bluuebunny/crossref_metadata_2025 huggingface dataset:
Using PyMOL as a platform for computational drug design
Authors: Yuan Shuguang , Chan H.C. Stephen , Hu Zhenquan
Published: January 2017

PyMOL, a cross‐platform molecular graphics tool, has been widely used for three‐dimensional (3D) visualization of proteins, nucleic acids, small molecules, electron densities, surfaces, and trajectories. It is also capable of editing molecules, ray tracing, and making movies. This Python‐based software, alongside many Python plugin tools, has been developed to enhance its utilities and facilitate the drug design in PyMOL. To gain an insightful view of useful drug design tools and their functions in PyMOL, we present an extensive discussion on various molecular modeling modules in PyMOL, covering those for visualization and analysis enhancement, protein–ligand modeling, molecular simulations, and drug screening. This review provides an excellent introduction to present 3D structures visualization and computational drug design in PyMOL. WIREs Comput Mol Sci 2017, 7:e1298. doi: 10.1002/wcms.1298

This article is categorized under:

Structure and Mechanism > Molecular Structures

Computer and Information Science > Visualization

Molecular and Statistical Mechanics > Molecular Mechanics
Synthesis of Titanium Oxide Nanostructures in Ionic Liquids
Authors: Voepel Pascal , Smarsly Bernd M.
Published: January 2017

In recent years, the usage of ionic liquids (ILs) in the synthesis of metal oxides has been extensively studied, especially with respect to their possible advantageous effects in comparison to conventional syntheses protocols. Herein, an overview is given on the variety of different syntheses of TiO2‐based materials, which correlates to the diversity of different ionic liquids. Special emphasis is put on the historic development of the IL‐based synthesis of TiO2 materials in the general context of research on IL‐based materials synthesis. Also, the assumed advantages of both, the synthesis and the resulting TiO2 materials, are critically revised. It can be concluded that the application of ILs exerts a direct influence on several parameters, namely the phase composition, the dopants or the nanostructuring of the material. Importantly, the research on TiO2‐based materials enables fundamental insights into IL‐specific effects in the synthesis of inorganic materials in general.
Partial Splenectomy is Superior to Total Splenectomy for Selected Patients with Hemangiomas or Cysts
Authors: Wang Lei , Xu Jianwei , Li Feng , Zhan Hanxiang , Liu Han , Chen Wei , Hu Sanyuan
Published: January 2017

Background

The superiority of partial splenectomy (PS) as a treatment for benign tumors has not well been confirmed. This study aimed to identify the short‐ and long‐term outcomes of PS, to compare laparoscopic and laparotomic PS, and to demonstrate whether the effects of PS are superior to that of total splenectomy (TS).

Methods

Patients with either a hemangioma or cyst who underwent PS or TS from 2009 to 2015 at Qilu Hospital of Shandong University were included. Clinical parameters were collected and analyzed.

Results

A total of 17 patients underwent PS were collected, including 2 men and 15 women with a mean age of 43.9 ± 11.3 years old. Patients who underwent laparoscopic PS (9 cases) had a longer operative time and shorter postoperative hospital stay than those who underwent laparotomy (8 cases). Compared with TS (22 cases), PS significantly decreased the incidence of thrombocytosis, shortened time until drainage removal, and shortened postoperative hospital stay. After an average follow‐up of 34.8 months, patients who underwent TS showed a higher incidence of thrombocytosis and splenic vein thrombosis compared with patients underwent PS.

Conclusions

PS is technically feasible and provides favorable short‐ and long‐term outcomes for selected patients with either a hemangioma or cyst compared with TS. Laparoscopic PS shows lower morbidity and equal therapeutic efficacy compared with laparotomic PS and can be widely performed.
The Impact of Fatty Acid Composition on Transportation Fuel Yields via the Non‐Catalytic Cracking of Triacylglyceride Oils
Authors: Seames Wayne , Linnen Michael , Sander Blake , Wills Robert
Published: January 2017

A wide spectrum of triacylglyceride (TG) oils were decomposed in batch lab and continuous pilot‐scale reactors to generate an extensive database, which was then used to construct a model to predict the detailed composition of products generated during non‐catalytic cracking. The model was then coupled with additional simulated process steps to determine the yields of transportation products and other chemical co‐products meeting specifications of their petroleum analogs as validated with laboratory testing. A statistical study was then performed to use the model to analyze the impact that changes in TG oil composition have upon target product yields. In this study, the model was used to simulate a viable suite of products for every TG oil analyzed. The model predicts minor differences in the ratio of products from various different fatty acid compositions. For example, it was found that stearic (C18:0), oleic (C18:1), and erucic (C22:1) acids show a positive effect on fuel yields. By contrast, palmitic (C16:0), linoleic (C18:2), and linolenic (C18:3) acids have negative impacts on fuel yields. From these results, a hypothetical “ideal” TG oil was constructed. This oil turns out to have a composition that is very close to the composition of high oleic sunflower oil.
Evaluating the Consistency, Repeatability, and Reproducibility of Osteometric Data on Dry Bone Surfaces, Scanned Dry Bone Surfaces, and Scanned Bone Surfaces Obtained from Living Individuals
Authors: Corron L. , Marchal F. , Condemi S. , Chaumoître K. , Adalian P.
Published: January 2017

Applying dry bone osteometrics to virtual bone surfaces obtained via medical imaging raises the question of consistency between the variables. Variables obtained from virtual bone surfaces also need to be sufficiently repeatable and reproducible to be valid for anthropological studies. This is also true for the landmarks defining these variables and for their acquisition. The consistency between variables taken directly from dry bones and from the virtual surfaces of dry bones was tested on 40 clavicles. 30 virtual surfaces of iliae, fifth lumbar vertebrae, and clavicles reconstructed from computed tomography scans of living individuals were used to test the repeatability and reproducibility of 16 landmarks and 19 variables. Statistical tests, graphical and quantitative error evaluations, and intraclass correlation coefficients were applied. The differences between all variables taken on dry and virtual clavicles were less than ±1 mm. Bland–Altman plots showed more than 95% reliability between variables obtained on dry bone and their virtually reconstructed surfaces, confirming their consistency and thus validating their use in osteometric studies independently of the medium of study. Although not all landmarks were repeatable and reproducible, most variables were. To assess intra- or inter-observer errors, graphical representations or coefficients are more precise and accurate than statistical tests. These two evaluation methods should be given priority to test the repeatability and reproducibility of osteometric variables.
Spontaneous Spinal Epidural Haematoma in a 34-week Pregnant Woman: A Case Report and Literature Review
Authors: Ka-Chi Lau , Ching-Lik Hui , Sun-Wing Lau , Karen Luk Man-Sze , Raymond Wong Nang Man
Published: January 2017

Acute spontaneous spinal epidural haematoma is uncommon; however, it can result in permanent neurological damage if not promptly treated. It occurs very rarely during pregnancy. We report a case of acute spontaneous spinal epidural hematoma in a 34-year-old primigravida woman at 34 weeks’ gestation who presented with sudden back pain and paraplegia. Emergency spinal decompression surgery was done with the continuation of pregnancy. We discuss the presentation and management of the rare condition with a review of the literature.
Teaching about Social Business: The Intersection of Economics Instruction and Civic Engagement
Authors: Whitlock Annie McMahon
Published: January 2017

This study describes the implementation of a curricular tool designed for students to develop civic engagement through running a social business in one fifth-grade classroom. The One Hen unit focuses on teaching elementary students the concept of social entrepreneurship through a project where students run their own social business to address a community need. This study has the potential to contribute to our understanding of how elementary students learn economics to increase civic engagement as the One Hen unit could lead to students’ becoming more aware of problems in their community and to gain experience planning for civic action.
ZETA ELEMENTS IN DEPTH 3 AND THE FUNDAMENTAL LIE ALGEBRA OF THE INFINITESIMAL TATE CURVE
Authors: BROWN FRANCIS
Published: January 2017

This paper draws connections between the double shuffle equations and structure of associators; Hain and Matsumoto’s universal mixed elliptic motives; and the Rankin–Selberg method for modular forms for $\text{SL}_{2}(\mathbb{Z})$. We write down explicit formulae for zeta elements $\unicode[STIX]{x1D70E}_{2n-1}$ (generators of the Tannaka Lie algebra of the category of mixed Tate motives over $\mathbb{Z}$) in depths up to four, give applications to the Broadhurst–Kreimer conjecture, and solve the double shuffle equations for multiple zeta values in depths two and three.
Inpatient Urine Cultures Are Frequently Performed Without Urinalysis or Microscopy: Findings From a Large Academic Medical Center
Authors: Carlson Abigail L. , Munigala Satish , Russo Anthony J. , McMullen Kathleen M. , Wood Helen , Jackups Ronald , Warren David K.
Published: January 2017

OBJECTIVE

To describe the frequency of urine cultures performed in inpatients without additional testing for pyuria

DESIGN

Retrospective cohort study

SETTING

A 1,250-bed academic tertiary referral center

PATIENTS

Hospitalized adults

METHODS

This study included urine cultures drawn on 4 medical and 2 surgical wards from 2009 to 2013 and in the medical and surgical intensive care units (ICUs) from 2012 to 2013. Patient and laboratory data were abstracted from the hospital’s medical informatics database. We identified catheter-associated urinary tract infections (CAUTIs) in the ICUs by routine infection prevention surveillance. Cultures without urinalysis or urine microscopy were defined as “isolated.” The primary outcome was the proportion of isolated urine cultures obtained. We used multivariable logistic regression to assess predictors of isolated cultures.

RESULTS

During the study period, 14,743 urine cultures were obtained (63.5 cultures per 1,000 patient days) during 11,820 patient admissions. Of these, 2,973 cultures (20.2%) were isolated cultures. Of the 61 CAUTIs identified, 31 (50.8%) were identified by an isolated culture. Predictors for having an isolated culture included male gender (adjusted odds ratio [aOR], 1.22; 95%; confidence interval [CI], 1.11–1.35], urinary catheterization (aOR, 2.15; 95% CI, 1.89–2.46), ICU admission (medical ICU aOR, 1.72; 95% CI, 1.47–2.00; surgical ICU aOR, 1.82; 95% CI, 1.51–2.19), and obtaining the urine culture ≥1 calendar day after admission (1–7 days aOR, 1.91; 95% CI. 1.71–2.12; >7 days after admission aOR, 2.81; 95% CI, 2.37–3.34).

CONCLUSIONS

Isolated urine cultures are common in hospitalized patients, particularly in patients with urinary catheters and those in ICUs. Interventions targeting inpatient culturing practices may improve the diagnosis of urinary tract infections.

Infect Control Hosp Epidemiol2017;38:455–460
A Randomized Trial to Determine the Impact of an Educational Patient Hand-Hygiene Intervention on Contamination of Hospitalized Patient’s Hands with Healthcare-Associated Pathogens
Authors: Sunkesula Venkata C. K. , Kundrapu Sirisha , Knighton Shanina , Cadnum Jennifer L. , Donskey Curtis J.
Published: January 2017

We conducted a non-blinded randomized trial to determine the impact of a patient hand-hygiene intervention on contamination of hospitalized patients’ hands with healthcare-associated pathogens. Among patients with negative hand cultures on admission, recovery of pathogens from hands was significantly reduced in those receiving the intervention versus those receiving standard care.

Infect Control Hosp Epidemiol 2017;38:595–597
Colour of turbulence
Authors: Zare Armin , Jovanović Mihailo R. , Georgiou Tryphon T.
Published: January 2017

In this paper, we address the problem of how to account for second-order statistics of turbulent flows using low-complexity stochastic dynamical models based on the linearized Navier–Stokes equations. The complexity is quantified by the number of degrees of freedom in the linearized evolution model that are directly influenced by stochastic excitation sources. For the case where only a subset of velocity correlations are known, we develop a framework to complete unavailable second-order statistics in a way that is consistent with linearization around turbulent mean velocity. In general, white-in-time stochastic forcing is not sufficient to explain turbulent flow statistics. We develop models for coloured-in-time forcing using a maximum entropy formulation together with a regularization that serves as a proxy for rank minimization. We show that coloured-in-time excitation of the Navier–Stokes equations can also be interpreted as a low-rank modification to the generator of the linearized dynamics. Our method provides a data-driven refinement of models that originate from first principles and captures complex dynamics of turbulent flows in a way that is tractable for analysis, optimization and control design.
Low-Flow Pressure Gradient Pumping for Active Absorption of CO2 on a Molecular Sieve
Authors: Cheng Peng , Wu Shugang , Fu Yunchong , Xiong Xiaohu , Niu Zhenchuan , Fan Yukun
Published: January 2017

The authors have developed an active absorption system combining a molecular sieve with a pressure gradient as a way to overcome the shortcomings of the phosphoric acid solution displacement method. Taking advantage of the pressure gradient produced between the inside and outside of a bottle, as water moves through it, CO2 in the atmosphere can actively be absorbed onto a molecular sieve in its pathway. A comparative study showed that the technique was in agreement with the phosphoric acid displacement method, within error. We applied the new method to collect not only atmospheric CO2 samples, but also CO2 samples from soil respiration to verify its utility. Simple yet practical, our method is well suited to extended collection times in a variety of environments, and capable of providing relatively large amounts of carbon for high-precision accelerator mass spectrometry (AMS) 14C analyses of atmospheric samples.
Preparation Methods of μg Carbon Samples for14C MeasuremenTS
Authors: Steier Peter , Liebl Jakob , Kutschera Walter , Wild Eva Maria , Golser Robin
Published: January 2017

Systematic investigations and experience from several application projects on small carbon samples over a number of years have resulted in measuring the radiocarbon content of 10 μg C samples with an overall precision of typically 1%. A substantial reduction of the carbon contamination during graphitization was achieved, resulting in 31±30 ng modern and <100 ng14C-free carbon. Thus, graphitization is no longer the limiting factor because earlier sample preparation steps usually introduce much larger contamination. The method has been extended to a variety of materials and applied to various projects. Realistic conditions for procedure development can only be achieved in the context of applications on true samples; methods developed are the lyophilization of samples in solution, combustion, ultraviolet oxidation, or carbonate hydrolysis with phosphoric acid, which allows to prepare samples for a wide range of applications. Insights gained from systematic investigations and from real applications are presented.
Lifting of the Vlasov–Maxwell bracket by Lie-transform method
Authors: Brizard A. J. , Morrison P. J. , Burby J. W. , de Guillebon L. , Vittot M.
Published: January 2017

The Vlasov–Maxwell equations possess a Hamiltonian structure expressed in terms of a Hamiltonian functional and a functional bracket. In the present paper, the transformation (‘lift’) of the Vlasov–Maxwell bracket induced by the dynamical reduction of single-particle dynamics is investigated when the reduction is carried out by Lie-transform perturbation methods. The ultimate goal of this work is to provide an explicit pathway to the Hamiltonian formulations for the guiding-centre and gyrokinetic Vlasov–Maxwell equations, which have found important applications in our understanding of turbulent magnetized plasmas. Here, it is shown that the general form of the reduced Vlasov–Maxwell equations possesses a Hamiltonian structure defined in terms of a reduced Hamiltonian functional and a reduced bracket that automatically satisfies the standard bracket properties.
Co-morbid obsessive–compulsive disorder and depression: a Bayesian network approach
Authors: McNally R. J. , Mair P. , Mugno B. L. , Riemann B. C.
Published: January 2017

Background

Obsessive–compulsive disorder (OCD) is often co-morbid with depression. Using the methods of network analysis, we computed two networks that disclose the potentially causal relationships among symptoms of these two disorders in 408 adult patients with primary OCD and co-morbid depression symptoms.

Method

We examined the relationship between the symptoms constituting these syndromes by computing a (regularized) partial correlation network via the graphical LASSO procedure, and a directed acyclic graph (DAG) via a Bayesian hill-climbing algorithm.

Results

The results suggest that the degree of interference and distress associated with obsessions, and the degree of interference associated with compulsions, are the chief drivers of co-morbidity. Moreover, activation of the depression cluster appears to occur solely through distress associated with obsessions activating sadness – a key symptom that ‘bridges’ the two syndromic clusters in the DAG.

Conclusions

Bayesian analysis can expand the repertoire of network analytic approaches to psychopathology. We discuss clinical implications and limitations of our findings.
Neural indicators of interpersonal anger as cause and consequence of combat training stress symptoms
Authors: Gilam G. , Lin T. , Fruchter E. , Hendler T.
Published: January 2017

Background

Angry outbursts are an important feature of various stress-related disorders, and commonly lead to aggression towards other people. Findings regarding interpersonal anger have linked the ventromedial prefrontal cortex (vmPFC) to anger regulation and the locus coeruleus (LC) to aggression. Both regions were previously associated with traumatic and chronic stress symptoms, yet it is unclear if their functionality represents a consequence of, or possibly also a cause for, stress symptoms. Here we investigated the relationship between the neural trajectory of these indicators of anger and the development and manifestation of stress symptoms.

Method

A total of 46 males (29 soldiers, 17 civilians) participated in a prospective functional magnetic resonance imaging experiment in which they played a modified interpersonal anger-provoking Ultimatum Game (UG) at two-points. Soldiers were tested at the beginning and end of combat training, while civilians were tested at the beginning and end of civil service. We assumed that combat training would induce chronic stress and result in increased stress symptoms.

Results

Soldiers showed an increase in stress symptoms following combat training while civilians showed no such change following civil service. All participants were angered by the modified UG irrespective of time point. Higher post-combat training stress symptoms were associated with lower pre-combat training vmPFC activation and with higher activation increase in the LC between pre- and post-combat training.

Conclusions

Results suggest that during anger-provoking social interactions, flawed vmPFC functionality may serve as a causal risk factor for the development of stress symptoms, and heightened reactivity of the LC possibly reflects a consequence of stress-inducing combat training. These findings provide potential neural targets for therapeutic intervention and inoculation for stress-related psychopathological manifestations of anger.
Performance and Value: The Work of Theatre in Karl Marx's Critique of Political Economy
Authors: Boyle Michael Shane
Published: January 2017

That theatre is a place of work seems beyond debate. But what kind of workplace is it? And under what conditions does theatre conform to a capitalist production process? At first glance these questions may seem obviously, even inextricably, linked; but investigating theatre as somewhere people go to work is a far different enterprise than specifying its economic connection to capital.
World Factory: Theatre, Labor, and China's “New Left”
Authors: Steen Shannon
Published: January 2017

In today's China, how are we supposed to understand the notion of “work,” after the chaos of the socialist period, and after the conversion to capitalism, and now after globalization? Marx said that labor makes people, this was one of his fundamental principles. So how are we supposed to understand labor today? What does it mean for us?

—Grass Stage,World Factory

The insistence on “socialism with Chinese characteristics” often sounds quite vacuous, and yet it is a constant reminder of the Chinese resistance to dissolution into capitalism and the continued reaffirmation of one kind of socialist past in the search for another kind of socialist future.

—Arif Dirlik, “Back to the Future”
M. Lamar: Singing Slave Insurrection to Marx
Authors: Wickstrom Maurya
Published: January 2017

This essay is about a performance by the musician, singer, and performance artist M. Lamar, who describes himself as a “Negrogothic Devil-worshipping free black man in the blues tradition.” I saw the piece,Destruction, in the American Realness Festival at Abrons Art Center in New York City in January 2016. During the seventy-minute-long performance, the countertenor sang and played the piano, and appeared in mediated form in a complexly assembled film montage. In both live and filmed form his performance was a labor to resurrect the dead into an insurrectionist revolt, an army of all the black people whose lives have been taken—from slavery to lynchings, to incarceration, to police shootings. The lush, sometimes heart-stopping sound environment was both live and recorded, a mix, mash-up, and collage of sounds and sources the core of which was Lamar's singing of fragments of slave spirituals. In what follows, I am prompted by Lamar's work to explore my own ongoing commitment to Marx through what I read as the work's temporal innovations. These innovations, I suggest, supplement Marx's failure to imagine a revolutionary strategy through anything but the standard progressivist notion of time and history. In so doing, I claim Lamar for an affiliation to Marxism and materialist thought by identifying in his work a material immortal.
Stakeholder Meeting: Integrated Knowledge Translation Approach to Address the Caregiver Support Gap
Authors: Holroyd-Leduc Jayna M. , McMillan Jacqueline , Jette Nathalie , Brémault-Phillips Suzette C. , Duggleby Wendy , Hanson Heather M. , Parmar Jasneet
Published: January 2017

Les aidants familiaux sont une partie intégrante et de plus en plus débordée du système de soins de santé. Il y a un écart entre ce que les données de recherche démontrent être bénéfique pour les soignants et ce qui est réellement fourni. À l’aide d’une approche basée sur l’application intégrée des connaissances (AC), une réunion des intervenants a inclus des chercheurs, des aidants familiaux, des associations de soignants, des cliniciens, des administrateurs de soins de santé et des décideurs. Les objectifs de la réunion étaient d’examiner les données issues des recherches en cours et de tenir un dialogue entre les intervenants multiples sur les lacunes, les facilitateurs et les obstacles à la fourniture d’un soutien aux aidants naturels. Cent vingt-trois individus ont participé à cette réunion. Trois populations cibles des aidants familiaux ont été identifiées pour discussion: soignants d’aînés atteints de démence, soignants en fin de vie et soignants d’aînés ayant des besoins de santé complexes. Les résultats de cette réunion sont et seront utilisés pour éclairer le développement des efforts visant à mettre en œuvre à la fois des recherches et des politiques afin de fournir un soutien aux aidants familiaux en se basant sur les preuves.
Climate-based prioritization of data collection for monitoring wintering birds in Latin America
Authors: AUER TOM , SOYKAN CANDAN U. , WILSEY CHAD B. , MICHEL NICOLE L. , JENSEN CAITLIN M. , LANGHAM GARY M. , LEBARON GEOFF , SANCHEZ CONNIE C. , TAKEKAWA JOHN
Published: January 2017

Recent studies have highlighted the threat that climate change poses to species, as areas of climatic suitability contract or shift across the landscape. North American Neotropical long-distant migrant bird species present a unique problem compared to sedentary species because climate change may differ significantly across their breeding and wintering grounds. Studying the potential future distributions of these birds is challenging on many levels, including the fact that our understanding of the wintering grounds of these species is quite poor. To address this issue, we analyse available eBird data during the winter season in the Western Hemisphere in an effort to further promote and direct citizen science efforts to focus on areas that are climatically undersampled. We used Mobility-Oriented Parity (MOP) to understand the areas where climates are most dissimilar from climates sampled by existing eBird checklists, creating a map that ranks the western hemisphere at a 10 km resolution for climatic sampling during the winter season. We found that parts of Mexico and Central America, areas of Colombia, almost the entire Amazon Basin, coastal Peru and Chile, and northern Argentina are climatically undersampled. As a test case, we then used the map of survey priorities to simulate additional sampling in Colombia and recalculated the rankings. Guiding additional sampling with the priorities reduced climate dissimilarities between sampled and unsampled grid cells more than when additional sampling expanded in proportion to current sampling efforts or based on geographic undersampling. Analyses of sampling coverage in environmental space, such as this, will be a useful tool for targeting monitoring effort for bird species.
CUT TO THE CHEESE – REPLY TO SPIEGEL'S ‘WHY FLATULENCE IS FUNNY’
Authors: Steinert Steffen
Published: January 2017

In number 35 of Think, James Spiegel presents reasons for why flatulence is funny. In this article I will address five issues that I find problematic in his account:

(1)

His claim that laughter always results from a pleasant psychological shift is false.

(2)

His argumentative move from what makes paradigm cases funny to what makes flatulence funny is unwarranted.

(3)

His notion of a psychological shift is not specific enough and lacks explanatory power.

(4)

The claim that funniness of flatulence involves superiority is doubtful.

(5)

His talk about ‘nervous energy’ is questionable and has implausible implications.
DID MOST BRITS FAIL IN THEIR CIVIC DUTIES IN THE EU REFERENDUM?
Authors: Easton Christina
Published: January 2017

What sorts of reasons should citizens have in mind when they cast votes? Arguments from both sides of the EU referendum debate are used here to raise questions about what our motivations should be when voting. The article introduces John Rawls's requirement to give public reasons that are acceptable to all reasonable people.
REPLY TO LOXTERKAMP
Authors: Cahn Steven M. , Vitrano Christine
Published: January 2017

Max Loxterkamp correctly attributes to us the view that people are living well if they act morally and find long-term satisfaction, regardless of the pursuits they choose. He disagrees with us, however, and suggests that lives are better if they benefit society, and he offers as examples a charity worker, a courageous soldier, and a philosopher of genius.
Risikowahrnehmung und Alkoholabhängigkeit
Authors: Klepper Sarah , Odenwald Michael , Rockstroh Brigitte
Published: January 2017

Zusammenfassung. Zielsetzung: Alkoholabhängige Personen (AP) zeigen riskanten Alkoholkonsum trotz des Wissens um dessen objektive Risiken. Um die Bedeutung des Konstrukts Risikowahrnehmung für diese Diskrepanz zu überprüfen, wurde die „accuracy“ Hypothese und der „optimistic bias“ bei Alkoholabhängigkeit untersucht. Methodik: Zur Hypothesenprüfung wurden vier Dimensionen alkoholbezogener Risikowahrnehmung bei 73 stationär behandelten AP und 75 Kontrollpersonen (KP) anhand eines neu entwickelten deutschsprachigen Fragebogens verglichen und mit Alkoholkonsum in Beziehung gesetzt. Ergebnisse: AP schätzten im Vergleich zu KP eigene Risiken als höher ein und bewerteten diese als bedrohlicher. Trotz realistischer Wahrnehmung tendierten sie zu optimistischer Unterschätzung der eigenen Risiken. Wahrgenommene Vulnerabilität und Peer Vulnerabilität klärten neben der Diagnose Varianz im Konsum (AP: vor Behandlungsbeginn) auf. Der positive Zusammenhang zwischen Konsumverhalten und affektiver Bewertung von Risiken zeigte sich nur bei AP. Schlussfolgerungen: Die „accuracy“ Hypothese wurde bestätigt und konnte die realistische Wahrnehmung der Alkoholrisiken bei AP erklären. Gleichzeitig zeigten AP einen „optimistic bias“, welcher zu fortdauernd riskantem Trinken beitragen könnte. Das Konstrukt Risikowahrnehmung bietet Hypothesen für längsschnittliche Therapiestudien an, durch die weiterer Erkenntnisgewinn zu erwarten ist.
Computational Psychiatry
Authors: Seifritz Erich , Hasler Gregor
Published: January 2017

Zusammenfassung. Neben der klassischen klinischen und präklinischen Forschung und der gegenseitigen Translation hat sich in den letzten Jahren ein innovativer neuer Forschungsansatz, die ‚Komputationale Psychiatrie‘ etabliert. Sie hat das Ziel, einen wissenschaftlichen Rahmen zu schaffen, um multidimensionale molekulare, zelluläre und systemische sowie psychologische und soziale Faktoren in mathematisch fundierten Modellen zu integrieren. Komputationale Ansätze versprechen Fortschritte in dem ätiologischen und pathophysiologischen Verständnis psychischer Erkrankungen und, davon abgeleitet, evidenzbasierte Grundlagen für diagnostische Klassifikationssysteme, welche die dimensionalen Eigenschaften abbilden sowie für personalisierte Therapien.
Komputationale Modelle in der psychiatrischen Forschung
Authors: Heinz Andreas , Schlagenhauf Florian , Mascarell Maricic Lea , Daedelow Laura S.
Published: January 2017

Zusammenfassung. Komputationale Methoden werden in einem weiten Bereich psychiatrischer Forschung eingesetzt v.a. beim Umgang mit großen Datensätzen. Hier diskutieren wir, wie mit Hilfe komputationaler Methoden das Entscheidungsverhalten in bestimmten Testsituationen in mathematischen Gleichungen abgebildet werden kann, um diesem Entscheidungsverhalten wiederum neurobiologischen Korrelaten zuordnen zu können. Ein bekanntes Beispiel ist das belohnungsabhängige Lernen, bei dem die Größe eines Vorhersagefehlers, d.h. des Unterschieds zwischen der erwarteten und der eingetroffenen Belohnung, mathematisch berechenbar ist und mit entsprechenden Signalen wie der Dopaminfreisetzung im ventralen Striatum in Tiermodellen oder entsprechenden funktionellen Bildgebungskorrelaten beim Menschen in Verbindung gebracht werden kann. Veränderungen dieser Lernmechanismen lassen sich nosologieübergreifend bei verschiedenen Störungsbildungen wie Suchterkrankungen, Psychosen und majoren affektiven Erkrankungen nachweisen und ermöglichen so einen dimensionalen Ansatz, mit dem neurobiologische Korrelate einzelner Mechanismen in verschiedenen Krankheitsbildern identifiziert und mit Teilaspekten der Symptomatik in Verbindung gebracht werden können. Die vorliegende Arbeit diskutiert entsprechende Ansätze im Bereich Pawlowschen Konditionierens und des belohnungsabhängigen, zielgerichteten und habituellen Entscheidungsverhaltens. Der Fokus auf Lernmechanismen betont hierbei die Vielfältigkeit und Veränderbarkeit menschlichen Verhaltens, beispielsweise durch Trainingsprogramme oder kognitiv-behaviorale Interventionen.
Das Negativsymptom Apathie
Authors: Kaiser Stefan , Hartmann-Riemer Matthias , Tobler Philippe N.
Published: January 2017

Zusammenfassung. Die Apathie ist eine Dimension von Negativsymptomen, die zu erheblichen Beeinträchtigungen in der Alltagsfunktion führt, ohne dass adäquate Behandlungsverfahren zur Verfügung stehen. Die Apathie wird heute zunehmend als eine Reduktion von zielgerichtetem Verhalten definiert. Die dem zielgerichteten Verhalten zugrundeliegenden Prozesse lassen sich in einem Modell verstehen, das verschiedene Phasen der Entscheidungsfindung beinhaltet. Hierzu gehören die Generierung von Handlungsoptionen, die Bewertung und Auswahl von Handlungsoptionen und schliesslich das Lernen aus Handlungsergebnissen. Diese Prozesse und ihre Dysfunktionen lassen sich quantitativ erfassen, wie wir am Beispiel von Studien bei Patienten mit Schizophrenie zeigen. Dysfunktionen in allen genannten Entscheidungsphasen sind mit der Apathie assoziiert. Dieses Modell kann dazu dienen, die Entwicklung psychologischer und biologischer Therapieverfahren gezielter auf die zugrundeliegenden dysfunktionalen Prozesse aufzubauen.
Retracing the First Spaceborne Electric Field Measurement
Authors: Zastrow Mark
Published: January 2017

Fifty years ago, a sounding rocket made history by taking the first measurement of an electric field in space. What techniques were used to capture this data?
Pinpointing the Trigger Behind Yellowstone's Last Supereruption
Authors: Woodward Aylin
Published: January 2017

Geologists suggest that mixing of magma melt pockets could have caused the explosion a little more than 600,000 years ago.
Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration
Authors: Golestaneh Nady , Chu Yi , Xiao Yang-Yu , Stoleru Gianna L , Theos Alexander C
Published: January 2017

Age-related macular degeneration (AMD) is a devastating neurodegenerative disease and a major cause of blindness in the developed world. Owing to its complexity and the lack of an adequate human model that recapitulates key aspects of the disease, the molecular mechanisms of AMD pathogenesis remain poorly understood. Here we show that cultured human retinal pigment epithelium (RPE) from AMD donors (AMD RPE) are functionally impaired and exhibit distinct phenotypes compared with RPE cultured from normal donors (normal RPE). Accumulation of lipid droplets and glycogen granules, disintegration of mitochondria, and an increase in autophagosomes were observed in AMD RPE cultures. Compared with normal RPE, AMD RPE exhibit increased susceptibility to oxidative stress, produce higher levels of reactive oxygen species (ROS) under stress conditions, and showed reduced mitochondrial activity. Measurement of the ratio of LC3-II/ LC3-I, revealed impaired autophagy in AMD RPE as compared with normal RPE. Autophagic flux was also reduced in AMD RPE as compared with normal RPE, as shown by inability of AMD RPE to downregulate p62 levels during starvation. Impaired autophagic pathways were further shown by analyzing late autophagic vesicles; immunostaining with lysosome-associated membrane protein 1 (LAMP-1) antibody revealed enlarged and annular LAMP-1-positive organelles in AMD RPE as opposed to smaller discrete puncta observed in normal RPE. Our study provides insights into AMD cellular and molecular mechanisms, proposes dysfunctional autophagy as an underlying mechanism contributing to the pathophysiology of the disease, and opens up new avenues for development of novel treatment strategies.
The TAZ–miR-224–SMAD4 axis promotes tumorigenesis in osteosarcoma
Authors: Ma Jianjun , Huang Kangmao , Ma Yan , Zhou Menglu , Fan Shunwu
Published: January 2017

Transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo signaling pathway that participates in tumorigenesis. The aim of this study was to identify the miRNA counterpart for TAZ and elucidate the mechanism underlying the tumorigenic effect of TAZ. We demonstrated that TAZ is upregulated in osteosarcoma (OS) tissues and cell lines, and that TAZ overexpression can induce cell migration, invasion and proliferation. Moreover, miRNA-224 (miR-224), a TAZ phenocopy that functions downstream of TAZ, was found to be upregulated with TAZ overexpression. Further, a mechanistic study revealed that miR-224 functions by inhibiting the tumor suppressor, SMAD4, to support the proliferation and migration of OS cells. Our findings indicate that targeting TAZ and miR-224 could be a promising approach for the treatment of OS.
Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation
Authors: Tahara Yu , Takatsu Yuta , Shiraishi Takuya , Kikuchi Yosuke , Yamazaki Mayu , Motohashi Hiroaki , Muto Aya , Sasaki Hiroyuki , Haraguchi Atsushi , Kuriki Daisuke , Nakamura Takahiro J , Shibata Shigenobu
Published: January 2017

The ability of the circadian clock to adapt to environmental changes is critical for maintaining homeostasis, preventing disease, and limiting the detrimental effects of aging. To date, little is known about age-related changes in the entrainment of peripheral clocks to external cues. We therefore evaluated the ability of the peripheral clocks of the kidney, liver, and submandibular gland to be entrained by external stimuli including light, food, stress, and exercise in young versus aged mice using in vivo bioluminescence monitoring. Despite a decline in locomotor activity, peripheral clocks in aged mice exhibited normal oscillation amplitudes under light–dark, constant darkness, and simulated jet lag conditions, with some abnormal phase alterations. However, age-related impairments were observed in peripheral clock entrainment to stress and exercise stimuli. Conversely, age-related enhancements were observed in peripheral clock entrainment to food stimuli and in the display of food anticipatory behaviors. Finally, we evaluated the hypothesis that deficits in sympathetic input from the central clock located in the suprachiasmatic nucleus of the hypothalamus were in part responsible for age-related differences in the entrainment. Aged animals showed an attenuated entrainment response to noradrenergic stimulation as well as decreased adrenergic receptor mRNA expression in target peripheral organs. Taken together, the present findings indicate that age-related circadian disorganization in entrainment to light, stress, and exercise is due to sympathetic dysfunctions in peripheral organs, while meal timing produces effective entrainment of aged peripheral circadian clocks.
Engineering glucose metabolism of Escherichia coli under nitrogen starvation
Authors: Chubukov Victor , Desmarais John James , Wang George , Chan Leanne Jade G , Baidoo Edward EK , Petzold Christopher J , Keasling Jay D , Mukhopadhyay Aindrila
Published: January 2017

A major aspect of microbial metabolic engineering is the development of chassis hosts that have favorable global metabolic phenotypes, and can be further engineered to produce a variety of compounds. In this work, we focus on the problem of decoupling growth and production in the model bacterium Escherichia coli, and in particular on the maintenance of active metabolism during nitrogen-limited stationary phase. We find that by overexpressing the enzyme PtsI, a component of the glucose uptake system that is inhibited by α-ketoglutarate during nitrogen limitation, we are able to achieve a fourfold increase in metabolic rates. Alternative systems were also tested: chimeric PtsI proteins hypothesized to be insensitive to α-ketoglutarate did not improve metabolic rates under the conditions tested, whereas systems based on the galactose permease GalP suffered from energy stress and extreme sensitivity to expression level. Overexpression of PtsI is likely to be a useful arrow in the metabolic engineer’s quiver as productivity of engineered pathways becomes limited by central metabolic rates during stationary phase production processes.
Segregation and pattern formation in dilute granular media under microgravity conditions
Authors: Opsomer Eric , Noirhomme Martial , Vandewalle Nicolas , Falcon Eric , Merminod Simon
Published: January 2017

Space exploration and exploitation face a major challenge: the handling of granular materials in low-gravity environments. Indeed, grains behave quite differently in space than on Earth, and the dissipative nature of the collisions between solid particles leads to clustering. Within poly-disperse materials, the question of segregation is highly relevant but has not been addressed so far in microgravity. From parabolic flight experiments on dilute binary granular media, we show that clustering can trigger a segregation mechanism, and we observe, for the first time, the formation of layered structures in the bulk.
Excessive early-life dietary exposure: a potential source of elevated brain iron and a risk factor for Parkinson’s disease
Authors: Hare Dominic J , Cardoso Bárbara Rita , Raven Erika P , Double Kay L , Finkelstein David I , Szymlek-Gay Ewa A , Biggs Beverley-Ann
Published: January 2017

Iron accumulates gradually in the ageing brain. In Parkinson’s disease, iron deposition within the substantia nigra is further increased, contributing to a heightened pro-oxidant environment in dopaminergic neurons. We hypothesise that individuals in high-income countries, where cereals and infant formulae have historically been fortified with iron, experience increased early-life iron exposure that predisposes them to age-related iron accumulation in the brain. Combined with genetic factors that limit iron regulatory capacity and/or dopamine metabolism, this may increase the risk of Parkinson’s diseases. We propose to (a) validate a retrospective biomarker of iron exposure in children; (b) translate this biomarker to adults; (c) integrate it with in vivo brain iron in Parkinson’s disease; and (d) longitudinally examine the relationships between early-life iron exposure and metabolism, brain iron deposition and Parkinson’s disease risk. This approach will provide empirical evidence to support therapeutically addressing brain iron deposition in Parkinson’s diseases and produce a potential biomarker of Parkinson’s disease risk in preclinical individuals.
The emergent role of small-bodied herbivores in pre-empting phase shifts on degraded coral reefs
Authors: Kuempel Caitlin D. , Altieri Andrew H.
Published: January 2017

Natural and anthropogenic stressors can cause phase shifts from coral-dominated to algal-dominated states. In the Caribbean, over-fishing of large herbivorous fish and disease among the long-spined urchin, Diadema, have facilitated algal growth on degraded reefs. We found that diminutive species of urchin and parrotfish, which escaped die-offs and fishing pressure, can achieve abundances comparable to total herbivore biomass on healthier, protected reefs, and exert sufficient grazing function to pre-empt macroalgal dominance following mass coral mortality. Grazing was highest on the most degraded reefs, and was driven by small herbivores that made up >93% of the average herbivore biomass (per m2). We suggest that previously marginal species can achieve a degree of functional redundancy, and that their compensatory herbivory may play an important role in ecosystem resilience. Management strategies should consider the potential role of these additional herbivore functional groups in safeguarding natural controls of algal growth in times of increased uncertainty for the world’s reefs.
Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma
Authors: Neira José L. , Bintz Jennifer , Arruebo María , Rizzuti Bruno , Bonacci Thomas , Vega Sonia , Lanas Angel , Velázquez-Campoy Adrián , Iovanna Juan L. , Abián Olga
Published: January 2017

Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor developmentin vivoon xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ‘fuzzy’ interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.
Phosphorylation impact on Spleen Tyrosine kinase conformation by Surface Enhanced Raman Spectroscopy
Authors: Cottat Maximilien , Yasukuni Ryohei , Homma Yo , Lidgi-Guigui Nathalie , Varin-Blank Nadine , Lamy de la Chapelle Marc , Le Roy Christine
Published: January 2017

Spleen Tyrosine Kinase (Syk) plays a crucial role in immune cell signalling and its altered expression or activation are involved in several cancers. Syk activity relies on its phosphorylation status and its multiple phosphorylation sites predict several Syk conformations. In this report, we characterized Syk structural changes according to its phosphorylation/activation status by Surface Enhanced Raman Spectroscopy (SERS). Unphosphorylated/inactive and phosphorylated/active Syk forms were produced into two expression systems with different phosphorylation capability. Syk forms were then analysed by SERS that was carried out in liquid condition on a lithographically designed gold nanocylinders array. Our study demonstrated that SERS signatures of the two Syk forms were drastically distinct, indicating structural modifications related to their phosphorylation status. By comparison with the atomic structure of the unphosphorylated Syk, the SERS peak assignments of the phosphorylated Syk nearest gold nanostructures revealed a differential interaction with the gold surface. We finally described a model for Syk conformational variations according to its phosphorylation status. In conclusion, SERS is an efficient technical approach for studying in vitro protein conformational changes and might be a powerful tool to determine protein functions in tumour cells.