cssi/SciSciGPT-SciSciNet huggingface dataset:
Increased effector–target cell conjugate formation due to HLA restricted specific antigen recognition

The T cell receptor (TCR) orchestrates T cell mediated-cytotoxicity through a complex interaction that results in an antigen-specific effector–target cell conjugate formation. While it is well recognized that specific TCR/antigen interactions generate the immunological synapse, their direct contribution to the effector–target cell conjugate has not been conclusively demonstrated. Moreover, since human cytotoxic T lymphocyte (CTL) clones are also susceptible to antigen-independent adhesion to target cells, it remains unclear whether effector–target cell conjugate formation can serve as an indicator of specific antigen recognition by the TCR. To address this question, a well-characterized epitope-specific CTL clone recognizing the melanoma-associated antigen epitope gp100:209–217 in association with HLA-A*0201 was tested against melanoma cell lines lacking or expressing the HLA-A*0201 allele and/or gp100. In this model, TCR/HLA/antigen interactions cooperated with accessory/adhesion molecules to facilitate effector–target cell conjugate formation. HLA-restricted antigen recognition played a dominant role resulting in up to 2-fold increases in conjugate frequency, and a 50% increase of CTL binding to tumor cells over background. The increased number of CTL contained in conjugates correlated with the number of IFN-γ producing CTL. These results warrant further investigation to evaluate conjugate assays as a potential tool to detect and isolate viable and functionally active CTL. Since conjugate formation analysis does not require knowledge of the target antigen, this assay could potentially be used for enrichment of CTL directed against novel antigens.
Electrochemical impedance spectroscopic measurement of potential of zero charge of octanethiolate-protected Au and Pd nanoparticles

Abstract Electrochemical impedance spectroscopic (EIS) method was used to determine potential of zero charge (PZC) of octanethiolate-protected Au and Pd nanoparticles (NPs) of about 2-nm and 3-nm sizes respectively. The PZC values so obtained were compared with those obtained by the more conventional differential pulse voltammetry (DPV)/z-plot method. Good agreements were found between the PZC values obtained by these two very different methods, attesting the validity of the EIS-based method whose applicability is not limited by the NP size and is therefore expected to have broader implications in terms of measuring PZC of metal NPs.
AN IN VITRO MODEL FOR THE STUDY OF TRANSFORMATION: TEMPERATURE-SENSITIVE (TS) MUTANT

Ts systems provide an opportunity to induce a cell with a defined genotype to express either the transformed or normal phenotype by simply manipulating temperature. Rat kidney fibroblasts transformed by a Ts derivative of the Kirsten murine sarcoma virus grow on agar or a preexisting monolayer at the permissive temperature (32°C) but are unable to grow under these conditions at the nonpermissive temperature (39°C). The purpose of this study was to determine the suitability of this model to study processes accompanying “phenotypic transformation” (normal ⇌ transformed). Growth characteristics (clonal/mass culture), cell size, cAMP levels, and surface morphology were periodically monitored following the manipulation of temperature from 39°C ⇌ 32°C. Ts, normal and transformed control cells grew slower at 32°C, but attained a saturation density equivalent to cells grown at 39°C. Cell size was inversely related to the growth rate; each cell type was smallest during the period of maximal growth rate and became larger as division slowed and cells reached confluency. cAMP levels were also inversely related to growth rate; all cells growing at similar rates had similar cAMP levels. Scanning EM showed that cells maintained at 32°C became spindle-shaped and “piled up” at low density and low serum concentration while cells at 39°C formed flat, confluent monolayers and required greater serum concentration for growth. This system may provide the means to distinguish cellular changes due to transformation from those common to “normal” cells with similar growth rates.
Lattice Boltzmann Modeling of Three-Dimensional, Multicomponent Mass Diffusion in a Solid Oxide Fuel Cell Anode

The lattice Boltzmann method (LBM) was used to study the three-dimensional (3D) mass diffusion of three species (H 2 H 2 0, and N 2 ) in the pore phase of a porous solid oxide fuel cell (SOFC) anode. The method used is an extension of a two-dimensional (2D) LBM model (2007, "Lattice Boltzmann Method for Continuum, Multi-Component Mass Diffusion in Complex 2D Geometries, " J. Phys. D, 40, pp. 2961-2971) to study mass transport in SOFC anodes (2007, "Lattice Boltzmann Modeling of 2D Gas Transport in a Solid Oxide Fuel Cell Anode, " J. Power Sources, 164, pp. 631-638). The 3D porous anode geometry is initially modeled using a set of randomly packed and overlapping solid spheres. Results using this simple geometry model are then compared with results for an actual SOFC anode geometry obtained using X-ray computed tomography (XCT) at sub-50 nm resolution. The effective diffusivity D eff of the porous anode is a parameter, which is widely used in system-level models. However, empirical relationships often used to calculate this value may not be accurate for the porous geometry that is actually used. Solution of the 3D Laplace equation provides a more reliable and accurate means to estimate the effective diffusivity for a given anode geometry. The effective diffusivity is calculated for different geometries and for a range of porosity values, both for the 3D sphere packing model and for the real geometry obtained by XCT. The LBM model is then used to predict species mole fractions within the spherical packing model geometry and the XCT geometry. The mole fraction variation is subsequently used to calculate the concentration polarization. These predictions compare well with previously obtained 2D results and with results reported in the literature. The 3D mass transport model developed in this work can be eventually coupled with other transport models and be used to optimize the anode microstructure geometry.
Synchronization of Coupled Laser Arrays With All-to-All and Limited Coupling Topology

Synchronization of coupled laser arrays is required in many applications of high-power laser systems. While the problem is approached by numerical or experimental methods traditionally, we propose a new approach to rigorously characterize the synchronization condition inspired by recent advances in cooperative control. We study synchronization of an array of coupled solid state lasers where each individual laser is modeled by a second-order nonlinear oscillators. We analyze synchronization conditions over a mean-field model for all-to-all coupling configuration, and prove that the coupled lasers with identical frequencies can be stabilized on the synchronization state for any positive coupling strength. We then extend the all-to-all coupling to the limited communication case, and similar synchronization conditions are proved for undirected connected graphs. Our analysis is conducted using tools from algebraic graph theory and Lyapunov dynamic system theory. Simulation examples are given to illustrate the results.Copyright © 2012 by ASME
Advanced Engineering: Future Directions for the Agricultural and Biological Engineering Profession☆

Abstract We are having breakthroughs in materials, genomics, information systems and high-speed electronics. These technologies will require engineers to work at a minute level such as atomic or molecular. Currently, we use technologies such as transient finite element analysis, system control and simulation dynamic mass modelling, three-dimensional design and assembly. In the next 10 years, we will be solving problems and doing research in biosensors, biomaterials, bioelectronics, inert materials, magnetic materials, and fluorescent materials, which will require the expertise of multi-disciplinary teams of scientists and engineers. Specifics on these areas are presented to enhance our profession's involvement in the future. The engineering environment in the future is also discussed.
Blood meal manipulation and in vitro colony maintenance of Haematobia irritans (Diptera: Muscidae).

A series of experiments was conducted to determine survival and reproductive potential of Haematobia irritans (L.) adults that were fed sodium citrated-bovine blood diluted with deionized water, 0.5 M glucose, or 0.15 M sodium chloride (NaCl), or supplemented with adenosine triphosphate (ATP). Reproductive potential, measured by total number of larvae produced per female during 10-d experimental periods, improved when adult H. irritans were fed blood diluted by <22% with deionized water, NaCl, or glucose, whereas female survival improved when fed blood diluted with deionized water or NaCl (by ≈25%). Male survival declined whenever blood meals were diluted. Larval production also improved when blood previously stored at −20°C was diluted by ≈21% with deionized water. Addition of ATP to blood stored at 3°C did not improve larval production or female survival; however, ATP added to blood stored at −20°C increased larval production and female survival. Male survival was not improved by addition of ATP to previously refrigerated or frozen blood. Blood meals were toxic to H. irritans when &5 × 10−2 M ATP was added to previously refrigerated or frozen blood. A colony of H. irritans was maintained for five generations by feeding adult flies on citrated bovine blood that had been stored at −20°C, supplemented with 5 × 10∼3 M ATP, and diluted with deionized water. Flies were fed through a nylon-reinforced silicone membrane throughout this experimental period. Female survival and larval production were unaffected by the adult fly feeding regimen. Male survival was reduced during the F1; F2, and F3 generations; however, declines did not affect colony maintenance. Percentage pupation increased during the F2 and F3 generations and adult eclosion declined in the F3 and F4 generations, changes attributed to conditions of larval rearing. Potential for colony population growth was estimated using F4 female survival and resulting larval production, pupation, and adult eclosion. An ≈24-fold increase in population size per generation could be realized by collecting all eggs produced by 6–12-d-old females.
Comparative immobilization of wild felids in Thailand.

We immobilized individuals of four free-ranging felid species, leopard cat (Prionailurus bengalensis), clouded leopard (Neofelis nebulosa), Asiatic golden cat (Catopuma temminckii), and marbled cat (Pardofelis marmorata) with ketamine hydrochloride and xylazine hydrochloride (KH-XH) and with tiletamine hydrochloride and zolazepam hydrochloride (TH-ZH) between March 1998 and July 2002. Mean (±SD) dose of KH and XH was 26.51±5.71 mg/kg and 1.89±0.43 mg/kg, respectively (n=25), and mean dose of TH-ZH was 11.61±3.39 mg/kg (n=28). Dose was significantly correlated with induction time (P<0.001) and duration of anesthesia (P<0.05), but not with recovery time. There were significant differences between the drug combinations in time to induction (P<0.03) and time to anesthesia (P<0.01); recovery times were not significantly different. We conclude that immobilization of these felids with TH-ZH and KH-XH is effective and safe, but TH-ZH is preferred because of the smaller volume of drug necessary for sedation, faste...
High-Resolution Orientation and Depth of Insertion of the Voltage-Sensing S4 Helix of a Potassium Channel in Lipid Bilayers

The opening and closing of voltage-gated potassium (Kv) channels are controlled by several conserved Arg residues in the S4 helix of the voltage-sensing domain. The interaction of these positively charged Arg residues with the lipid membrane has been of intense interest for understanding how membrane proteins fold to allow charged residues to insert into lipid bilayers against free-energy barriers. Using solid-state NMR, we have now determined the orientation and insertion depth of the S4 peptide of the KvAP channel in lipid bilayers. Two-dimensional (15)N correlation experiments of macroscopically oriented S4 peptide in phospholipid bilayers revealed a tilt angle of 40 degrees and two possible rotation angles differing by 180 degrees around the helix axis. Remarkably, the tilt angle and one of the two rotation angles are identical to those of the S4 helix in the intact voltage-sensing domain, suggesting that interactions between the S4 segment and other helices of the voltage-sensing domain are not essential for the membrane topology of the S4 helix. (13)C-(31)P distances between the S4 backbone and the lipid (31)P indicate a approximately 9 A local thinning and 2 A average thinning of the DMPC (1,2-dimyristoyl-sn-glycero-3-phosphochloline)/DMPG (1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol) bilayer, consistent with neutron diffraction data. Moreover, a short distance of 4.6 A from the guanidinium C(zeta) of the second Arg to (31)P indicates the existence of guanidinium phosphate hydrogen bonding and salt bridges. These data suggest that the structure of the Kv gating helix is mainly determined by protein-lipid interactions instead of interhelical protein-protein interactions, and the S4 amino acid sequence encodes sufficient information for the membrane topology of this crucial gating helix.
Port reform and privatization in conditions of limited competition: the experience in Colombia, Costa Rica and Nicaragua

Governments in their port reform efforts have experimented with liberalization and commercialization to improve port operations. Because of their failure to meet expectations or because of changing competitive environments, these options have generally been discarded in favour of privatization. In mature large–volume port systems, privatization was a relatively obvious solution, because interport or interterminal competition would be achieved to the extent that the monopolistic tendencies characteristic of their predecessor organizations would cease to exist. In countries with a limited number of ports having relatively small cargo volumes, however, the case is quite different. These countries would have to pursue strategies that would still induce competition in spite of their limited cargo volumes if they hoped to achieve the same privatization benefits and market disciplines enjoyed in other countries. This article examines the port reform approaches used in three distinct competitive settings;the expe...
High energy neutrinos from neutralino annihilations in the Sun

Neutralino annihilations in the Sun to weak boson and top-quark pairs lead to high-energy neutrinos that can be detected by the IceCube and KM3 experiments in the search for neutralino dark matter. We calculate the neutrino signals from real and virtual WW, ZZ, Zh, and tt production and decays, accounting for the spin dependences of the matrix elements, which can have important influences on the neutrino energy spectra. We take into account neutrino propagation including neutrino oscillations, matter-resonance, absorption, and {nu}{sub {tau}} regeneration effects in the Sun and evaluate the neutrino flux at the Earth. We concentrate on the compelling focus point (FP) region of the supergravity model that reproduces the observed dark matter relic density. For the FP region, the lightest neutralino has a large bino-Higgsino mixture that leads to a high neutrino flux and the spin-dependent neutralino capture rate in the Sun is enhanced by 10{sup 3} over the spin-independent rate. For the standard estimate of neutralino captures, the muon signal rates in IceCube are identifiable over the atmospheric neutrino background for neutralino masses above M{sub Z} up to 400 GeV.
Effects of mental fatigue on the development of physical fatigue: a neuroergonomic approach.

OBJECTIVE: The present study used a neuroergonomic approach to examine the interaction of mental and physical fatigue by assessing prefrontal cortex activation during submaximal fatiguing handgrip exercises. BACKGROUND: Mental fatigue is known to influence muscle function and motor performance, but its contribution to the development of voluntary physical fatigue is not well understood. METHOD: A total of 12 participants performed separate physical (control) and physical and mental fatigue (concurrent) conditions at 30% of their maximal handgrip strength until exhaustion. Functional near infrared spectroscopy was employed to measure prefrontal cortex activation, whereas electromyography and joint steadiness were used simultaneously to quantify muscular effort. RESULTS: Compared to the control condition, blood oxygenation in the bilateral prefrontal cortex was significantly lower during submaximal fatiguing contractions associated with mental fatigue at exhaustion, despite comparable muscular responses. CONCLUSION: The findings suggest that interference in the prefrontal cortex may influence motor output during tasks that require both physical and cognitive processing. APPLICATION: A neuroergonomic approach involving simultaneous monitoring of brain and body functions can provide critical information on fatigue development that may be overlooked during traditional fatigue assessments. Language: en
Recent advances in shock tube/laser diagnostic methods for improved chemical kinetics measurements

Shock tubes combined with laser diagnostics provide state-of-the-art capabilities for studying the chemical kinetics of combustion processes. We report here several new concepts and methods designed to improve shock tube performance and modeling, extend shock tube operating regimes, provide access to low vapor pressure fuels, and quantitatively measure species time-histories using continuous wave laser absorption. These new methods are discussed in the context of studying ignition processes of hydrocarbon fuels at practical engine conditions; examples of the use of these methods to study the chemical kinetics of real fuels and to resolve current issues related to shock tube facility effects are given.
Characterizing learning deficits and hippocampal neuron loss following transient global cerebral ischemia in rats.

Abstract The 2-vessel-occlusion + hypotension (2VO + H) model of transient global cerebral ischemia results in neurodegeneration within the CA1 field of the hippocampus, but previous research has failed to demonstrate robust or reliable learning/memory deficits in rats subjected to this treatment. In the present study, sensitive behavioral protocols were developed in an effort to characterize the cognitive impairments following 2VO + H more precisely. Adult rats were exposed to 10 min of bilateral carotid occlusion with simultaneous hypotension. Following recovery, 2VO + H and control rats were subjected to a series of behavioral tests (locomotor activity, sensorimotor battery, water maze [cued, place, learning set], object recognition, and radial arm maze) over an extended recovery period followed by an assessment of neuronal loss in the dorsal hippocampus. The 2VO + H treatment was associated with long-lasting spatial learning deficits in the absence of other behavioral impairments and with neurodegeneration in dorsal hippocampal CA1. Water maze protocols that placed higher memory demands upon the rats (relatively “hard” vs. “easy”) were more sensitive for detecting ischemia-induced deficits. We have shown that the use of appropriate behavioral tests (e.g., a relatively difficult place learning task) allowed for the observation of robust spatial learning deficits in a model previously shown to induce relatively subtle behavioral effects. Thus, the 2VO + H model induces both hippocampal neuronal loss and long-term learning deficits in rats, providing a potentially useful model for evaluating therapeutic efficacy.
The gag coding region of the Drosophila telomeric retrotransposon, HeT-A, has an internal frame shift and a length polymorphic region.

A major component of Drosophila telomeres is the retrotransposonHeT-A, which is clearly related to other retrotransposons and retroviruses. This retrotransposon is distinguished by its exclusively telomeric location, and by the fact that, unlike other retrotransposons, it does not encode its own reverse transcriptase.HeT-A coding sequences diverge significantly, even between elements within the same genome. Such rapid divergence has been noted previously in studies ofgag genes from other retroelements. Sequence comparisons indicate that the entireHeT-A coding region codes forgag protein, with regions of similarity to other insect retrotransposongag proteins found throughout the open reading frame (ORF). Similarity is most striking in the zinc knuckle region, a region characteristic ofgag genes of most replication-competent retroelements. We identify a subgroup of insect non-LTR retrotransposons with three zinc knuckles of the form: (1) CX2CX4HX4C, (2) CX2CX3HX4C, (3) CX2CX3HX6C. The first and third knuckles are invariant, but the second shows some differences between members of this subgroup. This subgroup includesHeT-A and a second Drosophila telomeric retrotransposon,TART. Unlike other gag regions,HeT-A requires a −1 frameshift for complete translation. Such frameshifts are common between thegag andpol sequences of retroviruses but have not before been seen within agag sequence. The frameshift allowsHeT-A to encode two polypeptides; this mechanism may substitute for the post-translational cleavage that creates multiplegag polypeptides in retroviruses.D. melanogaster HeT-A coding sequences have a polymorphic region with insertions/deletions of 1–31 codons and many nucleotide changes. None of these changes interrupt the open reading frame, arguing that only elements with translatable ORFs can be incorporated into the chromosomes. PerhapsHeT-A translation products act incis to target the RNA to chromosome ends.
Osmotic Ultrafiltration with Dextran Sodium Sulfate Potential for use in Peritoneal Dialysis

Dextran sodium sulfate was evaluated in vitro as a potential non-absorbable osmotic agent for peritoneal dialysis. It was compared to poly(sodium acrylate) which has been shown previously to be effective in rats, but probably toxic. Dextran sodium sulfate induced osmotic ultrafiltration rates as high as 20 ml/min in water but only 2 ml/min in solution containing non-polymer electrolytes presumably because of Gibbs-Donnan effects. Compared to acrylate the dextran polymer has less sodium per gram, lower osmotic activity of polymer sodium, and yields less ultrafiltration at given transmembrane osmolalities. A nontoxic polymer more like acrylate would seem more promising as an osmotic agent for peritoneal dialysis.
Effect of dose and uremia on plasma and urine profiles of propranolol metabolites

The relationship between plasma levels of 4 propranolol metabolites—naphthoxylactic acid (NLA), 4-hydroxypropranolol (4-OH), naphthoxy acetic acid (NAA), and propranolol glycol (PG)—and propranolol plasma levels was determined in healthy, adult male subjects after increasing single oral doses of propranolol. NLA was present at plasma levels 6 to 25 times that of propranolol. More than 90% of circulating NLA was in the plasma fraction, where it was 95% protein bound. The ratio of plasma concentrations of the pharmacologically active metabolite 4-OH to propranolol approached unity 0.5 hr after propranolol, 160 mg or 320 mg orally, but fell rapidly. Plasma levels of NAA were in the same range as propranolol, especially as time progressed. PG circulated at plasma levels less than 12% of propranolol. As oral doses of propranolol were increased from 20 to 320 mg, there was a decrease in intrinsic plasma clearance (Cli) from 425 to 200 l/hr. Half-life rose from 3 to 5 hr. Urinary recovery of 4-OH fell as Cli rose. Urinary recovery of propranolol conjugates, NLA, and N-desisopropylpropranolol (NDIPP) rose as Cli fell. Our results suggest that naphthalene ring oxidation of propranolol represents a high-affinity low-capacity enzymatic pathway(s) that plays an important role in the extensive hepatic extraction of propranolol after small doses orally. Plasma NLA and plasma NAA were determined before and after hemodialysis in 14 uremic patients receiving long-term propranolol therapy. Mean plasma NLA was 4,372 ng/ml, and mean plasma NAA level was 238 ng/ml when mean plasma propranolol level was 15 ng/ml. Clinical Pharmacology and Therapeutics (1980) 27, 744–755; doi:10.1038/clpt.1980.105
Wildlife herbivory and rare plants : the effects of white-tailed deer, rodents, and insects on growth and survival of Turk's cap lily

Abstract Current land-use changes in eastern deciduous forests, such as fragmentation, may affect population sizes of native wildlife that may exacerbate declines in rare and endangered wildflower populations in the eastern deciduous forests. In this study, we examined the influence of herbivory by rodents (Peromyscus leucopus, Sciurus sp., and Tamias striatus) and white-tailed deer (Odocoileus virginianus) on the growth and survival of Turk's cap lily (Lilium superbum) planted in Virginia. Bulbs were planted in pairs and in patches. One plant per pair was protected from deer damage with a wire cage, and patches consisted of two, 10 and 25 bulbs planted within 0.04 ha. Rodents dug up and consumed 9% of all the bulbs planted, and fatal rodent damage was 3 times greater in successional than in upland hardwood and creek bottom habitats. White-tailed deer consumed the apical meristem of 28% of the unprotected lilies that emerged, reducing mean plant height and stopping growth and reproduction for that season. Deer and insects, but not rodents, damaged a greater proportion of plants emerging in small patches (1–2 plants/0.04 ha) than on larger patches (3–20 plants/0.04 ha). Therefore, when protecting remaining populations or restoring new populations of rare perennial wildflowers in the eastern deciduous forest, methods for protecting plants from herbivory by rodents and white-tailed deer should be considered.
Lattice calculation for lepton capture from vacuum-pair production in relativistic heavy-ion collisions

The new colliding-beam heavy-ion accelerators, designed to investigate nuclear matter at high temperatures and densities, have motivated great interest during the last decade concerning possible new electromagnetic phenomena. One of the most interesting of these processes is the sparking of the vacuum to produce lepton-antilepton pairs. The process of electron capture from vacuum pair production is a principal beam-loss mechanism for highly charged relativistic ions in a storage ring, and thus must be considered in the design and the operation of these machines. In this paper, I present calculated impact-parameter-dependent probabilities and cross sections for muon capture from vacuum production in collisions of relativistic heavy ions by solving the time-dependent Dirac equation in unrestricted three-dimensional space using lattice-collocation techniques. Calculations are performed for muonpair production with capture into the K-shell in collisions of {sup 197}Au + {sup 197}Au at collider kinetic energies of 2 GeV per nucleon.
Sigmoidal activation of proportional integral control applied to water management

A conventional proportional integral ~PI! controller is modified with a nonlinear activation function ~sigmoid function! applied directly to the controller output in order to improve the stability and target fidelity of the system response to large variational inputs in both state and internal controller gain variables. The controller is implemented in a simulated water management role applied to a major subregional pumping station between Lake Okeechobee, the Loxahatchee National Wildlife Refuge ~WCA1!, and the West Palm Beach supply canal ~C51! in the South Florida geographic region. The simulation consists of an integrated hydrological numerical model implemented in the Regional Simulation Model ~RSM!, which is currently under development at the South Florida Water Management District. Analysis of the modified controller in the Laplace domain establishes the expected control behavior, and subsequent results of the simulation for the conventional PI and the sigmoid modified controller are presented and compared. The modified controller achieves significant improvement in stability while simultaneously reducing the control signal energy.
Current contrast during hypothalamic self-stimulation

Hypothalamic self-stimulation rates of six rats were measured under varying combinations of the current intensities of the reinforcing and continuous background stimuli at the same hypothalamic locus. Response rate increased with intensity of reinforcement, up to a point and then remained constant. Reductions in response rate were associated with increasing background current. A second experiment demonstrated that locomotor behavior increased with increasing background current during self-stimulation sessions. Results suggest that background stimulation elicited responses Which were incompatible with operan t responding.
A multimodal approach to time-invariant scene retrieval from single overhead image

We investigate a practical problem of time-invariant scene retrieval from single airport overhead image. A multimodal approach is developed to solving for the problem, in which an efficient method using image modality data is developed for time-specific object detection, and a method using graphics modality data is developed for removal of the detected objects. Theoretical analyses and experimental evaluations show the efficiency and the effectiveness of the approach.
Nebivolol: A third-generation β-blocker for hypertension

Abstract Background: Nebivolol is a third-generation β 1 -selective β-blocker that is approved for the treatment of hypertension. Objective: This article reviews the clinical pharmacology of nebivolol and its efficacy and safety profile in clinical studies of hypertension (the US Food and Drug Administration-approved indication) and heart failure (off-label use). Methods: Pertinent articles were identified through searches of MEDLINE and Current Contents from 1966 through December 15, 2008, using the terms nebivolol, drug interaction, pharmacokinetics, and pharmacology . The reference lists of the identified publications were reviewed for additional references. Abstracts presented at meetings of the American Heart Association and the American Society of Hypertension from 2006 through 2008 were also reviewed. All human clinical trials were included, regardless of design. Results: Twelve published clinical trials were identified that evaluated the use of nebivolol in the management of hypertension; 1 was placebo controlled, 1 was placebo and active controlled, and 10 involved direct comparisons with other antihypertensive agents. Nebivolol was reported to be as effective in lowering blood pressure (BP) as other β-blockers (atenolol and bisoprolol), angiotensin-converting enzyme inhibitors (lisinopril and enalapril), the angiotensin-receptor blocker telmisartan, and calcium channel blockers (nifedipine and amlodipine). No published studies were identified that evaluated the effect of nebivolol on long-term cardiovascular outcomes. In data from a study in heart failure, nebivolol was associated with a 14% reduction in all-cause mortality and cardiovascular hospitalization at 12 months ( P Conclusions: Nebivolol is a cardioselective β-blocker that has been reported to be efficacious and well tolerated for achieving BP control in patients with hypertension. Preliminary evidence suggests a potential for reduced mortality in patients with heart failure.
A three-parameter fast Givens QR algorithm for superscalar processors

We present a three parameter fast Givens QR algorithm that exploits parallelism to improve performance on superscalar processors. We provide a selection of parameter values for which the new algorithm reduces to the standard algorithm, but show that non-standard values minimize the number of cache misses, memory references and pipeline stalls. Using a tractable model of a superscalar machine architecture, we derive rules for estimating the optimal combination of parameter values. Applying these rules, we observe a speedup over the standard algorithm of 2.4 on the Intel Pentium Pro system, 2.0 on a single thin POWER2 processor of the IBM SP2, 1.6 on a single wide POWER2 processor of the IBM SP2, and 4.2 on a single R8000 processor of the SGI POWER Challenge XL.
Photoinactivation of Superoxide Synthases of the Plasma Membrane from Rose (Rosa damascena Mill.) Cells

The UVC-induced synthesis of hydrogen peroxide (H2O2) by cultured rose (Rosa damascena Mill, cv Gloire de Guilan) cells is inhibited by broad-band radiation containing UVA, UVB and blue wavelengths. In order to understand the basis for this inhibition, we tested the effects of broad-band radiation and of monochromatic radiation on NADH- and NADPH-dependent O2- synthases of purified plasma membranes. Both activities were inhibited by wavelengths from 254 to 435 nm, with the NADPH-dependent enzyme being more sensitive than the NADH-dependent enzyme. Incubation in the presence of flavin adenine dinucleotide had a small but significant ameliorative effect on the inhibition of the O2- synthase activities of plasma membranes by 300 nm radiation. The data support the hypothesis that the NADH- and NADPH-dependent activities are catalyzed by different enzymes. The NADPH-dependent activity, but not the NADH-dependent activity, was sufficiently sensitive to account for the inhibition of H2O2 synthesis by the broad-band radiation.
The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation

Many studies have implicated the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors in regulating cardiac substrate metabolism and ATP generation. Recently, evidence from a variety of cell culture and organ systems has implicated ubiquitin and small ubiquitin-like modifier (SUMO) conjugation as post-translational modifications that regulate the activity of PPAR transcription factors and their coreceptors/coactivators. Here we introduce the ubiquitin and SUMO conjugation systems and extensively review how they have been shown to regulate all three PPAR isoforms (PPARα, PPARβ/δ, and PPARγ) in addition to the retinoid X receptor and PPARγ coactivator-1α subunits of the larger PPAR transcription factor complex. We then present how the specific ubiquitin (E3) ligases have been implicated and review emerging evidence that post-translational modifications of PPARs with ubiquitin and/or SUMO may play a role in cardiac disease. Because PPAR activity is perturbed in a variety of forms of heart disease and specific proteins regulate this process (E3 ligases), this may be a fruitful area of investigation with respect to finding new therapeutic targets.
A haemodynamic predictor of intraluminal thrombus formation in abdominal aortic aneurysms

Intraluminal thrombus (ILT) is present in over 75% of all abdominal aortic aneurysms (AAAs) and probably contributes to the complex biomechanics and pathobiology of these lesions. A reliable predictor of thrombus formation in enlarging lesions could thereby aid clinicians in treatment planning. The primary goal of this work was to identify a new phenomenological metric having clinical utility that is motivated by the hypothesis that two basic haemodynamic features must coincide spatially and temporally to promote the formation of a thrombus on an intact endothelium—platelets must be activated within a shear flow and then be presented to a susceptible endothelium. Towards this end, we propose a new thrombus formation potential (TFP) that combines information on the flow-induced shear history experienced by blood-borne particles that come in close proximity to the endothelium with information on both the time-averaged wall shear stress (WSS) and the oscillatory shear index (OSI) that locally affect the endothelial mechanobiology. To illustrate the possible utility of this new metric, we show computational results for 10 carotid arteries from five patients where regions of low WSS and high OSI tend not to be presented with activated platelets (i.e. they have a low TFP), consistent with the thrombo-resistance of the healthy carotid despite its complex haemodynamics. Conversely, we show results for three patients that high TFP co-localizes with regions of observed thin thrombus in AAAs, which contrasts with findings of low TFP for the abdominal aorta of three healthy subjects. We submit that these promising results suggest the need for further consideration of the TFP, or a similar combined metric, as a potentially useful clinical predictor of the possible formation of ILT in AAAs.
Tubular carcinoids of the appendix: the CK7/CK20 immunophenotype can be a diagnostic pitfall

Aims Tubular carcinoid is a rare variant of appendiceal well-differentiated neuroendocrine tumour. Although considered benign lesions, the small infiltrating tubules that characterise the tumour may raise concern for metastatic adenocarcinoma. To our knowledge, the cytokeratin 7 (CK7)/cytokeratin 20 (CK20) expression profile of these neoplasms remains unexplored. Methods The authors characterised the CK7/CK20 immunophenotype and Ki-67 expression of the eight available tubular carcinoids seen at their institution from 1991 to 2011. Results CK7 and CK20 staining was variable, ranging from none to focal staining for either or both CK7 and CK20, to diffuse expression of CK7 or CK20. Conclusions The CK7/CK20 expression profile is of limited value when the differential diagnosis includes primary tubular carcinoid and well-differentiated metastatic adenocarcinoma. In such cases, careful attention to the location of the neoplasm, mitotic count and presence or absence of an associated classic carcinoid component are more useful for arriving at the correct diagnosis.
A systems biology approach to understanding atherosclerosis.

Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large‐scale measurements ( e.g . transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems‐level studies of the disease.
Hyperthermic Treatment of Intraocular Tumors

• A 5.8-gigahertz (GHz) ophthalmic microwave applicator was used to treat choroidal melanoma (Greene strain) in rabbits. High-frequency electromagnetic radiation provides a favorable dose distribution to induce local hyperthermia in the treatment of intraocular tumors. Heating of the neoplasm, while sparing normal ocular structures, is best accomplished by a transscleral approach. A hyperthermia plaque is placed on the sclera at the base of the intraocular tumor. Contact (resistive) heating and electromagnetic radiation (radiofrequency and microwave) are best suited to a plaque technique. The advantages of electromagnetic heat induction, as compared with contact heating, are twofold: the depth of hyperthermic penetration can be modulated by frequency selection, and the tissues with low water content (sclera) remain relatively unaffected by microwaves. The 5.8-GHz ophthalmic microwave applicator satisfies the requirements for local hyperthermic treatment of intraocular tumors.
Strategy-proof, efficient, and nonbossy quota allocations

We consider the problem of designing a mechanism to allocate objects to agents when each agent has a quota that must be filled exactly. Agents are assumed to have responsive preferences over items. We show that the only strategy-proof, Pareto optimal, and nonbossy mechanisms are sequential dictatorships. We also show that the only strategy-proof, Pareto optimal, nonbossy, and neutral mechanisms are serial dictatorships. Since these negative results hold for responsive preferences, they hold for more general preferences as well.
Hyperparasitism by an exotic autoparasitoid: secondary host selection and the window of vulnerability of conspecific and native heterospecific hosts

Encarsia transvenais an ‘autoparasitoid’ in the hymenopteran family Aphelinidae. In this species, female eggs are laid in whitefly nymphs. Male eggs are laid externally on immature parasitoids enclosed within the whitefly integument, either their own species, or other primary parasitoids. We explored parasitism by E. transvenaof conspecific female immatures and those of a native primary parasitoid, Eretmocerus eremicus, in laboratory experiments. In the first experiment, female E. transvenawere offered different combinations of two stages of E. transvena(late larvae ‐ prepupae (ET2), and early pupae (ET3)), and one stage of E. eremicus (prepupae ‐ early pupae (EE2)) in paired choice tests. The results indicated very little parasitism of ET3 relative to the host it was paired with, either EE2 or ET2. However, when EE2 was offered with ET2, there was no statistically significant difference in parasitism. In a no-choice experiment in which oviposition patterns and male progeny development were examined in four stages of both species of wasp, clear differences were observed between the host species. Only one stage of E. transvena (ET2) was parasitized and supported development of male E. transvena to any significant degree. In contrast, in E. eremicus, EE2, EE3 (red-eyed pupae), and EE4 (late pupae) were all parasitized, and male E. transvenaemerged from all three stages, although fewer males emerged from EE4. In both species, wasp larvae that were still enclosed within the wet whitefly remains (ET1 and EE1) were parasitized at a very low rate. Lastly, an experiment that determined the length of the later developmental stages of E. transvenaand E. eremicussuggested that the duration of the period in which E. transvena is susceptible to parasitism by conspecific females is less than half the period of susceptibility of E. eremicus. These results taken together suggest the potential for interference of E. eremicus by E. transvena, but other factors not examined here may also influence the outcome of interactions in the field.
Part 1: Thinking Out of the Pro-Verbal Box.

Abstract As the World Wide Web and other visual media gain prominence in students’ lives, we, as teachers of composition, have to re-evaluate our strict adherence to the verbal medium. If our classrooms focus on a single mode of representation—the verbal—then the concurrent implication is that only one voice deserves to be heard. In such a classroom, students will not be able to recognize that verbal forms and visual forms—or better yet their combination—carry an equal degree of complexity, representative richness, and rhetorical power. Basing composition almost exclusively on verbal instruction counters the very nature of literacy education, because our current verbal-based education system produces illiterates in our highly visual and multimodal modern society. Drawing on composition scholarship published in three major composition journals, this article demonstrates composition’s verbal bias, argues that this bias is both politically and rhetorically suspect, and calls for a composition pedagogy that integrates verbal instruction with visual instruction.
Diverse convergent evidence in the genetic analysis of complex disease: coordinating omic, informatic, and experimental evidence to better identify and validate risk factors

In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false negative and false positive conclusions, as well as providing broad information for directing future research. The Diverse Convergent Evidence approach (DiCE) we propose integrates information from multiple sources (omics, informatics, and laboratory experiments) to estimate the strength of the available corroborating evidence supporting a given association. This process is designed to yield an evidence metric that has utility when etiologic heterogeneity, variable risk factor frequencies, and a variety of observational data imperfections might lead to false conclusions. We provide proof of principle examples in which DiCE identified strong evidence for associations that have established biological importance, when standard validation methods alone did not provide support. If used as an adjunct to standard validation methods this approach can leverage multiple distinct data types to improve genetic risk factor discovery/validation, promote effective science communication, and guide future research directions.
Keratin sponge/hydrogel II: Active agent delivery

Keratin sponge/hydrogels, described in Part I as the products of oxidation and reduction hydrolysis of fine and coarse wool fibers, were examined as excipient-platforms for the delivery of riboflav...
A real-time semi-quantitative RT–PCR assay demonstrates that the pilE sequence dictates the frequency and characteristics of pilin antigenic variation in Neisseria gonorrhoeae

A semi-quantitative real-time RT–PCR assay was designed to measure gonococcal pilin antigenicvariation (SQ-PCR Av assay). This assay employs 17 hybridization probe sets that quantitate subpopulations of pilin transcripts carrying different silent pilin copy sequences and one set that detects total pilE transcript levels. Mixtures of a DNA standard carrying the silent copy being detected and a clone encoding the starting pilE sequence, which is the majority pilE template, provided amplification curves that closely matched the experimental data and allowed an analysis of the contribution of different silent pilin copies to variation. The SQ-PCR Av assay was verified using DNA sequence analysis to demonstrate that this methodology allowed an accurate analysis of pilin variation. Both assays showed that with a specific starting pilE sequence, only a subset of the silent pilin copies recombine into pilE at a detectable level, and that this limited subset was reproducibly detected in replicate cultures. When an isogenic pilE sequence variant was examined using both assays, a new subset of silent copy sequences were detected recombining into pilE and the overall frequency of variation was increased. Thus, the parental pilE sequence influences the frequency of variation and the repertoire of pilin variants produced.