bluuebunny/crossref_metadata_2025 huggingface dataset:
PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia
Authors: Ito Matthew K. , Santos Raul D.
Published: May 2016

Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid‐modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low‐density lipoprotein cholesterol, as well as reductions in non‐high‐density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long‐term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid‐modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia.
Testing a weather generator for downscaling climate change projections over Switzerland
Authors: Keller D. E. , Fischer A. M. , Liniger M. A. , Appenzeller C. , Knutti R.
Published: May 2016

Climate information provided by global or regional climate models (RCMs) are often too coarse and prone to substantial biases for local assessments or use in impact models. Hence, statistical downscaling becomes necessary. For the Swiss National Climate Change Initiative (CH2011), a delta‐change approach was used to provide daily climate scenarios at the local scale. Here, we analyse a Richardson‐type weather generator (WG) as an alternative method to downscale daily precipitation, minimum and maximum temperature. The WG is calibrated for 26 Swiss stations and the reference period is 1980–2009. It is perturbed with change factors derived from RCMs (ENSEMBLES) to represent the climate of 2070–2099 assuming the SRES A1B emission scenario. The WG can be run in multi‐site mode, making it especially attractive for impact‐modellers that rely on a realistic spatial structure in downscaled time‐series. The results from the WG are benchmarked against the original delta‐change approach that applies mean additive or multiplicative adjustments to the observations.

According to both downscaling methods, the results reveal mean temperature increases and a precipitation decrease in summer, consistent with earlier studies. For the summer drying, the WG indicates primarily a decrease in wet‐day frequency and correspondingly an increase in mean dry spell length of between 18 and 40% at low‐elevation stations. By definition, these potential changes cannot be represented by a delta‐change approach. In winter, both methods project a shortening of the frost period (−30 to −60 days) and a decrease of snow days (−20 to −100%). The WG demonstrates though, that almost present‐day conditions in snow‐days could still occur in the future. As expected, both methods have difficulties in representing extremes. If users focus on changes in temporal sequences and need a large number of future realizations, it is recommended to use data from a WG instead of a delta‐change approach.
Harnessing Poly(ionic liquid)s for Sensing Applications
Authors: Guterman Ryan , Ambrogi Martina , Yuan Jiayin
Published: May 2016

The interest in poly(ionic liquid)s for sensing applications is derived from their strong interactions to a variety of analytes. By combining the desirable mechanical properties of polymers with the physical and chemical properties of ILs, new materials can be created. The tunable nature of both ionic liquids and polymers allows for incredible diversity, which is exemplified in their broad applicability. In this article we examine the new field of poly(ionic liquid) sensors by providing a detailed look at the current state‐of‐the‐art sensing devices for solvents, gases, biomolecules, pH, and anions.

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Hybrid procedure for total laryngectomy with a flexible robot‐assisted surgical system
Authors: Schuler Patrick J. , Hoffmann Thomas K. , Veit Johannes A. , Rotter Nicole , Friedrich Daniel T. , Greve Jens , Scheithauer Marc O.
Published: May 2016

Introduction

Total laryngectomy is a standard procedure in head‐and‐neck surgery for the treatment of cancer patients. Recent clinical experiences have indicated a clinical benefit for patients undergoing transoral robot‐assisted total laryngectomy (TORS‐TL) with commercially available systems. Here, a new hybrid procedure for total laryngectomy is presented.

Methods

TORS‐TL was performed in human cadavers (n = 3) using a transoral‐transcervical hybrid procedure. The transoral approach was performed with a robotic flexible robot‐assisted surgical system (Flex®) and compatible flexible instruments. Transoral access and visualization of anatomical landmarks were studied in detail.

Results

Total laryngectomy is feasible with a combined transoral‐transcervical approach using the flexible robot‐assisted surgical system. Transoral visualization of all anatomical structures is sufficient. The flexible design of the robot is advantageous for transoral surgery of the laryngeal structures.

Conclusion

Transoral robot assisted surgery has the potential to reduce morbidity, hospital time and fistula rates in a selected group of patients. Initial clinical studies and further development of supplemental tools are in progress. Copyright © 2016 John Wiley & Sons, Ltd.
Enhanced Charge Separation through ALD‐Modified Fe2O3/Fe2TiO5 Nanorod Heterojunction for Photoelectrochemical Water Oxidation
Authors: Li Chengcheng , Wang Tuo , Luo Zhibin , Liu Shanshan , Gong Jinlong
Published: May 2016

Hematite suffers from poor charge transport and separation properties for solar water splitting. This paper describes the design and fabrication of a 3D Fe2O3/Fe2TiO5 heterojunction photoanode with improved charge separation, via a facile hydrothermal method followed by atomic layer deposition and air annealing. A highly crystallized Fe2TiO5 phase forms with a distinct interface with the underlying Fe2O3 core, where a 4 nm Fe2TiO5 overlayer leads to the best photoelectrochemical performance. The favorable band offset between Fe2O3 and Fe2TiO5 establishes a type‐II heterojunction at the Fe2O3/Fe2TiO5 interface, which drives electron–hole separation effectively. The Fe2O3/Fe2TiO5 composite electrode exhibits a dramatically improved photocurrent of 1.63 mA cm−2 at 1.23 V versus reversible hydrogen electrode (RHE) under simulated 1 sun illumination (100 mW cm−2), which is 3.5 times that of the bare Fe2O3 electrode. Decorating the Fe2O3/Fe2TiO5 heterojunction photoanode with earth‐abundant FeNiOx cocatalyst further expedites surface reaction kinetics, leading to an onset potential of 0.8 V versus RHE with a photocurrent of 2.7 mA cm−2 at 1.23 V and 4.6 mA cm−2 at 1.6 V versus RHE. This sandwich photoanode shows an excellent stability for 5 h and achieves an overall Faradaic efficiency of 95% for O2 generation. This is the best performance ever reported for Fe2O3/Fe2TiO5 photoanodes.
Climate change, malaria, and public health: accounting for socioeconomic contexts in past debates and future research
Authors: Suk Jonathan E.
Published: May 2016

Infectious diseases have long been a focal point of climate change impacts research, with malaria prominent among them. Although it is universally acknowledged that malaria transmission is affected by temperature and rainfall, projections of future levels of malaria under different climate change scenarios have been the object of scientific controversy. One underappreciated reason for this is because modeling research has not consistently accounted for the role of socioeconomic factors in malaria transmission. There is now a growing awareness that greater and more explicit discussion about the impact of socioeconomic factors on malaria transmission under climate change scenarios is needed, but this will require deepened multidisciplinary collaboration and greater attention to climate change vulnerability science. In order to address this need and to ensure that that outputs from this research help address the needs of public health, the following activities are suggested: systematic analyses of past events to assess the relative role of climatic and socioeconomic drivers of malaria transmission, the development of a consistent definition of vulnerability, the development of metrics and indicators for the key components of vulnerability to malaria, greater collaboration with stakeholders, and the development of health‐specific climate change scenarios under the shared socioeconomic pathways (SSPs). Finally, researchers should more explicitly detail how their assumptions about future socioeconomic development affect research findings. WIREs Clim Change 2016, 7:551–568. doi: 10.1002/wcc.406

This article is categorized under:

Social Status of Climate Change Knowledge > Knowledge and Practice
Mitochondrial metabolic remodeling in response to genetic and environmental perturbations
Authors: Hollinshead Kate E.R. , Tennant Daniel A.
Published: May 2016

Mitochondria are metabolic hubs within mammalian cells and demonstrate significant metabolic plasticity. In oxygenated environments with ample carbohydrate, amino acid, and lipid sources, they are able to use the tricarboxylic acid cycle for the production of anabolic metabolites and ATP. However, in conditions where oxygen becomes limiting for oxidative phosphorylation, they can rapidly signal to increase cytosolic glycolytic ATP production, while awaiting hypoxia‐induced changes in the proteome mediated by the activity of transcription factors such as hypoxia‐inducible factor 1. Hypoxia is a well‐described phenotype of most cancers, driving many aspects of malignancy. Improving our understanding of how mitochondria change their metabolism in response to this stimulus may therefore elicit the design of new selective therapies. Many of the recent advances in our understanding of mitochondrial metabolic plasticity have been acquired through investigations of cancer‐associated mutations in metabolic enzymes, including succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase. This review will describe how metabolic perturbations induced by hypoxia and mutations in these enzymes have informed our knowledge in the control of mitochondrial metabolism, and will examine what this may mean for the biology of the cancers in which these mutations are observed. WIREs Syst Biol Med 2016, 8:272–285. doi: 10.1002/wsbm.1334

This article is categorized under:

Biological Mechanisms > Metabolism

Physiology > Mammalian Physiology in Health and Disease
The Relationship between the Supervision Role and Compassion Fatigue and Burnout in Genetic Counseling
Authors: Allsbrook Katlin , Atzinger Carrie , He Hua , Engelhard Chalee , Yager Geoffrey , Wusik Katie
Published: May 2016

Many genetic counselors provide supervision to students during their career. Previous studies have shown genetic counselors, in general, are at increased risk for developing compassion fatigue. The purpose of this study was to determine if there was a difference in compassion fatigue and burnout levels in genetic counselors who currently supervise compared to genetic counselors who do not. Genetic counselors who currently practice in a clinical setting (N = 391) completed an online survey containing demographic questions, the Professional Quality of Life Scale, the State‐Trait Anxiety Inventory, and questions specific to the genetic counselor's experiences with supervision. Overall, when controlling for trait‐anxiety, the supervision role by itself was not independently associated with the risk for compassion fatigue and burnout among genetic counselors. Within supervisors, however, there were several factors which were associated with this risk. Those with less supervision experience reported more secondary traumatic stress. Those supervisors reporting less confidence had decreased compassion satisfaction. Those with less experience or less confidence in their supervision role were most likely to be at increased risk for developing compassion fatigue. Training in supervision and support for dealing with compassion fatigue and burnout may be beneficial to supervisors with less experience.
Superballistic wavepacket spreading in double kicked rotors
Authors: Fang Ping , Wang Jiao
Published: May 2016

We investigate possible ways in which a quantum wavepacket spreads. We show that in a general class of double kicked rotor system, a wavepacket may undergo superballistic spreading; i.e., its variance increases as the cubic of time. The conditions for the observed superballistic spreading and two related characteristic time scales are studied. Our results suggest that the symmetry of the studied model and whether it is a Kolmogorov-Arnold-Moser system are crucial to its wavepacket spreading behavior. Our study also sheds new light on the exponential wavepacket spreading phenomenon previously observed in the double kicked rotor system.
Fascial Manipulation Associated With Standard Care Compared to Only Standard Postsurgical Care for Total Hip Arthroplasty: A Randomized Controlled Trial
Authors: Busato Massimo , Quagliati Cristian , Magri Lara , Filippi Alessandra , Sanna Alberto , Branchini Mirco , Marchand Aurelie Marie , Stecco Antonio
Published: May 2016

Background

Postsurgical physiotherapy programs after total hip arthroplasty (THA) show important differences between types and numbers of treatment sessions. To increase functional recovery in postsurgical patients, manual therapy can be added to traditional physiotherapy programs. Fascial manipulation (FM) has been demonstrated to be effective in decreasing pain and increasing muscular capacity.

Objective

To compare the effectiveness of FM when added to a standard protocol of care.

Design

Randomized controlled trial.

Setting

Rehabilitation center.

Patients

A total of 51 patients were recruited after total hip arthroplasty. Inclusion criteria were first THA surgery, posterior‐lateral access, and onset of pain within a maximum 2 years. Exclusion criteria were previous hip or knee prosthesis, congenital hip dysplasia, elective THA secondary to trauma, real leg‐length discrepancy (≥1.5 cm), cognitive impairment, concomitant rheumatic pathology in acute phase, and serious comorbidities such as cardiac, respiratory, and/or neuromuscular pathologies.

Methods

Patients were randomized into 2 groups; both followed a standard protocol based on 2 daily sessions of active exercises for 45 minutes. In the study group, 2 sessions were replaced by FM. The clinical trial was registered at clinicaltrials.gov (NCT02576028).

Main Outcome Measures

Functional outcome measures were collected before and after treatment and at the end of the rehabilitation program. The measures included the Harris Hip Score; Timed Up‐and‐Go test; articular range of motion in abduction, flexion, extension, and bilateral external rotation with heels together; and verbal numerical scale.

Results

Statistically significant differences were observed in degrees of flexion between the study and control group with 25.4 (±11.3) and 18.7 (±9.5), respectively (P = .04); for abduction with 16.8 (±7.0) and 11.1 (±6.1), respectively (P = .005); for extension with 16.2 (±4.9) and 9.3 (±3.8), respectively (P = .001); for bilateral external rotation with heels together with 8.3 (±4.3) and 5.5 (±4.6), respectively (P = .04); for the Harris Hip Score 23.3 (±8.9) and 14.5 (±8.5), respectively (P = .002); and for verbal numerical scale score 1.1 (±2.1) and 0.5 (±1.1), respectively.

Conclusions

This study demonstrates that 2 FM sessions are able to significantly improve several functional outcomes in patients compared to usual treatment after THA.

Level of Evidence

II
Hospital Evacuation and Shelter-in-Place: Who Is Responsible for Decision-Making?
Authors: McGinty Meghan D. , Burke Thomas A. , Barnett Daniel J. , Smith Katherine C. , Resnick Beth , Rutkow Lainie
Published: May 2016

Objective

During natural disasters, hospital evacuation may be necessary to ensure patient safety and care. We aimed to examine perceptions of stakeholders involved in these decisions throughout the Mid-Atlantic region of the United States during Hurricane Sandy in October 2012.

Methods

Semistructured interviews were conducted from March 2014 to February 2015 to characterize stakeholders’ perceptions about authority and responsibility for acute care hospital evacuation/shelter-in-place decision-making in Delaware, Maryland, New Jersey, and New York during Hurricane Sandy. Interviews were recorded, transcribed, and thematically analyzed using a framework approach.

Results

We interviewed 42 individuals from 32 organizations. Hospital executives from all states reported having authority and responsibility for evacuation/shelter-in-place decision-making. In New York and Maryland, government officials stated that they could order hospital evacuation, whereas officials in Delaware and New Jersey said the government lacked enforcement capacity and therefore could not mandate evacuation.

Conclusions

Among government officials, perceived authority for hospital evacuation/shelter-in-place decision-making was viewed as a prerequisite to ordering evacuation. When both hospital executives and government officials perceive themselves to possess decision-making authority, there is the potential for inaction. Future work should examine whether a single entity bearing ultimate responsibility or regional emergency response coalitions would improve decision-making. (Disaster Med Public Health Preparedness. 2016;10:320–324)
The effects of vitamin D, K and calcium co-supplementation on carotid intima-media thickness and metabolic status in overweight type 2 diabetic patients with CHD
Authors: Asemi Zatollah , Raygan Fariba , Bahmani Fereshteh , Rezavandi Zohreh , Talari Hamid Reza , Rafiee Motahereh , Poladchang Somayyeh , Darooghegi Mofrad Manijeh , Taheri Sara , Mohammadi Ali Akbar , Esmaillzadeh Ahmad
Published: May 2016

This study was conducted to examine the effects of vitamin D, K and Ca co-supplementation on carotid intima-media thickness (CIMT) and metabolic status in overweight diabetic patients with CHD. This randomised, double-blind, placebo-controlled trial was conducted among sixty-six diabetic patients with CHD. Participants were randomly allocated into two groups to take either 5µg vitamin D, 90 µg vitamin K plus 500 mg Ca supplements (n33) or placebo (n33) twice a day for 12 weeks. Fasting blood samples were obtained at the beginning of the study and after the 12-week intervention period to determine related markers. Vitamin D, K and Ca co-supplementation resulted in a significant reduction in maximum levels of left CIMT (−0·04 (sd0·22)v. +0·04 (sd0·09) mm,P=0·02). Changes in serum vitamin D (+6·5 (sd7·8)v. +0·4 (sd2·2) ng/ml,P<0·001), Ca (+0·6 (sd0·3)v. +0·1 (sd0·1) mg/dl,P<0·001) and insulin concentrations (−0·9 (sd3·1)v. +2·6 (sd7·2) µIU/ml,P=0·01), homoeostasis model for assessment of estimated insulin resistance (−0·4 (sd1·2)v. +0·7 (sd2·3),P=0·01),β-cell function (−2·1 (sd9·0)v. +8·9 (sd23·7),P=0·01) and quantitative insulin sensitivity check index (+0·007 (sd0·01)v. −0·006 (sd0·02),P=0·01) in supplemented patients were significantly different from those in patients in the placebo group. Supplementation resulted in significant changes in HDL-cholesterol (+2·7 (sd7·0)v. −2·5 (sd5·7) mg/dl,P=0·002), high-sensitivity C-reactive protein (−1320·1 (sd3758·3)v. +464·0 (sd3053·3) ng/ml,P=0·03) and plasma malondialdehyde concentrations (−0·4 (sd0·5)v. −1·0 (sd1·1) µmol/l,P=0·007) compared with placebo. Overall, vitamin D, K and Ca co-supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on maximum levels of left CIMT and metabolic status. The effect of vitamin D, K and Ca co-supplementation on maximum levels of left CIMT could be a chance finding.
LOYALISTS AND LOYALISM IN A SOUTHERN IRISH COMMUNITY, 1921–1922
Authors: HUGHES BRIAN
Published: May 2016

A second Irish Grants Committee met for the first time in October 1926 to deal with claims for compensation from distressed southern Irish loyalists. By the time it had ceased its work, the committee had dealt with over 4,000 applications and recommended 2,237 ex-gratia grants. The surviving files constitute over 200 boxes of near-contemporary witness testimony and supplementary material making them an incomparable, if problematic, source for the study of the southern loyalist experience of the Irish Revolution – a topic of much current historiographical interest. Applicants had to prove that they had suffered loss on account of their ‘allegiance to the government of the United Kingdom’, and by applying labelled themselves as both ‘loyalist’ and ‘victim’. A study of the claim files from one district, Arva in County Cavan, offers unique perspectives on the loyalist experience of revolution in a southern Irish community, personal definitions of loyalty, and the relationship between behaviour and allegiance during war. The Arva applicants often struggled to present their financial losses as resulting directly from their ‘loyalty to the Crown’. Their statements, and the way they were treated by the committee, serve to complicate an often over-simplified understanding of civilian behaviour and popular support.
Maladaptive mood repair, atypical respiratory sinus arrhythmia, and risk of a recurrent major depressive episode among adolescents with prior major depression
Authors: Kovacs M. , Yaroslavsky I. , Rottenberg J. , George C. J. , Kiss E. , Halas K. , Dochnal R. , Benák I. , Baji I. , Vetró A. , Makai A. , Kapornai K.
Published: May 2016

Background

Because depressive illness is recurrent, recurrence prevention should be a mainstay for reducing its burden on society. One way to reach this goal is to identify malleable risk factors. The ability to attenuate sadness/dysphoria (mood repair) and parasympathetic nervous system functioning, indexed as respiratory sinus arrhythmia (RSA), are impaired during depression and after it has remitted. The present study therefore tested the hypothesis that these two constructs also may mirror risk factors for a recurrent major depressive episode (MDE).

Method

At time 1 (T1), 178 adolescents, whose last MDE had remitted, and their parents, reported on depression and mood repair; youths’ RSA at rest and in response to sad mood induction also were assessed. MDE recurrence was monitored until time 2 (T2) up to 2 years later. Mood repair at T1 (modeled as a latent construct), and resting RSA and RSA response to sadness induction (RSA profile), served to predict onset of first recurrent MDE by T2.

Results

Consistent with expectations, maladaptive mood repair predicted recurrent MDE, above and beyond T1 depression symptoms. Further, atypical RSA profiles at T1 were associated with high levels of maladaptive mood repair, which, in turn, predicted increased risk of recurrent MDE. Thus, maladaptive mood repair mediated the effects of atypical RSA on risk of MDE recurrence.

Conclusions

This study documented that a combination of behavioral and physiological risk factors predicted MDE recurrence in a previously clinically referred sample of adolescents with depression histories. Because mood repair and RSA are malleable, both could be targeted for modification to reduce the risk of recurrent depression in youths.
Communicative relevance: Color references in bilingual and trilingual speakers
Authors: PAVLENKO ANETA , JARVIS SCOTT , MELNYK SVITLANA , SOROKINA ANASTASIA
Published: May 2016

The study examined granularity of lexical partitioning of the blue area in speakers of English, which encodes the termblue; Russian, which encodes two terms, sinij[dark/navy blue] andgoluboj[light/sky blue]; and Ukrainian, which encodes the termssynij[dark/navy blue] andblakytnyjandgolubyj[light/sky blue]. Five groups of participants took part in the study: (1) 30 L1 speakers of English, (2) 30 L1 speakers of Russian, (3) 30 Russian–English bilinguals, (4) 30 English–Russian bilinguals, and (5) 25 Ukrainian–Russian–English trilinguals. Quantitative and qualitative analyses revealed that L1 Russian speakers referred to different types of blue significantly more frequently than all other groups, while bilinguals patterned with L1 English speakers. These findings suggest that classroom exposure to L2 Russian does not make the distinction betweensinijandgolubojcommunicatively relevant for L1 English speakers and that everyday use of L2 English may trigger attrition of the contrast in L1 Russian.
Emerging role of immunoproteasomes in pathophysiology
Authors: Kaur Gagandeep , Batra Sanjay
Published: May 2016

The immunoproteasome is a proteasome variant that is found only in jawed vertebrates. It is responsible for degrading intracellular proteins to generate a major source of peptides with substantial major histocompatibility complex I binding affinity. The immunoproteasome also has roles in T‐cell survival, differentiation and proliferation in various pathological conditions. In humans, any alteration in the expression, assembly or function of the immunoproteasome can lead to cancer, autoimmune disorders or inflammatory diseases. Although the roles of the immunoproteasome in cancer and neurodegenerative disorders have been extensively studied, its significance in other disease conditions has only recently become known. Therefore, there is renewed interest in the development of drugs, vaccines and biomarkers that target the immunoproteasome. The current review highlights the involvement of this complex in disease pathology in addition to the advances made in immunoproteasome research.
Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange
Authors: Pennington Luke F. , Tarchevskaya Svetlana , Brigger Daniel , Sathiyamoorthy Karthik , Graham Michelle T. , Nadeau Kari Christine , Eggel Alexander , Jardetzky Theodore S.
Published: May 2016

Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, in combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. This combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.
Large reversible caloric effect in FeRh thin films via a dual-stimulus multicaloric cycle
Authors: Liu Yang , Phillips Lee C. , Mattana Richard , Bibes Manuel , Barthélémy Agnès , Dkhil Brahim
Published: May 2016

Giant magnetocaloric materials are promising for solid-state refrigeration, as an alternative to hazardous gases used in conventional cooling devices. A giant magnetocaloric effect was discovered near room temperature in near-equiatomic FeRh alloys some years before the benchmark study in Gd5Si2Ge2 that launched the field. However, FeRh has attracted significantly less interest in cooling applications mainly due to irreversibility in magnetocaloric cycles associated with the large hysteresis of its first-order metamagnetic phase transition. Here we overcome the irreversibility via a dual-stimulus magnetic-electric refrigeration cycle in FeRh thin films via coupling to a ferroelectric BaTiO3 substrate. This experimental realization of a multicaloric cycle yields larger reversible caloric effects than either stimulus alone. While magnetic hysteretic losses appear to be reduced by 96% in dual-stimulus loops, we show that the losses are simply transferred into an elastic cycle, contrary to common belief. Nevertheless, we show that these losses do not necessarily prohibit integration of FeRh in practical refrigeration systems. Our demonstration of a multicaloric refrigeration cycle suggests numerous designs for efficient solid-state cooling applications.
A global meta-analysis on the ecological drivers of forest restoration success
Authors: Crouzeilles Renato , Curran Michael , Ferreira Mariana S. , Lindenmayer David B. , Grelle Carlos E. V. , Rey Benayas José M.
Published: May 2016

Two billion ha have been identified globally for forest restoration. Our meta-analysis encompassing 221 study landscapes worldwide reveals forest restoration enhances biodiversity by 15–84% and vegetation structure by 36–77%, compared with degraded ecosystems. For the first time, we identify the main ecological drivers of forest restoration success (defined as a return to a reference condition, that is, old-growth forest) at both the local and landscape scale. These are as follows: the time elapsed since restoration began, disturbance type and landscape context. The time elapsed since restoration began strongly drives restoration success in secondary forests, but not in selectively logged forests (which are more ecologically similar to reference systems). Landscape restoration will be most successful when previous disturbance is less intensive and habitat is less fragmented in the landscape. Restoration does not result in full recovery of biodiversity and vegetation structure, but can complement old-growth forests if there is sufficient time for ecological succession.
Amplification, Decoherence and the Acquisition of Information by Spin Environments
Authors: Zwolak Michael , Riedel C. Jess , Zurek Wojciech H.
Published: May 2016

Quantum Darwinism recognizes the role of the environment as a communication channel: Decoherence can selectively amplify information about the pointer states of a system of interest (preventing access to complementary information about their superpositions) and can make records of this information accessible to many observers. This redundancy explains the emergence of objective, classical reality in our quantum Universe. Here, we demonstrate that the amplification of information in realistic spin environments can be quantified by the quantum Chernoff information, which characterizes the distinguishability of partial records in individual environment subsystems. We show that, except for a set of initial states of measure zero, the environment always acquires redundant information. Moreover, the Chernoff information captures the rich behavior of amplification in both finite and infinite spin environments, from quadratic growth of the redundancy to oscillatory behavior. These results will considerably simplify experimental testing of quantum Darwinism, e.g., using nitrogen vacancies in diamond.
Punctuated Shutdown of Atlantic Meridional Overturning Circulation during Greenland Stadial 1
Authors: Hogg Alan , Southon John , Turney Chris , Palmer Jonathan , Bronk Ramsey Christopher , Fenwick Pavla , Boswijk Gretel , Friedrich Michael , Helle Gerhard , Hughen Konrad , Jones Richard , Kromer Bernd , Noronha Alexandra , Reynard Linda , Staff Richard , Wacker Lukas
Published: May 2016

The Greenland Stadial 1 (GS-1; ~12.9 to 11.65 kyr cal BP) was a period of North Atlantic cooling, thought to have been initiated by North America fresh water runoff that caused a sustained reduction of North Atlantic Meridional Overturning Circulation (AMOC), resulting in an antiphase temperature response between the hemispheres (the ‘bipolar seesaw’). Here we exploit sub-fossil New Zealand kauri trees to report the first securely dated, decadally-resolved atmospheric radiocarbon (14C) record spanning GS-1. By precisely aligning Southern and Northern Hemisphere tree-ring 14C records with marine 14C sequences we document two relatively short periods of AMOC collapse during the stadial, at ~12,920-12,640 cal BP and 12,050-11,900 cal BP. In addition, our data show that the interhemispheric atmospheric 14C offset was close to zero prior to GS-1, before reaching ‘near-modern’ values at ~12,660 cal BP, consistent with synchronous recovery of overturning in both hemispheres and increased Southern Ocean ventilation. Hence, sustained North Atlantic cooling across GS-1 was not driven by a prolonged AMOC reduction but probably due to an equatorward migration of the Polar Front, reducing the advection of southwesterly air masses to high latitudes. Our findings suggest opposing hemispheric temperature trends were driven by atmospheric teleconnections, rather than AMOC changes.
Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals
Authors: Ozaki N. , Nellis W. J. , Mashimo T. , Ramzan M. , Ahuja R. , Kaewmaraya T. , Kimura T. , Knudson M. , Miyanishi K. , Sakawa Y. , Sano T. , Kodama R.
Published: May 2016

Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.
The nitrogen responsive transcriptome in potato (Solanum tuberosum L.) reveals significant gene regulatory motifs
Authors: Gálvez José Héctor , Tai Helen H. , Lagüe Martin , Zebarth Bernie J. , Strömvik Martina V.
Published: May 2016

Nitrogen (N) is the most important nutrient for the growth of potato (Solanum tuberosum L.). Foliar gene expression in potato plants with and without N supplementation at 180 kg N ha−1 was compared at mid-season. Genes with consistent differences in foliar expression due to N supplementation over three cultivars and two developmental time points were examined. In total, thirty genes were found to be over-expressed and nine genes were found to be under-expressed with supplemented N. Functional relationships between over-expressed genes were found. The main metabolic pathway represented among differentially expressed genes was amino acid metabolism. The 1000 bp upstream flanking regions of the differentially expressed genes were analysed and nine overrepresented motifs were found using three motif discovery algorithms (Seeder, Weeder and MEME). These results point to coordinated gene regulation at the transcriptional level controlling steady state potato responses to N sufficiency.
The Essential Role of H19 Contributing to Cisplatin Resistance by Regulating Glutathione Metabolism in High-Grade Serous Ovarian Cancer
Authors: Zheng Zhi-Guo , Xu Hong , Suo Sha-Sha , Xu Xiao-Li , Ni Mao-Wei , Gu Lin-Hui , Chen Wei , Wang Liang-Yan , Zhao Ye , Tian Bing , Hua Yue-Jin
Published: May 2016

Primary and acquired drug resistance is one of the main obstacles encountered in high-grade serous ovarian cancer (HGSC) chemotherapy. Cisplatin induces DNA damage through cross-linking and long integrated non-coding RNAs (lincRNAs) play an important role in chemical induced DNA-damage response, which suggests that lincRNAs may be also associated with cisplatin resistance. However, the mechanism of long integrated non-coding RNAs (lincRNAs) acting on cisplatin resistance is not well understood. Here, we showed that expression of lin-RECK-3, H19, LUCAT1, LINC00961 and linc-CARS2-2 was enhanced in cisplatin-resistant A2780-DR cells, while transcriptome sequencing showed decreased Linc-TNFRSF19-1 and LINC00515 expression. Additionally, we verified that different H19 expression levels in HGSC tissues showed strong correlation with cancer recurrence. H19 knockdown in A2780-DR cells resulted in recovery of cisplatin sensitivity in vitro and in vivo. Quantitative proteomics analysis indicated that six NRF2-targeted proteins, including NQO1, GSR, G6PD, GCLC, GCLM and GSTP1 involved in the glutathione metabolism pathway, were reduced in H19-knockdown cells. Furthermore, H19-knockdown cells were markedly more sensitive to hydrogen-peroxide treatment and exhibited lower glutathione levels. Our results reveal a previously unknown link between H19 and glutathione metabolism in the regulation of cancer-drug resistance.
Comparative analysis of the integument transcriptomes of the black dilute mutant and the wild-type silkworm Bombyx mori
Authors: Wu Songyuan , Tong Xiaoling , Peng Chenxing , Xiong Gao , Lu Kunpeng , hu Hai , Tan Duan , Li Chunlin , Han Minjin , Lu Cheng , Dai Fangyin
Published: May 2016

The insect cuticle is a critical protective shell that is composed predominantly of chitin and various cuticular proteins and pigments. Indeed, insects often change their surface pigment patterns in response to selective pressures, such as threats from predators, sexual selection and environmental changes. However, the molecular mechanisms underlying the construction of the epidermis and its pigmentation patterns are not fully understood. Among Lepidoptera, the silkworm is a favorable model for color pattern research. The black dilute (bd) mutant of silkworm is the result of a spontaneous mutation; the larval body color is notably melanized. We performed integument transcriptome sequencing of the wild-type strain Dazao and the mutant strains +/bd and bd/bd. In these experiments, during an early stage of the fourth molt, a stage at which approximately 51% of genes were expressed genome wide (RPKM ≥1) in each strain. A total of 254 novel transcripts were characterized using Cuffcompare and BLAST analyses. Comparison of the transcriptome data revealed 28 differentially expressed genes (DEGs) that may contribute to bd larval melanism, including 15 cuticular protein genes that were remarkably highly expressed in the bd/bd mutant. We suggest that these significantly up-regulated cuticular proteins may promote melanism in silkworm larvae.
Therapeutic Blockade of Immune Complex-Mediated Glomerulonephritis by Highly Selective Inhibition of Bruton’s Tyrosine Kinase
Authors: Chalmers Samantha A. , Doerner Jessica , Bosanac Todd , Khalil Sara , Smith Dustin , Harcken Christian , Dimock Janice , Der Evan , Herlitz Leal , Webb Deborah , Seccareccia Elise , Feng Di , Fine Jay S. , Ramanujam Meera , Klein Elliott , Putterman Chaim
Published: May 2016

Lupus nephritis (LN) is a potentially dangerous end organ pathology that affects upwards of 60% of lupus patients. Bruton’s tyrosine kinase (BTK) is important for B cell development, Fc receptor signaling, and macrophage polarization. In this study, we investigated the effects of a novel, highly selective and potent BTK inhibitor, BI-BTK-1, in an inducible model of LN in which mice receive nephrotoxic serum (NTS) containing anti-glomerular antibodies. Mice were treated once daily with vehicle alone or BI-BTK-1, either prophylactically or therapeutically. When compared with control treated mice, NTS-challenged mice treated prophylactically with BI-BTK-1 exhibited significantly attenuated kidney disease, which was dose dependent. BI-BTK-1 treatment resulted in decreased infiltrating IBA-1+ cells, as well as C3 deposition within the kidney. RT-PCR on whole kidney RNA and serum profiling indicated that BTK inhibition significantly decreased levels of LN-relevant inflammatory cytokines and chemokines. Renal RNA expression profiling by RNA-seq revealed that BI-BTK-1 dramatically modulated pathways related to inflammation and glomerular injury. Importantly, when administered therapeutically, BI-BTK-1 reversed established proteinuria and improved renal histopathology. Our results highlight the important role for BTK in the pathogenesis of immune complex-mediated nephritis, and BTK inhibition as a promising therapeutic target for LN.
Network-assisted investigation of virulence and antibiotic-resistance systems in Pseudomonas aeruginosa
Authors: Hwang Sohyun , Kim Chan Yeong , Ji Sun-Gou , Go Junhyeok , Kim Hanhae , Yang Sunmo , Kim Hye Jin , Cho Ara , Yoon Sang Sun , Lee Insuk
Published: May 2016

Pseudomonas aeruginosa is a Gram-negative bacterium of clinical significance. Although the genome of PAO1, a prototype strain of P. aeruginosa, has been extensively studied, approximately one-third of the functional genome remains unknown. With the emergence of antibiotic-resistant strains of P. aeruginosa, there is an urgent need to develop novel antibiotic and anti-virulence strategies, which may be facilitated by an approach that explores P. aeruginosa gene function in systems-level models. Here, we present a genome-wide functional network of P. aeruginosa genes, PseudomonasNet, which covers 98% of the coding genome, and a companion web server to generate functional hypotheses using various network-search algorithms. We demonstrate that PseudomonasNet-assisted predictions can effectively identify novel genes involved in virulence and antibiotic resistance. Moreover, an antibiotic-resistance network based on PseudomonasNet reveals that P. aeruginosa has common modular genetic organisations that confer increased or decreased resistance to diverse antibiotics, which accounts for the pervasiveness of cross-resistance across multiple drugs. The same network also suggests that P. aeruginosa has developed mechanism of trade-off in resistance across drugs by altering genetic interactions. Taken together, these results clearly demonstrate the usefulness of a genome-scale functional network to investigate pathogenic systems in P. aeruginosa.
Legionella pneumophila strain associated with the first evidence of person-to-person transmission of Legionnaires’ disease: a unique mosaic genetic backbone
Authors: Borges Vítor , Nunes Alexandra , Sampaio Daniel A. , Vieira Luís , Machado Jorge , Simões Maria J. , Gonçalves Paulo , Gomes João P.
Published: May 2016

A first strong evidence of person-to-person transmission of Legionnaires’ Disease (LD) was recently reported. Here, we characterize the genetic backbone of this case-related Legionella pneumophila strain (“PtVFX/2014”), which also caused a large outbreak of LD. PtVFX/2014 is phylogenetically divergent from the most worldwide studied outbreak-associated L. pneumophila subspecies pneumophila serogroup 1 strains. In fact, this strain is also from serogroup 1, but belongs to the L. pneumophila subspecies fraseri. Its genomic mosaic backbone reveals eight horizontally transferred regions encompassing genes, for instance, involved in lipopolysaccharide biosynthesis or encoding virulence-associated Dot/Icm type IVB secretion system (T4BSS) substrates. PtVFX/2014 also inherited a rare ~65 kb pathogenicity island carrying virulence factors and detoxifying enzymes believed to contribute to the emergence of best-fitted strains in water reservoirs and in human macrophages, as well as a inter-species transferred (from L. oakridgensis) ~37.5 kb genomic island (harboring a lvh/lvr T4ASS cluster) that had never been found intact within L. pneumophila species. PtVFX/2014 encodes another lvh/lvr cluster near to CRISPR-associated genes, which may boost L. pneumophila transition from an environmental bacterium to a human pathogen. Overall, this unique genomic make-up may impact PtVFX/2014 ability to adapt to diverse environments, and, ultimately, to be transmitted and cause human disease.
Plasmon enhanced optical tweezers with gold-coated black silicon
Authors: Kotsifaki D. G. , Kandyla M. , Lagoudakis P. G.
Published: May 2016

Plasmonic optical tweezers are a ubiquitous tool for the precise manipulation of nanoparticles and biomolecules at low photon flux, while femtosecond-laser optical tweezers can probe the nonlinear optical properties of the trapped species with applications in biological diagnostics. In order to adopt plasmonic optical tweezers in real-world applications, it is essential to develop large-scale fabrication processes without compromising the trapping efficiency. Here, we develop a novel platform for continuous wave (CW) and femtosecond plasmonic optical tweezers, based on gold-coated black silicon. In contrast with traditional lithographic methods, the fabrication method relies on simple, single-step, maskless tabletop laser processing of silicon in water that facilitates scalability. Gold-coated black silicon supports repeatable trapping efficiencies comparable to the highest ones reported to date. From a more fundamental aspect, a plasmon-mediated efficiency enhancement is a resonant effect and therefore, dependent on the wavelength of the trapping beam. Surprisingly, a wavelength characterization of plasmon-enhanced trapping efficiencies has evaded the literature. Here, we exploit the repeatability of the recorded trapping efficiency, offered by the gold-coated black silicon platform and perform a wavelength-dependent characterization of the trapping process, revealing the resonant character of the trapping efficiency maxima. Gold-coated black silicon is a promising platform for large-scale parallel trapping applications that will broaden the range of optical manipulation in nanoengineering, biology and the study of collective biophotonic effects.
Fast response to human voices in autism
Authors: Lin I-Fan , Agus Trevor R. , Suied Clara , Pressnitzer Daniel , Yamada Takashi , Komine Yoko , Kato Nobumasa , Kashino Makio
Published: May 2016

Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level.