bluuebunny/crossref_metadata_2025 huggingface dataset:
Allowing for uncertainty due to missing continuous outcome data in pairwise and network meta‐analysis
Authors: Mavridis Dimitris , White Ian R. , Higgins Julian P. T. , Cipriani Andrea , Salanti Georgia
Published: November 2014

Missing outcome data are commonly encountered in randomized controlled trials and hence may need to be addressed in a meta‐analysis of multiple trials. A common and simple approach to deal with missing data is to restrict analysis to individuals for whom the outcome was obtained (complete case analysis). However, estimated treatment effects from complete case analyses are potentially biased if informative missing data are ignored. We develop methods for estimating meta‐analytic summary treatment effects for continuous outcomes in the presence of missing data for some of the individuals within the trials. We build on a method previously developed for binary outcomes, which quantifies the degree of departure from a missing at random assumption via the informative missingness odds ratio. Our new model quantifies the degree of departure from missing at random using either an informative missingness difference of means or an informative missingness ratio of means, both of which relate the mean value of the missing outcome data to that of the observed data. We propose estimating the treatment effects, adjusted for informative missingness, and their standard errors by a Taylor series approximation and by a Monte Carlo method. We apply the methodology to examples of both pairwise and network meta‐analysis with multi‐arm trials. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
A Bayesian approach for instrumental variable analysis with censored time‐to‐event outcome
Authors: Li Gang , Lu Xuyang
Published: November 2014

Instrumental variable (IV) analysis has been widely used in economics, epidemiology, and other fields to estimate the causal effects of covariates on outcomes, in the presence of unobserved confounders and/or measurement errors in covariates. However, IV methods for time‐to‐event outcome with censored data remain underdeveloped. This paper proposes a Bayesian approach for IV analysis with censored time‐to‐event outcome by using a two‐stage linear model. A Markov chain Monte Carlo sampling method is developed for parameter estimation for both normal and non‐normal linear models with elliptically contoured error distributions. The performance of our method is examined by simulation studies. Our method largely reduces bias and greatly improves coverage probability of the estimated causal effect, compared with the method that ignores the unobserved confounders and measurement errors. We illustrate our method on the Women's Health Initiative Observational Study and the Atherosclerosis Risk in Communities Study. Copyright © 2014 John Wiley & Sons, Ltd.
Assessing temporal agreement between central and local progression‐free survival times
Authors: Zeng Donglin , Cornea Emil , Dong Jun , Pan Jean , Ibrahim Joseph G.
Published: November 2014

In oncology clinical trials, progression‐free survival (PFS), generally defined as the time from randomization until disease progression or death, has been a key endpoint to support licensing approval. In the U.S. Food and Drug Administration guidance for industry, May 2007, concerning the PFS as the primary or co‐primary clinical trial endpoint, it is recommended to have tumor assessments verified by an independent review committee blinded to study treatments, especially in open‐label studies. It is considered reassuring about the lack of reader‐evaluation bias if treatment effect estimates from the investigators' and independent review committees' evaluations agree. The agreement between these evaluations may vary for subjects with short or long PFS, while there exist no such statistical quantities that can completely account for this temporal pattern of agreements. Therefore, in this paper, we propose a new method to assess temporal agreement between two time‐to‐event endpoints, while the two event times are assumed to have a positive probability of being identical. This method measures agreement in terms of the two event times being identical at a given time or both being greater than a given time. Overall scores of agreement over a period of time are also proposed. We propose a maximum likelihood estimation to infer the proposed agreement measures using empirical data, accounting for different censoring mechanisms, including reader's censoring (event from one reader dependently censored by event from the other reader). The proposed method is demonstrated to perform well in small samples via extensive simulation studies and is illustrated through a head and neck cancer trial. Copyright © 2014 John Wiley & Sons, Ltd.
The Relationship Between Perceived Stress and Telomere Length: A Meta‐analysis
Authors: Schutte Nicola S. , Malouff John M.
Published: November 2014

Telomeres protect the ends of chromosomes, and short telomere length is associated with poor health and mortality. This study reports a meta‐analytic investigation of the relationship between perceived stress and telomere length, including results from eight studies with a total of 1143 participants. A meta‐analytic effect size of r = −0.25, p < 0.001, indicated that higher levels of perceived stress were associated with shorter telomere length. Examination of the studies for moderators of effect size identified some significant moderators, such as a difference in effect sizes between samples comprised of only women and mixed‐sex samples. These results are only suggestive as they are based on a small set of studies, and funnel plot analyses indicated a publication bias. A significant relationship between more perceived stress and shorter telomere length is consistent with theoretical frameworks positing that stress induces physiological changes that result in shortened telomeres. Copyright © 2014 John Wiley & Sons, Ltd.
Effect of Interpersonal and Cognitive Stressors on Habituation and the Utility of Heart Rate Variability to Measure Habituation
Authors: Feda Denise M. , Roemmich James N.
Published: November 2014

Habituation is a decrease in responding to a repeated stimulus. Operant responding and salivation measure habituation in eating behaviour research. Stress may increase eating by acting as a distractor, yielding spontaneous recovery and prolonging responding for food. Our research tested differences in the ability of cognitive and interpersonal stressors to recover responding for food. We also tested heart rate variability (HRV) as a measure of habituation. Twenty women worked for portions of macaroni and cheese for 15 trials on three separate laboratory visits. Between the 12th and 13th trial, one of three different stressor types (speech, stroop and subtraction) was presented during each visit. HRV was measured continuously throughout the laboratory visits. Responding for food declined across the 12 trials with no difference in rate of habituation by visit (p > 0.8) There was no difference between stressor type in the magnitude of spontaneous recovery after each stressor (p > 0.8). Rates of habituation of HRV variables correlated (p < 0.02) with the rate of operant responding habituation. Cognitive and interpersonal stressors do not differ in their ability to recover reduced responding for food. HRV variables may measure habituation to food similar to operant responding. Copyright © 2014 John Wiley & Sons, Ltd.
Physiological, Perceptual and Psychological Responses of Career versus Volunteer Firefighters to Live‐fire Training Drills
Authors: Petruzzello Steven J. , Poh Paula Y.S. , Greenlee Tina A. , Goldstein Eric , Horn Gavin P. , Smith Denise L.
Published: November 2014

A primary objective of the present study was to examine the effect of short‐term live‐fire firefighting activities on key physiological, perceptual and psychological variables and whether occupational status influenced these responses. It was also of interest to examine whether individual difference factors differentiated the occupational status groups and if so, whether such individual difference factors influenced perceptual and psychological responses to firefighting activities. Male firefighters (n = 52 career, n = 53 volunteer firefighters) participated in 18 min of simulated firefighting activity in a training structure that contained live fires. Measures of heart rate (HR) and Tcore were obtained before and after firefighting activities along with perceptions of thermal sensations, exertion, respiratory distress and affect. Firefighting activities resulted in significant elevations in HR and Tcore, whereas thermal sensations, respiratory distress, exertion and affect all showed significant and sizable changes reflecting greater distress and dysphoria. Occupational status and individual difference factors accounted for some of this negative change. The findings replicate and extend previous work by demonstrating the influence of occupational status and individual difference factors in the psychological responses to firefighting activity. Copyright © 2014 John Wiley & Sons, Ltd.
Protein‐based functional nanomaterial design for bioengineering applications
Authors: Desai Malav S. , Lee Seung‐Wuk
Published: November 2014

In this review article, we describe recent progress in the field of protein‐based bionanomaterial design with focus on the four well‐characterized proteins: mammalian elastin and collagen, and insect‐derived silk and resilin. These proteins are important structural components and understanding their physical and biochemical properties has allowed us to not only replicate them but also create novel smart materials. The ‘smart’ properties of a material include its ability to self‐assemble, respond to stimuli, and/or promote cell interactions. Such properties can be attributed to unique structural modules from elastin, collagen, silk, and resilin as well as functional modules identified from other proteins directly or using display techniques such as phage display. Thus, the goal of this article is to not only emphasize the types of protein‐based peptide modules and their uses but also encourage and inspire the reader to create new toolsets of smart polypeptides to overcome their challenges. WIREs Nanomed Nanobiotechnol 2015, 7:69–97. doi: 10.1002/wnan.1303

This article is categorized under:

Implantable Materials and Surgical Technologies > Nanomaterials and Implants

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Neuropsychological Outcome after Endoscopic Third Ventriculostomy
Authors: Hader Walter J. , Brooks Brian L. , Partlo Lisa , Hamilton Mark
Published: November 2014

Background:Cognitive dysfunction is a common complaint associated with obstructive hydrocephalus. The purpose of this study was to determine the effect of endoscopic third ventriculostomy (ETV) on the neuropsychological outcome in patients presenting with cognitive decline and obstructive hydrocephalus.Methods:A retrospective review of patients who underwent ETV at the University of Calgary and had both pre and post operative neuropsychological testing, was completed. Presenting clinical features, etiology of hydrocephalus and ventricle size utilizing frontal occipital horn ratio was obtained. Outcomes and complications of the ETV were recorded. Detailed measures of intelligence, attention and concentration, executive function, visual and verbal memory, language functions and fine motor skills were completed. Post treatment change was determined utilizing Reliable Change Index.Results:A total of 13 patients were identified. Etiology of the hydrocephalus was aqueductal stenosis in 8 and tectal glioma in 4. The majority of patients (11 of 13, 85%) demonstrated cognitive dysfunction at the borderline (≤1 SD) or impairment level (≤1.5 SDs) in at least one domain. Nine patients (69%) showed reliable improvement in at least one cognitive domain. The greatest improvement was seen with visual memory (42%). One quarter to one third of patients demonstrated improvement on tests of intelligence quotient, verbal memory, attention and concentration, and executive function. Two patients declined in executive functioning. Ventricle size improved in eight patients.Conclusions:ETV is a safe effective procedure, capable of producing reliable improvements in cognitive dysfunction with hydrocephalus. Patients with cognitive complaints alone may benefit from ETV.
Is psychiatry only neurology? Or only abnormal psychology? Déjà vu after 100 years
Authors: de Leon Jose
Published: November 2014

Forgetting history, which frequently repeats itself, is a mistake. In General Psychopathology, Jaspers criticised early 20th century psychiatrists, including those who thought psychiatry was only neurology (Wernicke) or only abnormal psychology (Freud), or who did not see the limitations of the medical model in psychiatry (Kraepelin). Jaspers proposed that some psychiatric disorders follow the medical model (Group I), while others are variations of normality (Group III), or comprise schizophrenia and severe mood disorders (Group II). In the early 21st century, the players’ names have changed but the game remains the same. The US NIMH is reprising both Wernicke’s brain mythology and Kraepelin’s marketing promises. The neo-Kraepelinian revolution started at Washington University, became pre-eminent through the DSM-III developed by Spitzer, but reached a dead end with the DSM-5. McHugh, who described four perspectives in psychiatry, is the leading contemporary representative of the Jaspersian diagnostic approach. Other neo-Jaspersians are: Berrios, Wiggins and Schwartz, Ghaemi, Stanghellini, Parnas and Sass. Can psychiatry learn from its mistakes? The current psychiatric language, organised at its three levels, symptoms, syndromes, and disorders, was developed in the 19th century but is obsolete for the 21st century. Scientific advances in Jaspers’ Group III disorders require collaborating with researchers in the social and psychological sciences. Jaspers’ Group II disorders, redefined by the author as schizophrenia, catatonic syndromes, and severe mood disorders, are the core of psychiatry. Scientific advancement in them is not easy because we are not sure how to delineate between and within them correctly.
THE INFLUENCE OF NON-GENETIC FACTORS ON EARLY GROWTH OF HALABA KIDS UNDER SMALLHOLDER MANAGEMENT SYSTEMS, SOUTHERN ETHIOPIA
Authors: TALORE DERIBE G. , ABEBE GIRMA , TEGEGNE AZAGE
Published: November 2014

Stagnant early growth and mortality are the major constraints for goat production in Ethiopia. We evaluated the effects of non-genetic factors on early growth performance of kids in Halaba district of southern Ethiopia, on-farm monitoring with 587 kids owned by 60 households from 2008 to 2009. Body weight (kilograms) of kids at birth, 30, 60, 90, 120 and 150 days were 2.34, 4.39, 6.61, 9.85, 11.8 and 13.7, respectively, while the average daily gain (ADG; gram) from birth to 30, 60, 90, 120 and 150 days were 68.3, 70.4, 82.3, 78.3 and 75.0, respectively. Season had profound effect on body weights of kids at all ages (except at 120 days) and ADG. There was significant sex effect on body weights from 30 to 120 days (P < 0.05). Parity influenced body weights of kids at birth (P < 0.01) and 30, 60, 120 and 150 days (P < 0.05). Type of birth affected pre-weaning body weights (P < 0.05) and ADG from birth to 30, 60 days (P < 0.01) and birth to 90 days (P < 0.05). There were significant (P < 0.05) effects of parity by sex and parity by type of birth on body weights and ADG at weaning. The non-genetic factors evaluated in this study are important sources of variation and need to be taken into account in the improvement plan of Halaba goats under semi-arid tropical conditions.
SOIL AND PLANT SILICON STATUS IN OIL PALM CROPS IN COLOMBIA
Authors: MUNEVAR M. F. , ROMERO F. A.
Published: November 2014

A study was conducted, including 17 oil palm (Elaeis guineensisJacq) crops distributed throughout Colombia, to determine how much silicon (Si) this plant species accumulates in their leaves, and also to determine the available Si levels in the soils. The study was conceived as a preliminary step of a research project aimed at determining whether the beneficial effects of Si, which have been identified for other species also, occur in the oil palm crop. Available Si varied among soils; lower levels were found in the soils with characteristics associated with greater weathering as compared with less weathered soils. Relatively high leaf Si levels were found in all of the sites studied and this was interpreted as an indication that oil palm could be considered a Si accumulator. An increase in Si concentration with leaf age was found, indicating that this element probably behaves as a non-mobile element in the plant. A defined relationship between soil available Si and Si concentration in the leaves was not found, however. The results indicate that it is worthwhile conducting specific studies to determine the effects of Si on oil palm growth and behaviour, and provide useful criteria for the design of future studies.
Hermann von Helmholtz's Empirico-Transcendentalism Reconsidered: Construction and Constitution in Helmholtz's Psychology of the Object
Authors: De Kock Liesbet
Published: November 2014

Argument

This paper aims at contributing to the ongoing efforts to get a firmer grasp of the systematic significance of the entanglement of idealism and empiricism in Helmholtz's work. Contrary to existing analyses, however, the focal point of the present exposition is Helmholtz's attempt to articulate a psychological account of objectification. Helmholtz's motive, as well as his solution to the problem of the object are outlined, and interpreted against the background of his scientific practice on the one hand, and that of empiricist and (transcendental) idealist analyses of experience on the other. The specifically psychological angle taken, not only prompts us to consider figures who have hitherto been treated as having only minor import for Helmholtz interpretation (most importantly J.S. Mill and J.G. Fichte), it furthermore sheds new light on some central tenets of the latter's psychological stance that have hitherto remained underappreciated. For one thing, this analysis reveals an explicit voluntarist tendency in Helmholtz's psychological theory. In conclusion, it is argued that the systematic significance of Helmholtz's empirico-transcendentalism with respect to questions of the mind is best understood as an attempt to found his empirical theory of perception in a second order, normative account of epistemic subjectivity.
Bedgap: where next for Antarctic subglacial mapping?
Authors: Pritchard Hamish D.
Published: November 2014

The recently published Bedmap2 datasets mark the culmination of several decades of subice and subocean Antarctic topographic surveying by many nations, but maps of the topographic data distribution show that in the global context, the Antarctic bed remains very poorly sampled. Most of the remaining large unmapped areas on Earth lie under Antarctic ice and polar surveying continues to be difficult and expensive, thus it is important to identify where future efforts should be concentrated. A survey of 75 experts in various aspects of polar science shows that a lack of adequate topographic data is an important constraint in several themes, but the data gaps and the data needs do not tend to coincide. There is strong demand for higher resolution surveying in previously visited areas, particularly in the most dynamic and most rapidly changing regions as identified by glaciologists, oceanographers, hydrologists, biologists and geomorphologists, while geologists and ice core scientists focus on the most important areas for understanding Antarctica over deeper time. The data requirements identified here could be addressed for most areas given sufficient time and funding, but the technology needed to survey the interiors of the large ice shelf cavities has only just been developed.
Useful Scores: Multiple formats for electroacoustic performers to study, rehearse and perform
Authors: Hron Terri
Published: November 2014

This short article presents the author’s ideas about different score formats for instrumental performers of mixed electroacoustic music. Following a trajectory from initial understanding through effective rehearsal and ending in performance, different score formats are discussed. Each is based on and addresses performers’ needs and improves documentation and transmission of the composer’s intentions and the performer’s contribution. The author bases these suggestions on her experience as a performer/commissioner and composer of new mixed electroacoustic works, many of which are collaborative creations.
Biased access? Exploring selection to advisory committees
Authors: Rasmussen Anne , Gross Vlad
Published: November 2014

The existing literature on bias in interest group access faces the challenge that there is often no clear benchmark for judging whether a given distribution of interest groups involved in policy making is biased. To tackle this challenge, we link two new data sets on registered European Union (EU) interest groups and membership of the advisory committees of the European Commission and examine the factors affecting selection to these committees. Our approach allows us to qualify the conclusions of the existing literature. We see that, even if business interests dominate advisory committees, they are not generally privileged over other group types in the selection processes and their degree of access varies considerably between policy areas. Instead, supranational interest groups enjoy selection privileges, which are particularly pronounced on permanent committees. Finally, we find some evidence that, even though lobbying budgets are important for getting access, their value varies across group types. In this way, our study has implications for future theory building on resource exchanges between interest group types and decision makers.
Wie beeinflusst Schokolade die Blutgefässe?
Authors: Flammer Andreas J. , Sudano Isabella
Published: November 2014

Seit Jahrtausenden ist Kakao ein beliebtes Nahrungsmittel, dem eine gesundheitsfördernde Wirkung nachgesagt wird. Beobachtungsstudien sowie grosse epidemiologische Studien weisen auf eine mögliche günstige Wirkung von dunkler Schokolade auf die kardiovaskuläre Gesundheit hin. Mehrere kleine kontrollierte Studien zeigen tatsächlich eine Verbesserung der endothelialen Dysfunktion – also der Verbesserung der Fehlfunktion der Gefässinnenschicht – nach Einnahme von dunkler, Flavanol-reicher Schokolade. Dies ist insbesondere deshalb wichtig, da eine gestörte Endothelfunktion ein wichtiger Marker für die Entstehung der Atherosklerose und eine wichtige Vorhersage für kardiovaskuläre Ereignisse ist. Dieser Artikel fasst die akutelle Literatur zusammen.
Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival
Authors: Eaton G J , Zhang Q-S , Diallo C , Matsuzawa A , Ichijo H , Steinbeck M J , Freeman T A
Published: November 2014

Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has clinical potential to treat fractures or to slow osteoarthritic progression by enhancing chondrocyte survival and slowing hypertrophy.
Customized patterned substrates for highly versatile correlative light-scanning electron microscopy
Authors: Benedetti Lorena , Sogne Elisa , Rodighiero Simona , Marchesi Davide , Milani Paolo , Francolini Maura
Published: November 2014

Correlative light electron microscopy (CLEM) combines the advantages of light and electron microscopy, thus making it possible to follow dynamic events in living cells at nanometre resolution. Various CLEM approaches and devices have been developed, each of which has its own advantages and technical challenges. We here describe our customized patterned glass substrates, which improve the feasibility of correlative fluorescence/confocal and scanning electron microscopy.
Two-electron Rabi oscillations in real-time time-dependent density-functional theory
Authors: Habenicht Bradley F. , Tani Noriyuki P. , Provorse Makenzie R. , Isborn Christine M.
Published: November 2014

We investigate the Rabi oscillations of electrons excited by an applied electric field in several simple molecular systems using time-dependent configuration interaction (TDCI) and real-time time-dependent density-functional theory (RT-TDDFT) dynamics. While the TDCI simulations exhibit the expected single-electron Rabi oscillations at a single resonant electric field frequency, Rabi oscillations in the RT-TDDFT simulations are a two-electron process. The existence of two-electron Rabi oscillations is determined both by full population inversion between field-free molecular orbitals and the behavior of the instantaneous dipole moment during the simulations. Furthermore, the Rabi oscillations in RT-TDDFT are subject to an intensity threshold of the electric field, below which Rabi oscillations do not occur and above which the two-electron Rabi oscillations occur at a broad range of frequencies. It is also shown that at field intensities near the threshold intensity, the field frequency predicted to induce Rabi oscillations by linear response TDDFT only produces detuned Rabi oscillations. Instead, the field frequency that yields the full two-electron population inversion and Rabi oscillation behavior is shown to be the average of single-electron transition frequencies from the ground S0 state and the doubly-excited S2 state. The behavior of the two-electron Rabi oscillations is rationalized via two possible models. The first model is a multi-photon process that results from the electric field interacting with the three level system such that three level Rabi oscillations may occur. The second model suggests that the mean-field nature of RT-TDDFT induces paired electron propagation.
Quantum partition functions of composite particles in a hydrogen-helium plasma via path integral Monte Carlo
Authors: Wendland D. , Ballenegger V. , Alastuey A.
Published: November 2014

We compute two- and three-body cluster functions that describe contributions of composite entities, like hydrogen atoms, ions H−, \documentclass[12pt]{minimal}\begin{document}${\rm H}_2^+$\end{document}H2+, and helium atoms, and also charge-charge and atom-charge interactions, to the equation of state of a hydrogen-helium mixture at low density. A cluster function has the structure of a truncated virial coefficient and behaves, at low temperatures, like a usual partition function for the composite entity. Our path integral Monte Carlo calculations use importance sampling to sample efficiently the cluster partition functions even at low temperatures where bound state contributions dominate. We also employ a new and efficient adaptive discretization scheme that allows one not only to eliminate Coulomb divergencies in discretized path integrals, but also to direct the computational effort where particles are close and thus strongly interacting. The numerical results for the two-body function agree with the analytically known quantum second virial coefficient. The three-body cluster functions are compared at low temperatures with familiar partition functions for composite entities.
Damage in spherical cellular membrane generated by the shock waves: Coarse-grained molecular dynamics simulation of lipid vesicle
Authors: Sliozberg Yelena , Chantawansri Tanya
Published: November 2014

Traumatic Brain Injury is a major health issue that is hard to diagnose since it often occurs without signs of external injuries. While it is well known that exposure of biological cells to shock waves causes damage to the cell membrane, it is currently unknown by which mechanisms damage is caused, and how it depends on physical parameters such as shock wave velocity, shock pulse duration, or shock pulse shape. In this computational study, we use a coarse-grained model of the lipid vesicle as a generic model of a cell membrane to elucidate the general principles of the cellular damage induced by the shock wave direct passage through the cranium. Results indicate that the extent of the liposome compression does not strongly depend on the pressure pulse and that liposome extension is very sensitive to the change in the negative pressure phase. The structural integrity of the vesicle is altered as pores form in the lipid membrane at overall pressure impulses generated by supersonic shock waves, which are greater than 5 Pa·s at single or repetitive exposure. Consequently, these permeability changes may lead to changes in the influx of sodium, potassium, and calcium ions.
2D-Raman-THz spectroscopy: A sensitive test of polarizable water models
Authors: Hamm Peter
Published: November 2014

In a recent paper, the experimental 2D-Raman-THz response of liquid water at ambient conditions has been presented [J. Savolainen, S. Ahmed, and P. Hamm, Proc. Natl. Acad. Sci. U. S. A. 110, 20402 (2013)]. Here, all-atom molecular dynamics simulations are performed with the goal to reproduce the experimental results. To that end, the molecular response functions are calculated in a first step, and are then convoluted with the laser pulses in order to enable a direct comparison with the experimental results. The molecular dynamics simulation are performed with several different water models: TIP4P/2005, SWM4-NDP, and TL4P. As polarizability is essential to describe the 2D-Raman-THz response, the TIP4P/2005 water molecules are amended with either an isotropic or a anisotropic polarizability a posteriori after the molecular dynamics simulation. In contrast, SWM4-NDP and TL4P are intrinsically polarizable, and hence the 2D-Raman-THz response can be calculated in a self-consistent way, using the same force field as during the molecular dynamics simulation. It is found that the 2D-Raman-THz response depends extremely sensitively on details of the water model, and in particular on details of the description of polarizability. Despite the limited time resolution of the experiment, it could easily distinguish between various water models. Albeit not perfect, the overall best agreement with the experimental data is obtained for the TL4P water model.
Strain mapping at the nanoscale using precession electron diffraction in transmission electron microscope with off axis camera
Authors: Vigouroux M. P. , Delaye V. , Bernier N. , Cipro R. , Lafond D. , Audoit G. , Baron T. , Rouvière J. L. , Martin M. , Chenevier B. , Bertin F.
Published: November 2014

Precession electron diffraction is an efficient technique to measure strain in nanostructures by precessing the electron beam, while maintaining a few nanometre probe size. Here, we show that an advanced diffraction pattern treatment allows reproducible and precise strain measurements to be obtained using a default 512 × 512 DigiSTAR off-axis camera both in advanced or non-corrected transmission electron microscopes. This treatment consists in both projective geometry correction of diffraction pattern distortions and strain Delaunay triangulation based analysis. Precision in the strain measurement is improved and reached 2.7 × 10−4 with a probe size approaching 4.2 nm in diameter. This method is applied to the study of the strain state in InGaAs quantum-well (QW) devices elaborated on Si substrate. Results show that the GaAs/Si mismatch does not induce in-plane strain fluctuations in the InGaAs QW region.
Alternating brittle and ductile response of coherent twin boundaries in nanotwinned metals
Authors: Sinha Tanushree , Kulkarni Yashashree
Published: November 2014

Nanotwinned metals have opened exciting avenues for the design of high strength and high ductility materials. In this work, we investigate crack propagation along coherent twin boundaries in nanotwinned metals using molecular dynamics. Our simulations reveal that alternating twin boundaries exhibit intrinsic brittleness and ductility owing to the opposite crystallographic orientations of the adjoining twins. This is a startling consequence of the directional anisotropy of an atomically sharp crack along a twin boundary that favors cleavage in one direction and dislocation emission from the crack tip in the opposite direction. We further find that a blunt crack exhibits ductility in all cases albeit with very distinct deformation mechanisms and yield strength associated with intrinsically brittle and ductile coherent twin boundaries.
Nanoscale order and crystallization in nitrogen-alloyed amorphous GeTe
Authors: Darmawikarta Kristof , Raoux Simone , Bishop Stephen G. , Abelson John R.
Published: November 2014

The nanoscale order in amorphous GeTe thin films is measured using fluctuation transmission electron microscopy (FTEM). The order increases upon annealing at 145 °C, which indicates a coarsening of subcritical nuclei. This correlates with a reduction in the nucleation delay time in laser crystallization. A shift in the FTEM peak positions may indicate a transformation in local bonding. In samples alloyed with 12 at. % nitrogen, the order does not change upon annealing, the peak does not shift, and the nucleation time is longer. The FTEM data indicate that nitrogen suppresses the structural evolution necessary for the nucleation process and increases the thermal stability of the material.
Multi-color persistent luminescence in transparent glass ceramics containing spinel nano-crystals with Mn2+ ions
Authors: Zhuang Yixi , Ueda Jumpei , Tanabe Setsuhisa
Published: November 2014

Transparent inorganic materials showing persistent luminescence can act as cover layer and emergency lighting for security signs in the dark. Herein, we report a Mn2+-activated glass and transparent glass ceramics containing spinel-type Zn1+xGa2−2xGexO4 (0 ≤ x ≤ 1) nano-crystals, which show multi-color persistent luminescence for more than 10 min. The color of persistent luminescence showed a remarkable change from red, to orange, greenish, and green with respect to the increase of annealing temperature. The effect has been explained due to the variation of crystal field strength surrounding the Mn2+ ions.
Spatially nonreciprocal Bragg gratings based on surface plasmons
Authors: Keshmarzi Elham Karami , Tait R. Niall , Berini Pierre
Published: November 2014

Using the concept of parity-time symmetry in optics, we propose a spatially non-reciprocal Bragg grating at near infrared wavelengths, operating with long-range surface plasmon polaritons, by employing balanced modulation of index and gain/loss in a step-in-width configuration. The index perturbation is created by stepping the width of an Ag stripe supporting long-range plasmons. Gain/loss modulation is generated by periodically doping the top polymer cladding of the structure with IR-140 dye molecules and pumping the grating optically from top. Loss exists inherently in the undoped regions due to plasmonic propagation loss. The transmission matrix method was employed as an accurate modeling technique to compute the reflectance and transmittance spectra of the proposed structures. Simulation results exhibit a strong reflectance from one end of the grating at about 880 nm as opposed to nearly no reflectance from the other end at the same wavelength.
Fission yeast profilin is tailored to facilitate actin assembly by the cytokinesis formin Cdc12
Authors: Bestul Andrew J. , Christensen Jenna R. , Grzegorzewska Agnieszka P. , Burke Thomas A. , Sees Jennifer A. , Carroll Robert T. , Sirotkin Vladimir , Keenan Robert J. , Kovar David R.
Published: November 2014

The evolutionarily conserved small actin-monomer binding protein profilin is believed to be a housekeeping factor that maintains a general pool of unassembled actin. However, despite similar primary sequences, structural folds, and affinities for G-actin and poly-l-proline, budding yeast profilin ScPFY fails to complement fission yeast profilin SpPRF temperature-sensitive mutant cdc3-124 cells. To identify profilin's essential properties, we built a combinatorial library of ScPFY variants containing either WT or SpPRF residues at multiple positions and carried out a genetic selection to isolate variants that support life in fission yeast. We subsequently engineered ScPFY(9-Mut), a variant containing nine substitutions in the actin-binding region, which complements cdc3-124 cells. ScPFY(9-Mut), but not WT ScPFY, suppresses severe cytokinesis defects in cdc3-124 cells. Furthermore, the major activity rescued by ScPFY(9-Mut) is the ability to enhance cytokinesis formin Cdc12-mediated actin assembly in vitro, which allows cells to assemble functional contractile rings. Therefore an essential role of profilin is to specifically facilitate formin-mediated actin assembly for cytokinesis in fission yeast.
tRNA thiolation links translation to stress responses inSaccharomyces cerevisiae
Authors: Damon Jadyn R. , Pincus David , Ploegh Hidde L.
Published: November 2014

Although tRNA modifications have been well catalogued, the precise functions of many modifications and their roles in mediating gene expression are still being elucidated. Whereas tRNA modifications were long assumed to be constitutive, it is now apparent that the modification status of tRNAs changes in response to different environmental conditions. The URM1 pathway is required for thiolation of the cytoplasmic tRNAs tGluUUC, tGlnUUG, and tLysUUUin Saccharomyces cerevisiae. We demonstrate that URM1 pathway mutants have impaired translation, which results in increased basal activation of the Hsf1-mediated heat shock response; we also find that tRNA thiolation levels in wild-type cells decrease when cells are grown at elevated temperature. We show that defects in tRNA thiolation can be conditionally advantageous, conferring resistance to endoplasmic reticulum stress. URM1 pathway proteins are unstable and hence are more sensitive to changes in the translational capacity of cells, which is decreased in cells experiencing stresses. We propose a model in which a stress-induced decrease in translation results in decreased levels of URM1 pathway components, which results in decreased tRNA thiolation levels, which further serves to decrease translation. This mechanism ensures that tRNA thiolation and translation are tightly coupled and coregulated according to need.
Optimization method for obtaining nearest-neighbour DNA entropies and enthalpies directly from melting temperatures
Authors: Weber Gerald
Published: November 2014

Motivation: Free energy nearest-neighbour (NN) thermodynamics is widely used in DNA biochemistry, ranging from the calculation of melting temperatures to the prediction of secondary structures. Methods to calculate NN parameters require the knowledge of total sequence entropies and enthalpies, which are not always available.

Results: Here, we implement and test a new melting temperature optimization method where we obtain the NN parameters directly from the temperatures. In this way, we bypass the constraints imposed by total sequence entropies and enthalpies. This enabled us to calculate the missing NN entropies and enthalpies for some published datasets, including salt-dependent parameters. Also this allowed us to combine 281 sequences from different types of melting temperature data for which we derived a new set of NN parameters, which have a smaller uncertainty and an improved predictive power.

Availability and implementation: C++ source code and compiled binaries for several Linux distributions are available from https://sites.google.com/site/geraldweberufmg/vargibbs and from OpenSuse build service at https://build.opensuse.org/package/show/home:drgweber/VarGibbs. The software package contains scripts and data files to reproduce all results presented here.

Contact:  gweberbh@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents
Authors: Lakshminarayana Suresh B. , Huat Tan Bee , Ho Paul C. , Manjunatha Ujjini H. , Dartois Véronique , Dick Thomas , Rao Srinivasa P. S.
Published: November 2014

Objectives

The discovery and development of TB drugs has met limited success, with two new drugs approved over the last 40 years. Part of the difficulty resides in the lack of well-established in vitro or in vivo targets of potency and physicochemical and pharmacokinetic parameters. In an attempt to benchmark and compare such properties for anti-TB agents, we have experimentally determined and compiled these parameters for 36 anti-TB compounds, using standardized and centralized assays, thus ensuring direct comparability across drugs and drug classes.

Methods

Potency parameters included growth inhibition, cidal activity against growing and non-growing bacteria and activity against intracellular mycobacteria. Pharmacokinetic parameters included basic physicochemical properties, solubility, permeability and metabolic stability. We then attempted to establish correlations between physicochemical, in vitro and in vivo pharmacokinetic and pharmacodynamic indices to tentatively inform future drug discovery efforts.

Results

Two-thirds of the compounds tested showed bactericidal and intramacrophage activity. Most compounds exhibited favourable solubility, permeability and metabolic stability in standard in vitro pharmacokinetic assays. An analysis of human pharmacokinetic parameters revealed associations between lipophilicity and volume of distribution, clearance, plasma protein binding and oral bioavailability. Not surprisingly, most compounds with favourable pharmacokinetic properties complied with Lipinski's rule of five.

Conclusions

However, most attempts to detect in vitro–in vivo correlations were unsuccessful, emphasizing the challenges of anti-TB drug discovery. The objective of this work is to provide a reference dataset for the TB drug discovery community with a focus on comparative in vitro potency and pharmacokinetics.
A novel formulation by Lagrangian variational principle for rotational equilibria: towards multidimensional stellar evolutions
Authors: Yasutake Nobutoshi , Fujisawa Kotaro , Yamada Shoichi
Published: November 2014

We have developed a new formulation to obtain self-gravitating, axisymmetric configurations in permanent rotation. The formulation is based on the Lagrangian variational principle, and treats not only barotropic but also baroclinic equations of state, for which angular momentum distributions are not necessarily cylindrical. We adopt a Monte Carlo technique, which is analogous to those employed in other fields, e.g. nuclear physics, in minimizing the energy functional, which is evaluated on a triangulated mesh. This Letter is a proof of principle and detailed comparisons with existing results will be reported in the sequel, but some test calculations are presented, in which we have achieved an error of O(10−4) in the virial relation. We have in mind the application of this method to two-dimensional calculations of the evolutions of rotating stars, for which the Lagrangian formulation is best suited.
PII Overexpression in Lotus japonicus Affects Nodule Activity in Permissive Low-Nitrogen Conditions and Increases Nodule Numbers in High Nitrogen Treated Plants
Authors: D’Apuzzo Enrica , Valkov Vladimir Totev , Parlati Aurora , Omrane Selim , Barbulova Ani , Sainz Maria Martha , Lentini Marco , Esposito Sergio , Rogato Alessandra , Chiurazzi Maurizio
Published: November 2014

We report here the first characterization of a GLNB1 gene coding for the PII protein in leguminous plants. The main purpose of this work was the investigation of the possible roles played by this multifunctional protein in nodulation pathways. The Lotus japonicus LjGLB1 gene shows a significant transcriptional regulation during the light-dark cycle and different nitrogen availability, conditions that strongly affect nodule formation, development, and functioning. We also report analysis of the spatial profile of expression of LjGLB1 in root and nodule tissues and of the protein’s subcellular localization. Transgenic L. japonicus lines overexpressing the PII protein were obtained and tested for the analysis of the symbiotic responses in different conditions. The uncoupling of PII from its native regulation affects nitrogenase activity and nodule polyamine content. Furthermore, our results suggest the involvement of PII in the signaling of the nitrogen nutritional status affecting the legumes’ predisposition for nodule formation.
Genome-Assisted Development of a Diagnostic Protocol for Distinguishing High Virulence Pseudomonas syringae pv. tomato Strains
Authors: Jones Lisa A. , Saha Surya , Collmer Alan , Smart Christine D. , Lindeberg Magdalen
Published: November 2014

A severe outbreak of bacterial speck of tomato, caused by Pseudomonas syringae pv. tomato, occurred in central New York in 2009. Isolate 09150, collected from this outbreak and subsequently named NYS-T1, was found to be highly virulent on tomato. To better understand the relationship of 09150 to other P. syringae strains and develop a diagnostic assay for aggressive strains of this pathogen, the 09150 genome was sequenced. Genome comparison revealed it to be highly similar to a previously sequenced isolate, T1. Genetic factors linked to host interaction including type III effectors, toxin biosynthetic genes, and elicitors of host innate immunity were identified. Type III effector repertoires were compared with other strains in the high virulence T1-like subgroup and lower virulence DC3000/P. syringae pv. maculicola subgroup within P. syringae phylogenetic Group I. Primers for conventional PCR were developed using sequences for avrA, hopW, conserved in the former subgroup and hopN, present in the latter. These were tested on isolates in the two subgroups, other pseudomonads, and other bacterial pathogens of tomato. Primers developed for avaA and hopW were diagnostic for more virulent strains of P. syringae pv. tomato while primers for hopN were diagnostic for P. syringae pv. tomato DC3000 and related P. syringe pv. maculicola strains. Primers designed against hopR distinguished both of these P. syringae subgroups from other P. syringae strains.