Combined quantum Monte Carlo - effective fragment molecular orbital method: fragmentation across covalent bonds.

The previously developed combined Quantum Monte Carlo-Effective Fragment Molecular Orbital (QMC-EFMO) method is extended to systems in which the fragmentation process cuts across covalent molecular bonds. The extended QMC-EFMO capability is demonstrated on a few model systems: the glycine tetramer, the diglycine reaction to form a dipeptide, silica-based rings, and polyalanine chains of increasing length. The agreement between full QMC and QMC-EFMO for the correlation energy is within 2 kcal mol-1 and for the correlation energy differences is within 1 kcal mol-1.

The daily progress system: A proof of concept pilot study of a recovery support technology tool for outpatient substance abuse treatment.

BACKGROUND: Illicit substance use remains highly prevalent in the US, and epidemiological surveillance surveys estimate that in 2015, over 27 million individuals (10.1% of the US population) 12 years of age or older used illicit drugs in the past 30 days.1 Outpatient treatment delivered in community-based settings is the dominant modality for addiction treatment, typically involving weekly psychosocial counseling sessions in an individual and/or group format.2,3 Unfortunately, relapse and premature treatment discontinuation are quite common in outpatient treatment.3-5 Objectives: This is a pilot proof of concept feasibility study involving clients presenting for outpatient SUD treatment. This study sought to examine the feasibility and acceptability of the Daily Progress System (DPS), a telephone-based software program, using interactive voice response (IVR), designed to enhance quality care and improve client outcomes. METHODS: Individuals who presented at the participating treatment clinic, who met study eligibility criteria, and who provided written informed consent to participate were included in the study (N = 15; 53.3% females). Incentives were paid to participants for calls completed. RESULTS: Participants completed 65% of scheduled daily call-ins, representing 273 person-days of data on client cravings, mood, substance use, and involvement in recovery support activities. The average call duration was approximately 2 minutes and 42 seconds. There was a high degree of client and counselor acceptance and satisfaction using the system. Conclusions and Clinical Significance: Findings suggest that the DPS appears to be a feasible means of potentially addressing relapse and treatment engagement issues based on client and counselor engagement and satisfaction with the system.

Pathway to the piezoelectronic transduction logic device.

The piezoelectronic transistor (PET) has been proposed as a transduction device not subject to the voltage limits of field-effect transistors. The PET transduces voltage to stress, activating a facile insulator-metal transition, thereby achieving multigigahertz switching speeds, as predicted by modeling, at lower power than the comparable generation field effect transistor (FET). Here, the fabrication and measurement of the first physical PET devices are reported, showing both on/off switching and cycling. The results demonstrate the realization of a stress-based transduction principle, representing the early steps on a developmental pathway to PET technology with potential to contribute to the IT industry.

Giant piezoresistive on/off ratios in rare-earth chalcogenide thin films enabling nanomechanical switching.

Sophisticated microelectromechanical systems for device and sensor applications have flourished in the past decade. These devices exploit piezoelectric, capacitive, and piezoresistive effects, and coupling between them. However, high-performance piezoresistivity (as defined by on/off ratio) has primarily been observed in macroscopic single crystals. In this Letter, we show for the first time that rare-earth monochalcogenides in thin film form can modulate a current by more than 1000 times due to a pressure-induced insulator to metal transition. Furthermore, films as thin as 8 nm show a piezoresistive response. The combination of high performance and scalability make these promising candidates for nanoscale applications, such as the recently proposed piezoelectronic transistor (PET). The PET would mechanically couple a piezoelectric thin film with a piezoresistive switching layer, potentially scaling to higher speeds and lower powers than today's complementary metal-oxide-semiconductor technology.

Salmon jumping: behavior, kinematics and optimal conditions, with possible implications for fish passageway design.

Behavioral and kinematic properties and capacities of wild migratory salmonid fishes swimming upstream and jumping up waterfalls generally have played only minor roles in the design and construction of passageways intended to help these fishes get past dams and other human-made obstacles blocking their movements. This paper reports the results of an experimental study of relevant behavioral and kinematic properties of adult kokanee salmon (Oncorhynchus nerka) jumping up waterfalls as they migrate upstream. We used a portable, adjustable apparatus to study in the field fish responding to artificial waterfalls under a range of flow conditions. We observed fish under conditions of varying water flow rates, pool depths, fall heights and fall angles. We analyzed digital video recordings of their behaviors. Kokanee salmon spontaneously jump up waterfalls within a relatively narrow range of conditions, including low flow speeds, near vertical angles and pool depth to fall height ratios near 1.0. Preferred values for each parameter are, to some extent, dependent on other parameters. In contrast to previous misconceptions, jumping behavior is initiated by running S-start accelerations from beneath the boils formed in the plunge pools below waterfalls, as opposed to C-start standing jumps from the surface. S-starts are immediately followed by burst swimming to the point of takeoff at the surface. These results can contribute to an improved basis for developing designs of fish passageways that may ultimately make them more effective and efficient.

Clinical efficacy and safety in head lice infection by Pediculus humanis capitis De Geer (Anoplura: Pediculidae) of a capillary spray containing a silicon-oil complex.

Head lice are endemic worldwide. Resistance to permethrin and doubts about the safety of pesticides promoted the use of physical therapies (wet-combing, dry-on suffocation). The aim of our study was to test the pediculicidal and ovicidal effects of one application of a silicon-oil complex composed of dimethiconol and castor oil. The study was a prospective cohort of 108 infested patients (11 males, 97 females; 58 children, 50 adults), in Sri-Lanka. Pediculicidal efficacy was evaluated as the percentage of patients free of live lice one hour after the application of the treatment and at day 1 (wet combing). Ovicidal efficacy was calculated as the proportion of subjects without larval stages at days 1 and 7 among subjects followed up all over the study. In normal conditions of use, in this open cohort, a pediculicidal effect of a dimethiconol-castor-oil lotion was.shown one hour after application in 99/108 (91.7%) treated subjects and at day 1 in 86/99 (87%) subjects and an ovicidal effect at day 7 in 79/108 (73.2%) treated subjects. A second application of the same product was necessary to increase the cure rate to 79.6% (86/108) at day 8. In our study, the second application of the same product was performed seven days later, but the best time for additional applications should be defined in further studies. However, the efficacy of this safe physical treatment was similar to that of chemical pediculicides (malathion, permethrin).

Nanojets, electrospray, and ion field evaporation: molecular dynamics simulations and laboratory experiments.

The energetics, interfacial properties, instabilities, and fragmentation patterns of electrosprays made from formamide salt solutions are investigated in a mass spectrometric vacuum electrospray experiment and using molecular dynamics (MD) simulations. The electrospray source is operated in a Taylor cone-jet mode, with the nanojet that forms being characterized by high surface-normal electric field strengths in the vicinity of 1 V/nm. Mass-to-charge ratios were determined for both positive and negative currents sprayed from NaI-formamide solutions with solute-solvent mole ratios of 1:8.4 and 1:36.9, and from KI-formamide solutions with mole ratios of 1:41 and 1:83. The molecular dynamics simulations were conducted on isolated 10 nm NaI-formamide droplets at mole ratios of 1:8 and 1:16. The droplet was subjected to a uniform electric field with strengths ranging between 0.5 and 1.5 V/nm. Both the experiments and simulations demonstrate a mixed charge emission regime where field-induced desorption of solvated ions and charged droplets occurs. The macroscopic parameters, such as average mass-to-charge ratio and maximum surface-normal field strengths deduced from the simulations are found to be in good agreement with the experimental work and consistent with electrohydrodynamic theory of cone-jets. The observed mass spectrometric Na (+) and I (-) solvated ion distributions are consistent with a thermal evaporation process, and are correctly reproduced by the simulation after incorporation of the different flight times and unimolecular ion dissociation rates in the analysis. Alignment of formamide dipoles and field-induced reorganization of the positive and negative ionic charges in the interfacial region are both found to contribute to the surface-normal field near the points of charge emission. In the simulations the majority of cluster ions are found to be emitted from the tip of the jet rather than from the neck region next to the Taylor cone. This finding is consistent with the experimental energy distributions of the solvated ions which demonstrate that indeed most ions are emitted closer to the jet region, that is, beyond the cone-neck region where ohmic losses occur. This observation is also consistent with continuum electrohydrodynamic predictions of cluster-ion evaporation at surface regions of high curvature and therefore maximum surface electric field strengths, which may be the cone-neck region, the breakup region of the jet (usually near the tip of the jet), or the emitted charged droplets. In the nanoscale jets observed in this study, the regions of highest spatial curvature are at the ends of the jets where nascent drops either are forming or have just detached.

Evidence of self-correcting spiral flows in swimming boxfishes.

The marine boxfishes have rigid keeled exteriors (carapaces) unlike most fishes, yet exhibit high stability, high maneuverability and relatively low drag given their large cross-sectional area. These characteristics lend themselves well to bioinspired design. Based on previous stereolithographic boxfish model experiments, it was determined that vortical flows develop around the carapace keels, producing self-correcting forces that facilitate swimming in smooth trajectories. To determine if similar self-correcting flows occur in live, actively swimming boxfishes, two species of boxfishes (Ostracion meleagris and Lactophrys triqueter) were induced to swim against currents in a water tunnel, while flows around the fishes were quantified using digital particle image velocimetry. Significant pitch events were rare and short lived in the fishes examined. When these events were observed, spiral flows around the keels qualitatively similar to those observed around models were always present, with greater vortex circulation occurring as pitch angles deviated from 0 degrees . Vortex circulation was higher in live fishes than models presumably because of pectoral fin interaction with the keel-induced flows. The ability of boxfishes to modify their underlying self-correcting system with powered fin control is important for achieving high levels of both stability and maneuverability. Although the challenges of performing stability and maneuverability research on fishes are significant, the results of this study together with future studies employing innovative new approaches promise to provide valuable inspiration for the designers of bioinspired aquatic vehicles.

IR photodissociation spectroscopy and theory of Au+(CO)n complexes: nonclassical carbonyls in the gas phase.

Au+(CO)n complexes are produced in the gas phase via pulsed laser vaporization, expanded in a supersonic jet, and detected with a reflectron time-of-flight mass spectrometer. Complexes up to n = 12 are observed, with mass channels corresponding to the n = 2 and n = 4 showing enhanced intensity. To investigate coordination and structure, individual complexes are mass-selected and probed with infrared photodissociation spectroscopy. Spectra in the carbonyl stretching region are measured for the n = 3-7 species, but no photodissociation is observed for n = 1, 2 due to the strong metal cation-ligand binding. The carbonyl stretch in these systems is blue-shifted 50-100 cm-1 with respect to the free CO vibration (2143 cm-1), providing evidence that these species are so-called "nonclassical" metal carbonyls. Theory at the MP2 and CCSD(T) levels provides structures for these complexes and predicted spectra to compare to the experiment. Excellent agreement is obtained between experiment and theory, establishing that the n = 3 complex is trigonal planar and the n = 4 complex is tetrahedral.

Accurate ab initio potential energy curve of F2. II. Core-valence correlations, relativistic contributions, and long-range interactions.

The nonrelativistic, valence-shell-only-correlated ab initio potential energy curve of the F(2) molecule, which was reported in the preceding paper, is complemented by determining the energy contributions that arise from the electron correlations that involve the core electrons as well as the contributions that are due to spin-orbit coupling and scalar relativistic effects. The dissociation curve rises rather steeply toward the energy of the dissociated atoms because, at larger distances, the atomic quadrupole-quadrupole repulsion and spin-orbit coupling counteract the attractive contributions from incipient covalent binding and correlation forces including dispersion.

Accurate ab initio potential energy curve of F2. III. The vibration rotation spectrum.

An analytical expression is found for the accurate ab initio potential energy curve of the fluorine molecule that has been determined in the preceding two papers. With it, the vibrational and rotational energy levels of F(2) are calculated using the discrete variable representation. The comparison of this theoretical spectrum with the experimental spectrum, which had been measured earlier using high-resolution electronic spectroscopy, yields a mean absolute deviation of about 5 cm(-1) over the 22 levels. The dissociation energy with respect to the lowest vibrational energy is calculated within 30 cm(-1) of the experimental value of 12 953+/-8 cm(-1). The reported agreement of the theoretical spectrum and dissociation energy with experiment is contingent upon the inclusion of the effects of core-generated electron correlation, spin-orbit coupling, and scalar relativity. The Dunham analysis [Phys. Rev. 41, 721 (1932)] of the spectrum is found to be very accurate. New values are given for the spectroscopic constants.

Infrared spectra and ab initio calculations for the F- -(CH4)n (n = 1-8) anion clusters.

Infrared spectra of mass-selected F- -(CH4)n (n = 1-8) clusters are recorded in the CH stretching region (2500-3100 cm-1). Spectra for the n = 1-3 clusters are interpreted with the aid of ab initio calculations at the MP2/6-311++G(2df 2p) level, which suggest that the CH4 ligands bind to F- by equivalent, linear hydrogen bonds. Anharmonic frequencies for CH4 and F--CH4 are determined using the vibrational self-consistent field method with second-order perturbation theory correction. The n = 1 complex is predicted to have a C3v structure with a single CH group hydrogen bonded to F-. Its spectrum exhibits a parallel band associated with a stretching vibration of the hydrogen-bonded CH group that is red-shifted by 380 cm-1 from the nu1 band of free CH4 and a perpendicular band associated with the asymmetric stretching motion of the nonbonded CH groups, slightly red-shifted from the nu3 band of free CH4. As n increases, additional vibrational bands appear as a result of Fermi resonances between the hydrogen-bonded CH stretching vibrational mode and the 2nu4 overtone and nu2+nu4 combination levels of the methane solvent molecules. For clusters with n < or = 8, it appears that the CH4 molecules are accommodated in the first solvation shell, each being attached to the F- anion by equivalent hydrogen bonds.

Interference with nuclear factor kappa B and c-Jun NH2-terminal kinase signaling by TRAF6C small interfering RNA inhibits myeloma cell proliferation and enhances apoptosis.

The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) family of six adaptor proteins (TRAF1-6) links the TNFR superfamily to the nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) transcriptional activators. Unlike other TRAFs, TRAF6 is also involved in Toll-like/interleukin (IL)-1 receptor (TIR) signal transduction. Thus, inhibition of TRAF6 function could interrupt both CD40 (TNFR family) and IL-1 growth signals, pathways critical to myeloma proliferation. To block TRAF6-mediated IL-1 signaling, we constructed small interfering RNA (siRNA) against TRAF6. We found that siRNA targeting the TRAF6 C-terminal (siTRAF6C) receptor interaction domain specifically reduced only TRAF6 protein expression, without affecting TRAF2 or 5 levels, and substantially interfered with IL-1-induced NF-kappaB and c-Jun/AP-1 activation. Inhibition by siTRAF6C was concentration-dependent. SiTRAF6C also significantly reduced myeloma proliferation and enhanced apoptosis in a similar dose-dependent fashion in vitro. More importantly, marked siTRAF6C growth inhibition was detected in vivo when these cells were implanted into the bone marrow of irradiated normal mice. In contrast, introduction of siRNA derived from the TRAF6 Zn-finger domain or an irrelevant siRNA construct failed to alter cell growth or cell death. These studies suggest that TRAF6 may be a new molecular target to block cell signal transduction important for the survival and proliferation of multiple myeloma cells.

Synthesis of hydroxy and methoxy perylene quinones, their spectroscopic and computational characterization, and their antiviral activity.

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (approximately 450-800 nm) and relatively more intense and narrow features at wavelengths < or = 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S0 to S2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin.

Adoption and integration of simulation-based learning technologies into the curriculum of a UK Undergraduate Education Programme.

CONTEXT: At a time of significant changes in medical education world-wide, the international dimensions and global issues relating to the application of new learning technologies have been recognised. OBJECTIVE: The aim of this paper is to describe the adoption and integration within the curriculum in one United Kingdom (UK) medical school of 'Harvey', the Cardiology Patient Simulator, and the UMedic multimedia computer-based cardiology curriculum - resources developed in a medical school in the USA. PARTICIPANTS: The integration of the resources into the curriculum is described by 3 teachers actively involved in the cardiology curriculum of the UK medical school and 3 teachers associated with the development of resources in the USA. ASPECTS CONSIDERED: The review considers the adoption of Harvey and UMedic in the UK in programmes in relation to: curricular issues, training needs, learning outcomes, curriculum content and sequences of content, educational strategies, teaching and learning methods, assessment, communication about the curriculum and management of the curriculum. CONCLUSIONS: Learning resources, in the form of simulators and computer-based learning modules, developed in one country can be successfully adopted and implemented in another. Facets that facilitated the adoption included close liaison between the developers of the resources in the USA and the implementers in the UK, and careful and systematic planning including in-depth integration of the simulation-based resources into the required curriculum rather than their relegation to a peripheral ad hoc position. The successful use of simulators such as Harvey requires the presence of a 'champion', a clinician educator and a supporting administrative staff who ensure the simulator's appropriate use.

Changes in bodily awareness induced by immersive virtual reality.

The recent proliferation of virtual reality technology has attracted the interest of social scientists who study human behavior and perceptual experience. Such computer simulations are able to present technologically rendered environments, where the properties of the physical world are approximated or manipulated to varying degrees. The present study sought to investigate the influence of an immersive virtual experience on the perceptual awareness of the body. A body awareness questionnaire was administered to users of a desktop and an immersive implementation of a virtual environment (the Cityscape). The results indicated a significant main effect for the mode of presentation (i.e., desktop or immersive), no gender effects, and no interaction effect between gender and the mode of presentation. Test of between-subjects effects for the mode of presentation found significant differences on a number of body awareness dimensions. The desktop group were found to experience higher levels of skin, muscular, and cardiovascular awareness, while the immersive group experienced higher levels of body boundary ambiguity and aural awareness.

Identification of a vibrational frequency corresponding to H-atom translocation in hypericin.

Using time-resolved infrared spectroscopy, ab initio quantum mechanical calculations and synthetic organic chemistry a region in the infrared spectrum of triplet hypericin has been found between 1400 and 1500 cm-1 corresponding to the translocation of the hydrogen atom between the enol and the keto oxygens, O...H...O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.

Epoetin treatment of anemia associated with cancer therapy: a systematic review and meta-analysis of controlled clinical trials.

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Audiovisual Speech Web-Lab: an Internet teaching and research laboratory.

Internet resources now enable laboratories to make full-length experiments available on line. A handful of existing web sites offer users the ability to participate in experiments and generate usable data. We have integrated this technology into a web site that also provides full discussion of the theoretical and methodological aspects of the experiments using text and simple interactive demonstrations. The content of the web site (http://www.psych.ucr.edu/avspeech/lab) concerns audiovisual speech perception and its relation to face perception. The site is designed to be useful for users of multiple interests and levels of expertise.

Outpatient biochemotherapy with interleukin-2 and interferon alfa-2b in patients with metastatic malignant melanoma: results of two phase II cytokine working group trials.

PURPOSE: The Cytokine Working Group performed a randomized phase II trial of two outpatient biochemotherapy regimens to identify an outpatient regimen with high antitumor activity and less toxicity than inpatient regimens which might be compared with chemotherapy or inpatient biochemotherapy regimens in future phase III trials. PATIENTS AND METHODS: Eighty-one patients with metastatic malignant melanoma received dacarbazine 250 mg/m(2)/d intravenously (IV) and cisplatin 25 mg/m(2)/d IV on days 1, 2, and 3, plus interferon (IFN) alfa-2b 5 mU/m(2) subcutaneously (SC) on days 6, 8, 10, 13, and 15, given every 28 days. Interleukin-2 (IL-2) was given daily on days 6 to 10 and 13 to 15. In group 1, IV IL-2 was given at 18.0 MU/m(2), and in group 2, SC IL-2 was given at 5.0 mU/m(2). RESULTS: In group 1 (IV IL-2), there were five complete responses (CRs) and 11 partial responses (PRs) among 44 patients (objective response rate [ORR], 36%; 95% confidence interval [CI], 22% to 51%). In group 2 (SC IL-2), there was one CR and five PRs among the 36 patients (ORR, 17%; 95% CI, 4% to 29%). The median survival was 10.7 months in group 1 and 7.3 months in group 2. Eleven patients in group 1 and four patients in group 2 remain alive as of the last follow-up. Toxicities in both groups were similar. No patient required hospitalization for neutropenic fever. CONCLUSION: Biochemotherapy has activity in these outpatient regimens with acceptable toxicity. The antitumor activity observed with the IV IL-2 regimen seems similar to that of inpatient biochemotherapy regimens. If inpatient biochemotherapy regimens develop an established role in the management of melanoma, future phase III trial comparisons with this outpatient IV IL-2 regimen would be appropriate.