cssi/SciSciGPT-SciSciNet huggingface dataset:
Cardiorespiratory Response to Moderate Hypercapnia in Female College Students Expressing Behaviorally Inhibited Temperament

Behaviorally inhibited (BI) temperament is marked by heightened behavioral sensitivity to environmental threats. The degree to which threat sensitivity is reflected in cardiorespiratory responses has been relatively unexplored. Female college students were exposed to modest hypercapnia (7.0% CO2) or ambient air (AA) while engaging in a computerized task with cued reinforcement features. All physiological variables except for blood pressure were processed in 4 min epochs corresponding to pre-exposure, exposure, and post-exposure. Primary respiratory measures were respiratory frequency (fb), tidal volume (VT), and minute ventilation (VE). Electrocardiograms (ECGs) were processed using ARTiiFACT software with resultant heart rate variability (HRV) measures in the frequency domain and time domain. Consistent with the literature, modest hypercapnia increased VT, Fb, and VE. No differences in respiratory parameters were detected between BI and non-behaviorally inhibited individuals (NI). For HRV in the time domain, RMSSD and NN50 values increased during CO2 inhalation which then returned to pre-exposure levels after CO2 cessation. Hypercapnia increased high frequency (HF) power which then recovered. BI exhibited reduced low frequency (LF) power during the pre-exposure period. For NI, LF power reduced over the subsequent phases ameliorating differences between BI and NI. Hypercapnia improved the task performance of BI. This is the largest study of female reactivity to hypercapnia and associated HRV to date. In general, hypercapnia increased time domain HRV and HF power, suggesting a strong vagal influence. Those expressing BI exhibited similar respiratory and HRV reactivity to NI despite inherently reduced LF power. Although 7% CO2 represents a mild challenge to the respiratory and cardiovascular systems, it is nonetheless sufficient to explore inherent difference in stress reactivity in those vulnerable to develop anxiety disorders.
Bayesian Weighted Sums: A Flexible Approach to Estimate Summed Mixture Effects.

Objectives: Methods exist to study exposure mixtures, but each is distinct in the research question it aims to address. We propose a new approach focused on estimating both the summed effect and individual weights of one or multiple exposure mixtures: Bayesian Weighted Sums (BWS). Methods: We applied BWS to simulated and real datasets with correlated exposures. The analytic context in our real-world example is an estimation of the association between polybrominated diphenyl ether (PBDE) congeners (28, 47, 99, 100, and 153) and Autism Spectrum Disorder (ASD) diagnosis and Social Responsiveness Scores (SRS). Results: Simulations demonstrate that BWS performs reliably. In adjusted models using Early Autism Risk Longitudinal Investigation (EARLI) data, the odds of ASD for a 1-unit increase in the weighted sum of PBDEs were 1.41 (95% highest posterior density 0.82, 2.50) times the odds of ASD for the unexposed and the change in z-score standardized SRS per 1 unit increase in the weighted sum of PBDEs is 0.15 (95% highest posterior density −0.08, 0.38). Conclusions: BWS provides a means of estimating the summed effect and weights for individual components of a mixture. This approach is distinct from other exposure mixture tools. BWS may be more flexible than existing approaches and can be specified to allow multiple exposure groups based on a priori knowledge from epidemiology or toxicology.
Accessing Rights and Mitigating Revictimization: The Role of the Victim’s Legal Counsel in the Swedish Criminal Justice System:

Rape victims often face secondary victimization by the criminal justice system, prompting their advocates to promote a variety of procedural changes, including the provision of an independent legal counsel for victims. Sweden implemented a legal counsel for victims of sexual assault and rape in the late 1980s, yet research about their role remains limited. This article draws upon interviews with victim-lawyers in Sweden and suggests that having access to an independent legal counsel can mitigate the risks for secondary victimization by empowering victims to access their rights and providing emotional support and connectedness in the criminal justice system.
Residency match interview scheduling: quantifying the applicant experience

Background The process of offering and scheduling residency interviews varies widely among programmes. Applicants report distress and have advocated for reform. However, there is a paucity of quantitative data to characterise applicant concerns. Objective We quantified the interview scheduling experience for US allopathic medical students in the 2020 main residency match. Methods An anonymous, 13 question survey was sent to student representatives from each Association of American Medical Colleges member institution. Recipients were asked to forward the survey to their entire fourth-year class. Results Of 4314 applicants to whom the survey was sent, 786 (18.2%) responded. Overall, 20.4% reported missing the opportunity to interview at a programme because they did not have adequate time to respond to an invitation; applicants into surgical specialties were significantly more likely than their non-surgical peers to report this experience (26.4% vs 18.4%, p Conclusions About one in five respondents missed the opportunity to interview at a programme because they did not respond to an invitation in time. Most respondents scheduled interviews knowing that they were likely to cancel them in the future. Standardisation of the interview invitation timeline would address these concerns.
Beginning Teacher Support Model: Elementary Teachers’ Resilience and Retention in Arizona

In the United States, beginning teacher retention rates are extraordinarily low; only 50% of teachers remain in the classroom after five years. In particular, the State of Arizona has been recruiting significant numbers of teachers from out of state and attempting to retain them with minimal success. This persistent problem has led the neediest of students to have teachers with lower levels of professional experience, leaving those students with continually lower achievement gains. Drawing on integrated action research and grounded theory methodology, this study’s took place in a large kindergarten to eighth grade elementary school district located in a high-poverty neighborhood in Arizona. The study invited six new teachers in their first year of teaching to explore innovative strategies to increase these teachers’ retention in the profession. The ultimate goal was to understand how such support might alter a beginning teacher’s perceptions of their own persistence and resilience in dealing with the challenges of first-year teaching, thereby reducing beginning teacher attrition. The study finds that teachers must be nurtured and cared for in order for them to fully devote their time and energy to effectively care for the students in their classroom. Increasing self-awareness and resiliency has the potential to create a ripple effect to retain more beginning teachers, as they become more likely to persevere, ask for help, connect with others, and achieve a healthy life/work balance while positively impacting students and their community.
H2 Emission from the Inner 400 Parsecs of the Galaxy

We have mapped the H2 v = 1 → 0 S(1) (λ = 2.1215 μm) emission line along a 400 pc-long strip and in a 50 pc region in the Galactic center. There is H2 emission throughout the surveyed region. The typical dereddened (AK = 2.5 mag) H2 v = 1 → 0 S(1) surface brightness, ~3 × 10-5 ergs s-1 cm-2 sr-1, is similar to the surface brightness in large-scale photon-dominated regions in the Galactic disk. We investigate two possible excitation mechanisms for the H2 emission, UV excitation by photons from OB stars and shock waves, and conclude that UV excitation is more likely. The total H2 v = 1 → 0 S(1) luminosity in the inner 400 pc region of the Galaxy is 8000 L☉. The ratio of the H2 to far-IR luminosity in the inner 400 pc of the Galaxy agrees with that in starburst galaxies and ultraluminous IR-bright galaxies.
Forward Thinking: The Evolving Field of Human–Animal Interactions

Abstract This chapter focuses on the field of human–animal interactions, its early leaders, the challenges of standardizing definitions, training, certification, and the lack of empirical evidence. This chapter acknowledges and explores the progression of animal-assisted interaction (AAI) specializations while substantiating future essential directions in AAI practice, including focused development of the evidence base and strategic movement toward professionalization.
Survey of Recent Results on Weak Stability Boundaries and Applications

A region of transitional stability in the three-body problem has proved to have interesting mathematical properties and also important applications to several fields. This region, called the weak stability boundary, was first discovered for its use in providing a methodology for computing new types of low energy transfers. Up to recently, understanding it’s underlying structure has been elusive. Recent results on understanding the mathematical structure of this region are presented as well as associated dynamics. This includes both numerical and theoretical results indicating the underlying complicated structure of invariant hyperbolic manifolds. Associated resonance dynamics are described. Recent applications are described within the field of astronomy on a theory for the origin of the Moon and also on the minimal energy transfer of solid material between planetary systems.
Market-Oriented Reforms as a Tool of State-Building: Russian Pension Reform in 2001

Despite domestic opposition and several policy alternatives, in 2001 the Russian government adopted a pension reform that was potentially costly and had uncertain long-term benefits. Demographic and fiscal pressures created the desire to reform and a more cooperative Duma made it possible to do so. These points do not explain why Putin chose the pension privatisation option. Russia's pension reform is best understood as part of a state-building strategy to diminish the role of powerful bureaucracies. Russia's welfare state was not merely the product of a powerful and popular president, but rather a tool to create a stronger executive.
Effect of AlN and Al2O3 additions on the phase relationships and morphology of SiC Part I Compositions and properties

X-ray diffraction was utilized to follow the transformation from β-SiC (3C) to the various α-SiC polytypes in the presence of AlN and Al2O3 additives after hot pressing from 1700 to 2100°C. The 2H- and 6H-polytypes of α-SiC were the predominate polytypes with additions of only AlN or Al2O3, respectively. The amount of 2H- and 6H-polytypes, and subsequently the microstructural morphology of the SiC materials, were found to be controlled by varying the amount of AlN and Al2O3. Improvements in fracture toughness to ∼9 MPa-√m were achieved with flexural strengths ranging from 600 to 900 MPa. These results suggest that accurate control of the polytypic make-up of SiC-based materials, along with their mechanical properties, can be achieved through AlN and Al2O3 additions.
Advertising and Competition

A critical aspect of the advertising budgeting process involves competitive issues—anticipated spending levels of major competitors, effects that competitive advertising may have on the firm’s market share, sales, and profit, and the interactive nature of a competitor’s advertising with a firm’s own. Competition is ignored only at the firm’s peril; empirical studies (e.g., Little 1979; also see the empirical survey below) have shown quite clearly that competitive advertising can have a direct, and negative, effect on a company’s market share. Also, management practice appears to recognize the importance of competition; in a survey of leading U.S. advertisers, Lancaster and Stern (1983) reveal that, among various general characteristics describing the advertising budgeting process, “competitive effects” were considered by 52% of the sample (second only to “communication effects” at 55%).
Trends and pacing items in computational aerodynamics

A perspective is presented of trends in computational aerodynamics, and of important technology development items that pace future advanced applications. From a survey of AIAA Journal papers published during the past two decades, the growth trends and the progressively increasing emphasis on code development for viscous, compressible, turbulent flow are illustrated. These trends are reflected in the chronology of introduction by the aerospace industry of new computational methods in aircraft design. Key pacing items outlined are: automatic grid generation for nonlinear inviscid computations; advanced computers, improved efficiency of numerical methods, and improved turbulence models for Reynolds-averaged Navier-Stokes computations; advanced computers, time-dependent three-dimensional law-of-the-wall, code development, improved efficiency of numerical methods, and improved subgrid-scale turbulence modeling for large eddy simulations.
Methotrexate and Dipyridamole Combination Chemotherapy Based upon Inhibition of Nucleoside Salvage in Humans

We have carried out a clinical trial in 23 patients to determine whether dipyridamole modulates the clinical effect of methotrexate. This trial was based upon in vitro studies which indicate that dipyridamole potentiates the cytotoxic action of methotrexate through inhibition of thymidine salvage. Methotrexate was given as a bolus injection 24 h after initiation of a high dose dipyridamole infusion. The trial was designed so that methotrexate was escalated in individuals until toxicity occurred and then the methotrexate dose resulting in toxicity was repeated without dipyridamole. During the course of this study the methotrexate dose was escalated from 10 to 130 mg/m2. While individual patient tolerance varied, moderate to severe myelosuppression and/or mucositis occurred frequently in patients receiving the combination with methotrexate doses ≧60 mg/m2. Ten of 10 patients who experienced moderate or severe toxicity with the combination had significantly less toxicity when treated with methotrexate alone. Dipyridamole did not increase toxicity by an alteration in methotrexate elimination. The potentiation of methotrexate by dipyridamole in these patients suggests that physiological thymidine levels are sufficient to perturb the clinical effects of methotrexate and that thymidine salvage may represent a mechanism for clinical resistance to methotrexate. These results also suggest that a high dose dipyridamole regimen can be used as a pharmacological approach to test the role of nucleoside membrane flux on the clinical action of other standard chemotherapeutic drugs. Phase II studies testing the clinical efficacy of this combination should use a methotrexate dose of 60 mg/m2 with a provision for methotrexate dose escalation based upon individual patient tolerance.
Delta-Opioid Receptor Antagonists Prevent Sensitization to the Conditioned Rewarding Effects of Morphine

Background Functional interactions between μ- and δ-opioid receptors (MOPr and DOPr, respectively) are implicated in morphine tolerance and dependence. The contribution of DOPr to the conditioned rewarding effects of morphine and the enhanced conditioned response that occurs after repeated morphine administration is unknown. This issue was addressed with the conditioned place preference procedure (CPP). Methods Rats received home cage injections of saline or morphine (5.0 mg/kg/day × 5 days) before conditioning. For sensitization studies, DOPr antagonists (DOPr1/2: naltrindole, DOPr2: naltriben, DOPr1: 7-benzylidenenaltrexone) were administered before morphine injections. Conditioning sessions (2 morphine; 2 saline) commenced 3 days later. To assess the influence of acute DOPr blockade on the conditioning of morphine reward in naive animals, 3 morphine and 3 saline conditioning sessions were employed. Antagonists were administered before morphine conditioning sessions. Results Morphine was ineffective as a conditioning stimulus after two conditioning sessions in naive rats. However, doses ≥ 3.0 mg/kg produced significant CPP in morphine pre-exposed rats, confirming that sensitization develops to the conditioned rewarding effects of morphine. In animals that received morphine pre-exposure with naltrindole or naltriben but not 7-benzylidenenaltrexone, sensitization was prevented. No attenuation of morphine CPP was observed in animals that received DOPr antagonists acutely, before conditioning sessions. Conclusions These data indicate a critical role of DOPr systems in mediating sensitization to the conditioned rewarding effects of morphine. The efficacy of naltrindole and naltriben in preventing the enhanced response to morphine suggest the specific involvement of DOPr2 in the sensitization process.
Academic Dishonesty in Graduate Business Programs: Prevalence, Causes, and Proposed Action

Little is currently known about cheating among graduate business students. We collected data from more than 5,000 business (mostly MBA) and nonbusiness graduate students at 32 colleges and universities in the United States and Canada during the 2002–2003 and 2003–2004 academic years to test a series of hypotheses regarding the prevalence of graduate business student cheating and reasons why these students cheat. We found that graduate business students cheat more than their nonbusiness-student peers. Correlation results found cheating to be associated with perceived peer behavior, as well as the perceived certainty of being reported by a peer, and the understanding and acceptance of academic integrity policies by students and faculty. But, regression analysis results suggest that perceived peer behavior has the largest effect. Drawing from these findings and past research on undergraduate students, we propose strategies that business schools and faculty can use to promote academic integrity in graduate business programs.
JBP1 and JBP2 Proteins Are Fe2+/2-Oxoglutarate-dependent Dioxygenases Regulating Hydroxylation of Thymidine Residues in Trypanosome DNA

We have recently demonstrated that O-linked glucosylation of thymine in trypanosome DNA (base J) regulates polymerase II transcription initiation. In vivo analysis has indicated that base J synthesis is initiated by the hydroxylation of thymidine by proteins (JBP1 and JBP2) homologous to the Fe2+/2-oxoglutarate (2-OG)-dependent dioxygenase superfamily where hydroxylation is driven by the oxidative decarboxylation of 2-OG, forming succinate and CO2. However, no direct evidence for hydroxylase activity has been reported for the JBP proteins. We now demonstrate recombinant JBP1 hydroxylates thymine specifically in the context of dsDNA in a Fe2+-, 2-OG-, and O2-dependent manner. Under anaerobic conditions, the addition of Fe2+ to JBP1/2-OG results in the formation of a broad absorption spectrum centered at 530 nm attributed to metal chelation of 2-OG bound to JBP, a spectroscopic signature of Fe2+/2-OG-dependent dioxygenases. The N-terminal thymidine hydroxylase domain of JBP1 is sufficient for full activity and mutation of residues involved in coordinating Fe2+ inhibit iron binding and thymidine hydroxylation. Hydroxylation in vitro and J synthesis in vivo is inhibited by known inhibitors of Fe2+/2-OG-dependent dioxygenases. The data clearly demonstrate the JBP enzymes are dioxygenases acting directly on dsDNA, confirming the two-step J synthesis model. Growth of trypanosomes in hypoxic conditions decreases JBP1 and -2 activity, resulting in reduced levels of J and changes in parasite virulence previously characterized in the JBP KO. The influence of environment upon J biosynthesis via oxygen-sensitive regulation of JBP1/2 has exciting implications for the regulation of gene expression and parasite adaptation to different host niches.
Distribution of Particulate-Bound Metals for Source Area Snow in the Lake Tahoe Watershed

The porous matrix and long residence time of snow in traffic corridors can result in the accretion of particulate matter (PM) and metals. This temporary repository contributes PM-based and dissolved metals to surrounding environs during snowmelt. This study focused on distribution and settling of PM-based metals (Al, As, Cd, Cr, Cu, Fe, Pb, and Zn) in snow. Snow was sampled from six sites during four winter seasons. PM-based metals are examined herein as a function of PM granulometry, specifically particle-size distributions (PSDs) and PM surface area. Cumulative metal mass distributions across each PSD are modeled as gamma functions. Results indicate Al (15 g/kg) and Fe (4.2 g/kg) are the highest PM-based concentrations; Cd (0.18 mg/kg) and As (4.9 mg/kg) are the lowest. The PM size ( d50 m ) associated with the median metal mass ranges from 179 to 542 μm . The constitutive gamma results are integrated with Hazen’s settling algorithm to model PM-bound metal separation for a sedimentation basin at a local...
Effects of weave architecture on mechanical response of 2D ceramic composites

A meso-scale finite element model is developed to investigate effects of weave architecture on strain and stress evolution in an eight harness-satin SiC/SiCN composite. Fiber tows are modeled explicitly using elastic rebar layers embedded within elastic/plastic effective medium elements. Effects of through-thickness constraint are investigated using several idealized test geometries, ranging from a single (unconstrained) ply to a fully-constrained two-ply lay-up with periodic boundary conditions in the through-thickness direction. A parallel experimental study of surface strain evolution in a representative SiC/SiCN composite is used to assess the model predictions. The results indicate that, because of bending and straightening of wavy tow segments at the locations of tow cross-overs, strain and stress concentrations arise. The effects are exacerbated by reductions in the constraints on bending and straightening caused by matrix damage, especially in surface plies. The implications of the results in the fracture process and on potential mitigation strategies are discussed.
DNA SYNTHESIS IN ALVEOLAR CELLS OF THE MAMMARY GLAND: ACCELERATION BY OVARIAN HORMONES.

In normal alveolar cells of the mammary gland of C3H/HeJ female mice, DNA synthesis lasts an average of 20.7 hours with a coefficient of variation of 26.6 percent. Treatment of the mice with I microgram of 17-β-estradiol and 1 milligram of progesterone per day for 3 to 4 days decreases the average duration to 10.7 hours and the coefficient of variation to 13.8 percent.
Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice.

Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4 + and CD8 + T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer.
Comparison of simulation results for giant air showers

Comparisions have been made between shower parameters from MOCCA simulations, featured in many Auger Project design studies and from results available from other simulations. Average values of electron and muon components in vertical proton showers are compared for depth of maximum, shower sizes at sea level and particle densities at distance of 600 meters on the ground. Systematic differences are found, the differences increasing with proton energy. At 10 19 eV the MOCCA predictions, compared with recent simulations based on quark gluon string and other models, show considerably larger average depth of maximum and electron shower size at the ground, but about a factor of two smaller muon and electron densities at 600 meters from the core. These features, of particular interest for energy and composition determinations from ground arrays, are consistent with expectations for increasing inelasticities and transverse momenta in ultra high energy hadron-air interactions.
Generation of 110 W infrared power and 65W green power from a 1.3-GHz sub-picosecond fiber amplifier

A fiber amplifier that achieves sub-picosecond pulse duration and greater than 100 W average power at 1.3-GHz repetition rate is reported. Frequency-doubling of the amplified pulses yields 65 W green power.
Inherent structure analysis of defect thermodynamics and melting in silicon

The inherent structure landscapes associated with various types of microstructure in crystalline silicon are probed within the empirical Environment-Dependent Interatomic Potential. Inherent structure sampling is carried out using a combination of molecular dynamics simulation and energy minimisation. Several isolated point defect clusters are analysed first, followed by the more complex phenomenon of crystal melting. In the latter case, both homogeneous and surface-driven melting phenomena are considered, and selected comparisons are made to face-centered cubic aluminium represented by an embedded-atom potential. It is shown that inherent structure theory provides a useful framework for consolidating various aspects of microstructure thermodynamics in crystals, and also naturally allows for the treatment of more complex situations such as applied mechanical fields.
Bisphenols That Stimulate Cells To Release Alkali Metal Cations: A Structure−Activity Study

The laxative action of phenolphthalein (5) is believed to result from induction of potassium and water efflux from the colon epithelium. In cultured cells, K+ efflux is promoted by 5 and by a contaminant (1) present in commercial phenol red. Six compounds with chemical structures related to those of 5 and 1 were tested for ability to induce the release of 86Rb from COS-7 cells preloaded with this isotope: 4,4'-(9-fluorenylidene)diphenol (2), 4, 4'-(9-fluorenylidene)dianiline, 4, 4'-(9-fluorenylidene)bisphenoxyethanol, 1,1'-bi-2-naphthol, 4, 4'-biphenol, and bis(4-hydroxyphenyl)methane. With one exception these compounds were all inactive at a concentration of 10 microM. However, 2 caused profound 86Rb efflux at concentrations as low as 100 nM. Concentrations of 5 1-2 orders of magnitude higher were needed to achieve similar levels of activity. The three compounds known to be active in this experimental system share a common feature that is absent in all the inactive compounds: a five-membered ring structure, one of whose carbon atoms is disubstituted with p-hydroxyphenyl residues. Because 2 and 5 are readily available, comparative studies on the mechanism of action of these biphenols at the cellular level can now be undertaken.
The energy landscape of glassy dynamics on the amorphous hafnium diboride surface

Direct visualization of the dynamics of structural glasses and amorphous solids on the sub-nanometer scale provides rich information unavailable from bulk or conventional single molecule techniques. We study the surface of hafnium diboride, a conductive ultrahigh temperature ceramic material that can be grown in amorphous films. Our scanning tunneling movies have a second-to-hour dynamic range and single-point current measurements extend that to the millisecond-to-minute time scale. On the a-HfB2 glass surface, two-state hopping of 1–2 nm diameter cooperatively rearranging regions or “clusters” occurs from sub-milliseconds to hours. We characterize individual clusters in detail through high-resolution (<0.5 nm) imaging, scanning tunneling spectroscopy and voltage modulation, ruling out individual atoms, diffusing adsorbates, or pinned charges as the origin of the observed two-state hopping. Smaller clusters are more likely to hop, larger ones are more likely to be immobile. HfB2 has a very high bulk glass...
Pulmonary function studies before and after jejunoileal bypass surgery

Nine out of twelve obese patients (75%) demonstrated diminished minute ventilation volume (MVV) prior to jejunoileal bypass surgery. Seven out of the nine patients (78%) showed improvement in the MVV as weight reduction ensued following surgery. Other parameters, including arterial blood gases, did not change after weight loss. Weight reduction as a result of jejunoileal bypass surgery brings about an improvement in pulmonary function.
Efficient simulation procedures: comparison with a standard via fully sequential procedures

We develop fully sequential procedures for comparison with a standard. The goal is to find systems whose expected performance measures are larger or smaller than a single system referred to as a standard and, if there is any, to find the one with the largest or smallest performance. Our procedures allow for unequal variances across systems, the use of common random numbers and known or unknown expected performance of the standard. Experimental results are provided to compare the efficiency of the procedure with other existing procedures.
Molybdenum oxychlorides I. Electrochemistry of MoO2Cl2: oxidation, dimerization, and electrodeposition at a platinum electrode

Abstract This paper describes the electrochemical behavior of MoO 2 Cl 2 at a platinum electrode in acetonitrile, methylene carbonate, and propylene carbonate solvents. Cyclic voltammetry, bulk electrolysis, and chemical reduction are used to show that on one-electron reduction of MoO 2 Cl 2 , MoO 2 Cl − 2 reacts with MoO 2 Cl 2 to form an unusual Mo(VI)Mo(V) dimer. This dimer can undergo both oxidation and further reduction. Oxidation to the Mo(VI)Mo(VI) oxidation state is irreversible at low scan rates but reversible at high scan rates. Reduction of the dimer occurs in a reversible one-electron process to yield an Mo(V)Mo(V) dimer which can be reduced further in a one-electron irreversible process. MoO 2 Cl 2 partially ionizes in these solvents to give MoO 2+ 2 , MoO 2 Cl 2− 4 and possibly MoO 2 Cl − 3 : MoO 2+ 2 and MoO 2 Cl 2− 4 are electrochemically active. Reduction of MoO 2+ 2 leads to electrodeposition of MoO 2 (s). An unusual irreversible oxidation wave is observed for MoO 2 Cl 2 , a d 0 species, which is due to oxidation of MoO 2 Cl 2− 4 . Solutions of MoO 2 Cl 2 oxidize ferrocene: the solid obtained on drying was characterized by elemental analysis and IR spectroscopy.
ACQUIRED PULMONIC STENOSIS DUE TO EXTERNAL CARDIAC COMPRESSION.

Abstract A report of a patient with acquired pulmonic stenosis due to external cardiac compression from thymoma is presented. The value of angiocardiography and cardiac catheterization in the diagnosis of these lesions is demonstrated. The granulomatous changes found in the thymoma resembled Hodgkin's disease histologically, although there is a controversy concerning its exact nature. The pertinent literature was reviewed and briefly discussed.
Preparation of unilamellar liposomes of intermediate size (0.1–0.2 μm) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes

Liposomes can be prepared by a combination of reverse phase evaporation and sequential extrusion through polycarbonate membranes. The vesicles have diameters in the range 0.05-0.5 micron and are mostly unilamellar as indicated by electon microscopy, capture volume, and availability of reactive groups to periodate oxidation. Sequential extrusion leads to a decrease in the encapsulation efficiency by 2-4-fold, depending upon the lipid composition. The inclusion of cholesterol at a 1 : 1 molar ratio of cholesterol-to-phospholipid increases both the mean size and the size heterogeneity of the liposomes as measured by negative-stain electron microscopy. The mean size of vesicles with an equal molar ratio of cholesterol-to-phospholipid after extrusion through a 0.1 micron membrane is 0.140 micron. Vesicles composed of phosphatidylglycerol/phosphatidylcholine (1 : 4) have a mean size of 0.08 micron after extrusion through a 0.1 micron membrane. The intermediate-size (0.1-0.2 micron) vesicles formed by this process have an aqueous space-to-lipid ratio of 3 : 5 and capture between 12 and 25% of the aqueous phase. The procedure is relatively simple, rapid, and yields almost quantitative recovery of vesicles that encapsulate a large percentage of the total aqueous space.
New developments in the treatment of metastatic melanoma – role of dabrafenib–trametinib combination therapy

Development of selective inhibitors of BRAF has improved the survival of patients with BRAF-mutant melanoma. The progression-free survival after treatment with a BRAF inhibitor is modest, however, and BRAF inhibitors induce cutaneous toxicity, likely due to paradoxical activation of the mitogen-activated protein kinase pathway. Combining selective BRAF and MEK inhibition, such as the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, has been shown to improve the response rate and progression-free survival in patients with advanced melanoma while significantly alleviating the paradoxical activation of mitogen-activated protein kinase. This combination treatment results in a reduction in skin toxicity relative to that seen with a BRAF inhibitor alone; however, addition of the MEK inhibitor adds other toxicities, such as pyrexia and gastrointestinal or ocular toxicity. While combined BRAF–MEK inhibition appears primed to become a standard molecular approach for BRAF-mutant melanoma, the utility of the combination has to be considered in the rapidly changing landscape of immunotherapeutics, such as immune checkpoint blockade using anti-cytotoxic T lymphocyte antigen-4 and anti-programmed death-1/programmed death-L1 antibodies. Here we review the development of the dabrafenib plus trametinib combination, the characteristics of each drug and the combination, and the role of this combination in the management of patients with BRAF-mutant melanoma.
Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease

Abstract Purpose: An elevated plasma homocysteine level is an established risk factor for atherosclerotic coronary heart disease (CHD), cerebrovascular disease (CVD), and lower extremity occlusive disease (LED). An elevated plasma homocysteine level can be reduced by therapy with folate and vitamins B6 and B12. An accurate evaluation of the role of vitamin therapy requires knowledge of the influence of plasma homocysteine levels on the progression of CHD, CVD, and LED. Methods: The Homocysteine and Progression of Atherosclerosis Study is a blinded prospective study of the influence of homocysteine and of other atherosclerotic risk factors on the progression of disease in patients with symptomatic CVD, LED, or both. This study is set in a university hospital vascular surgery clinic and the General Clinical Research Center. Consecutive patients with stable symptomatic CVD or LED underwent baseline clinical, laboratory, and vascular laboratory testing for homocysteine and other risk factors and were examined every 6 months. The primary endpoints were ankle brachial pressure index, duplex scan–determined carotid stenosis, and death. The secondary endpoints were the clinical progressions of CHD, LED, and CVD. The hypothesis that was tested was whether the progression of symptomatic CVD or LED was more frequent or more rapid in patients with elevated plasma homocysteine levels. Results: After a mean follow-up period of 37 months (range, 1 to 78 months) for deaths from all causes (>14 μmol/L; elevated, 18.6%; normal, 9.4%; P = .022), deaths from cardiovascular disease (elevated, 12.5%; normal, 6.3%; P = .05) and the clinical progression of CHD (highest 20% of homocysteine levels, 80%; lowest 20% of homocysteine levels, 39%; P = .007) were significantly more frequent or more rapid by life-table analysis when the homocysteine levels were elevated. Multivariate Cox proportional hazards regression model showed a significant independent and increasing relationship between the plasma homocysteine levels and the time to death (relative risk for highest one third of homocysteine values, 1.6; 95% confidence interval [CI], 1.04 to 2.56; P = .029; and relative risk for highest one fifth of homocysteine values, 3.13; 95% CI, 1.69 to 6.64; P = .0001). After an adjustment for age, smoking, hypertension, diabetes, cholesterol, and the vascular laboratory progression of CVD or LED, each 1.0 μmol/L increase in the plasma homocysteine levels resulted in a 3.6% increase (95% CI, 0.0% to 6.6%; P = .06) in the risk of death (all causes) at 3 years and a 5.6% increase (95% CI, 2.2% to 8.5%; P = .003) in the risk of death from cardiovascular disease. Conclusion: We conclude that elevated plasma homocysteine levels are associated significantly with death, with death from cardiovascular disease, and with the progression of CHD in patients with symptomatic CVD or LED. These results strongly mandate clinical trials of homocysteine-lowering vitamin therapy in such patients. (J Vasc Surg 1999;29:8-21.)
Diabetes and the associated incidence of subclinical atherosclerosis and coronary artery disease: Implications for management.

Abstract Background We sought to examine the prevalence, sensitivity, and specificity of coronary calcium (CC), a marker of atherosclerosis, in a population of symptomatic and asymptomatic diabetic persons. Methods We used electron beam tomography (EBT) to quantitate CC in 168 symptomatic (chest pain or anginal equivalent) persons with diabetes who underwent coronary angiography and then compared this with a cohort of 155 asymptomatic persons with diabetes. Results In the 168 symptomatic diabetic persons, 124 (74%) had obstructive coronary artery disease (CAD) by angiography. Receiver-operator characteristic curve analysis was used to maximize sensitivity and specificity for obstructive CAD (>50% stenosis), which established a CC score of 102 as optimal. With use of this cut point, EBT has a sensitivity of 77% and a specificity of 77% for detecting obstructive CAD. Of the 155 asymptomatic diabetic persons, 72% had CC and 48% had a CC score >102. The presumed prevalence of obstructive disease (on the basis of EBT scores and prevalence of CC) among asymptomatic diabetic persons is quite high (as high as symptomatic persons without diabetes). Analyzing the 323 diabetic patients demonstrated no significant age difference in CC scores between women and men. Conclusions This study confirms that higher CC scores should be used in diabetic patients to improve the specificity of CC to determine obstructive disease. EBT can allow a noninvasive diagnosis of CAD before clinical presentation, allowing for more therapy for those in which CC is detected. These results suggest that asymptomatic diabetic persons have the same atherogenic burden of those patients with CAD without diabetes. The high prevalence of CC in asymptomatic persons with diabetes supports the need for aggressive management of diabetes and associated risk factors. (Am Heart J 2001;141:637-44.)
Physical sciences: circularly polarized visible light from jupiter.

WE have discovered circular polarization of the reflected light from Jupiter, the first detection at optical wavelengths of this type of polarization in light from a planet. The discovery was made at Mauna Kea Observatory, Hawaii, with a photoelastic polarimeter used also in measurements on magnetic white dwarf stars1. The first results were obtained with the 88 inch telescope on the night of March 31, 1971, and protracted observations were made with a 24 inch telescope on the nights of April 11, 20 and 21.
Tweening grammars: Deformation rules for representing change between discrete geographic entities

Data concerning dynamic geographic processes are commonly captured and stored as discrete temporal snapshots. Snapshot data often require interpolation to compensate for large data collection intervals. Metamorphosis (morphing or tweening) is the study of how an object changes over time. Tweening was developed to perform basic transformations rather than to represent a particular geographic process that might be informing the change (e.g., wildfire). This paper describes a means for making the interpolation between two snapshots more effective and efficient by introducing process-informed rules to guide the tweening. Tweening grammars are devised to enable dynamic deformation between source and target shapes. A hybrid approach using a semi-automated correspondence rule and medial axis transformation is explored, followed by a case study of tweening an actual wildfire and an example of validating a set of tweening rules.
Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2

Viruses use specific receptor molecules to bind selectively to target cells. Receptors have often been considered as mere docking sites, but they may also possess intrinsic signaling capacities that serve to prime the cell for entry and infection. Poliovirus (PV) initiates infection by binding to the PV receptor (PVR) and causes paralytic poliomyelitis by replicating within motor neurons of the brain and spinal cord. We have examined the process by which PV enters cultured human brain microvascular endothelial cells (HBMEC), an in vitro model of the blood–brain barrier. We found that PV enters HBMEC by dynamin-dependent caveolar endocytosis, and that entry depends on intracellular signals triggered by virus attachment to PVR. Tyrosine kinase and RhoA GTPase activation initiated by PVR ligation were both essential. Virus attachment also induced tyrosine phosphorylation of PVR; this permitted the association of PVR with SHP-2, a protein tyrosine phosphatase whose activation was required for entry and infection. The results indicate that receptor-induced signals promote virus entry and suggest a role for tyrosine phosphatases in viral pathogenesis.
Asymmetric Hydrovinylation of Vinylindoles. A Facile Route to Cyclopenta[g]indole Natural Products (+)-cis-Trikentrin A and (+)-cis-Trikentrin B

Vinylindoles undergo Ni(II)-catalyzed asymmetric hydrovinylation under very mild conditions (−78 °C, 1 atm ethylene, 4 mol % catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantioselectivities. Hydroboration of the alkene and oxidation to an acid, followed by Friedel–Crafts annulation, gives an indole-annulated cyclopentanone that is a suitable precursor for the syntheses of cis-trikentrins and all known herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is converted into (+)-cis-trikentin A in four steps (Wittig reaction, alkene isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The previous synthesis of this molecule from (S)-(−)-malic acid involved more than 20 steps and a preparative HPLC separation of diastereomeric intermediates.
An adiabatic model of chemisorbed molecules: electron spectroscopy and excited-state potential-energy surfaces

Abstract We review models that have been used to understand excited states of chemisorbed species, focussing on CO and NO, and encounter problems in attempting to fit all observables. We then introduce a new model. We show that a purely-electronic adiabatic approximation leads to an accurate solution for the system wavefunction in the limit that the molecule-substrate interaction is weak. This produces a configuration-interaction theory that has a Hubbard-like form. We derive semi-empirical parameters for the NO:Pt(111) system and find that the transfer integral for the 2π-substrate interaction is small for all choices of the screened electron-electron interaction, U. This suggests, for this system, that the substrate indeed adiabatically follows the fluctuations in adsorbate charge which are inherent in a covalent bond. We propose that our model is robust and applies to many adsorbed molecules. We then investigate low-lying excited-states of the metal-molecule bond.
Synthetic mucin fragments. Methyl 6-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-beta-D-galactopyranoside, methyl 3,4-di-O-(2-acetamido-2-deoxy- beta-D-glucopyranosyl)-beta-D-galactopyranoside, and methyl O-(2-acetamido-2- deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D-galactopyranosyl-(1---- 3)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-beta-D-galactopyr ano side.

Condensation of methyl 2,6-di-O-benzyl-beta-D-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-alpha-D-glucopyrano)-[2,1 -d]-2- oxazoline (1) in 1,2-dichloroethane, in the presence of p-toluenesulfonic acid, afforded a trisaccharide derivative which, on deacetylation, gave methyl 3,4-di-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2,6-di-O-benzyl-bet a-D- galactopyranoside (5). Hydrogenolysis of the benzyl groups of 5 furnished the title trisaccharide (6). A similar condensation of methyl 2,3-di-O-benzyl-beta-D-galactopyranoside with 1 produced a partially-protected disaccharide derivative, which, on O-deacetylation followed by hydrogenolysis, gave methyl 6-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-beta-D-galactopyranoside (10). Condensation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D- glucopyranosyl)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside with 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2,4,6 -tri-O-acetyl-alpha-D-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of powdered mercuric cyanide gave a fully-protected tetrasaccharide derivative, which was O-deacetylated and then subjected to catalytic hydrogenation to furnish methyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta- D-galactopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl )- (1----3)-beta-D-galactopyranoside (15). The structures of 6, 10, and 15 were established by 13C-n.m.r. spectroscopy.
Simulation applied to a three hundred degree polynomial

Abstract A simulation technique called multi stage Monte Carlo optimization (MSMCO) is used to approximate the roots to a 300 degree polynomial. MSMCO consists of repeated random searches in an ever-narrowing focused region centred about the “best answer so far”. This process continues until a good approximate root is produced. Then it is factored out of the polynomial equation and the search for the next root begins in a similar fashion. Multi stage is a general purpose solution technique that can work on a wide variety of problems. Its best potential for application is for the approximate solutions to difficult problems.
The Roles of Ultra Wideband in Cognitive Networks

Cognitive radio is a recent concept that is expected to lead wireless communications to a new era. A proper candidate for the physical layer implementation of cognitive radio networks is ultra wideband (UWB), because UWB is highly competent in satisfying many basic requirements of cognitive radio. Beside this, UWB can also provide various kinds of supportive uses to cognitive radio systems that are realized by means of other wireless technologies. In this paper, a number of possible roles that UWB can take in cognitive networks are discussed in detail.