bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Access and Mobility within a New Model of Supported Housing for People with Neurotrauma: A Pilot Study
Authors: Callaway Libby , Tregloan Kate , Williams Gavin , Clark Ross
Published: April 2016

Objectives: (1) Evaluate the features of purpose-built apartment living on access, environmental control, and home and community mobility of people living with neurotrauma and (2) Examine tenant perceptions of those features.

Research design: Observational case series pilot study.Setting:Three apartments within a residential development in Melbourne, Australia.Participants:Three males (aged 30–55 years) with traumatic brain and/or spinal cord injury living in the three separate apartments.

Method and procedures:Measures:Two-published measures of user experience of built and technology environments, coupled with customised interdisciplinary post-occupancy evaluation (POE) methods and GPS-enabled mobility tracking.Analysis:Measures completed per manual guidelines and data reported descriptively. Customised measured drawings produced to represent tenants’ physical access and mobility. GPS community mobility data plotted on Google Earth.

Results: Built design features which enabled access and mobility included linear paths of travel, well-located furnishings, and joinery design that allowed approach from either side using a wheelchair. Personal home furnishing choices posed barriers to physical access. Home automation technologies positively influenced participants’ sense of control and independence, but posed learning challenges. Close proximity of housing to accessible public transport and services enabled community travel options.

Conclusion: Findings from this pilot study indicate the combination of housing location, design and technologies used, together with availability of local community services, provides an acceptable level of environmental control, access, mobility and tenant experience. Further research is required to determine validity of the novel measures used, and deliver rigorous research design to evaluate those features most important in achieving optimal outcomes.
Rise of Marxist Classes
Authors: U Eddy
Published: April 2016

How did “capitalists”, “petty bourgeoisie”, and other class categories based on Marxist critiques of capitalism become highly visible in local society while communist regimes abolished capitalist institutions? Conventional approaches to class lack the necessary tools for unraveling such “Marxist classes”, let alone their impact on class formation in the common sociological sense. I use Weber, Foucault, and others (together with a study of the emergence of a “petty bourgeoisie” in a Chinese school system) to highlight the bureaucratic struggle of the state to classify everyone with a Marxist schema of classes. Spotlighted are “textual corroboration” and “workplace ascription” of class status, two everyday processes carried out by state representatives that normalized the class categories as well as muddied their boundaries. I contend that official conversion of jobholders into different kinds of predefined class subjects rendered any “class-in-itself” or “class-for-itself” virtually impossible. The conclusion suggests how further research on bureaucratic classification and Marxist classes can advance understanding of state-society relations under communism, especially in comparative terms.
THE RATIO OF CO2–C EMISSION TO GRAIN YIELD IN SUMMER MAIZE CULTIVATED UNDER DIFFERENT SOIL TILLAGE AND STRAW APPLICATION CONDITIONS
Authors: HAN HUI FANG , NING TANG YUAN , LI ZENG JIA , CAO HONG MING
Published: April 2016

The relationship between climate, crop growth and crop yield is complicated. This study aimed to determine the ratio of CO2–C emission to grain yield, the field treatments were initiated in 2003, but the measurements for this analysis were collected during the summer maize-growing seasons of 2011 and 2012 in the North China Plain. The experiment showed that conventional tillage with straw application significantly increased grain yield and the ratio of CO2–C emission to grain yield of summer maize. The mean soil CO2–C emission rate with no tillage was significantly lower than that when conventional tillage was used; however, straw application significantly increased the soil CO2–C emission rate, irrespective of whether tillage was performed or not. This was mainly because straw application changed the soil total porosity and organic carbon content. In conclusion, the results of this study support the hypothesis that the ratio of CO2–C emission to grain yield in the North China Plain can be increased by straw application, whereas no tillage decreases this ratio.
In the Land of the International
Authors: Esmeir Samera
Published: April 2016

The preamble to the 1948 Universal Declaration of Human Rights establishes a peculiar hierarchy between rebellion and human rights. The preamble affirms that “whereas it is essential, if man is not to be compelled to have recourse, as a last resort, to rebellion against tyranny and oppression, that human rights should be protected by the rule of law.” According to the declaration, rebellion against oppression and tyranny is an act that individuals can only be compelled to pursue, and only once other choices are exhausted. Rebellion descends upon the oppressed “man” from without and he cannot refuse it. It is a force that takes over desperate men. Human rights, in turn, police against rebellion by prevailing in the law. They are the preferred weapon against two extremes: oppression and rebellion. And if rebellion is the space of compelled political action, human rights is the space of uncompelled, free, and authentic action against oppression and tyranny.
The Drowned, the Saved, and the Forgotten: Genocide Survivors and Modern Humanitarianism
Authors: Watenpaugh Keith David
Published: April 2016

Dominant narratives of the Eastern Mediterranean's 20th century exclude the study of Western humanitarianism and refugee survivors of the 1915 genocide of the Ottoman Armenians. Reasons for this exclusion abound. At the forefront is the abject nature of the human beings who populate that history, something which often induces revulsion on the part of historians in the present: these were people who left little of the appealing and elegant traces left by a Beiruti journalist, a Damascene urban notable, or an elite Constantinopolitan feminist. They appear as an undifferentiated mass of survivors of intense violence, disease, and starvation who are bereft of any agency; slaves, and serially raped and pregnant teenagers in bureaucratic documents stored at the League of Nations archive or packs of feral emaciated street children roving the narrow alleyways of Aleppo's old city in the paternalistic memoirs of Western relief workers—usually American or Scandinavian female healthcare professionals. Their own voices are obscured, showing up in the occasional self-published autobiography written by an elderly genocide survivor for his grandchildren, or in handwritten accounts and letters in lost dialects inherited by descendants unable to read them.
Anin vitroinvestigation of dynamic processes occurring in the schistosome tegument, using compounds known to disrupt secretory processes
Authors: Wilson R. A. , Barnes P. E.
Published: April 2016

The structure of the schistosome tegument can be changed byin vitroincubation of worms in medium containing chemicals selected for their ability to disrupt secretion in other cell systems. The observed structural changes support the hypothesis that the function of the discoid granules is to maintain the integrity of the tegument ground substance. They further support the idea that the multilaminate vesicles and/or their contents are incorporated into or on to the worm surface as part of a mechanism of surface turnover. Vesicle life appears to be similar to that estimated for other trematodes and in cestodes. In addition the worm surface appears to be replaced more rapidly than the worm acquires and loses its disguise of host antigens. It is suggested that the surface channels of the tegument may be a variable feature, and that transfer of fluids between environment and interstitial spaces may occur across the tegument.
The Maze of the Logos: Euripides, Suppliants 163-249
Authors: Michelini Ann
Published: April 2016

In Euripides' Suppliants as one commentator remarks, ‘the play consists of talk’. Much of the talk is about ideas, which weave a tantalizing and complex intellectual dance through the debates of the central figures. The tone is set by the first debate, between the suppliant Adrastus and the young Theseus. The former makes a plea in terms that he himself seems to characterize as inadequate, while the latter rejects the suppliant with a bravura speech that offers no less than a philosophy of religion, morality and politics. Theseus' ideas are marked by severe internal contradictions, and they are subjected to further contradictions by later statements of Theseus and others. Yet this puzzling philosophy is assigned to a character who seems entirely free from the misjudgments typical of other tragic protagonists. The Euripidean tag that ‘the gods ordain things counter to expectation’ appears not to be true in Theseus' case. Here is a tragic hero who, in a just cause, plans a brief war from which he hopes to return home successful, without major harm to his people and without offense to the gods; and—unlike the protagonists of several Aeschylean plays and Adrastus in this play— the Athenian king succeeds in all his aims. Even when Theseus reverses his initial rejection of Adrastus, he is careful to point out that his initial moral assessment was and is correct (334-36). The reversal itself suggests that, if Theseus has a susceptibility to error, the hamartēma may be located in the fit between logos and ergon, thought and reality, a famous dilemma in the intellectual history of the fifth century.
A new look at age and area: the geographic and environmental expansion of genera during the Ordovician Radiation
Authors: Miller Arnold I.
Published: April 2016

Although available paleobiological data indicate that the geographic ranges of marine species are maintained throughout their entire observable durations, other evidence suggests, by contrast, that the ranges of higher taxa expand as they age, perhaps in association with increased species richness. Here, I utilize a database of Ordovician genus occurrences collected from the literature for several paleocontinents to demonstrate that a significant aging of the global biota during the Ordovician Radiation was accompanied by a geographic and environmental expansion of genus ranges. The proportion of genera occurring in two or more paleocontinents in the database, and two or more environmental zones within a six-zone onshore-offshore framework, increased significantly in the Caradocian and Ashgillian. Moreover, widespread genera tended to be significantly older than their endemic counterparts, suggesting a direct link between their ages and their environmental and geographic extents. Expansion in association with aging was corroborated further by demonstrating this pattern directly among genera that ranged from the Tremadocian through the Ashgillian. Taken together, these results are significant not only for what they reveal about the kinetics of a major, global-scale diversification, but also for what they suggest about the interpretation of relationships between diversity trends at the α (within-community) and β (between-community) levels.
XXII.—Random Paths in Two and Three Dimensions
Authors: McCrea W. H. , Whipple F. J. W.
Published: April 2016

1. In a previous note (McCrea, 1936) the following problem was enunciated: A rectangular lattice is given; a particle P moves from one lattice-point to another in such a way that, when it is at any interior point, it is equally likely to move to any of its four neighbouring points. P is liberated at any given lattice-point and it is required to find the probability that it will ultimately reach any stated point in the boundary of the lattice, assuming that on arrival at a boundary point its movement ceases.
XVII.—On the Asymptotic Expansion of the Characteristic Numbers of the Mathieu Equation
Authors: Goldstein Sydney
Published: April 2016

An asymptotic formula has recently been given for the characteristic numbers of the Mathieu equation

From tabular values, it will be seen that the formula provides good numerical approximations to the characteristic numbers of integral order; but as pointed out by Ince, it provides better approximations to the characteristic numbers of order (m + ½), where m is a positive integer or zero. In this paper we shall first attempt to find out why this should be so, and then go on to show that the formula is probably an asymptotic expansion, in the Poincaré sense, for any characteristic number. A new asymptotic formula is then found for the difference between two characteristic numbers.
Integration of the normal power approximation
Authors: Berger Gottfried
Published: April 2016

Consider the set of functions

Obviously, π1(x) represents the net premium of the excess cover over the priority x, and the variance thereof.

If a distribution function F(x) = 1 − π0(x) is given, the set (1) can be generated by means of the recursion formulae

Let us study the special class of d.fs. F(x) which satisfy

where

If these conditions are met, the integrals (1) have the solution:

Aj(y) and Bj(y), respectively, are polynomials of rank jk and jk − 1. Their coefficients are determined by the equations:

The system (5) is obtained by differentiation of (4) with respect to y, and observing (2).
Our Future in a Changing Society
Authors: Tustin Don
Published: April 2016

The address examines qualities of behavioural therapists since the inception of ABMA. Attention is also given to current issues that require objective analysis; especially issues of individual and social responsibility, the role of families, and adult relationships. There is a need to identify frameworks that assist objective analyses of social situations. A behavioural decision-making approach appears useful for analysing responsibility, as the approach includes concepts to describe both individual choice and social pressures, allowing an assessment of the extent to which individuals or groups should change. There is also a need to find objective measures of values, both of individuals and of small groups. We can expect to see further changes in behavioural theories as more concepts and principles are introduced by behavioural practitioners who address current social problems.
Desert and Punishment for Acts Preparatory to the Commission of a Crime
Authors: Ohana Daniel
Published: April 2016

Conduct preparatory to the commission of a crime typically comprises acts such as gathering vital information, making initial contact with the prospective victim, reconnoitering the site of the crime, obtaining materials and tools, and gaining expertise knowledge. Many Western penal codes categorically distinguish preparatory actions from a punishable attempt in attending to cases whereby an actor engages in conduct planned to culminate in the commission of an offence. The article focuses on the desert of an actor who, after having formed an intention to commit a crime, conceives a plan and gets underway by performing acts of preparation - without commencing to commit the substantial offence, let alone bringing about its consummation. The actor’s failure to carry out the offence may be attributed to a vast array of causes, ranging from a decision on his part, prompted by a sudden change of heart, to discontinue the operation, through an inability to gain access to crucial information or tools, to the disappearance of the targeted victim or property. The article is divided in two parts. The first part addresses the factors which affect the blameworthiness of an actor intent on committing a crime as he gradually implements his plan by laying the groundwork for his undertaking. By considering the punishment of acts preparatory to the commission of a crime in the light of the principle of individual autonomy and the dilemma of moral luck, it explores the various respects in which the culpability of an actor who only engages in preparatory conduct differs from that of an actor who commences to commit the targeted offence. The second part takes the analysis a step further by probing the exceptional conditions under which preparatory actions may be sufficiently wrongful to warrant pressing the criminal law into service to provide for a punitive response. In this respect, attention focuses on such factors as the operational significance of the preparatory conduct; the acquisition of specialized tools and equipment; the organizational support available; and the seriousness of the substantial offense targeted.
What Have We Learned? Coordination
Authors: Oyegbite Kayode
Published: April 2016

This paper outlines each aspect of coordination as it relates to the responses made by various organizations in the disaster-affected areas. It is a synthesis of the presentations and discussions pertaining to coordination during the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO), in Phuket, Thailand, 04–06 May 2005. Coordination is defined, and two important questions are answered: (1) What coordination was done well?; and (2) What coordination could have been done better?.
Impact of Hurricane Sandy on the Staten Island University Hospital Emergency Department
Authors: Greenstein Josh , Chacko Jerel , Ardolic Brahim , Berwald Nicole
Published: April 2016

Introduction

On October 29, 2012, Hurricane Sandy touched down in New York City (NYC; New York USA) causing massive destruction, paralyzing the city, and destroying lives. Research has shown that considerable damage and loss of life can be averted in at-risk areas from advanced preparation in communication procedures, evacuation planning, and resource allocation. However, research is limited in describing how natural disasters of this magnitude affect emergency departments (EDs).

Hypothesis/Problem

The aim of this study was to identify and describe trends in patient volume and demographics, and types of conditions treated, as a result of Hurricane Sandy at Staten Island University Hospital North (SIUH-N; Staten Island, New York USA) site ED.

Methods

A retrospective chart review of patients presenting to SIUH-N in the days surrounding the storm, October 26, 2012 through November 2, 2012, was completed. Data were compared to the same week of the year prior, October 28, 2011 through November 4, 2011. Daily census, patient age, gender, admission rates, mode of arrival, and diagnoses in the days surrounding the storm were observed.

Results

A significant decline in patient volume was found in all age ranges on the day of landfall (Day 0) with a census of 114; -55% compared to 2011. The daily volume exhibited a precipitous drop on the days preceding the storm followed by a return to usual volumes shortly after.

A notably larger percentage of patients were seen for medication refills in 2012; 5.8% versus 0.4% (P<.05). Lacerations and cold exposure also were increased substantially in 2012 at 7.6% versus 2.8% (P<.05) and 3.8% versus 0.0% (P<.05) of patient visits, respectively.

A large decline in admissions was observed in the days prior to the storm, with a nadir on Day +1 at five percent (-22%). Review of admitted patients revealed atypical admissions for home care service such as need for supplemental oxygen or ventilator.

In addition, a drop in Emergency Medical Services (EMS) utilization was seen on Days 0 and +1. The SIUH-N typically sees 18% of patients arriving via EMS. On Day +1, only two percent of patients arrived by ambulance.

Conclusion

The daily ED census saw a significant decline in the days preceding the storm. In addition, the type of conditions treated varied from baseline, and a considerable drop in hospital admissions was seen. Data such as these presented here can help make predictions for future scenarios.

GreensteinJ, ChackoJ, ArdolicB, BerwaldN. Impact of Hurricane Sandy on the Staten Island University Hospital emergency department. Prehosp Disaster Med. 2016;31(3):335–339.
Duration of Untreated Illness as a Predictor of Treatment Response and Clinical Course in Generalized Anxiety Disorder
Authors: Altamura A. Carlo , Dell'Osso Bernardo , D'Urso Nazario , Russo Michela , Fumagalli Sara , Mundo Emanuela
Published: April 2016

Introduction:

The aim of the present study was to investigate the impact of the duration of untreated illness (DUI)—defined as the time elapsing between the onset of generalized anxiety disorder (GAD) and the first adequate pharmacologic treatment—on treatment response and clinical course in a sample of subjects with GAD.

Methods:

One hundred patients with GAD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria, were enrolled and their main demographic and clinical features collected. Patients were then treated with selective serotonin reuptake inhibitors or venlafaxine for 8 weeks in open-label conditions. Treatment response and other clinical variables were analyzed after dividing the sample into two groups according to DUI (DUI ≤12 months and DUI >12 months).

Results:

When the DUI was computed with respect to the first antidepressant treatment (DUI-AD), a higher improvement (Clinical Global Impressions-Severity of Illness scale) after the pharmacologic treatment was found in the group with a shorter DUI (analysis of variance with repeated measures: time effect F=654.975, P<.001; group effect: F=4.369, P=.O39). When computed with respect to the first treatment with benzodiazepines (DUI-BDZ), the two groups did not show any significant difference in treatment response (time effect: F=652.183, P<.001; group effect: F=0.009, P=.924). In addition, patients with a longer DUI (DUI-BDZ or DUI-AD) showed an earlier age at onset, a longer duration of illness and a higher rate of comorbid psychiatric disorders with onset later than GAD.

Conclusion:

Results from this preliminary study seem to suggest that a shorter DUI-AD may determine a better response to pharmacologic treatment in patients with GAD, and that a longer DUI (DUI-BDZ and DUI-AD) may be associated to a worse clinical course. Further investigation on the relationship between DUI and GAD is needed.
Uses of wonder in popular science:Cosmos: A Personal Voyageand the origin of life
Authors: Helsing Daniel
Published: April 2016

This paper analyses the use of wonder in the TV-seriesCosmos: A Personal Voyage(1980). Popular science has been studied extensively (e.g. Broks 2006; Leane 2007; Perrault 2013), and wonder has been studied moderately (e.g. Daston & Park 1998; Fuller 2006; Vasalou 2015). However, there are very few studies of wonder in popular science. This paper explores how and why wonder is used inCosmos, with the wider aim of understanding uses of wonder in popular science. The studies that discuss wonder in popular science (Fahnestock 1986; Perrault 2013) argue that wonder is used to enthuse the audience about science, but they do not discuss why wonder has this ability, nor whether wonder has other functions. This paper argues that Fuller's (2006) psychological and evolutionary account of wonder can elucidate why wonder has the ability to enthuse; it discerns three senses of ‘wonder’ (related to objects, emotions and attitudes); and it discusses other functions of wonder (existential, aesthetic and ethical). Due to the centrality of astrobiological questions inCosmos, this paper also highlights the relation of these questions to the senses and functions of wonder inCosmos.
A 280 W LDMOS broadband Doherty PA with 52% of fractional bandwidth based on a multi-line impedance inverter for DVB-T applications
Authors: Cidronali Alessandro , Giovannelli Niccolò , Maddio Stefano , Del Chiaro Andrea , Schuberth Christian , Magesacher Thomas , Singerl Peter
Published: April 2016

We introduce a new technique for the design of an output combiner for Doherty power amplifier (DPA) and its effective exploitation for the development of a wideband laterally diffused metal oxide semiconductor (LDMOS) DPA. The design is enabled by a two-line impedance inverter for the DPA back-off operation, which is capable of 52% of fractional bandwidth. The technique is validated by the development of a DPA prototype for Ultra high frequency terrestrial digital video broadcast (DVB-T) applications, with optimized peak power and efficiency over 470–806 MHz. The prototype delivers between 40 and 53% of average efficiency across the band, at 49 dBm output power in average across the bandwidth, and supporting DVB-T signals with 8 MHz bandwidth and a peak-to-average power ratio of 10.5 dB. It achieves the target adjacent channel power ratio of −52 dBc at 750 MHz if digital pre-distortion is applied, and provides 47.8 dBm of output power with a drain efficiency of 44.3%.
BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors
Authors: Korfi K , Smith M , Swan J , Somervaille T C P , Dhomen N , Marais R
Published: April 2016

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception of some BCR-ABL1+ patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for adult B-ALL patients and chemotherapy remains first-line therapy despite adverse side effects and poor efficacy. We show that, although the MEK/ERK pathway is activated in B-ALL cells driven by different oncogenes, MEK inhibition does not suppress B-ALL cell growth. However, MEK inhibition synergized with BCL-2/BCL-XL family inhibitors to suppress proliferation and induce apoptosis in B-ALL cells. We show that this synergism is mediated by the pro-apoptotic factor BIM, which is dephosphorylated as a result of MEK inhibition, allowing it to bind to and neutralize MCL-1, thereby enhancing BCL-2/BCL-XL inhibitor-induced cell death. This cooperative effect is observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential.
Genetic and environmental influences interact with age and sex in shaping the human methylome
Authors: van Dongen Jenny , Nivard Michel G. , Willemsen Gonneke , Hottenga Jouke-Jan , Helmer Quinta , Dolan Conor V. , Ehli Erik A. , Davies Gareth E. , van Iterson Maarten , Breeze Charles E. , Beck Stephan ,   BIOS Consortium, Hoen Peter A.C.’t , Pool René , van Greevenbroek Marleen M.J. , Stehouwer Coen D.A. , Kallen Carla J.H. van der , Schalkwijk Casper G. , Wijmenga Cisca , Zhernakova Sasha , Tigchelaar Ettje F. , Beekman Marian , Deelen Joris , van Heemst Diana , Veldink Jan H. , van den Berg Leonard H. , van Duijn Cornelia M. , Hofman Bert A. , Uitterlinden André G. , Jhamai P. Mila , Verbiest Michael , Verkerk Marijn , van der Breggen Ruud , van Rooij Jeroen , Lakenberg Nico , Mei Hailiang , Bot Jan , Zhernakova Dasha V. , van’t Hof Peter , Deelen Patrick , Nooren Irene , Moed Matthijs , Vermaat Martijn , Luijk René , Bonder Marc Jan , van Dijk Freerk , van Galen Michiel , Arindrarto Wibowo , Kielbasa Szymon M. , Swertz Morris A. , van Zwet Erik W. , Isaacs Aaron , Franke Lude , Suchiman H. Eka , Jansen Rick , van Meurs Joyce B. , Heijmans Bastiaan T. , Slagboom P. Eline , Boomsma Dorret I.
Published: April 2016

The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation.
Giant spin-torque diode sensitivity in the absence of bias magnetic field
Authors: Fang Bin , Carpentieri Mario , Hao Xiaojie , Jiang Hongwen , Katine Jordan A. , Krivorotov Ilya N. , Ocker Berthold , Langer Juergen , Wang Kang L. , Zhang Baoshun , Azzerboni Bruno , Amiri Pedram Khalili , Finocchio Giovanni , Zeng Zhongming
Published: April 2016

Microwave detectors based on the spin-torque diode effect are among the key emerging spintronic devices. By utilizing the spin of electrons in addition to charge, they have the potential to overcome the theoretical performance limits of their semiconductor (Schottky) counterparts. However, so far, practical implementations of spin-diode microwave detectors have been limited by the necessity to apply a magnetic field. Here, we demonstrate nanoscale magnetic tunnel junction microwave detectors, exhibiting high-detection sensitivity of 75,400 mV mW−1 at room temperature without any external bias fields, and for low-input power (micro-Watts or lower). This sensitivity is significantly larger than both state-of-the-art Schottky diode detectors and existing spintronic diodes. Micromagnetic simulations and measurements reveal the essential role of injection locking to achieve this sensitivity performance. This mechanism may provide a pathway to enable further performance improvement of spin-torque diode microwave detectors.
Synthetic and systems biology for microbial production of commodity chemicals
Authors: Chubukov Victor , Mukhopadhyay Aindrila , Petzold Christopher J , Keasling Jay D , Martín Héctor García
Published: April 2016

The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.
Erratum: Mating dynamics in a nematode with three sexes and its evolutionary implications
Authors: Chaudhuri Jyotiska , Bose Neelanjan , Tandonnet Sophie , Adams Sally , Zuco Giusy , Kache Vikas , Parihar Manish , von Reuss Stephan H. , Schroeder Frank C. , Pires-daSilva Andre
Published: April 2016

Scientific Reports 5: Article number: 17676; Published online: 03 December 2015; Updated: 07 April 2016 This Article contains an error in Supplementary Figure 1 where the value of the male chemotaxis index towards ascr#9 ‘0.26 ± 0.07’ was incorrectly depicted as ‘0.38 ± 0.07’. The correct Supplementary Figure 1 appears below as Figure 1.
An Adaptive Weighting Algorithm for Interpolating the Soil Potassium Content
Authors: Liu Wei , Du Peijun , Zhao Zhuowen , Zhang Lianpeng
Published: April 2016

The concept of spatial interpolation is important in the soil sciences. However, the use of a single global interpolation model is often limited by certain conditions (e.g., terrain complexity), which leads to distorted interpolation results. Here we present a method of adaptive weighting combined environmental variables for soil properties interpolation (AW-SP) to improve accuracy. Using various environmental variables, AW-SP was used to interpolate soil potassium content in Qinghai Lake Basin. To evaluate AW-SP performance, we compared it with that of inverse distance weighting (IDW), ordinary kriging, and OK combined with different environmental variables. The experimental results showed that the methods combined with environmental variables did not always improve prediction accuracy even if there was a strong correlation between the soil properties and environmental variables. However, compared with IDW, OK, and OK combined with different environmental variables, AW-SP is more stable and has lower mean absolute and root mean square errors. Furthermore, the AW-SP maps provided improved details of soil potassium content and provided clearer boundaries to its spatial distribution. In conclusion, AW-SP can not only reduce prediction errors, it also accounts for the distribution and contributions of environmental variables, making the spatial interpolation of soil potassium content more reasonable.
Vesicle Size Regulates Nanotube Formation in the Cell
Authors: Su Qian Peter , Du Wanqing , Ji Qinghua , Xue Boxin , Jiang Dong , Zhu Yueyao , Ren He , Zhang Chuanmao , Lou Jizhong , Yu Li , Sun Yujie
Published: April 2016

Intracellular membrane nanotube formation and its dynamics play important roles for cargo transportation and organelle biogenesis. Regarding the regulation mechanisms, while much attention has been paid on the lipid composition and its associated protein molecules, effects of the vesicle size has not been studied in the cell. Giant unilamellar vesicles (GUVs) are often used for in vitro membrane deformation studies, but they are much larger than most intracellular vesicles and the in vitro studies also lack physiological relevance. Here, we use lysosomes and autolysosomes, whose sizes range between 100 nm and 1 μm, as model systems to study the size effects on nanotube formation both in vivo and in vitro. Single molecule observations indicate that driven by kinesin motors, small vesicles (100–200 nm) are mainly transported along the tracks while a remarkable portion of large vesicles (500–1000 nm) form nanotubes. This size effect is further confirmed by in vitro reconstitution assays on liposomes and purified lysosomes and autolysosomes. We also apply Atomic Force Microscopy (AFM) to measure the initiation force for nanotube formation. These results suggest that the size-dependence may be one of the mechanisms for cells to regulate cellular processes involving membrane-deformation, such as the timing of tubulation-mediated vesicle recycling.
Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study
Authors: Zheng Yi-Zi , Hu Xin , Shao Zhi-Ming
Published: April 2016

To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289–1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients.
Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin
Authors: Verespy III Stephen , Mehta Akul Y. , Afosah Daniel , Al-Horani Rami A. , Desai Umesh R.
Published: April 2016

Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (<500 nM) and high selectivity for thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding.
RXR controlled regulatory networks identified in mouse brain counteract deleterious effects of Aβ oligomers
Authors: Nam Kyong Nyon , Mounier Anais , Fitz Nicholas F. , Wolfe Cody , Schug Jonathan , Lefterov Iliya , Koldamova Radosveta
Published: April 2016

Bexarotene, a selective agonist for Retinoid X receptors (RXR) improves cognitive deficits and amyloid-β (Aβ) clearance in mice. Here we examine if the effect of bexarotene on RXR cistrome and transcriptomes depend on APOE isoform and Aβ deposition. We found bexarotene increased RXR binding to promoter regions in cortex of APOE3 mice. Rho family GTPases and Wnt signaling pathway were highly enriched in ChIP-seq and RNA-seq datasets and members of those pathways - Lrp1, Lrp5, Sfrp5 and Sema3f were validated. The effect of APOE isoform was compared in APOE3 and APOE4 mice and we found significant overlapping in affected pathways. ChIP-seq using mouse embryonic stem cells and enrichment levels of histone marks H3K4me3 and H3K27me3 revealed that, bexarotene induced epigenetic changes, consistent with increased neuronal differentiation and in correlation with changes in transcription. Comparison of transcriptome in APOE3 and APP/APOE3 mice revealed that amyloid deposition significantly affects the response to bexarotene. In primary neurons, bexarotene ameliorated the damaged dendrite complexity and loss of neurites caused by Aβ42. Finally, we show that the disruption of actin cytoskeleton induced by Aβ42in vitro was inhibited by bexarotene treatment. Our results suggest a mechanism to establish RXR therapeutic targets with significance in neurodegeneration.
Empirical insights into the stochasticity of small RNA sequencing
Authors: Qin Li-Xuan , Tuschl Thomas , Singer Samuel
Published: April 2016

The choice of stochasticity distribution for modeling the noise distribution is a fundamental assumption for the analysis of sequencing data and consequently is critical for the accurate assessment of biological heterogeneity and differential expression. The stochasticity of RNA sequencing has been assumed to follow Poisson distributions. We collected microRNA sequencing data and observed that its stochasticity is better approximated by gamma distributions, likely because of the stochastic nature of exponential PCR amplification. We validated our findings with two independent datasets, one for microRNA sequencing and another for RNA sequencing. Motivated by the gamma distributed stochasticity, we provided a simple method for the analysis of RNA sequencing data and showed its superiority to three existing methods for differential expression analysis using three data examples of technical replicate data and biological replicate data.
Predicting the response of olfactory sensory neurons to odor mixtures from single odor response
Authors: Marasco Addolorata , De Paris Alessandro , Migliore Michele
Published: April 2016

The response of olfactory receptor neurons to odor mixtures is not well understood. Here, using experimental constraints, we investigate the mathematical structure of the odor response space and its consequences. The analysis suggests that the odor response space is 3-dimensional, and predicts that the dose-response curve of an odor receptor can be obtained, in most cases, from three primary components with specific properties. This opens the way to an objective procedure to obtain specific olfactory receptor responses by manipulating mixtures in a mathematically predictable manner. This result is general and applies, independently of the number of odor components, to any olfactory sensory neuron type with a response curve that can be represented as a sigmoidal function of the odor concentration.
PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway
Authors: Wang Yuan , Yan Feng , Ye Qing , Wu Xiao , Jiang Fan
Published: April 2016

Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.
A Tricholoma matsutake Peptide with Angiotensin Converting Enzyme Inhibitory and Antioxidative Activities and Antihypertensive Effects in Spontaneously Hypertensive Rats
Authors: Geng Xueran , Tian Guoting , Zhang Weiwei , Zhao Yongchang , Zhao Liyan , Wang Hexiang , Ng Tzi Bun
Published: April 2016

Hypertension is a major risk factor for cardiovascular disease. A crude water extract of the fruiting bodies of a highly prized mushroom Tricholoma matsutakei exerted an antihypertensive action on spontaneously hypertensive rats (SHRs) at a dosage of 400 mg/kg. An angiotensin converting enzyme (ACE) inhibitory peptide with an IC50 of 0.40 μM was purified from the extract and designated as TMP. Its amino acid sequence was elucidated to be WALKGYK through LC-MS/MS analysis. The Lineweaver-Burk plot suggested that TMP was a non-competitive inhibitor of ACE. A short-term assay of antihypertensive activity demonstrated that TMP at the dosage of 25 mg/kg could significantly lower the systolic blood pressure (SBP) of SHRs. TMP exhibited remarkable stability over a wide range of temperatures and pH values. It also demonstrated 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. The aforementioned activities of TMP were corroborated by utilizing the synthetic peptide. Hence T. matsutake can be used as a functional food to help prevent hypertension- associated diseases.
Super Stable Ferroelectrics with High Curie Point
Authors: Gao Zhipeng , Lu Chengjia , Wang Yuhang , Yang Sinuo , Yu Yuying , He Hongliang
Published: April 2016

Ferroelectric materials are of great importance in the sensing technology due to the piezoelectric properties. Thermal depoling behavior of ferroelectrics determines the upper temperature limit of their application. So far, there is no piezoelectric material working above 800 °C available. Here, we show Nd2Ti2O7with a perovskite-like layered structure has good resistance to thermal depoling up to 1400 °C. Its stable behavior is because the material has only 180° ferroelectric domains, complex structure change at Curie point (Tc) and their sintering temperature is below their Tc, which avoided the internal stresses produced by the unit cell volume change at Tc. The phase transition at Tcshows a first order behavior which involving the tilting and rotation of the octahedron. The Curie – Weiss temperature is calculated, which might explain why the thermal depoling starts at about 1400 °C.
Effect of pH on the structure and drug release profiles of layer-by-layer assembled films containing polyelectrolyte, micelles, and graphene oxide
Authors: Han Uiyoung , Seo Younghye , Hong Jinkee
Published: April 2016

Layer by layer (lbl) assembled multilayer thin films are used in drug delivery systems with attractive advantages such as unlimited selection of building blocks and free modification of the film structure. In this paper, we report the fundamental properties of lbl films constructed from different substances such as PS-b-PAA amphiphilic block copolymer micelles (BCM) as nano-sized drug vehicles, 2D-shaped graphene oxide (GO), and branched polyethylenimine (bPEI). These films were fabricated by successive lbl assembly as a result of electrostatic interactions between the carboxyl group of BCM and amine group of functionalized GO or bPEI under various pH conditions. We also compared the thickness, roughness, morphology and degree of adsorption of the (bPEI/BCM) films to those in the (GO/BCM) films. The results showed significant difference because of the distinct pH dependence of each material. In addition, drug release rates of the GO/BCM film were more rapid those of the (bPEI/BCM) film in pH 7.4 and pH 2 PBS buffer solutions. In (bPEI/BCM/GO/BCM) film, the inserted GO layers into bPEI/BCM multilayer induced rapid drug release. We believe that these materials & pH dependent film properties allow developments in the control of coating techniques for biological and biomedical applications.