gebhart/patrepeval huggingface dataset:
PP.13.11 (2015)

Objective: Coffee consumption may be associated with reduced risk of cardiovascular disease (CVD). The mechanisms by which coffee can exert potential protective effects remain unclear. Dietary polyphenols are potential contributors for improved cardiovascular health. Coffee is one of the richest sources of dietary polyphenols in a coffee drinking population, the most abundant form being chlorogenic acid (CGA). Endothelial dysfunction (ED) is an early and major risk factor for CVD, and oxidative stress plays a critical role in the development of ED. Nitric Oxide (NO) is a key factor in regulation of endothelial function. Heme oxygenase-1 (Hmox-1) is an inducible isoform of heme oxygenase that is produced in response to stressors such as oxidative stress and may play a key role in vascular protection. Design and method: Aortic rings from 10-week-old C57BL mice were collected and incubated with or without CGA, before exposure to HOCl. Endothelial depend relaxations were determined using myography. Confluent human aortic endothelial cells (HAECs) were serum starved before pre-treatment with CGA and exposure to HOCl. MTS formation was used to determine cell viability and western blot to determine eNOS phosphorylation, dimer formation and Hmox-1 induction. NO production was measure by gas phase chemiluminescence. Results: Pre-treatment of isolated aortic rings with 10 uM CGA protects vessels against HOCl-induced endothelial dysfunction (P < 0.05). Pre-treatment of cultured HAECs with 10 uM CGA increased endothelial cell viability following exposure to HOCl (P < 0.05). Moreover, CGA increases NO production in HAECs culture media in a dose-dependent manner, peaking 6 h (P < 0.05). In addition, CGA induced Hmox-1 protein expression in HAECs. Conclusions: These results are consistent with the cardiovascular protective effects of coffee polyphenols and demonstrate that CGA can protect vessels and cultured endothelial cells against oxidant-induced damage. The mechanism behind the beneficial effect of CGA appears to be in part via increased production of NO and induction of Hmox-1.
LC-MS characterization and purity assessment of a prototype bispecific antibody (2013)

Bispecific IgG asymmetric (heterodimeric) antibodies offer enhanced therapeutic efficacy, but present unique challenges for drug development. These challenges are related to the proper assembly of heavy and light chains. Impurities such as symmetric (homodimeric) antibodies can arise with improper assembly. A new method to assess heterodimer purity of such bispecific antibody products is needed because traditional separation-based purity assays are unable to separate or quantify homodimer impurities. This paper presents a liquid chromatography-mass spectrometry (LC-MS)-based method for evaluating heterodimeric purity of a prototype asymmetric antibody containing two different heavy chains and two identical light chains. The heterodimer and independently expressed homodimeric standards were characterized by two complementary LC-MS techniques: Intact protein mass measurement of deglycosylated antibody and peptide map analyses. Intact protein mass analysis was used to check molecular integrity and composition. LC-MS(E) peptide mapping of Lys-C digests was used to verify protein sequences and characterize post-translational modifications, including C-terminal truncation species. Guided by the characterization results, a heterodimer purity assay was demonstrated by intact protein mass analysis of pure deglycosylated heterodimer spiked with each deglycosylated homodimeric standard. The assay was capable of detecting low levels (2%) of spiked homodimers in conjunction with co-eluting half antibodies and multiple mass species present in the homodimer standards and providing relative purity differences between samples. Detection of minor homodimer and half-antibody C-terminal truncation species at levels as low as 0.6% demonstrates the sensitivity of the method. This method is suitable for purity assessment of heterodimer samples during process and purification development of bispecific antibodies, e.g., clone selection.
Performance comparison of four kinds of flat nonimaging Fresnel lenses made of polycarbonates and polymethyl methacrylate for concentrated photovoltaics (2011)

Solar concentrators made of a single refractive primary optics are limited to a concentration ratio of about 1000× [Opt. Express 19, A280 (2011)], due only to longitudinal chromatic aberration, while mirrors are limited to ∼46,000× by the angular size of the Sun. To reduce the chromatic aberration while keeping cost-effective systems for concentrated photovoltaics, a study of four different kinds of flat Fresnel doublets made of polycarbonates and polymethyl methacrylate is presented. It reveals that Fresnel doublets may have fewer optical losses than non-Fresnel doublets, with a lower lateral chromatic split allowing for even higher concentration ratio.
Submucosal reflexes: distension-evoked ion transport in the guinea pig distal colon (1992)

Muscle-stripped segments of distal colon from guinea pigs were mounted in modified flux chambers to determine the effect of distension on mucosal secretion. Ion secretion was monitored as changes in short-circuit current (Isc). Distending forces were pressure gradients established by controlled reduction in liquid volume of the submucosal compartment of the chamber. Volume removal for 10 s or 5 min evoked a monophasic or biphasic increase in Isc, which returned to baseline within 5-20 min. The amplitude of the response correlated with the volume removed and was reduced by bumetanide and Cl-free solutions but not by tetraethylammonium or amiloride. Tetrodotoxin and atropine also suppressed the response. Neither the nicotinic receptor antagonist mecamylamine, the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930, or the prostaglandin synthesis inhibitor piroxicam altered the response. Addition of prostaglandin D2 to the submucosal bath significantly enhanced the response. The results suggest that distension of the colon evokes anion secretion by activation of reflex circuits with cholinergic neurons and muscarinic synapses. Prostaglandins and 5-hydroxytryptamine acting at 5-HT3 receptors appear not to be signal substances in the reflex pathway, which evokes the secretory response to distension.
Perturbation of neuronal differentiation and axon guidance in the spinal cord of mouse embryos lacking a floor plate: analysis of Danforth’s shorttail mutation (1991)

The floor plate of the vertebrate nervous system has been implicated in the guidance of commissural axons at the ventral midline. Experiments in chick have also suggested that at earlier stages of development the floor plate induces the differentiation of motor neurons and other neurons of the ventral spinal cord. Here we have examined the development of the spinal cord in a mouse mutant, Danforth's short-tail, in which the floor plate is absent from caudal regions of the neuraxis. In affected regions of the spinal cord, commissural axons exhibited aberrant projection patterns as they reached and crossed the ventral midline. In addition, motor neurons were absent or markedly reduced in number in regions of the spinal cord lacking a floor plate. Our results suggest that the floor plate is indeed an intermediate target in the projection of commissural axons and support the idea that several different mechanisms operate in concert in the guidance of axons to their cellular targets in the developing nervous system. In addition, these experiments suggest that the mechanisms that govern the differentiation of the floor plate and other ventral cell types in the neural tube are common to mammals and lower vertebrates.
Ischaemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke (1998)

Recent trials of plasminogen activators in acute ischaemic stroke underscore the delicate balance between promise of benefit and risk. Attempts to manage clinical outcome by systemic infusion of recombinant tissue plasminogen activator (rt-PA) have so far had mixed success.1 2 The benefits seen in the National Institutes of Neurological Diseases and Stroke (NINDS) trial of rt-PA in acute ischaemic stroke were a significant absolute improvement in disability outcome.2 3 However, the risks in that study and in the European Cooperative Acute Stroke Study (ECASS)1 included further disability and mortality associated with haemorrhagic consequences of the plasminogen activator (PA).1 2 Three recent studies of streptokinase in acute ischaemic stroke were terminated because of safety concerns.4-9 In all five trials, the risk of symptomatic haemorrhage associated with the PA was significantly increased over placebo (table 1). In addition, approaches which effect recanalisation of documented cerebral arterial thrombotic occlusions by intravenous or intra-arterial PA infusion have yet to be rigorously shown to promote overall benefit, although anecdotal evidence suggests that individual patients may improve clinically.10-24 The reasons are practical. The perceived risks, those of angiography and the interventional procedures required for intra-arterial PA delivery, have not been fully evaluated,25 although the relative risks of diagnostic angiography are low.26-28 Clearly, this assessment hides many important differences in PA behaviour, study design and conduct, patient populations, diagnostic and therapeutic procedures, disease severity, comorbidity, and a host of other potential contributors. None the less, concerns which may erode the promise of benefit of thrombolytic agents in acute ischaemic stroke include the accentuation of innate risks associated with the evolution of ischaemic injury after the stroke event itself.29-34 These include early mortality caused by severe brain oedema and the development of haemorrhagic transformation which causes clinical deterioration or …
Implementing Pushback: Router-Based Defense Against DDoS Attacks (2002)

Pushback is a mechanism for defending against distributed denial-of-service (DDoS) attacks. DDoS attacks are treated as a congestion-control problem, but because most such congestion is caused by malicious hosts not obeying traditional end-to-end congestion control, the problem must be handled by the routers. Functionality is added to each router to detect and preferentially drop packets that probably belong to an attack. Upstream routers are also notified to drop such packets (hence the term Pushback) in order that the router's resources be used to route legitimate traffic. In this paper we present an architecture for Pushback, its implementation under FreeBSD, and suggestions for how such a system can be implemented in core routers.
TM4: A Free, Open-Source System for Microarray Data Management and Analysis (2003)

Microarrays have emerged as the premier tool for studying gene expression on a genomic scale. Advances in the precision of array printers and scanners as well as improved laboratory protocols (11) allow for assays of tremendous complexity and scope. Scientists seeking to harness the potential of this technique are often challenged by the large quantities of data produced. Well-designed, user-friendly software is the key to tracking, integrating, qualifying, and ultimately deriving scientific insight from the experimental results. In support of our ongoing work in microarray analysis of gene expression, we developed a suite of software that allow users in the laboratory to capture, manage, and analyze effectively data from DNA microarray experiments. The TM4 suite of tools consist of four major applications, Microarray Data Manager (MADAM), TIGR_Spotfinder, Microarray Data Analysis System (MIDAS), and Multiexperiment Viewer (MeV), as well as a Minimal Information About a Microarray Experiment (MIAME)-compliant MySQL database, all of which are freely available to the scientific research community at http://www.tigr.org/software. Although these software tools were developed for spotted two-color arrays, many of the components can be easily adapted to work with single-color formats such as filter arrays and GeneChips (Affymetrix, Santa Clara, CA, USA). Three of the TM4 applications, MADAM, MIDAS, and MeV, were developed in Java and have been tested on Microsoft Windows, Linux , Unix , and MacOS X platforms; TIGR Spotfinder was written in C/C++ and runs only on Windows systems. The TM4 software system represents a comprehensive, extensible, open-source, and freely available collection of tools that we believe will be of use to a wide range of laboratories conducting microarray experiments. We further hope that by providing source code along with the executable software, we can encourage others to develop new analysis methods and utilities that will further enhance the capabilities of this software system.
Oxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology (2013)

Hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis, which is disrupted in disorders affecting the circulatory system and in cancer. The role of HIFs in these diseases has been elucidated by clinical studies and by analyses of mouse models. HIFs play a protective role in the pathophysiology of myocardial ischemia due to coronary artery disease, limb ischemia due to peripheral arterial disease, pressure-overload heart failure, wound healing, and chronic rejection of organ transplants. In contrast, HIFs contribute to the pathogenesis of pulmonary arterial hypertension, systemic hypertension associated with sleep apnea, ocular neovascularization, hereditary erythrocytosis, and cancer.
Colonic epithelial impedance analysis in a murine model of large-bowel cancer (1986)

• Death rates from large-bowel cancer have remained essentially unchanged over the past 40 years because the diagnosis is made late, after the tumor has spread to other sites. This study was undertaken to examine whether alterations in mucosal electrical capacitance precede the development of gross malignancy, since this parameter may reflect functional or structural changes in the colonocyte plasma membrane, which is of importance in the regulation of cell growth. Distal colonic mucosal capacitance was decreased at low frequencies after only four weeks of treatment with the carcinogen dimethylhydrazine in C<sub>1</sub>mice. Alterations in electrical capacitance may be a useful marker in identifying patients with a propensity to develop large-bowel cancer. (<i>Arch Surg</i>1986;121:1253-1258)
A Workflow for Modeling and Simulation of Hydraulic Fractures in Unconventional Gas Reservoirs (2012)

Abstract Economic production from an unconventional gas reservoir is possible only if a complex fracture network can be created that connects a huge reservoir area to the wellbore effectively. This fracture network can be created by hydraulic fracturing. Several techniques can be used to present hydraulic fractures in a simulation model. In a simple model it is assumed that the fractures lie in the single plane of local tartan grid cells that best approximates the true geometric orientation of the fracture. The local refinement is symmetrically placed within the plane of host cells and has small cells close to the fracture that logarithmically increase in size away from the fracture. Explicitly calculated transmissibility multipliers on the faces of the cells that intersect the fracture are used to model the flow between matrix and the hydraulic fracture. The spacing and conductivity of the hydraulic fractures are critical parameters that control well performance. A new reservoir modeling and simulation technique has been developed for these complex fracture networks that combines discrete fracture network (DFN) modeling and unstructured fracture (UF) modelingto simulate well performance and improve stimulation design. This is very important for modeling and simulation of a well with hydraulic fractures in a shale gas reservoir with natural fractures. Results from this new model show a gas shale reservoir can be drained more effectively if a complex fracture network can be created by hydraulic fracture stimulation. In addition to a large increase in the production, the number of fracture treatment stages can be reduced if a high-conductivity fracture can be created, adding to the economic viability of the development of unconventional gas sources. The modeling and simulation technique presented in this paper can help identify stimulation and completion strategies that will significantly improve well performance and ultimate recovery from an unconventional gas reservoir.
Soluble β‐1,3/1,6‐glucan from yeast inhibits experimental periodontal disease in Wistar rats (2005)

Soluble beta-1,3/1,6-glucan administered by the oral route diminishes ligature-induced periodontal bone loss in this model. This effect may be attributable to the well documented ability of beta-1,3/1,6-glucan to stimulate macrophage phagocytosis and to skew the T helper (Th)1/Th2 balance towards Th1 and T regulatory responses. The HPA axis may play a significant role in beta-1,3/1,6-glucan induced immune modulation.
Development of siRNA Payloads to Target KRAS -Mutant Cancer (2014)

To advance RNAi therapy for KRAS-mutant cancer, we developed a validated siRNA library against RAS pathway genes that enables combination gene silencing. Using an in vivo model for real-time siRNA delivery tracking, we show that siRNA-mediated inhibition of KRAS as well as RAF or PI3K combinations can impair KRAS-mutant colorectal cancer in xenograft models.
Internet demand experiment: technology and market trial (2001)

Internet Demand Experiment: Technology and Market Trial by Richard John Edell Doctor of Philosophy in Engineering – Electrical Engineering and Computer Sciences University of California at Berkeley Professor Pravin P. Varaiya, Chair Successful growth of Internet and other sophisticated network services requires providers to offer combinations of service quality and price that meet the needs of a diverse user population. But to do this, providers need to understand the structure of user demand. Market data cannot provide this information, because service providers today offer a very narrow range of quality-price combinations. Providers would also find it difficult to offer variable quality and price using their current systems. The Internet Demand Experiment (INDEX) Project measures demand over a wide range of service quality and price structures. The project has several objectives, including: • Estimation of user demand for Internet access as a function of Quality of Service (QoS), price structure, and application (i.e. a market trial); and • Demonstration of an end-to-end system that provides network access to a diverse group of users at attractive quality-price combinations (i.e. a technology trial). The 18 month-long experiment involves a representative group of 70+ users from the University of California, Berkeley campus. These users purchase Internet access from the project. (i.e. they spend real money in exchange for Internet access services.) Ten experiments are run, testing different quality dimensions and pricing schemes.
Peroxisome Proliferator-Activated Receptor-γ-Mediated Positive Energy Balance in the Rat Is Associated with Reduced Sympathetic Drive to Adipose Tissues and Thyroid Status (2008)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation up-regulates thermogenesis-related genes in rodent white and brown adipose tissues (WAT and BAT) without increasing whole-body energy expenditure. We tested here whether such dissociation is the result of a negative modulation of sympathetic activity to WAT and BAT and thyroid axis components by PPARgamma activation. Administration of the PPARgamma agonist rosiglitazone (15 mg/kg.d) for 7 d to male Sprague Dawley rats increased food intake (10%), feed efficiency (31%), weight gain (45%), spontaneous motor activity (60%), and BAT and WAT mass and reduced whole-body oxygen consumption. Consistent with an anabolic setting, rosiglitazone markedly reduced sympathetic activity to BAT and WAT (>50%) and thyroid status as evidenced by reduced levels of plasma thyroid hormones (T(4) and T(3)) and mRNA levels of BAT and liver T(3)-generating enzymes iodothyronine type 2 (-40%) and type 1 (-32%) deiodinases, respectively. Rosiglitazone also decreased mRNA levels of the thyroid hormone receptor (THR) isoforms alpha1 (-34%) and beta (-66%) in BAT and isoforms alpha1 (-20%) and alpha2 (-47%) in retroperitoneal WAT. These metabolic effects were associated with a reduction in mRNA levels of the pro-energy expenditure peptides CRH and CART in specific hypothalamic nuclei. A direct central action of rosiglitazone is, however, unlikely based on its low brain uptake and lack of metabolic effects of intracerebroventricular administration. In conclusion, a reduction in BAT sympathetic activity and thyroid status appears to, at least partly, explain the PPARgamma-induced reduction in energy expenditure and the fact that up-regulation of thermogenic gene expression does not translate into functional stimulation of whole-body thermogenesis in vivo.
Increased Immunogenicity and Protective Efficacy in Outbred and Inbred Mice by Strategic Carboxyl-Terminal Truncation of Japanese Encephalitis Virus Envelope Glycoprotein (1993)

We constructed recombinant vaccinia viruses expressing the full-length envelope (E) glycoprotein of Japanese encephalitis virus (JEV) or a strategically truncated E glycoprotein, approximately 80% of the N-terminal sequence, and compared their antigenic structure and protective immunity in mice. The truncation site in the JEV E glycoprotein sequence corresponds to the position that had been shown to increase the immunogenicity of dengue type 4 or type 2 virus E glycoprotein. Analysis of the JEV E glycoprotein in recombinant virus-infected cells showed that C-terminally truncated E retains an antigenic structure similar to that of the full-length E glycoprotein. The full-length JEV E glycoprotein was detected predominantly intracellularly, while a small fraction (< 2%) was present on the cell surface. On the other hand, the truncated 80% E glycoprotein exhibited an alteration in the intracellular transport pathway resulting in increased accumulation (10-25%) on the cell surface and secretion (6-10%) into the medium. The C-terminally truncated E glycoprotein induced a greater antibody response and a higher level of protective immunity than did the full-length E glycoprotein in outbred CD-1 mice as well as in two strains of inbred mice that differ in their resistance to intraperitoneal (ip) JEV infection. In the case of outbred CD-1 and inbred C57/Bl mice, which possess a dominant autosomal genetic locus that controls resistance to a high dose of ip infection of JEV or the capacity to acquire resistance to intracerebral JEV infection, truncated E glycoprotein induced a higher titer of JEV neutralizing antibodies.