bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of insulin infusion on the metabolism of amyloid β peptides in plasma
Authors: Karczewska‐Kupczewska Monika , Lelental Natalia , Adamska Agnieszka , Nikołajuk Agnieszka , Kowalska Irina , Górska Maria , Zimmermann Rüdiger , Kornhuber Johannes , Strączkowski Marek , Lewczuk Piotr
Published: October 2012

Background

Accumulating body of evidence suggests pathophysiologic links between Alzheimer's disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid β (Aβ) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady‐state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity.

Objective

The aim of this study was to analyze the influence of insulin on the plasma concentrations of Aβ peptides.

Methods

Blood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aβ1‐42, Aβx‐42, Aβ1‐40, and Aβx‐40 were performed with multiplexing technology. Furthermore, concentrations of the Aβ peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy.

Results

When applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aβ42 (full length and N‐terminally shortened) but not of Aβ40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aβx‐40). We did not observe differences between Aβ peptide concentrations in healthy subjects and those in type 1 DM patients.

Conclusion

Infusion of insulin in nonphysiologic high doses increases plasma concentrations of Aβ peptides; in case of Aβ40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aβ peptides to the degradation of insulin.
A Study of the Clinical Outcome of Laminoplasty for Cervical Compressive Myelopathy
Authors: Stephen Chung Chor-Yat , Kwok-Ho Wong , Ming-Yu Chiu , Yuen-Fong Ho
Published: October 2012

Purpose

To evaluate the prognostic factors that affect the surgical outcome of laminoplasty in patients with cervical compressive myelopathy.

Methods

This is a retrospective review of 43 cases of multilevel cervical compressive myelopathy treated operatively with expansive laminoplasty (Itoh surgical technique), from June 1989 to August 2008. The mean follow-up duration was 7 years. The Japanese Orthopaedic Association score, Hirabayashi recovery rate and improvement of Pavlov's ratio were used to assess the clinical results after laminoplasty.

Results

The mean Japanese Orthopaedic Association score improved from 9.7 to 13.7 points after laminoplasty (p < 0.001), with 65.1% excellent or good results. The Pavlov ratio improved from 0.71 to 0.9 after operation (p < 0.001). Excellent or good surgical outcome is demonstrated in patients aged <70 years.

Conclusion

Laminoplasty is a viable surgical option for patients with three or more levelsofcervical cord compression. Patients youngerthan 70 years predict a favourable surgical outcome.
Ethical food standard schemes and global trade: Paralleling the WTO?
Authors: Daugbjerg Carsten , Botterill Linda Courtenay
Published: October 2012

Global food trade embodies a range of different interpretations of the nature of food and its role in society. On the one hand, the WTO food regulation regime, in particular the SPS agreement, is based upon a somewhat instrumental value of food consumption in which food is seen as a commodity to be traded in accordance with international trade rules. At the same time, a number of private standards, such as GlobalG.A.P and various organic standards, are emerging which embody broadly postmaterialist values that suggest that food purchasing and consumption are also social, ethical and perhaps even political activities. This paper analyses the relationship between the WTO food trade regime on the one hand and the GlobalG.A.P and organic food trade regimes on the other. We suggest that competing values can co-exist in parallel institutions and in a commensalistic relationship which protects the values base of each institution while giving expression to both materialist and postmaterialist understandings of the nature of food.
THE ARCHAEOBOTANICAL EVIDENCE OF THE LATE BRONZE AGE AND PROTOGEOMETRIC OCCUPATION UNDER THE ROMAN VILLA DIONYSUS, KNOSSOS, CRETE, AND AN OVERVIEW OF THE PROTOGEOMETRIC DATA OF GREECE
Authors: Livarda Alexandra
Published: October 2012

Archaeobotanical material was collected from the Bronze Age fill and the Protogeometric phases underneath the Roman Villa Dionysus, Knossos, Crete. The Bronze Age assemblage was poor, representing only accidental intrusions to a tight fill of sherds and stones. The Protogeometric data were more plentiful, providing a rare glimpse into the everyday life of the period. Glume wheat, barley, legumes, fruits, nuts and several wild species were present across two Protogeometric floors. No significant differences were observed in their spatial and temporal distribution. The plant remains, along with other bio-archaeological classes of material, indicated a series of domestic activities, including cooking and consumption events, the remnants of which gradually accumulated in the habitation floors. The archaeobotanical evidence from Villa Dionysus was then compared with other Protogeometric Cretan and Greek mainland sites. An overview of these sites allowed some general trends to be observed, tentatively suggesting a picture more similar to Bronze Age than Iron Age archaeobotanical assemblages. It also highlighted differences, which would both dictate and be shaped by different socio-economic systems, and the need for more contextualised studies.
Non-commutative Iwasawa theory of elliptic curves at primes of multiplicative reduction
Authors: LEE CHERN–YANG
Published: October 2012

This paper studies the compactp∞-Selmer Iwasawa moduleX(E/F∞) of an elliptic curveEover a False Tate curve extensionF∞, whereEis defined over ℚ, having multiplicative reduction at the odd primep. We investigate thep∞-Selmer rank ofEover intermediate fields and give the best lower bound of its growth under certain parity assumption onX(E/F∞), assuming this Iwasawa module satisfies theH(G)-Conjecture proposed by Coates–Fukaya–Kato–Sujatha–Venjakob.
Nature's Radar
Authors: Gooley Tristan
Published: October 2012

The author uses a personal account of a short-handed small boat voyage, from the Orkney Islands into the Arctic Circle, to determine whether nature can help a navigator estimate their distance from land. As part of this exercise the author reinforces his argument (Gooley, 2010) that natural navigation clues add not only to safety and general awareness, but offer the navigator a richer experience than relying solely on electronic navigation. The main aim of this expedition and paper is to establish whether some of the traditional methods of navigation, used by Pacific Island and Viking navigators, can be of any value to the modern navigator. Recorded sightings of birds, cetaceans, fish, jellyfish, water behaviour and colour are used to support the author's findings. The paper also contains the author's reflections on the experience of undertaking a voyage of this kind and leads to one surprising conclusion.
Determinants of suboptimal breast-feeding practices in Pakistan
Authors: Hazir Tabish , Akram Dure-Samin , Nisar Yasir Bin , Kazmi Narjis , Agho Kingsley E , Abbasi Saleem , Khan Amira M , Dibley Michael J
Published: October 2012

Objective

Exclusive breast-feeding is estimated to reduce infant mortality in low-income countries by up to 13 %. The aim of the present study was to determine the risk factors associated with suboptimal breast-feeding practices in Pakistan.

Design

A cross-sectional study using data extracted from the multistage cluster sample survey of the Pakistan Demographic and Health Survey 2006–2007.

Setting

A nationally representative sample of households.

Subjects

Last-born alive children aged 0–23 months (total weighted sample size 3103).

Results

The prevalences of timely initiation of breast-feeding, bottle-feeding in children aged 0–23 months, exclusive breast-feeding and predominant breast-feeding in infants aged 0–5 months were 27·3 %, 32·1 %, 37·1 % and 18·7 %, respectively. Multivariate analysis indicated that working mothers (OR = 1·48, 95 % CI 1·16, 1·87; P = 0·001) and mothers who delivered by Caesarean section (OR = 1·95, 95 % CI 1·30, 2·90; P = 0·001) had significantly higher odds for no timely initiation of breast-feeding. Mothers from North West Frontier Province were significantly less likely (OR = 0·37, 95 % CI 0·23, 0·59; P < 0·001) not to breast-feed their babies exclusively. Mothers delivered by traditional birth attendants had significantly higher odds to predominantly breast-feed their babies (OR = 1·96, 95 % CI 1·18, 3·24; P = 0·009). The odds of being bottle-fed was significantly higher in infants whose mothers had four or more antenatal clinic visits (OR = 1·93, 95 % CI 1·46, 2·55; P < 0·001) and belonged to the richest wealth quintile (OR = 2·41, 95 % CI 1·62, 3·58; P < 0·001).

Conclusions

The majority of Pakistani mothers have suboptimal breast-feeding practices. To gain the full benefits of breast-feeding for child health and nutrition, there is an urgent need to develop interventions to improve the rates of exclusive breast-feeding.
A healthy trend: less food used in fundraising and as rewards and incentives in Minnesota middle and high schools
Authors: Kubik Martha Y , Farbakhsh Kian , Lytle Leslie A
Published: October 2012

Objective

To assess change in the 4-year prevalence (2006–2009) of the use of food in school fundraising and as rewards and incentives for students, following implementation of federal legislation in the USA in 2006.

Design

Serial cross-sectional design using trend analysis to assess school-level data collected over four consecutive years from 2006/2007 to 2009/2010.

Setting

Minneapolis/St. Paul, MN.

Subjects

Convenience sample of middle and high schools participating in two longitudinal, aetiological studies that examined youth, their environment and obesity-related factors.

Results

A significant and sustained decrease was demonstrated in the use of low-nutrient, energy-dense foods in school fundraising activities and the use of food and food coupons as rewards and incentives by teachers and school staff.

Conclusions

Results support the utility of policy and legislative action as a tool for creating healthy, sustainable environmental change.
Association of the PDYN gene with alcohol dependence and the propensity to drink in negative emotional states
Authors: Karpyak Victor M. , Winham Stacey J. , Preuss Ulrich W. , Zill Peter , Cunningham Julie M. , Walker Denise L. , Lewis Kriste A. , Geske Jennifer R. , Colby Colin L. , Abulseoud Osama A. , Hall-Flavin Daniel K. , Loukianova Larissa L. , Schneekloth Terry D. , Frye Mark A , Bazov Igor , Heit John A. , Bakalkin Georgy , Mrazek David A. , Biernacka Joanna M.
Published: October 2012

Synthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.
Reversible transformation between α-oxo acids and α-amino acids on ZnS particles: a photochemical model for tuning the prebiotic redox homoeostasis
Authors: Wang Wei , Liu Xiaoyang , Yang Yanqiang , Su Wenhui
Published: October 2012

How prebiotic metabolic pathways could have formed is an essential question for the origins of life on early Earth. From the abiogenetic point of view, the emergence of primordial metabolism may be postulated as a continuum from Earth's geochemical processes to chemoautotrophic biochemical procedures on mineral surfaces. In the present study, we examined in detail the reversible amination of α-ketoglutarate on UV-irradiated ZnS particles under variable reaction conditions such as pH, temperature, hole scavenger species and concentrations, and different amino acids. It was observed that the reductive amination of α-ketoglutarate and the oxidative amination of glutamate were both effectively performed on ZnS surfaces in the presence and absence of a hole scavenger, respectively. Accordingly, a photocatalytic mechanism was proposed. The reversible photochemical reaction was more efficient under basic conditions but independent of temperature in the range of 30–60 °C. SO32−was more effective than S2−as the hole scavenger. Finally, we extended the glutamate dehydrogenase-like chemistry to a set of other α-amino acids and their corresponding α-oxo acids and found that hydrophobic amino acid side chains were more conducive to the reversible redox reactions. Since the experimental conditions are believed to have been prevalent in shallow water hydrothermal vent systems of early Earth, the results of this work not only suggest that the ZnS-assisted photochemical reaction can regulate the redox equilibrium between α-amino acids and α-oxo acids, but also provide a model of how prebiotic metabolic homoeostasis could have been developed and regulated. These findings can advance our understanding of the establishment of archaic non-enzymatic metabolic systems and the origins of autotrophy.
Das Adolf-Würth-Zentrum für Geschichte der Psychologie der Universität Würzburg
Authors: Gundlach Horst , Stock Armin
Published: October 2012

Der Artikel beschreibt die historische Entwicklung einer der weltweit umfangreichsten Sammlungen zur Geschichte der Psychologie. Begründet wurde die Sammlung durch Werner Traxel als Institut für Geschichte der Neueren Psychologie an der Universität Passau 1981. Neben dem Sammeln und Bewahren der Apparate und Dokumente konnte Traxel eine psychologiegeschichtliche Schriftenreihe etablieren und verschiedene Tagungen zu psychologiehistorischen Themen organisieren. Ab 1990 gelang es nachfolgend Horst Gundlach die Sammlung erheblich zu erweitern, die Schriftenreihe fortzusetzen und gleichermaßen Kongresse und Ausstellungen zu veranstalten. Seit dem Umzug an die Universität Würzburg im Jahr 2009 hat Armin Stock die Verantwortung für die Sammlung übernommen. Der Beitrag dokumentiert neben der geschichtlichen Entwicklung exemplarisch einige Glanzstücke des Adolf-Würth-Zentrums.
Wilhelm Wundts Wissenschaftstheorie der Psychologie
Authors: Fahrenberg Jochen
Published: October 2012

Wilhelm Wundt entwickelte seine Wissenschaftstheorie der Psychologie–die erste überhaupt–in einem weiten theoretischen Horizont, der durch seine neurophysiologischen, psychologischen und philosophischen Arbeiten bestimmt war. Er postuliert den Prozesscharakter des Bewusstseins und gibt den Transzendenzbezug des Seelenbegriffs auf. Der Mensch als denkendes und wollendes Subjekt ist nicht in den Begriffen der Naturwissenschaften zu erfassen; die Psychologie erfordert spezielle Kategorien und eigenständige Erkenntnisprinzipien. Sie ist einerseits empirische Geisteswissenschaft, soll jedoch andererseits ihre physiologischen Grundlagen nicht ausklammern. Wundts Ansatz ist perspektivisch, er verlangt ein „komplementäres” Denken in verschiedenen Bezugssystemen und einen entsprechenden Wechsel der Methoden. Die Psychologie soll mit der Philosophie in Verbindung bleiben, um die Erkenntniskritik der unter Psychologen verbreiteten metaphysischen Voraussetzungen zu fördern.

Der Versuch einer Rekonstruktion von Wundts Wissenschaftstheorie ist Bestandteil einer Rezeptionsanalyse seines Werks, über die hier nur kurz berichtet wird. Aufgrund von etwa 200 zeitgenössischen und späteren Rezensionen sowie weiterer Quellen werden Hypothesen abgeleitet, weshalb Wundt noch zu Lebzeiten vom Gründervater fast zum Außenseiter wurde.
ShakeOut drill emphasizes importance of earthquake preparedness, education
Authors: Showstack Randy
Published: October 2012

“Please pardon this interruption,” Aimee Monticchio, principal of Langston Hughes Middle School in Reston, Va., announced over the school's public address system at 10:18 A.M. on 18 October. Time to drop, cover, and hold on, she told the 965 seventh and eighth graders. They were practicing the safety steps in an earthquake drill along with an estimated 1.8 million other people in the southeastern United States taking part in the region's first Great ShakeOut awareness exercise. ShakeOut exercises have been held in California since 2008, and the drills have gradually spread to other parts of the United States and to other countries as well.
Honors
Authors: Anonymous
Published: October 2012

Many AGU members are among the American Meteorological Society's (AMS) 2013 honorary members, awardees, lecturers, and fellows. Among the AMS honorary members is Susan Solomon, the Ellen Swallow Richards Professor of Atmospheric Chemistry and Climate Science at the Massachusetts Institute of Technology (MIT). Dennis Hartmann, of the University of Washington, Seattle, is the recipient of AMS's Carl‐Gustaf Rossby Research Medal “for significant contributions to the synthesis of knowledge of radiative and dynamical processes leading to a deeper understanding of the climate system.” R. Alan Plumb, professor of meteorology at MIT, receives the Jule G. Charney Award “for fundamental contributions to the understanding of geophysical fluid dynamics, stratospheric dynamics, chemical transport, and the general circulation of the atmosphere and oceans.” The Verner E. Suomi Award has been given to Richard Johnson, professor of atmospheric science at Colorado State University, Fort Collins, “for exquisite design of rawinsonde networks in field campaigns and insightful analysis of interactions between convective clouds and the largescale atmospheric circulation.” W. Kendall Melville, professor of oceanography at the Scripps Institution of Oceanography, University of California, San Diego, has been awarded the Sverdrup Gold Medal Award “for pioneering contributions in advancing knowledge on the role of surface wave breaking and related processes in air‐sea interaction.” AMS announced that Laurence Armi, also a professor of oceanography at Scripps, is recipient of the Henry Stommel Research Award “for his deeply insightful studies of stratified flow, his pioneering work on boundary mixing and other turbulent mechanisms.”
Science policy events at the 2012 AGU Fall Meeting
Authors: Hankin Erik
Published: October 2012

Are you interested in the intersection of science and policy, looking to make an impact on Capitol Hill, or concerned about the increasing number of attacks against scientists and their academic freedom? AGU Public Affairs offers many events at the 2012 Fall Meeting to assist member involvement in political processes and inform scientists of their rights and options should their research come under legal fire. Learn how you can share your science with policy makers to help inform policy at two luncheon events at the Fall Meeting. If you have ever considered working as a science expert for a member of Congress or reporting science in a mass media outlet, then you should attend the first luncheon, How to be a Congressional Science Fellow or Mass Media Fellow. The event will feature current AGU Congressional Science Fellows detailing their experiences working in Congress as well as past AGU Mass Media Fellows sharing their stories of reporting for a news organization. The luncheon will be held on Tuesday, 4 December, from 12:30 to 1:30 P.M. at the Marriott Hotel, in room Golden Gate B. In addition, current and former fellows will be available for one‐on‐one interactions at the AGU Marketplace from 3:30 to 4:30 P.M. on Tuesday, 4 December, through Thursday, 6 December.
A new remote sensing technique to measure global reservoir storage
Authors: Schultz Colin
Published: October 2012

Nearly 60% of the world's large rivers are affected by dams, with more than 33,000 large dams holding back upward of 8300 cubic kilometers of water across the planet. Reservoirs are employed worldwide, helping to ensure regular access to fresh water, mitigate flash flooding, and maintain minimum river flow levels. However, not all reservoirs have adequate and accessible monitoring systems. Having no easily accessible method with which to monitor changing reservoir storage volumes hinders long‐term planning and efforts to model the Earth's climate.
Annual Southern Ocean heat flux measured for first time
Authors: Schultz Colin
Published: October 2012

The Southern Ocean makes up nearly a quarter of the global ocean by surface area and plays a powerful role in regulating Earth's climate by affecting ocean and atmospheric circulation patterns. Modeled representations of the Southern Ocean, however, are plagued by uncertainty. Obtaining direct observations of Southern Ocean properties with which to confirm the modeled estimates is difficult in such hostile polar conditions. To help overcome this shortfall, the Southern Ocean Flux Station (SOFS), the first moored sensor array to ever be successfully deployed in the Southern Ocean, was set up south of Australia.
High‐speed imagery captures new sea spray formation mechanism
Authors: Schultz Colin
Published: October 2012

When strong winds blow over ocean waves, small droplets of sea spray rise into the air, enhancing the exchange of heat, mass, and energy between the air and the sea. How effective sea spray is at mediating each of these dynamics depends on the rate at which droplets are created and the drop size distribution of the mist. Unfortunately, research has been limited by a dearth of observational evidence that could explain the details of sea spray generation, including understanding the drop size distribution or the effects of different wind speeds. Previous research with high‐speed cameras aiming to capture the moment of drop formation was limited by camera resolutions too low to see all but the largest drops.
Relation of substorm pre‐onset arc to large‐scale field‐aligned current distribution
Authors: Nishimura Y. , Lyons L. R. , Kikuchi T. , Angelopoulos V. , Donovan E. F. , Mende S. B. , Lühr H.
Published: October 2012

Substorm auroral onset often occurs along a pre‐existing arc that is associated with an enhanced upward field‐aligned current (FAC). To determine the location of the upward FAC of the pre‐onset arc relative to the large‐scale region 1 (R1) and 2 (R2) FACs, we present coordinated observations of the THEMIS all‐sky imagers and CHAMP satellite, where CHAMP passed over relatively stable, pre‐onset arcs within the 30 min period before substorm auroral onset. We found that the upward FAC corresponding to the pre‐onset arc is latitudinally separated from the upward R1 FAC within the onset MLT range. In contrast, the arc is located near the R1‐R2 boundary to the west and east of the onset MLT range. This MLT dependence suggests that an east‐west oriented upward FAC sheet forms within the downward R2 FAC as a precursor FAC signature for substorm auroral onset.
Midlatitude F region peak height changes in response to interplanetary magnetic field conditions and modeling results
Authors: Blanch Estefania , Altadill David
Published: October 2012

The response of the electron density peak height of the F2 region, hmF2, to geomagnetic storms has been investigated and a characteristic behavior of the peak height disturbance in relation to local‐time, season and conditions of the interplanetary magnetic field has been obtained. The experimental results support the storm scenario which the change in the thermospheric wind is the main physical mechanism raising the ionospheric peak height. A real‐time forecasting tool modeling the hmF2 disturbance, ΔhmF2, by analytical time‐dependent functions has been developed. The empirical model predicts ΔhmF2 for latitudes of the Iberian Peninsula with an 86% of success and without false alarms. The behavior of the model fits to the experimental observations at other latitudes and longitudes within Europe which would allow extending its usefulness at wider latitudinal ranges.
Chronocoulometry for quantitative control of mass removal in micro-structures and sensors
Authors: Nowakowski B. K. , Smith S. T. , Pratt J. R. , Shaw G. A.
Published: October 2012

In this work, tungsten wires have been etched in a KOH electrolyte solution. Based on the oxidation state of the electrolytic dissolution reaction's product and time integration of the Faradaic current produced during the reaction, this method is capable of providing a direct measurement of the change in mass of a structure from anodic dissolution. To assess the application of this process for controlled mass removal spanning sub-micrograms to milligrams, two experimental studies and accompanying uncertainty analyses have been undertaken. In the first of these, 5 tungsten wires of length 30 mm were used to remove mass values ranging from 50 to 350 μg. Uncertainty estimates indicate relative combined standard uncertainties of less than 0.3% in the mass changes determined from the measurement of Faradaic current. Comparison of the mass change determined using the electrolytic method, and using a precision ultra-microbalance agreed within this uncertainty. The charge-based method was then applied to modify the dynamic characteristics of a quartz tuning fork oscillator. In these experiments, tungsten fiber attached to one tine of the oscillator was etched in 5 μg increments up to 120 μg of total removed mass. In general, frequency shifts of 2.8 Hz·μg−1 were observed, indicating sub-microgram resolution for the characterization of probes based on frequency shift and charge-based mass measurement. Taken together, this study provides the basis for a precision method for determining changes in mass based on electrical measurements from an electrochemical system. The utility of this technique is demonstrated through controlled modification of the dynamic properties of a mechanical oscillator.
Electrified free-surface flow of an inviscid liquid past topography
Authors: Binder Benjamin J. , Blyth M. G.
Published: October 2012

The flow of an electrified liquid layer moving over a prescribed topography is studied with the aim of determining the shape of the free surface. The steady flow is assumed to be inviscid, incompressible, and irrotational. The liquid is assumed to act as a perfect conductor and the air above the layer is assumed to act as a perfect dielectric. The electric field is produced by placing one or more charged electrodes at a distance above the free surface. A weakly nonlinear one-dimensional analysis is used to classify the possible solutions and nonlinear solutions are obtained numerically by boundary integral equation methods. It is found that the shape of the liquid layer's surface can be manipulated (using charged electrodes) to become wave-free.
Restricted active space spin-flip configuration interaction: Theory and examples for multiple spin flips with odd numbers of electrons
Authors: Zimmerman Paul M. , Bell Franziska , Goldey Matthew , Bell Alexis T. , Head-Gordon Martin
Published: October 2012

The restricted active space spin flip (RAS-SF) method is extended to allow ground and excited states of molecular radicals to be described at low cost (for small numbers of spin flips). RAS-SF allows for any number of spin flips and a flexible active space while maintaining pure spin eigenfunctions for all states by maintaining a spin complete set of determinants and using spin-restricted orbitals. The implementation supports both even and odd numbers of electrons, while use of resolution of the identity integrals and a shared memory parallel implementation allow for fast computation. Examples of multiple-bond dissociation, excited states in triradicals, spin conversions in organic multi-radicals, and mixed-valence metal coordination complexes demonstrate the broad usefulness of RAS-SF.
Experimental characterization of active acoustic metamaterial cell with controllable dynamic density
Authors: Akl Wael , Baz Amr
Published: October 2012

Controlling wave propagation pattern within acoustic fluid domains has been the motivation for the acoustic metamaterials developments to target applications ranging from acoustic cloaking to passive noise control techniques. Currently, various numerical and analytical approaches exist to predict the fluid domain material properties necessary for specific propagation pattern. Physical attempts to realize such material properties have revealed engineered material constructions that are focused on predefined wave propagation patterns. In the current paper, coupled fluid-structure one-dimensional metamaterial cell, in which piezoelectric active ingredient has been introduced, is manufactured to achieve controllable dynamic density. The density-controllable cell has been manufactured by coupling a water-filled cavity with piezoelectric elements in a cell of 4.5 cm length and 4.1 cm diameter subject to impulse excitation. A finite element model of the cell has been developed and its predictions are validated against the experimental results. The validated model is utilized to predict the changes in the pressure gradient inside the developed cell which is a direct measure of the changes introduced to the dynamic density of the acoustic metamaterial domain. With such predictions, it is demonstrated that densities as high as 3.2 gm/cm3 and as low as 0.72 gm/cm3 can be achieved experimentally for excitation frequencies ranging between 100 Hz and 500 Hz.
The magneto-optical behaviors modulated by unaggregated system for γ-Fe2O3–ZnFe2O4 binary ferrofluids
Authors: Li Jian , Fu Jun , Lin Yueqiang , Liu Xiaodong , Lin Lihua , Chen Longlong
Published: October 2012

Under an external magnetic field, when circularly polarized light was transmitted through binary ferrofluids based on strongly magnetic γ-Fe2O3 and weakly magnetic ZnFe2O4 nanoparticles, the birefringence Δn and dichroism Δk arising from the chains of γ-Fe2O3 particles system were modulated and decreased by the unchained ZnFe2O4 particles. In our experiments, we used two types of ZnFe2O4 nanoparticles: one consisted of ZnFe2O4(1) particles with higher moments, and the other consisted of ZnFe2O4(2) particles with lower moments. Comparing the birefringence and dichroism of the γ-Fe2O3–ZnFe2O4(1) and γ-Fe2O3–ZnFe2O4(2) binary ferrofluids, it was found that the modulating action of the ZnFe2O4(2) particle system with lower moments was larger than that of the ZnFe2O4(1) particle system with higher moments. Using a model for a bi-dispersed system based on chained and unchained particles, the behavior of the modulating action was explained by an additional effective relative magnetic permeability, which depends on the background of the unchained ZnFe2O4 particles for the chained γ-Fe2O3 particles and a field-induced demixing phase transition. These results showed that for binary ferrofluids based on both strong and weak magnetic nanoparticles, the power of the modulation of the magneto-optical effects depends on the difference in magnetization between the particles.
Research and development supporting risk-based wildfire effects prediction for fuels and fire management: status and needs
Authors: Hyde Kevin , Dickinson Matthew B. , Bohrer Gil , Calkin David , Evers Louisa , Gilbertson-Day Julie , Nicolet Tessa , Ryan Kevin , Tague Christina
Published: October 2012

Wildland fire management has moved beyond a singular focus on suppression, calling for wildfire management for ecological benefit where no critical human assets are at risk. Processes causing direct effects and indirect, long-term ecosystem changes are complex and multidimensional. Robust risk-assessment tools are required that account for highly variable effects on multiple values-at-risk and balance competing objectives, to support decision making. Providing wildland fire managers with risk-analysis tools requires a broad scientific foundation in fire behaviour and effects prediction as well as high quality computer-based tools and associated databases. We outline a wildfire risk-assessment approach, highlight recent developments in fire effects science and associated research needs, and recommend developing a comprehensive plan for integrated advances in wildfire occurrence, behaviour and effects research leading to improved decision support tools for wildland fire managers. We find that the current state of development in fire behaviour and effects science imposes severe limits on the development of risk-assessment technology. In turn, the development of technology has been largely disconnected from the research enterprise, resulting in a confusing array of ad hoc tools that only partially meet decision-support needs for fuel and fire management. We make the case for defining a common risk-based analytic framework for fire-effects assessment across the range of fire-management activities and developing a research function to support the framework.
Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease
Authors: Selvaraj Bhuvaneish Thangaraj , Frank Nicolas , Bender Florian L.P. , Asan Esther , Sendtner Michael
Published: October 2012

Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration.
Hypertrophic cardiomyopathy: Translating cellular cross talk into therapeutics
Authors: Teekakirikul Polakit , Padera Robert F. , Seidman J.G. , Seidman Christine E.
Published: October 2012

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with serious adverse outcomes, including heart failure, arrhythmias, and sudden cardiac death. The discovery that mutations in sarcomere protein genes cause HCM has enabled the development of mouse models that recapitulate clinical manifestations of disease. Studies in these models have provided unexpected insights into the biophysical and biochemical properties of mutated contractile proteins and may help to improve clinical diagnosis and management of patients with HCM.
Distinct properties of Ca2+–calmodulin binding to N- and C-terminal regulatory regions of the TRPV1 channel
Authors: Lau Sze-Yi , Procko Erik , Gaudet Rachelle
Published: October 2012

Transient receptor potential (TRP) vanilloid 1 (TRPV1) is a molecular pain receptor belonging to the TRP superfamily of nonselective cation channels. As a polymodal receptor, TRPV1 responds to heat and a wide range of chemical stimuli. The influx of calcium after channel activation serves as a negative feedback mechanism leading to TRPV1 desensitization. The cellular calcium sensor calmodulin (CaM) likely participates in the desensitization of TRPV1. Two CaM-binding sites are identified in TRPV1: the N-terminal ankyrin repeat domain (ARD) and a short distal C-terminal (CT) segment. Here, we present the crystal structure of calcium-bound CaM (Ca2+–CaM) in complex with the TRPV1-CT segment, determined to 1.95-Å resolution. The two lobes of Ca2+–CaM wrap around a helical TRPV1-CT segment in an antiparallel orientation, and two hydrophobic anchors, W787 and L796, contact the C-lobe and N-lobe of Ca2+–CaM, respectively. This structure is similar to canonical Ca2+–CaM-peptide complexes, although TRPV1 contains no classical CaM recognition sequence motif. Using structural and mutational studies, we established the TRPV1 C terminus as a high affinity Ca2+–CaM-binding site in both the isolated TRPV1 C terminus and in full-length TRPV1. Although a ternary complex of CaM, TRPV1-ARD, and TRPV1-CT had previously been postulated, we found no biochemical evidence of such a complex. In electrophysiology studies, mutation of the Ca2+–CaM-binding site on TRPV1-ARD abolished desensitization in response to repeated application of capsaicin, whereas mutation of the Ca2+–CaM-binding site in TRPV1-CT led to a more subtle phenotype of slowed and reduced TRPV1 desensitization. In summary, our results show that the TRPV1-ARD is an important mediator of TRPV1 desensitization, whereas TRPV1-CT has higher affinity for CaM and is likely involved in separate regulatory mechanisms.
Interactions of external K+ and internal blockers in a weak inward-rectifier K+ channel
Authors: Yang Lei , Edvinsson Johan , Palmer Lawrence G.
Published: October 2012

We investigated the effects of changing extracellular K+ concentrations on block of the weak inward-rectifier K+ channel Kir1.1b (ROMK2) by the three intracellular cations Mg2+, Na+, and TEA+. Single-channel currents were monitored in inside-out patches made from Xenopus laevis oocytes expressing the channels. With 110 mM K+ in the inside (cytoplasmic) solution and 11 mM K+ in the outside (extracellular) solution, these three cations blocked K+ currents with a range of apparent affinities (Ki (0) = 1.6 mM for Mg2+, 160 mM for Na+, and 1.8 mM for TEA+) but with similar voltage dependence (zδ = 0.58 for Mg2+, 0.71 for Na+, and 0.61 for TEA+) despite having different valences. When external K+ was increased to 110 mM, the apparent affinity of all three blockers was decreased approximately threefold with no significant change in the voltage dependence of block. The possibility that the transmembrane cavity is the site of block was explored by making mutations at the N152 residue, a position previously shown to affect rectification in Kir channels. N152D increased the affinity for block by Mg2+ but not for Na+ or TEA+. In contrast, the N152Y mutation increased the affinity for block by TEA+ but not for Na+ or Mg2+. Replacing the C terminus of the channel with that of the strong inward-rectifier Kir2.1 increased the affinity of block by Mg2+ but had a small effect on that by Na+. TEA+ block was enhanced and had a larger voltage dependence. We used an eight-state kinetic model to simulate these results. The effects of voltage and external K+ could be explained by a model in which the blockers occupy a site, presumably in the transmembrane cavity, at a position that is largely unaffected by changes in the electric field. The effects of voltage and extracellular K+ are explained by shifts in the occupancy of sites within the selectivity filter by K+ ions.
Cellular context and multiple channel domains determine cAMP sensitivity of HCN4 channels: Ligand-independent relief of autoinhibition in HCN4
Authors: Liao Zhandi , Lockhead Dean , St. Clair Joshua R. , Larson Eric D. , Wilson Courtney E. , Proenza Catherine
Published: October 2012

Hyperpolarization-activated, cyclic nucleotide–sensitive (HCN) channels produce the If and Ih currents, which are critical for cardiac pacemaking and neuronal excitability, respectively. HCN channels are modulated by cyclic AMP (cAMP), which binds to a conserved cyclic nucleotide–binding domain (CNBD) in the C terminus. The unliganded CNBD has been shown to inhibit voltage-dependent gating of HCNs, and cAMP binding relieves this “autoinhibition,” causing a depolarizing shift in the voltage dependence of activation. Here we report that relief of autoinhibition can occur in the absence of cAMP in a cellular context- and isoform-dependent manner: when the HCN4 isoform was expressed in Chinese hamster ovary (CHO) cells, the basal voltage dependence was already shifted to more depolarized potentials and cAMP had no further effect on channel activation. This “pre-relief” of autoinhibition was specific both to HCN4 and to CHO cells; cAMP shifted the voltage dependence of HCN2 in CHO cells and of HCN4 in human embryonic kidney (HEK) cells. The pre-relief phenotype did not result from different concentrations of soluble intracellular factors in CHO and HEK cells, as it persisted in excised cell-free patches. Likewise, it did not arise from a failure of cAMP to bind to the CNBD of HCN4 in CHOs, as indicated by cAMP-dependent slowing of deactivation. Instead, a unique ∼300–amino acid region of the distal C terminus of HCN4 (residues 719–1012, downstream of the CNBD) was found to be necessary, but not sufficient, for the depolarized basal voltage dependence and cAMP insensitivity of HCN4 in CHO cells. Collectively, these data suggest a model in which multiple HCN4 channel domains conspire with membrane-associated intracellular factors in CHO cells to relieve autoinhibition in HCN4 channels in the absence of cAMP. These findings raise the possibility that such ligand-independent regulation could tune the activity of HCN channels and other CNBD-containing proteins in many physiological systems.
XiP: a computational environment to create, extend and share workflows
Authors: Nagasaki Masao , Fujita André , Sekiya Yayoi , Saito Ayumu , Ikeda Emi , Li Chen , Miyano Satoru
Published: October 2012

XiP (eXtensible integrative Pipeline) is a flexible, editable and modular environment with a user-friendly interface that does not require previous advanced programming skills to run, construct and edit workflows. XiP allows the construction of workflows by linking components written in both R and Java, the analysis of high-throughput data in grid engine systems and also the development of customized pipelines that can be encapsulated in a package and distributed. XiP already comes with several ready-to-use pipeline flows for the most common genomic and transcriptomic analysis and ∼300 computational components.

Availability: XiP is open source, freely available under the Lesser General Public License (LGPL) and can be downloaded from http://xip.hgc.jp.

Contact:  nagasaki@megabank.tohoku.ac.jp
RIP-chip enrichment analysis
Authors: Erhard Florian , Dölken Lars , Zimmer Ralf
Published: October 2012

Motivation: RIP-chip is a high-throughput method to identify mRNAs that are targeted by RNA-binding proteins. The protein of interest is immunoprecipitated, and the identity and relative amount of mRNA associated with it is measured on microarrays. Even if a variety of methods is available to analyse microarray data, e.g. to detect differentially regulated genes, the additional experimental steps in RIP-chip require specialized methods. Here, we focus on two aspects of RIP-chip data: First, the efficiency of the immunoprecipitation step performed in the RIP-chip protocol varies in between different experiments introducing bias not existing in standard microarray experiments. This requires an additional normalization step to compare different samples and even technical replicates. Second, in contrast to standard differential gene expression experiments, the distribution of measurements is not normal. We exploit this fact to define a set of biologically relevant genes in a statistically meaningful way.

Results: Here, we propose two methods to analyse RIP-chip data: We model the measurement distribution as a gaussian mixture distribution, which allows us to compute false discovery rates (FDRs) for any cut-off. Thus, cut-offs can be chosen for any desired FDR. Furthermore, we use principal component analysis to determine the normalization factors necessary to remove immunoprecipitation bias. Both methods are evaluated on a large RIP-chip dataset measuring targets of Ago2, the major component of the microRNA guided RNA-induced silencing complex (RISC). Using published HITS-CLIP experiments performed with the same cell line as used for RIP-chip, we show that the mixture modelling approach is a necessary step to remove background, which computed FDRs are valid, and that the additional normalization is a necessary step to make experiments comparable.

Availability: An R implementation of REA is available on the project website (http://www.bio.ifi.lmu.de/REA) and as supplementary data file.

Contact:  florian.erhard@bio.ifi.lmu.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
STAR: ultrafast universal RNA-seq aligner
Authors: Dobin Alexander , Davis Carrie A. , Schlesinger Felix , Drenkow Jorg , Zaleski Chris , Jha Sonali , Batut Philippe , Chaisson Mark , Gingeras Thomas R.
Published: October 2012

Motivation: Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases.

Results: To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80–90% success rate, corroborating the high precision of the STAR mapping strategy.

Availability and implementation: STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.

Contact:  dobin@cshl.edu.