cssi/SciSciGPT-SciSciNet huggingface dataset:
Protein folding in the ER

The endoplasmic reticulum (ER) is a major protein folding compartment for secreted, plasma membrane and organelle proteins. Each of these newly-synthesized polypeptides folds in a deterministic process, affected by the unique conditions that exist in the ER. An understanding of protein folding in the ER is a fundamental biomolecular challenge at two levels. The first level addresses how the amino acid sequence programs that polypeptide to efficiently arrive at a particular fold out of a multitude of alternatives, and how different sequences obtain similar folds. At the second level are the issues introduced by folding not in the cytosol, but in the ER, including the risk of aggregation in a molecularly crowded environment, accommodation of post-translational modifications and the compatibility with subsequent intracellular trafficking. This review discusses both the physicochemical and cell biological constraints of folding, which are the challenges that the ER molecular chaperones help overcome.
EFFECTIVENESS OF ALUM IN A WEEDY, SHALLOW LAKE

: An alum treatment in Long Lake (mean depth, 2 m) in 1980 has been effective at controlling internal loading of phosphorus for four years. The fifth summer after treatment, the lake returned to its pro-treatment state. Lake P content decreased from a summer average of 65 μg/L during 1976–1978 to about 30 μg/L during four years following treatment. In 1985, summer P content was 61 μg/L. Algal abundance, species composition, and transparency have responded proportionately with P. Alum effectiveness apparently declined because the floe layer tended to sink and become dispersed at a deeper level in the sediment, as well as become covered with new, P-rich sediment. Iron-reduction may be the principal mechanism for internal P loading, although the lake is unstratified and anoxia is usually not pronounced.
Targeted inhibition of gene expression of pancreatitis-associated proteins exacerbates the severity of acute pancreatitis in rats.

Background: Pancreatitis‐associated protein (PAP) is a secretory protein not normally expressed in healthy pancreas but highly induced during acute pancreatitis. While PAP has been shown to be anti‐bacterial and anti‐apoptotic in vitro, its definitive biological function in vivo is not clear. Methods: To elucidate the function of PAP, antisense oligodeoxyribonucleotides (AS‐PAP) targeting all three isoforms of PAP were administered via intrapancreatic injections (5 mg kg −1 day −1 , 2 days) to rats prior to induction of pancreatitis. Results: Severity of pancreatitis and cytokine gene expression in peripheral blood mononuclear cells (PBMC) were evaluated. Administration of AS‐PAP, but not the scrambled oligodeoxyribonucleotide (SC‐PAP) control, reduced pancreatitis‐induced PAP expression by 55.2 ± 6.4%, 44.0 ± 8.9%, and 38.9 ± 10.7% for PAP isoforms I, II, and III, respectively, compared to saline‐treated controls (P < 0.05 for all). Inhibition of PAP expression significantly worsened pancreatitis: serum ...
KCNQ1 Expression Modulates Herg Current by Removing Inactivation

Experimental evidence indicates that KCNQ1 and HERG potassium channels can interact directly when co-expressed in heterologous cells. Recently we demonstrated that transient expression of wild type human KCNQ1 into cells stably expressing human HERG evokes current with ∼3-fold larger amplitude than the sum of individual HERG and KCNQ1 currents as well as unique gating and pharmacological properties. To further prove that this phenomenon is not merely the addition of separate currents, we transfected HERG stable cells with the non-functional, but trafficking competent KCNQ1-V254M mutant. Whole-cell currents were measured at the end of a 2s pulse from −80 to +50mV and at peak tail current (TC) recorded at 50mV. KCNQ1-V254M expression did not change HERG current amplitude (HERG+DsRed: +50mV= 4.9±0.6 and TC=13.1±1.2 pA/pF; HERG+KCNQ1-V254M: +50mV= 3.9±0.5 and TC=11.61±1.5 pA/pF) but it depolarized the voltage dependence of activation (6.6±1.5 mV, P<0.001) and induced sensitivity to the KCNQ1-specific blocker HMR-1556 (10μM; HERG+DsRed control TC=14.4±2.0; +HMR-1556 TC=13.8±2.0 pA/pF;. HERG+KCNQ1-V254M control TC=11.3±1.6; +HMR-1556 TC=5.4±1.1 pA/pF, P<0.05). Further, co-expression of wild type KCNQ1 and HERG channels yields large currents with no inactivation suggesting that KCNQ1 acts by eliminating or attenuating HERG inactivation. This mechanism was investigated by evaluating the sensitivity of HERG-KCNQ1 channels to VU0405601, a compound that increases HERG currents by impairing inactivation. VU0405601 (20μM) increased HERG current amplitude (control: +50 mV=3.3±0.6 and TC=11.0±1.6 pA/pF; +VU0405601: +50 mV=21.4±3.2 and TC=13.2±1.8 pA/pF) but had no effect on HERG-KCNQ1 currents (control: +50mV=36.1±7.2 and TC=12.0±1.5 pA/pF; +VU0405601: +50 mV=34.1±7.0 and TC=12.2±1.6 pA/pF). Our results demonstrate that KCNQ1 functionally modulates HERG through direct heteromultimerization and suggest that the mechanism involves removal of HERG inactivation.
Influence of Sequence Heterochrony on Hadrosaurid Dinosaur Postcranial Development

A goal of modern dinosaur paleobiology is to synthesize the understanding of dinosaurian development and phylogeny. This study explores the Iguanodontia, one clade that includes several taxa for which growth series are preserved. It is hypothesized that analysis of growth series of iguanodontian taxa will reveal important developmental differences at play during the evolution of the clade. Such differences can reflect the impact of sequence heterochrony on iguanodontian evolution. Data were collected on the growth stages of the postcranial skeleton of a basal iguanodontian, Tenontosaurus; a lambeosaurine hadrosaurid, Hypacrosaurus; and two hadrosaurine hadrosaurids, Brachylophosaurus and Maiasaura to test the hypothesis. The event-pairing method provides a framework for the comparison of ontogenetic sequences among related taxa to detect significant evolutionary changes in developmental sequence. Significant developmental events are identified for the group and then the relative timings of those events in the developmental sequence are compared among the different species. Synapomorphic characters of Hadrosauridae, including the development of a prominent biceps tubercle on the coracoid, appear to be the result of changes in the developmental sequences of hadrosaurid taxa compared to basal iguanodontian taxa. This analysis also recognizes the developmental sequence differences that result in the development of the robust appendicular elements that characterize Lambeosaurinae. This comparative methodology shows that the development of characters such as the well developed supraacetabular process of the ilium results from the early onset of the development of those characters in the lambeosaurine hadrosaurid Hypacrosaurus compared to the hadrosaurines Brachylophosaurus and Maiasaura. Anat Rec, 292:1427–1441, 2009. © 2009 Wiley-Liss, Inc.
ERKs activation and calcium signaling are both required for VEGF induction by vanadium in mouse epidermal Cl41 cells.

The previous studies have demonstrated that vanadium exposure can cause a variety of biological effects. However, the mechanisms involved in the biological effects caused by vanadium are not well understood. Our previous studies have shown that exposure of mouse epidermal Cl 41 cells to vanadate stimulated the phosphorylation of both ERKs and p38K, and calcium signaling leading NFAT activation. In view of the evidence that ERKs and p38 kinase contribute to VEGF induction, we investigated in the present study the potential roles of ERKs, p38K, and calcium signaling in VEGF induction caused by vanadium exposure. Exposure of Cl 41 cells to vanadium led to VEGF induction in both time- and dose-dependent manners. Pre-treatment of Cl 41 cells with PD98059, an inhibitor of MEK1/2-ERKs pathway, but not SB202190, an inhibitor for p38K pathway, resulted in a dramatic inhibition of VEGF induction by vanadium. More interesting, pre-treatment of Cl 41 cells with intracellular calcium chelator, but not calcium channel blocker, resulted in a dramatic decrease in VEGF induction by vanadium. However, both PI-3K inhibitors and overexpression of Δp85, a dominant negative PI-3K mutant, resulted in only a marginal decrease in VEGF induction by vanadium. Moreover, mTOR, as a downstream molecule of PI-3K, did not attribute to VEGF induction by vanadium because rapamycin pre-treatment did not show any inhibitory effect on VEGF induction. These results indicate that ERKs and intracellular stored calcium release play a critical role in VEGF induction by vanadium. PI-3K is partially involved in VEGF induction by vanadium, while p38K and mTOR are not involved. Those results will help us to understand the molecular mechanisms involved in vanadium-induced biological effects.
Fast global optimization of curvature

Two challenges in computer vision are to accommodate noisy data and missing data. Many problems in computer vision, such as segmentation, filtering, stereo, reconstruction, inpainting and optical flow seek solutions that match the data while satisfying an additional regularization, such as total variation or boundary length. A regularization which has received less attention is to minimize the curvature of the solution. One reason why this regularization has received less attention is due to the difficulty in finding an optimal solution to this image model, since many existing methods are complicated, slow and/or provide a suboptimal solution. Following the recent progress of Schoenemann et al. [28], we provide a simple formulation of curvature regularization which admits a fast optimization which gives globally optimal solutions in practice. We demonstrate the effectiveness of this method by applying this curvature regularization to image segmentation.
Hydrophobic Encapsulation of Hydrocarbon Gases

[reaction: see text] Encapsulation data for hydrophobic hydrocarbon gases within a water-soluble hemicarcerand in aqueous solution are reported. It is concluded that hydrophobic interactions serve as the primary driving force for the encapsulation, which can be used for the design of gas-separating polymers with intrinsic inner cavities.
Comparison of airborne measured and calculated spectral actinic flux and derived photolysis frequencies during the PEM Tropics B mission

[1] Scanning actinic flux spectroradiometer (SAFS) instruments were deployed on the National Aeronautics and Space Administration (NASA) DC-8 and P-3B research aircraft for the Pacific Exploratory Mission in the Tropical Pacific (PEM Tropics B mission). The SAFS instruments measured the wavelength-dependent downwelling and upwelling actinic flux from 282 to 420 nm. From the actinic flux spectra, photolysis frequencies of a number of molecules were calculated. Flight tracks during the PEM Tropics B mission varied in altitude from the surface up to 12 km, with much time spent above, below, and among broken and scattered clouds. Comparisons of the measured photolysis frequencies to the photolysis frequencies calculated with the National Center for Atmospheric Research (NCAR) tropospheric ultraviolet visible (TUV) radiative transfer model, assuming clear skies, demonstrate some expected differences in this complex radiation environment, while in general the agreement between the measurements and the model is within 15%. Differences between the measurements and the model are expected in and around clouds, because the radiation model is not equipped to input broken and scattered cloud effects, except on an individual case-by-case basis. The differences in the composite mean ratio of SAFS measurement to TUV model for total photolysis frequencies vary from 6% to 18% for jNO2 and from 6% to 11% for jO(1D) for both aircraft. The differences between the measurements and the models represent the accuracy that can be expected when using photolysis frequencies from clear-sky radiative transfer modeling in regional and global atmospheric chemistry models for regions with broken and scattered clouds in the troposphere.
Cytoplasts from cytotoxic t lymphocytes are resistant to perforin-mediated lysis

Cytotoxic T lymphocytes (CTL) contain a potent cytolytic pore-forming protein (PFP, perforin or cytolysin) localized in their cytoplasmic granules. In the presence of calcium, perforin lyses a variety of target cells (TC) non-specifically. CTL, however, are generally resistant to the lytic effect of perforin. In this work, cytoplasts from CTL and susceptible TC were made by centrifuging cells on a Ficoll density gradient in the presence of cytochalasin B. Characterization by electron microscopy and a serine esterase assay established that both CTL and TC cytoplasts were completely devoid of nuclei and CTL cytoplasts contained essentially no granules. CTL cytoplasts are just as resistant to perforin-mediated lysis as the intact CTL, and both TC and their corresponding cytoplasts are very sensitive to lysis. Furthermore, CTL cytoplasts are less effective than TC cytoplasts in inhibiting hemolysis, a property shared by the respective intact cells. These results indicate that soluble granular components do not confer resistance on CTL, and suggest that the protective agent(s) acts by impeding perforin binding to the CTL membrane.
Effect of microstructure on load-carrying and energy-dissipation capacities of UHPC

Abstract The load-carrying and energy dissipation capacities of ultra-high performance concrete (UHPC) under dynamic loading are evaluated in relation to microstructure composition at strain rates on the order of 10 5 s − 1 and pressures of up to 10 GPa. Analysis focuses on deformation and failure mechanisms at the mesostructural level. A cohesive finite element framework that allows explicit account of constituent phases, interfaces, and fracture is used. Three modes of energy dissipation are tracked, i.e., inelastic deformation, distributed cracking, and interfacial friction. Simulations are carried out over a range of volume fractions of constituent phases. Results show that (1) volume fractions of the constituents have more influence on the energy-dissipation than load-carrying capacity, (2) inelastic deformation is the source of over 70% of the energy dissipation, and (3) the presence of porosity changes the role of fibers in the dissipation process. Microstructure–behavior relations are established to facilitate materials design for target-specific applications.
Comparison Between Model Simulations and Field Results for In‐Situ Biorestoration of Chlorinated Aliphatics: Part 1. Biostimulation of Methanotrophic Bacteria

A nonsteady-state model is presented for the in-situ biostimulation of a microbial population in saturated porous media. The model includes basic processes of microbial growth, utilization of electron donor and acceptor, advective transport, dispersion, and sorption in porous media. Model simulations are compared with results from a series of controlled field experiments at the Moffett Naval Air Station, where the growth of an indigenous population of methane-utilizing bacteria (methanotrophs) was stimulated by the controlled addition of dissolved methane and oxygen (DO) into a semiconfined aquifer. Simulations provide good matches to the observed transient uptake of methane and DO, demonstrating that the observed response resulted from the growth of methanotrophs in the test zone. Simulations duplicate results from alternate pulsed addition of methane (electron donor) and oxygen (electron acceptor), used as a means for distributing microbial growth throughout the test zone. The model permits estimation of changes in microbial population distribution at various stages of the two-year experiment. Temporal changes in model-fitted kinetic parameters indicate that the microbial population evolved to one that more effectively utilized the methane at lower concentrations. These analyses demonstrate that a relatively simple model, which includes basic microbial and transport processes, can be of use in the design and evaluation of in-situ biotreatment processes. The model user, however, must provide judgment in the selection of appropriate input parameters, as well as being aware of model limitations.
Small Froude number asymptotics in two-dimensional two-phase flows

A nonlinear wave equation is derived describing the behavior of gas- and liquid-fluidized beds in the small Froude number regime. It represents a two-dimensional perturbation of the Korteweg\char21{}de Vries equation and is shown to constitute a valid approximation of the original system. While greatly simplifying the analytical and numerical investigation of two-phase flow in fluidized beds, it also leads to the conclusion that the underlying model does not significantly discriminate between gas- and liquid-fluidized beds near the stability limit. An amplitude equation is derived governing the growth and stability of solitary plane waves. The results are linked to those obtained by previous nonapproximative analyses. It is expected that this analysis is applicable to other multiphase and traffic flow models due to the similarity in the governing equations and the completeness of the reduced wave equation.
Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus.

Aspergillus fumigatus causes life-threatening infections in patients with qualitative and quantitative defects in phagocytic function. Here, we examined the contribution of Toll-like receptor (TLR)-2, TLR4, the adapter protein MyD88, and CD14 to signaling in response to the three forms of A. fumigatus encountered during human disease: resting conidia (RC), swollen conidia (SC), and hyphae (H). Compared with elicited peritoneal macrophages obtained from wild-type and heterozygous mice, TLR2−/− and MyD88−/− macrophages produced significantly less tumor necrosis factor-α (TNFα) followingA. fumigatus stimulation. In contrast, following stimulation with RC, SC, and H, TLR4−/− and CD14−/− macrophages exhibited no defects in tumor necrosis factor-α release. TLR2−/−, TLR4−/−, MyD88−/−, and CD14−/− macrophages bound similar numbers of RC and SC compared with wild-type macrophages. RC, SC, and H stimulated greater activation of a nuclear factor κ B (NFκB)-dependent reporter gene and greater release of tumor necrosis factor-α from the human monocytic THP-1 cell line stably transfected with CD14 compared with control cells stably transfected with empty vector. A. fumigatus stimulated NFκB-dependent reporter gene activity in the human embryonic kidney cell line, HEK293, only if the cells were transfected with TLR2. Moreover, activity increased when TLR2 and CD14 were co-transfected. Taken together, these data suggest that optimal signaling responses to A. fumigatus require TLR2 in both mouse and human cells. In contrast, a role for CD14 was found only in the human cells. MyD88 acts as a central adapter protein mediating signaling responses following stimulation with RC, SC, and H.
Molecular basis of a novel oncogenic mutation in GNAO1

Heterotrimeric G proteins are molecular switches that control signal transduction, and their dysregulation can promote oncogenesis. Somatic mutations in GNAS, GNAI2 and GNAQ genes induce oncogenesis by rendering Gα subunits constitutively activated. Recently the first somatic mutation, arginine(243) → histidine (R243H) in the GNAO1 (Gαo) gene was identified in breast carcinomas and shown to promote oncogenic transformation when introduced into cells. Here, we provide the molecular basis for the oncogenic properties of the Gαo R243H mutant. Using limited proteolysis assays, nucleotide-binding assays, and single-turnover and steady-state GTPase assays, we demonstrate that the oncogenic R234H mutation renders Gαo constitutively active by accelerating the rate of nucleotide exchange; however, this mutation does not affect Gαo's ability to become deactivated by GTPase-activating proteins (GAPs) or by its intrinsic GTPase activity. This mechanism differs from that of previously reported oncogenic mutations that impair GTPase activity and GAP sensitivity without affecting nucleotide exchange. The constitutively active Gαo R243H mutant also enhances Src-STAT3 signaling in NIH-3T3 cells, a pathway previously shown to be directly triggered by active Gαo proteins to promote cellular transformation. Based on structural analyses, we propose that the enhanced rate of nucleotide exchange in Gαo R243H results from loss of the highly conserved electrostatic interaction of R243 with E43, located in the in the P-loop that represents the binding site for the α- and β-phosphates of the nucleotide. We conclude that the novel R234H mutation imparts oncogenic properties to Gαo by accelerating nucleotide exchange and rendering it constitutively active, thereby enhancing signaling pathways, for example, src-STAT3, responsible for neoplastic transformation.
Professional supportive caring for children and adolescents with chronic neurobiological disorders.

For serious chronic biological disorders in children and adolescents, the focus of nonpharmacological therapy by health care professionals should be on supportive caring.
A Unified Total Synthesis of the Immunomodulators (−)-Rapamycin and (−)-27-Demethoxyrapamycin: Construction of the C(21−42) Perimeters

A total synthesis of the potent, naturally occurring immunomodulators (−)-rapamycin (1) and (−)-27-demethoxyrapamycin (2) has been achieved via a unified, highly convergent synthetic strategy. Both targets were elaborated from common building blocks A−E, the latter available in decagram quantities. Herein we present the construction of the ABC northern perimeters of 1 and 2. The accompanying paper describes the preparation of the southern perimeter DE segment, triene and deprotection model studies, and completion of the synthetic venture. Notable features of the approach include stereoselective σ-bond constructions of trisubstituted olefins and the union of advanced intermediates via efficient dithiane couplings.
Effects of methylphenidate on young adults' performance and event-related potentials in a vigilance and a paired-associates learning test.

Twenty-two normal young men received a counterbalanced and double blind administration of 20 mg methylphenidate and placebo. Two tasks were administered in counterbalanced order: an uninterrupted 45-min vigilance test and a paired-associates learning test. As previously reported, under placebo, accuracy and speed decreased monotonically over the course of the vigil. This degradation of performance was significantly reduced by the stimulant drug. Event-related potentials (ERPs) were derived for correctly detected targets and nontargets. The most salient pharmacologic effects involved a late positive wave (P464) identified as P3b. Methylphenidate reversed or reduced the decrease in amplitude and increase in latency of P464 present over phases of the placebo session. The results suggest that the stimulant-induced improvement in performance may be mediated by enhancement of evaluation processes. In the paired-associates test there were no pharmacologic effects. Instead there was an unexpected, pronounced improvement in learning in the second session, irrespective of the substance administered. However, the ERP evoked by the “stimulus” cue of each pair was systematically related to the achievement of learning criteria. A late positive was identified as P3b (P555) increased significantly in amplitude following the attainment of learning. There were no amplitude changes among ERPs evoked in the early post-criterion, late post-criterion, or overlearning “phases.” Nor were there amplitude changes between early and late pre-criterion categories. Thus, ERP amplitude displayed a binary association with the achievement of learning.
Radio-luminescence and absence of trapping defects in Nd-doped YAG single crystals

Abstract Nd-doped yttrium aluminum garnet (NdYAG) is an important solid-state laser material due to Nd 3+ interconfigurational transitions which result in intense infrared emission. This work shows that NdYAG crystals also emit visible radio-luminescence in response to exposure to beta particles due to other Nd 3+ interconfigurational 4f–4f transitions. Additionally, thermo-luminescence spectroscopy reveals the absence of traps in NdYAG, making it a potentially superior scintillation material. The fact that Nd is present in only one valence state in NdYAG leads to charge balance and results in the suppression of defect formation. This finding reveals fundamental understanding regarding defect formation in ionic crystals.
Higher-order explicit methods for laser-plasma interactions

The evolution of a short, intense laser pulse propagating in an underdense plasma is of particular interest for laser-plasma accelerator physics and, in some circumstances, is well-modeled by the cold Maxwell-fluid equations. Solving this system using conventional second-order explicit methods in a three-dimensional simulation over experimentally-relevant configurations is prohibitively expensive. This motivated a search for more efficient numerical methods to solve the fluid equations. Explicit methods tend to suffer from stability constraints which couple the maximum allowable time step to the spatial grid size. If the dynamics of the system evolves on a time scale much larger than the constrained time step, an explicit method would require many more update cycles than is physically necessary. In these circumstances implicit methods, which tend to be unconditionally stable, may be attractive. But when physical situations (e.g., Raman processes) need to resolve the fast dynamics, implicit methods are unlikely to exhibit much improvement over explicit methods. Thus, we look for higher-order explicit methods in space that would allow coarser spatial grids and larger time steps. We restrict our discussion to the one-dimensional case and present a comprehensive survey of a wide range of numerical methods to solve the fluid equations, including methods of order two through six in space and two through eight in time. A systematic approach to determine the stability condition is presented using linear stability analysis of numerical dispersion relations. Three higher-order methods are implemented to show their behavior, in terms of numerical stability and energy conservation.
Vaginal Delivery Increases the Risk of Candida Sepsis in Very Low Birth Weight Infants (≤1250g)

Vaginal Delivery Increases the Risk of Candida Sepsis in Very Low Birth Weight Infants (≤1250g)
Few cycle dynamics of multiphoton double ionization.

In intense field ionization, an electron removed from the atomic core oscillates in the combined fields of the laser and the parent ion. This oscillation forces repeated revivals of its spatial correlation with the bound electrons. The total probability of double ionization depends on the number of returns and therefore on the number of optical periods in the laser pulse. We observed the yield of ${\mathrm{Ne}}^{2+}$ relative to ${\mathrm{Ne}}^{+}$ with 12 fs pulses to be clearly less compared to 50 fs pulses in qualitative agreement with our theoretical model.
Exact versus approximate solution of Einstein's equations for rotating neutron stars☆

Abstract A redefined version of Hartle's perturbative method of solving Einstein's equations for rotating massive objects is applied for the investigation of the general relativistic Kepler frequency of a rotating neutron star. From the precise determination of rotating limiting mass neutron star models for seventeen representative neutron matter equations of state we find Kepler frequencies which are systematically larger by ≈ (10–15)% than those obtained from the empirical formula of Haensel and Zdunik. The latter results however can be reproduced from Hartle's method as well by accounting for a small mass uncertainty of the limiting star model of ≲2%. In comparison with an exact numerical solution, Hartle's method is relatively easy to implement and should prove to be a practical tool for testing the compatibility of nuclear equations of state on pulsar periods.
Fast, accurate MOS table model for circuit simulation using an unstructured grid and preserving monotonicity

In this work, we developed a highly memory-efficient, accurate table model that is 10/spl times/+ faster than its analytical counterparts: BSIM3/4 models. Speed derives from linear interpolation; accuracy and memory efficiency result from the unstructured grid founded on a BSP tree for discretizing the device function space. We also describe a methodology invoked during table generation to overcome the non-monotonic device behavior that results from interpolating the unstructured grid; the method preserves both continuity and monotonicity of the device quantities. These table models are now implemented in our production circuit simulator, TISpice. Overall speedups of 1.8/spl times/ to 4.8/spl times/ were observed on suites of industry circuits.
Driver Exposure to Combustion Particles in the U.S. Trucking Industry

A large study of combustion particle exposures for drivers of diesel-powered trucks was conducted in collaboration with an epidemiologic study of lung cancer outcomes for workers in the trucking industry. Three components of diesel exhaust combustion particles (PM 2.5 , elemental carbon, and organic carbon) were measured inside the driver cabs of diesel-powered trucks from 36 different trucking terminals across the United States between 2001 and 2005. In-cab particle exposures for drivers assigned to both short and long distance trips were observed, as well as information on the smoking status of the driver, truck characteristics such as age and model, and weather conditions during the sampling session. This article summarizes these findings and describes the relationship between exhaust particles and various determinants of exposure. The results suggest that in-cab particle exposures are positively related to smoking, ambient particle concentrations, truck age, and open windows, with other significant mo...
The role of high-dose chemotherapy followed by peripheral blood stem cell transplantation for the treatment of multiple myeloma

The management of multiple myeloma has changed significantly over the past 10 years. The results obtained with conventional chemotherapy were disappointing; however the use of high dose therapy (HDT) and stem cell transplantation has significantly improved survival. Autologous, allogeneic and tandem transplantation, along with different conditioning regimens, have been studied in an attempt to optimise and further improve outcomes. This review summarises the role of stem cell transplantation in multiple myeloma. The advent of novel therapies such as thalidomide, lenalidomide and bortezomib have started to redefine the role of peripheral stem cell transplantation, however, further study is needed to better understand how to most effectively use these agents in multiple myeloma in conjunction with HDT.
On-demand single-photon generation using a modular array of parametric downconverters with electro-optic polarization controls

We describe a method for generating single photons on demand by means of a modular array of spontaneous parametric downconverters that are mediated by electro-optic polarization controls. Our scheme allows easy addition of downconverter modules to improve single-photon generation performance while simultaneously further suppressing multiphoton events. We estimate that a single-photon generation probability of over 60% per pulse with a multiphoton probability of 1% is achievable with currently available technology. This on-demand source may significantly improve the performance of quantum key distribution, quantum communication, and quantum computation systems.
Solubilization from skeletal muscle of two components that specifically bind α-bungarotoxin☆

Abstract BuTX ∗∗ binds irreversibly to two components of skeletal muscle, one with apparent molecular weight (by gel filtration) of 550,000 and one of 200,000. Only the former, thought to contain the acetylcholine receptor, is elevated in denervated muscle, about 20-fold at its maximum. After solubilization, these components retain their specific properties.
Primary sarcoma of the pericardium

Abstract A case of primary sarcoma of the pericardium occurring in a 19 year old male patient is presented. The initial manifestations were fever, chest pain and pericardial effusion which appeared to subside concomitantly with the administration of corticosteroids while the tumor mass was increasing in size. There was no reponse to radiotherapy. The diagnosis was established at exploratory thoracotomy, but close adherence of the tumor to the great vessels and the heart allowed only partial removal. The occurrence of a primary malignant tumor of the pericardium should be suspected in a young patient, particularly male, with an unexplained pericardial effusion and an unusual or bizarre configuration of the cardiac silhouette.
Designing and Implementing a Computing Framework for Image-Guided Radiation Therapy Research

Research computing in radiation therapy is transitioning from small-scale computing to large software systems. Accelerator-mounted imaging devices collect multiple images at every treatment fraction, creating datasets of hundreds of images per patient. Compounding this challenge is the fact that software infrastructure upgrades are difficult to manage in academic environments, due to inadequate experience in large-scale software development.
Searching for evidence of curricular effect on the teaching and learning of mathematics: some insights from the LieCal project

Drawing on evidence from the Longitudinal Investigation of the Effect of Curriculum on Algebra Learning (LieCal) Project, issues related to mathematics curriculum reform and student learning are discussed. The LieCal Project was designed to longitudinally investigate the impact of a reform mathematics curriculum called the Connected Mathematics Project (CMP) in the USA on teachers’ teaching and students’ learning. Using a three-level conceptualization of curriculum (intended, implemented, and attained), a variety of evidence from the LieCal Project is presented to show the impact of mathematics curriculum reform on teachers’ teaching and students’ learning. This paper synthesizes findings from the two longitudinal studies spanning 7 years of the LieCal Project both to show the kind of impact curriculum has on teachers’ teaching and students’ learning and to suggest powerful but feasible ways researchers can investigate curriculum effect on both teaching and learning.
DEAD-Box Protein-103 (DP103, Ddx20) Is Essential for Early Embryonic Development and Modulates Ovarian Morphology and Function

The DEAD-box helicase DP103 (Ddx20, Gemin3) is a multifunctional protein that interacts with Epstein-Barr virus nuclear proteins (EBNA2/EBNA3) and is a part of the spliceosomal small nuclear ribonucleoproteins complex. DP103 also aggregates with the micro-RNA machinery complex. We have previously shown that DP103 interacts with the nuclear receptor steroidogenic factor-1 (SF-1, NR5A1), a key regulator of reproductive development, and represses its transcriptional activity. To further explore the physiological function of DP103, we disrupted the corresponding gene in mice. Homozygous Dp103-null mice die early in embryonic development before a four-cell stage. Although heterozygous mice are healthy and fertile, analysis of steroidogenic tissues revealed minor abnormalities in mutant females, including larger ovaries, altered estrous cycle, and reduced basal secretion of ACTH. Our data point to diverse functions of murine DP103, with an obligatory role during early embryonic development and also in modulation of steroidogenesis.
Women in Surgery Residency Programs: Evolving Trends from a National Perspective

Background Similar numbers of men and women are currently graduating from United States (US) medical schools; therefore, surgery residency programs need to attract graduates of both genders. This study compared gender distributions of allopathic US medical graduates (USMG) from academic years 1999-2000 through 2004-2005. In addition, the gender distributions of USMG and international medical graduates (IMG; analyzed separately) entering accredited general surgery (GS) programs and USMG entering other surgical specialty programs were compared across academic years 2000-2001 through 2005-2006. Study Design Data were extracted from the American College of Surgeons Resident Master File and the Association of American Medical Colleges FACTS Website and Data Warehouse. Chi-square statistics compared gender distributions across years for all USMG graduating and applying to GS programs each year between 1999-2000 and 2004-2005 and for USMG and IMG entering training between 2000-2001 and 2005-2006. Results During the study period, the proportion of women increased significantly (p Conclusions The gender gap among USMG entering GS training appears to be closing, concurrent with that of USMG overall during the study period. Surgery programs must continue to recruit and retain women to attract the best and brightest trainees.
DebugAdvisor: a recommender system for debugging

In large software development projects, when a programmer is assigned a bug to fix, she typically spends a lot of time searching (in an ad-hoc manner) for instances from the past where similar bugs have been debugged, analyzed and resolved. Systematic search tools that allow the programmer to express the context of the current bug, and search through diverse data repositories associated with large projects can greatly improve the productivity of debugging This paper presents the design, implementation and experience from such a search tool called DebugAdvisor. The context of a bug includes all the information a programmer has about the bug, including natural language text, textual rendering of core dumps, debugger output etc. Our key insight is to allow the programmer to collate this entire context as a query to search for related information. Thus, DebugAdvisor allows the programmer to search using a fat query, which could be kilobytes of structured and unstructured data describing the contextual information for the current bug. Information retrieval in the presence of fat queries and variegated data repositories, all of which contain a mix of structured and unstructured data is a challenging problem. We present novel ideas to solve this problem. We have deployed DebugAdvisor to over 100 users inside Microsoft. In addition to standard metrics such as precision and recall, we present extensive qualitative and quantitative feedback from our users.
A micromechanical finite element model for linear and damage‐coupled viscoelastic behaviour of asphalt mixture

SUMMARY This study presents a finite element (FE) micromechanical modelling approach for the simulation of linear and damage-coupled viscoelastic behaviour of asphalt mixture. Asphalt mixture is a composite material of graded aggregates bound with mastic (asphalt and fine aggregates). The microstructural model of asphalt mixture incorporates an equivalent lattice network structure whereby intergranular load transfer is simulated through an effective asphalt mastic zone. The finite element model integrates the ABAQUS user material subroutine with continuum elements for the effective asphalt mastic and rigid body elements for each aggregate. A unified approach is proposed using Schapery non-linear viscoelastic model for the rateindependent and rate-dependent damage behaviour. A finite element incremental algorithm with a recursive relationship for three-dimensional (3D) linear and damage-coupled viscoelastic behaviour is developed. This algorithm is used in a 3D user-defined material model for the asphalt mastic to predict global linear and damage-coupled viscoelastic behaviour of asphalt mixture. For linear viscoelastic study, the creep stiffnesses of mastic and asphalt mixture at different temperatures are measured in laboratory. A regression-fitting method is employed to calibrate generalized Maxwell models with Prony series and generate master stiffness curves for mastic and asphalt mixture. A computational model is developed with image analysis of sectioned surface of a test specimen. The viscoelastic prediction of mixture creep stiffness with the calibrated mastic material parameters is compared with mixture master stiffness curve over a reduced time period. In regard to damage-coupled viscoelastic behaviour, cyclic loading responses of linear and rate-independent damage-coupled viscoelastic materials are compared. Effects of particular microstructure parameters on the rate-independent damage-coupled viscoelastic behaviour are also investigated with finite element simulations of asphalt numerical samples. Further study describes loading rate effects on the asphalt viscoelastic properties and rate-dependent damage behaviour. Copyright # 2006 John Wiley & Sons, Ltd.
LONG-TERM PSEUDOMONAS COLONIZATION IN SPINAL CORD INJURY PATIENTS

In a previous study, patients with spinal cord injuries were observed to have a high incidence of colonizaion of the perineum, rectum, and urethra with Pseudomonas. In the current report, 10 men and 10 women with spinal cord injury were studied prospectively during their stay in hospital between June-Dec. 1977 (men) and Jan.-Nov. 1978 (women). Colonization seen in men (9/10 men: 14 episodes) was significantly more frequent than colonization in women (3/10 women: 5 episodes). Pseudomonas persisted in two or three sites for up to 105 days (mean 47 days) and serotyping showed that colonization was constant with one or two serotypes. Initial colonization occurred most frequently in the perineum and/or rectum. Colonization of the perineum was significantly more frequent than colonization of the rectum or urethra in men. Fifteen episodes of bacteriuria occurred only after (or with) colonization of perineum, urethra, and rectum. Rates of urethral colonization with Pseudomonas were higher in patients with external condom catheters than patients not using the external codon catheter. Urethral and perineal colonization usually resulted in colonization of the drainage bags even when these patients did not have significant bacteriuria. These drainage bags may be an important potential source of Pseudomonas for nosocomial infection. These studies indicate that Pseudomonas infections of the urinary tract may be prevented if acquisition of this pathogen in the perineum and/or rectum can be avoided.
Gigabit satellites in distributed supercomputing for global research

This paper will examine the application of the NASA advanced communications technology satellite (ACTS) for implementing a distributed supercomputer global climate model, and in remote observation and control of the Keck telescope in Hawaii.
Correlates of Gay and Lesbian Couples' Relationship Satisfaction and Relationship Dissolution

A sample of committed gay and lesbian cohabiting couples engaged in two conversations after being apart for at least 8 hours: (a) an events of the day conversation and (b) a conflict resolution conversation. Physiological data were collected during the conversations and a videotape record was made. Couples viewed the videotapes and rated their affect during the interaction. The video records were coded with a system that categorized specific affects displayed. Models derived from physiology, from the perception of interaction, and from specific affective behavior were related to relationship satisfaction, and to the prediction of relationship dissolution over a 12-year period. Results supported previous findings that satisfaction and stability in gay and lesbian relationships are related to similar emotional qualities as in heterosexual relationships.
Race and drug formulation influence on mycophenolic acid pharmacokinetics in stable renal transplant recipients.

Background Limited mycophenolic acid (MPA) data are available comparing racial influence on mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) pharmacokinetics. Methods Intrapatient MPA pharmacokinetics of MMF versus EC-MPS were compared in 13 male African American (AA) and 14 Caucasian (C) renal transplant recipients (RTRs). RTRs were switched to equivalent doses of the alternate formulation for at least 10 days prior to the second study. Mycophenolic acid clearance and dose-normalized area under the concentration-time curve(0-12) (AUC*) were determined. Mixed model statistics evaluated the main effects of race, drug formulation, and interaction of race and drug formulation (R × D) with albumin, cyclosporine trough, renal function, and diabetes and enterhepatic recirculation. Results Significant R × D was identified for MPA AUC* for EC-MPS (AA, 0.056 ± 0.029 [mg·h/L]/mg; C, 0.080 ± 0.044 [mg·h/L]/mg) compared with MMF (AA, 0.053 ± 0.019 [mg·h/L]/mg; C, 0.060 ± 0.025 [mg·h/L]/mg), P = .022. Significant R × D was identified with albumin in the model for MPA clearance for MMF (AA, 21.7 ± 8.9 L/h; C, 20.5 ± 10.8 L/h) compared with EC-MPS (AA, 22.2 ± 10.1 L/h; C, 16.2 ± 9.1 L/h), P = .032. Conclusions Race influences MPA exposure between MMF and EC-MPS and may warrant therapeutic monitoring during formulation conversion.
Lidocaine by Enzyme Immunoassay

The cardioactive drug lidocaine was measured by a homogeneous enzyme immunoassay procedure (EMIT| using a procedure similar to the one described for the determination of antiepiieptic drugs in serum. The assay requires 50/al of serum per determination and less than 5 minutes to perform. The assay is specific for lidocaine and does not cross-react with lidocaine metabolites or other cardioactive drugs. Twenty replicate analyses of a serum containing lidocaine gave a CV of 3.4%. Results attained with a large series of patients administered lidocaine alone or with other cardioactive drugs were compared with results by a gas liquid chromatographic procedure. The correlation coefficient (r) was 0.976. No false postives or negatives were encountered.
Employer valuations of employee commuting time : Case study of office tenants in North Dallas, Texas

A recently completed survey of office tenants in North Dallas, Texas, presented respondents with two hypothetical situations, each combining a temporary increase in commuting time with a temporary reduction in office rent. Respondents were asked whether the overall effect on their business would be positive, negative, or neutral. Although hypothetical, the questions were also topical. The respondents were all in the vicinity of a major highway project, the Dallas High Five Interchange, the construction of which has caused delays for some travelers. Econometric analysis of the survey responses provided estimates of the cost these office tenants attach to a temporary increase in the commuting time of their employees. This paper explains the derivation of these estimates and provides other findings relevant to their interpretation. The paper also motivates analysis by explaining how estimates of this sort can promote public awareness of the costs and benefits of highway projects.
Personality and Paired-Associate Learning

Abstract Eysenck has theorized that introverts are high in arousal and should show the pattern of results which has been displayed in several experiments by subjects confronted with high-arousal stimulus materials: poor performance on short-term and good performance on long-term measures of retention. Extraverts, on the other hand, are thought to be low in arousal and should show the reverse pattern as displayed by subjects confronted with low-arousal stimulus materials. The relevant experiments conducted in Britain confirm these predictions. The relevant United States studies do not. The method used in the present study, in which Americans were subjects, is that of an experiment of Kleinsmith and Kaplan (1964) which found the patterns of retention predicted on the basis of the subjects' exposure to high- or low-arousal stimulus materials. But, as in the other tests of Eysenck's predictions, arousal was measured in terms of introversion and extraversion. The results failed to support Eysenck's formulation.
A new approach to synthesis problems in linear system theory

We consider a rational nonlinear equation which is involved in the general synthesis (design) problem of linear multivariable systems. The complete solution of this equation, subject to causality, stability, and minimality constraints, is provided. Formal power series and, in particular, the theory of partial realizations, prove of central importance for the design problem.