strict energy constraints limit the resources available to meet these goals.We present Reference-Broadcast Synchronization, a scheme in which nodes send reference beacons to their neighbors using physical-layer broadcasts. A reference broadcast does not contain an explicit timestamp; instead, receivers use its arrival time as a point of reference for comparing their clocks. In this paper, we use measurements from two wireless implementations to show that removing the sender's nondeterminism from the critical path in this way produces high-precision clock agreement (1.85± 1.28μsec, using off-the-shelf 802.11 wireless Ethernet), while using minimal energy. We also describe a novel algorithm that uses this same broadcast property to federate clocks across broadcast domains with a slow decay in precision (3.68± 2.57μsec after 4 hops). RBS can be used without external references, forming a precise relative timescale, or can maintain microsecond-level synchronization to an external timescale such as UTC. We show a significant improvement over the Network Time Protocol (NTP) under similar conditions.
ATP Activates cAMP Production via Multiple Purinergic Receptors in MDCK-D1 Epithelial Cells (1998)

Extracellular nucleotides regulate function in many cell types via activation of multiple P2-purinergic receptor subtypes. However, it has been difficult to define which individual subtypes mediate responses to the physiological agonist ATP. We report a novel means to determine this by exploiting the differential activation of an autocrine/paracrine signaling pathway. We used Madin-Darby canine kidney epithelial cells (MDCK-D1) and assessed the regulation of cAMP formation by nucleotides. We found that ATP, 2-methylthio-ATP (MT-ATP) and UTP increase cAMP production. The cyclooxygenase inhibitor indomethacin completely inhibited UTP-stimulated, did not inhibit MT-ATP-stimulated, and only partially blocked ATP-stimulated cAMP formation. In parallel studies, ATP and UTP but not MT-ATP stimulated prostaglandin production. By pretreating cells with indomethacin to eliminate the P2Y2/prostaglandin component of cAMP formation, we could assess the indomethacin-insensitive P2 receptor component. Under these conditions, ATP displayed a ten-fold lower potency for stimulation of cAMP formation compared with untreated cells. These data indicate that ATP preferentially activates P2Y2 relative to other P2 receptors in MDCK-D1 cells (P2Y1 and P2Y11, as shown by reverse transcriptase polymerase chain reaction) and that P2Y2 receptor activation is the principal means by which ATP increases cAMP formation in these cells. Blockade of autocrine/paracrine signaling can aid in dissecting the contribution of multiple receptor subtypes activated by an agonist.
Diversity of Mammalian Voltage‐Gated Sodium Channels (1999)

A variety of different isoforms of mammalian voltage-gated sodium channels have been identified. These channels can be classified into three different types. Eight type 1 isoforms have been identified in the CNS, PNS, skeletal muscle, and heart. All of these channels have been expressed in exogenous systems, and all of the genes have been mapped. Three type 2 isoforms have been identified in heart, uterus, and muscle. These channels diverge from the type 1 channels in critical regions, and have not been functionally expressed, so their significance is unknown. A single isoform identified in the PNS may represent a third class of channels, in that it diverges from both type 1 and 2 channels. The type 3 channel has not been functionally expressed.
A 3-dimensional vision system for dental applications (2007)

There is an increasing demand for techniques that make use of 3-dimensional measurement in the field of dental research. This paper utilized a new 3-dimensional vision system for tooth surface information reconstruction. The system is based on a computational framework for constructing point cloud using digital fringe projection patterns. Surface information extracted from the point cloud can be used in various dental applications, for example, extracting characteristic features, building up a filling model for tooth restoration and determining molar movement during headgear treatment.
Recent Advances in the Synthesis of Indole and Quinoline Derivatives through Cascade Reactions (2009)

Indoles and quinolines are ubiquitous structural motifs in many natural products and biologically active pharmaceuticals. The pursuit of synthetic efficiency has stimulated the design and development of new synthetic strategies to construct these heterocycles. One of the most effective ways of achieving efficiency is to implement reaction cascades, enabling multiple bond-forming and bond-cleaving events to occur in a single synthetic operation, thus circumventing the waste associated with traditional stepwise synthesis. In general, cascade reactions offer the opportunity to access highly functionalized final products from simple starting materials. For all these reasons, it is not a surprise that most of the recently reported methods for the synthesis of indoles and quinolines are based on the use of cascade reactions. In this Focus Review we discuss some of the most representative and interesting recent reports on the synthesis of indoles and quinolines through cascade reactions.
Lead-Free Barium Titanate Ceramics with Large Piezoelectric Constant Fabricated by Microwave Sintering (2005)

A lead-free barium titanate (BaTiO 3 ) ceramics with a high density and a large piezoelectric constant, d 33 , as manufactured at 1320°C by microwave sintering, using a pure fine powder with a particle size of 100 nm produced by hydrothermal synthesis. The density of the ceramic with a 3.4 µm grain size was more than 98.3% of the theoretical value. The ceramic after poling had a dielectric constant of ε 33 T / ε 0 =4200, an electromechanical coupling factor planar mode of k p =36% and d 33 =350 pC/N. The value of d 33 is the largest one ever reported for lead-free BaTiO 3 ceramics.
Cellular and Molecular Mechanisms of Allograft Rejection (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Crystal structures of the Tudor domains of human PHF20 reveal novel structural variations on the Royal Family of proteins (2012)

The human PHD finger protein 20 (PHF20) is a putative transcription factor. While little is known about its cognate cellular role, antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula. PHF20 comprises two N-terminal Tudor domains, a central C2H2-link zinc finger domain and a C-terminal zinc-binding PHD domain, and is a component of some MLL methyltransferase complexes. Here, we report the crystal structures of the N-terminal Tudor domains of PHF20 and highlight the novel structural features of each domain. We also confirm previous studies suggesting that the second Tudor domain of PHF20 exhibits preference for dimethylated histone substrates.