bluuebunny/crossref_metadata_2025 huggingface dataset:
A Polycation Antimicrobial Peptide Mimic without Resistance Buildup against Propionibacterium Acnes
Authors: Nair Sithara S. , Zolotarskaya Olga Y. , Beckwith Matthew J. , Ohman Dennis E. , Wynne Kenneth J.
Published: June 2017

A preliminary study is reported for a polycation antimicrobial peptide (AMP) mimic against Propionibacterium acnes, which is associated with acne vulgaris, a common skin condition. Antibiotics are commonly used against P. acnes but buildup of resistance is well‐known. Worse, antibiotic regimens build up resistance for more sensitive bacteria such as Staphylococcus epidermidis. The polycation AMP mimic C12‐50, 1, is chosen for the present study as it has been previously shown to have high antimicrobial effectiveness. This study reports that C12‐50 is active against P. acnes (strain ATCC 6919) with a minimum inhibitory concentration (MIC) of 6.3 µg mL−1. To monitor resistance build‐up ten passages are conducted with C12‐50 against P. acnes. The MIC remains constant with no resistance buildup. Parallel studies with erythromycin confirm previously reported resistance buildup. The results point to a promising pathway to applications for polycation AMP mimics against P. acnes.
All‐Aqueous Nanoprecipitation: Spontaneous Formation of Hydrogen‐Bonded Nanoparticles and Nanocapsules Mediated by Phase Separation of Poly(N‐Isopropylacrylamide)
Authors: Wang Yuhao , Sukhishvili Svetlana A.
Published: June 2017

Spontaneous formation of polymer nanoparticles of well‐defined, <100 nm sizes with controlled solid/hollow morphology and fluorescent properties is reported. The nanoparticle formation is assisted by temperature‐triggered nucleation of an amphiphilic polymer—poly(N‐isopropylacrylamide) (PNIPAM)—and mediated by hydrogen bonding of the emerged nuclei with tannic acid (TA). The pH of solution and TA/PNIPAM ratios are explored as parameters that define TA/PNIPAM assembly. Well‐defined nanoparticles are formed in a wide range of neutral pH when the TA/PNIPAM ratio exceeds its critical, pH‐dependent value. Dynamic light scattering and zeta potential measurements as well as atomic force microscopy and electron energy loss spectroscopy indicate that solid nanoparticles or nanocapsules are formed depending on the solution pH and that enhanced ionization of TA favors hollow morphology. Nanocapsules exhibit label‐free fluorescence at neutral pH values and therefore can be useful in imaging applications.

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Microfluidic Programming of Compositional Hydrogel Landscapes
Authors: Allazetta S. , Negro A. , Lutolf M. P.
Published: June 2017

A droplet microfluidics strategy to rapidly synthesize, process, and screen up to hundreds of thousands of compositionally distinct synthetic hydrogels is presented. By programming the flow rates of multiple microfluidic inlet channels supplying individual hydrogel building blocks, microgel compositions and properties are systematically modulated. The use of fluorescent labels as proxies for the physical and chemical properties of the microgel permits the rapid screening and discovery of specific formulations through fluorescence microscopy or flow cytometry. This concept should accelerate the discovery of new hydrogel formulations for various novel applications.

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Pharmacoinformatic Study on the Selective Inhibition of the Protozoan Dihydrofolate Reductase Enzymes
Authors: Sharma Vishnu K. , Abbat Sheenu , Bharatam P. V.
Published: June 2017

Dihydrofolate reductase (DHFR) is an essential enzyme of the folate metabolic pathway in protozoa and it is a validated, potential drug target in many infectious diseases. Information about unique conserved residues of the DHFR enzyme is required to understand residual selectivity of the protozoan DHFR enzyme. The three dimensional crystal structures are not available for all the protozoan DHFR enzymes. Enzyme‐substrate/inhibitor interaction information is required for the binding mode characterization in protozoan DHFR for selective inhibitor design. In this work, multiple sequence analysis was carried out in all the studied species. Homology models were built for protozoan DHFR enzymes, for which 3D structures are not available in PDB. The molecular docking and Prime‐MMGBSA calculations of the natural substrate (dihydrofolate, DHF) and classical DHFR inhibitor (methotrexate, MTX) were performed in protozoan DHFR enzymes. Comparative sequence analysis showed that an overall sequence identity between the studied species ranging from 22.94 % (CfDHFR‐BgDHFR) to 94.61 % (LdDHFR‐LmDHFR). Interestingly, it was observed that most of the active site residues were conserved in all the cases and all the enzymes exhibit similar key binding interactions with DHF and MTX in molecular docking analysis, but there are a few key binding residues which differ in protozoan species that makes it suitable for target selectivity. This information can be used to design selective and potent protozoan DHFR enzyme inhibitors.
Technical Note: Ion chamber angular dependence in a magnetic field
Authors: Reynolds Michael , Rathee Satyapal , Fallone B. Gino
Published: June 2017

Purpose

There have been several studies investigating dose deposition effects within radiation detectors in the presence of a magnetic field. However, to date there has only been a passing investigation which explicitly investigates detector dose–response as a function of detector orientation. Herein we will investigate the dose–response as a function angular orientation of a PR06C ionization chamber. We will also benchmark the Monte Carlo code PENELOPE with the newly developed magnetic field Fano test.

Methods

The PENELOPE Monte Carlo package was used to simulate a PR06C ionization chamber in 0.35 T through 1.5 T magnetic fields oriented either parallel or orthogonal to an incident 6 MV radiation beam. The ionization chamber was rotated through a number of polar and azimuthal angles. The dose deposited within the chamber at each angular position and magnetic field strength was scored then normalized to that deposited in the same orientation with no magnetic field. The simulation was also benchmarked via a Fano test in magnetic field.

Results

The Fano test yielded a 0.4% difference between simulation and expected result, which is similar to previous findings and sufficient for the purposes of this study. The angular dose–response map in all cases where the magnetic field is oriented orthogonal to the radiation beam is quite varied and can range from 0.89 to 1.08. Angular deviations as small as 3° can lead to dose–response changes in excess of 1%. When the magnetic field is parallel to the photon beam, the angular dose–response map is homogeneous and less than 1% below 1.0 T.

Conclusions

Within a magnetic field‐oriented orthogonal to the radiation beam, the ionization chamber dose–response fluctuates greatly as a function of polar and azimuthal angle, where a parallel field yields a more homogeneous dose–response.
Amniotic fluid stem cells ameliorate bladder dysfunction induced by chronic bladder ischemia in rat
Authors: Liang Ching‐Chung , Shaw Sheng‐Wen Steven , Lin Yi‐Hao , Lee Tsong‐Hai
Published: June 2017

Aims

This study investigated the protective effect of human amniotic fluid‐derived stem cells (hAFSCs) against bladder overactivity in rat model of atherosclerosis‐induced chronic bladder ischemia.

Methods

Adult female Sprague‐Dawley rats were divided into six groups: (1) Normal control with a regular diet for 8 weeks, (2) Sham‐operation, (3) arterial balloon endothelial injury (AEI) of common iliac artery (AEI only), and post‐AEI consecutive hAFSCs treatment for (4) 1 day, (5) 3 days, and (6) 7 days. Groups 2‐6 were given 2% cholesterol diet for 8 weeks after operation (sham or AEI). Bladder functions were analyzed by cystometry at 8 weeks in controls and after operation in groups 2‐6. Wall morphology of common iliac artery was examined by hematoxylin and eosin stain. Bladder oxidative stress and inflammatory markers were studied by immunohistochemistry of 8‐hydroxy‐2′‐deoxyguanosine (8OHdG), malondialdehyde (MDA), and tumor necrosis factor‐alpha (TNF‐alpha).

Results

Bladder overactivity with decreased voided volumes and intercontraction intervals and increased residual volumes was seen in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days. Compared with controls and shams, the wall thickness of iliac artery was increased in AEI only group, but improved after hAFSCs treatment for 3 and 7 days. The expressions of 8OHdG, MDA, and TNF‐alpha were increased in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days.

Conclusions

Bladder overactivity caused by chronic bladder ischemia can be improved by hAFSCs treatment, probably by acting through down‐regulation of oxidative stress and TNF‐alpha expressions.
Potassium‐Ion‐Selective Fluorescent Sensors To Detect Cereulide, the Emetic Toxin of B. cereus, in Food Samples and HeLa Cells
Authors: García‐Calvo José , Ibeas Saturnino , Antón‐García Eva‐Clara , Torroba Tomás , González‐Aguilar Gerardo , Antunes Wilson , González‐Lavado Eloísa , Fanarraga Mónica L.
Published: June 2017

We report the development of new chemical probes for cereulide, a toxic metabolite produced by specific strains of Bacillus cereus, through displacement of potassium cations from a preformed specific complex and a subsequent change in the fluorescence emission. For this purpose, we designed fluorescent probes for potassium cations that were suitable for displacement assays with cereulide from organic extracts. The fluorescence detection of natural cereulide in rice samples was achieved by using synthetic cereulide as a reference and a potassium fluorescent reporter, and this was found to be useful as a portable and fast method for the in situ detection of cereulide in food extracts. To study the fate of cereulide in live cells, we designed a procedure that was suitable for live‐cell microscopy imaging of HeLa cells by comparing the cellular location of the potassium fluorogenic probe, which stained intracellular endolysosomes, in the absence and presence of cereulide; we concluded that in the presence of cereulide, the fluorescence of the probe was decreased because of complexation of the potassium ions by cereulide.
Cardiovascular Pharmacogenomics and Cognitive Function in Patients with Schizophrenia
Authors: Ward Kristen M. , Kraal A. Zarina , Flowers Stephanie A. , Ellingrod Vicki L.
Published: June 2017

The authors sought to examine the impact of multiple risk alleles for cognitive dysfunction and cardiovascular disease risk on cognitive function and to determine if these relationships varied by cognitive reserve (CR) or concomitant medication use in patients with schizophrenia. They conducted a cross‐sectional study in ambulatory mental health centers. A total of 122 adults with a schizophrenia spectrum diagnosis who were maintained on a stable antipsychotic regimen for at least 6 months before study enrollment were included. Patients were divided into three CR groups based on years of formal education: no high school completion or equivalent (low‐education group [18 patients]), completion of high school or equivalent (moderate‐education group [36 patients], or any degree of post–high school education (high‐education group [68 patients]). The following pharmacogenomic variants were genotyped for each patient: AGT M268T (rs699), ACE insertion/deletion (or ACE I/D, rs1799752), and APOE ε2, ε3, and ε4 (rs429358 and rs7412). Risk allele carrier status (identified per gene as AGT M268 T carriers, ACE D carriers, and APOE ε4 carriers) was not significantly different among CR groups. The Brief Assessment of Cognition in Schizophrenia (BACS) scale was used to assess cognitive function. The mean ± SD patient age was 43.9 ± 11.6 years. Cardiovascular risk factors such as hypertension and hyperlipidemia diagnoses, and use of antihypertensive and lipid‐lowering agents, did not significantly differ among CR groups. Mixed modeling revealed that risk allele carrier status was significantly associated with lower verbal memory scores for ACE D and APOE ε4 carriers, but AGT T carrier status was significantly associated with higher verbal memory scores (p=0.0188, p=0.0055, and p=0.0058, respectively). These results were only significant in the low‐education group. In addition, medication–gene interactions were not significant predictors of BACS scores. ACE D and APOE ε4 carrier status, independent of medication use, was associated with lower verbal memory scores in patients with schizophrenia who had relatively lower CR, as identified by formal education. These results suggest that increasing CR may be protective against cognitive impairment that may be worsened by select cardiovascular risk alleles in patients with schizophrenia.
Patients' and family caregivers' understanding of the cancer stage, treatment goal, and chance of cure: A study with patient‐caregiver‐physician triad
Authors: Shin Dong Wook , Cho Juhee , Kim So Young , Yang Hyung Kook , Park Keeho , Kweon Sun‐Seog , Koh Dai Ha , Nam Hae‐Sung , Park Jong‐Hyock
Published: June 2017

Objective

Accurate understanding of the extent of disease, treatment goal, and prognosis is a prerequisite for patients with cancer and their caregivers to make informed decision. We sought to evaluate patients' and family caregivers' understanding of the cancer stage, treatment goal, and chance of cure taking their own physician's evaluation as reference.

Methods

A national survey was performed with 750 patient‐caregiver dyads (75.5% participation rate) recruited by 134 oncologists in 13 cancer centers (93% participation rate) in South Korea. Both patients and caregivers were asked to report their knowledge of patient's cancer stage, treatment goal, and chance of cure. Concordance was evaluated with percentage agreement and weighted κ, and predictors of discordance of patient and caregiver's response with that of physician's were explored by multivariate regression analyses with mixed effect model.

Results

The agreement rates between patient‐physician and caregiver‐physician were 63.0% and 65.9% for disease stage, 69.0% and 70.0% for treatment goal, and 41.4% and 45.1% for chance of cure. When discordance occurs, patients and caregivers often had an optimistic view. Distant stage, older age, female sex, and absence of depression were associated with optimistic view of patients, and there was significant between‐physician variance for all 3 outcomes.

Conclusion

The discordance revealed that our study suggests the need for better communication between physician and patients, as well as the caregivers. Research is needed to develop a comprehensive strategy to improve the understanding of the patients and family so that treatment decisions are made based on realistic estimation.
Influence of rapid thermal processing on carrier concentration in high resistivity silicon
Authors: Capello Luciana , Bertrand Isabelle , Kononchuk Oleg
Published: June 2017

In this study, we report changes in the carrier concentration of high resistivity Si wafers after rapid thermal annealing (RTA) anneals measured by spreading resistance technique. Spreading resistance technique (SRP) profiles clearly show the generation of donor centers with concentrations and depth distributions comparable to those of vacancy‐related centers reported in the literature. Changes of carrier concentrations as a function of RTA temperature, duration, ramp down rate, and subsequent annealing in the 800–1000 °C range are consistent with the earlier literature data. The influence of annealing ambient is also studied. Annealing in pure Ar atmosphere leads to profiles dominated by in‐diffusion of vacancies generated at the surface, while annealing in oxidized ambient results in well‐known profiles controlled by out‐diffusion of vacancies generated in the wafer bulk. Studies of the wafers with different oxygen content show that the concentration of the generated donors is directly proportional to Oi concentration.
The drying tendency of shallow meridional circulations in monsoons
Authors: Zhai Jun , Boos William R.
Published: June 2017

Shallow meridional overturning circulations are superimposed on the deep circulations that produce precipitation in nearly all monsoon regions, and these shallow circulations transport subtropical, mid‐tropospheric dry air into the tropical monsoon precipitation maxima. Here horizontal moisture advection produced by shallow meridional circulations is characterized in the monsoon regions of West Africa, South Asia, Australia, and southern Africa during local summer. Horizontal flow in the upper and lower branches of the shallow meridional circulations consistently dries and moistens air, respectively, in the continental precipitation maxima of each region. The peak drying by horizontal advection occurs at a lower altitude than peak winds in the upper branch of the shallow circulations, consistent with the small scale height of water vapour. Advection of time‐mean moisture by time‐mean wind dominates horizontal moisture advection in South Asia and West Africa, while most horizontal moisture advection in Australia and southern Africa is produced by transient eddies. Much of the transient eddy advection can be accurately represented as a first‐order horizontal diffusion with a constant, globally uniform diffusivity. These results suggest that horizontal moisture advection in theoretical and conceptual models of seasonal mean monsoons can be adequately represented in terms of time‐mean winds plus a simple horizontal moisture diffusion. Finally, interannual variations in the summer mean regional averages of monsoon precipitation and horizontal advective drying in the lower free troposphere are shown to be negatively correlated in most regions, consistent with the hypothesis that advective drying by shallow meridional circulations inhibits monsoon precipitation.
Complex Cobalt Sulfide Nanobubble Cages with Enhanced Electrochemical Properties
Authors: Guan Bu Yuan , (David) Lou Xiong Wen
Published: June 2017

Metal–organic frameworks (MOFs) have been widely employed as precursors to prepare various nanostructured functional materials. Here, a “nanoparticles‐in‐MOF” dual‐template approach for generating complex cobalt sulfide (CoS) nanobubble cages is reported. A novel nanoparticles‐in‐MOF hybrid structure consisting of a Co‐based MOF polyhedron host and many encapsulated mesostructured TiO2 nanospheres is first prepared, followed by a sulfidation process to obtain a complex cage structure consisting of CoS nanobubbles in the shell. Importantly, this strategy can be extended to prepare many other functional nanoparticles‐in‐MOF hybrid structures. When evaluated as an electrode material for hybrid supercapacitors, the as‐derived CoS nanobubble cages display remarkable electrochemical performance with long cycle life and good rate capability.
On the mechanical interplay between Timoshenko and semirigid inclusions embedded in elastic bodies
Authors: Khludnev A. M. , Popova T. S.
Published: June 2017

In the paper, an equilibrium problem for elastic bodies with a thin elastic Timoshenko inclusion and a thin semirigid inclusion is analyzed. The inclusions are assumed to be delaminated from elastic bodies, thus forming a crack between the inclusions and the elastic matrix. Nonlinear boundary conditions are imposed at the crack faces to prevent a mutual penetration between the crack faces. The inclusions have a joint point. A passage to a limit is investigated as a rigidity parameter of the elastic inclusion goes to infinity. The limit model is investigated. Junction boundary conditions are found at the joint point for the problem analyzed as well as for the limit problem.
War on Two Fronts: The Fight against Parasites in Korea and Vietnam
Authors: Harrison Mark , Yim Sung Vin
Published: June 2017

The Vietnam War has long been regarded as pivotal in the history of the Republic of Korea, although its involvement in this conflict remains controversial. While most scholarship has focused on the political and economic ramifications of the war – and allegations of brutality by Korean troops – few scholars have considered the impact of the conflict upon medicine and public health. This article argues that the war had a transformative impact on medical careers and public health in Korea, and that this can be most clearly seen in efforts to control parasitic diseases. These diseases were a major drain on military manpower and a matter of growing concern domestically. The deployment to Vietnam boosted research into parasitic diseases of all kinds and accelerated the domestic campaign to control malaria and intestinal parasites. It also had a formative impact upon the development of overseas aid.
Beyond Institutions: Beliefs and Leadership
Authors: Alston Lee J.
Published: June 2017

Beliefs shape the choices of institutions. Beliefs are generally stable, but shocks that cause sufficiently unexpected economic and political outcomes make beliefs malleable. Within these windows of opportunity, leadership can play a role in shaping a new belief among the dominant organizations that in turn generates new institutions and over time a possible transition to a new developmental trajectory.
Novel market inefficiencies from early Victorian times
Authors: Odlyzko Andrew
Published: June 2017

A previously unknown pricing anomaly existed for a few years in the late 1840s in the British government bond market, in which the larger and more liquid of two very large bonds was underpriced. None of the published mechanisms explains this phenomenon. It may be related to another pricing anomaly that existed for much of the nineteenth century in which terminable annuities were significantly underpriced relative to so-called ‘perpetual’ annuities that dominated the government bond market. The reasons for these mispricings seem to lie in the early Victorian culture, since the basic economic incentives as well as laws and institutions were essentially the familiar modern ones. This provides new perspectives on the origins and nature of modern corporate capitalism.
Using Alumni Views to Connect the Past, Present, and Future in Political Science
Authors: Raile Eric D. , Shanahan Elizabeth A. , Wallner Michael P. , Young Linda M. , Avonius Marja , Young Micaela , Tayeb Nacer
Published: June 2017

This article describes the collection of views from political science alumni via a web-based survey as a central part of efforts to review and improve the curriculum and the broader political science program at a public university. Based on the literature and on interviews with faculty members and former students, we iteratively constructed a questionnaire containing five categories of items: program structure, content/knowledge, skills, outcomes, and learning environment. These categories were intended to capture curricular elements and outcomes that include but extend beyond employment and professional-skill attainment. Graduate students contributed in meaningful ways to the effort through a research-methods course. The article discusses how results of the survey fed into the curriculum-revision process specifically and program review and assessment considerations more generally.
Experiential Learning and Pathways to Carbon Neutrality
Authors: Rinfret Sara
Published: June 2017

To date, more than 650 university presidents across the United States have become signatories of the American College and University Presidents’ Climate Commitment (ACUPCC). A central goal of being a signatory is for a campus to achieve carbon neutrality. This article suggests that bringing the practice of experiential learning to the college classroom is a mechanism to help students understand and become involved in campus carbon-neutrality efforts. More specifically, it discusses the practical realities of using an undergraduate environmental-policy course to create policy proposals for our campus’s 2020 carbon-neutrality goal. The findings support a growing body of literature that demonstrates the value of experiential learning by enabling students to move from theory to practice.
Reconstruction of stochastic temporal networks through diffusive arrival times
Authors: Li Xun , Li Xiang
Published: June 2017

Temporal networks have opened a new dimension in defining and quantification of complex interacting systems. Our ability to identify and reproduce time-resolved interaction patterns is, however, limited by the restricted access to empirical individual-level data. Here we propose an inverse modelling method based on first-arrival observations of the diffusion process taking place on temporal networks. We describe an efficient coordinate-ascent implementation for inferring stochastic temporal networks that builds in particular but not exclusively on the null model assumption of mutually independent interaction sequences at the dyadic level. The results of benchmark tests applied on both synthesized and empirical network data sets confirm the validity of our algorithm, showing the feasibility of statistically accurate inference of temporal networks only from moderate-sized samples of diffusion cascades. Our approach provides an effective and flexible scheme for the temporally augmented inverse problems of network reconstruction and has potential in a broad variety of applications.
EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells
Authors: Neelakantan Deepika , Zhou Hengbo , Oliphant Michael U. J. , Zhang Xiaomei , Simon Lukas M. , Henke David M. , Shaw Chad A. , Wu Meng-Fen , Hilsenbeck Susan G. , White Lisa D. , Lewis Michael T. , Ford Heide L.
Published: June 2017

Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.
Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling
Authors: Zhang Gang , Kruse Thomas , López-Méndez Blanca , Sylvestersen Kathrine Beck , Garvanska Dimitriya H. , Schopper Simone , Nielsen Michael Lund , Nilsson Jakob
Published: June 2017

Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct interactions. Here we show that conserved domain 1 (CD1) in human Bub1 binds directly to Mad1 and a phosphorylation site exists in CD1 that stimulates Mad1 binding and SAC signalling. Importantly, fusion of minimal kinetochore-targeting Bub1 fragments to Mad1 bypasses the need for CD1, revealing that the main function of Bub1 is to position Mad1 close to KNL1 MELT repeats. Furthermore, we identify residues in Mad1 that are critical for Mad1 functionality, but not Bub1 binding, arguing for a direct role of Mad1 in the checkpoint. This work dissects functionally relevant molecular interactions required for spindle assembly checkpoint signalling at kinetochores in human cells.
Mutual synchronization of spin torque nano-oscillators through a long-range and tunable electrical coupling scheme
Authors: Lebrun R. , Tsunegi S. , Bortolotti P. , Kubota H. , Jenkins A. S. , Romera M. , Yakushiji K. , Fukushima A. , Grollier J. , Yuasa S. , Cros V.
Published: June 2017

The concept of spin-torque-driven high-frequency magnetization dynamics, allows the potential construction of complex networks of non-linear dynamical nanoscale systems, combining the field of spintronics and the study of non-linear systems. In the few previous demonstrations of synchronization of several spin-torque oscillators, the short-range nature of the magnetic coupling that was used has largely hampered a complete control of the synchronization process. Here we demonstrate the successful mutual synchronization of two spin-torque oscillators with a large separation distance through their long range self-emitted microwave currents. This leads to a strong improvement of both the emitted power and the linewidth. The full control of the synchronized state is achieved at the nanoscale through two active spin transfer torques, but also externally through an electrical delay line. These additional levels of control of the synchronization capability provide a new approach to develop spin-torque oscillator-based nanoscale microwave-devices going from microwave-sources to bio-inspired networks.
Erratum: GATA3 interacts with and stabilizes HIF-1α to enhance cancer cell invasiveness
Authors: Lin M-C , Lin J-J , Hsu C-L , Juan H-F , Lou P-J , Huang M-C
Published: June 2017

Correction to: Oncogene (2017) 36, 4243–4252; doi: 10.1038/onc.2017.8; published online 6 March 2017 The authors noted an error in the bottom panel of Figure 2c. A revised version is shown below and the text of the manuscript remains unchanged. The authors would like to apologize for any inconvenience caused and confirm that the conclusions drawn from this research are not affected by this error.
Limited nucleotide pools restrict Epstein–Barr virus-mediated B-cell immortalization
Authors: Hafez A Y , Messinger J E , McFadden K , Fenyofalvi G , Shepard C N , Lenzi G M , Kim B , Luftig M A
Published: June 2017

Activation of cellular oncogenes as well as infection with tumor viruses can promote aberrant proliferation and activation of the host DNA damage response. Epstein–Barr virus (EBV) infection of primary human B cells induces a transient period of hyper-proliferation, but many of these infected cells succumb to an ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/Chk2)-mediated senescence-like growth arrest. In this study, we assessed the role of DNA replicative stress and nucleotide pool levels in limiting EBV-infected B-cell outgrowth. We found that EBV triggered activation of the ataxia telangiectasia and Rad3-related (ATR) signaling pathway in the early rapidly proliferating cells, which were also significantly more sensitive to inhibition of the ATR pathway than late attenuated proliferating cells. Through nuclear halo assays, we determined that early EBV-infected cells displayed increased replicative stress and DNA damage relative to late proliferating cells. Finally, we found that early after infection, hyper-proliferating B cells exhibited limited deoxyribonucleotide triphosphate (dNTP) pools compared with late proliferating and EBV-immortalized lymphoblastoid cell lines with a specific loss of purine dNTPs. Importantly, supplementation with exogenous nucleosides before the period of hyper-proliferation markedly enhanced B-cell immortalization by EBV and rescued replicative stress. Together our results suggest that purine dNTP biosynthesis has a critical role in the early stages of EBV-mediated B-cell immortalization.
Global rise of potential health hazards caused by blue light-induced circadian disruption in modern aging societies
Authors: Hatori Megumi , Gronfier Claude , Van Gelder Russell N. , Bernstein Paul S. , Carreras Josep , Panda Satchidananda , Marks Frederick , Sliney David , Hunt Charles E. , Hirota Tsuyoshi , Furukawa Toshiharu , Tsubota Kazuo
Published: June 2017

Mammals receive light information through the eyes, which perform two major functions: image forming vision to see objects and non-image forming adaptation of physiology and behavior to light. Cone and rod photoreceptors form images and send the information via retinal ganglion cells to the brain for image reconstruction. In contrast, nonimage-forming photoresponses vary widely from adjustment of pupil diameter to adaptation of the circadian clock. nonimage-forming responses are mediated by retinal ganglion cells expressing the photopigment melanopsin. Melanopsin-expressing cells constitute 1–2% of retinal ganglion cells in the adult mammalian retina, are intrinsically photosensitive, and integrate photic information from rods and cones to control nonimage-forming adaptation. Action spectra of ipRGCs and of melanopsin photopigment peak around 480 nm blue light. Understanding melanopsin function lets us recognize considerable physiological effects of blue light, which is increasingly important in our modern society that uses light-emitting diode. Misalignment of circadian rhythmicity is observed in numerous conditions, including aging, and is thought to be involved in the development of age-related disorders, such as depression, diabetes, hypertension, obesity, and cancer. The appropriate regulation of circadian rhythmicity by proper lighting is therefore essential. This perspective introduces the potential risks of excessive blue light for human health through circadian rhythm disruption and sleep deprivation. Knowing the positive and negative aspects, this study claims the importance of being exposed to light at optimal times and intensities during the day, based on the concept of the circadian clock, ultimately to improve quality of life to have a healthy and longer life.
Platelet-rich plasma induces post-natal maturation of immature articular cartilage and correlates with LOXL1 activation
Authors: Zhang Yadan , Morgan Ben J. , Smith Rachel , Fellows Christopher R. , Thornton Catherine , Snow Martyn , Francis Lewis W. , Khan Ilyas M.
Published: June 2017

Platelet-rich plasma (PRP) is used to stimulate the repair of acute and chronic cartilage damage even though there is no definitive evidence of how this is achieved. Chondrocytes in injured and diseased situations frequently re-express phenotypic biomarkers of immature cartilage so tissue maturation is a potential pathway for restoration of normal structure and function. We used an in vitro model of growth factor-induced maturation to perform a comparative study in order to determine whether PRP can also induce this specific form of remodeling that is characterised by increased cellular proliferation and tissue stiffness. Gene expression patterns specific for maturation were mimicked in PRP treated cartilage, with chondromodulin, collagen types II/X downregulated, deiodinase II and netrin-1 upregulated. PRP increased cartilage surface cell density 1.5-fold (P < 0.05), confirmed by bromodeoxyuridine incorporation and proportionate increases in proliferating cell nuclear antigen gene expression. Atomic force microscopy analysis of PRP and growth factor treated cartilage gave a 5-fold increase in stiffness correlating with a 10-fold upregulation of lysyl oxidase like-1 gene expression (P < 0.001). These data show PRP induces key aspects of post-natal maturation in immature cartilage and provides the basis to evaluate a new biological rationale for its activity when used clinically to initiate joint repair.
Epitaxially stabilized thin films of ε-Fe2O3 (001) grown on YSZ (100)
Authors: Corbellini Luca , Lacroix Christian , Harnagea Catalin , Korinek Andreas , Botton Gianluigi A. , Ménard David , Pignolet Alain
Published: June 2017

Epsilon ferrite (ε-Fe2O3) is a metastable phase of iron(III) oxide, intermediate between maghemite and hematite. It has recently attracted interest because of its magnetocrystalline anisotropy, which distinguishes it from the other polymorphs, and results in a gigantic coercive field and a natural ferromagnetic resonance frequency in the THz range. Moreover, it possesses a polar crystal structure, making it a potential ferroelectric, hence a potential multiferroic. Due to the need of size confinement to stabilize the metastable phase, ε-Fe2O3has been synthesized mainly as nanoparticles. However, to favor integration in devices, and take advantage of its unique functional properties, synthesis as epitaxial thin films is desirable. In this paper, we report the growth of ε-Fe2O3as epitaxial thin films on (100)-oriented yttrium-stabilized zirconia substrates. Structural characterization outlined the formation of multiple in-plane twins, with two different epitaxial relations to the substrate. Transmission electron microscopy showed how such twins develop in a pillar-like structure from the interface to the surface. Magnetic characterization confirmed the high magnetocrystalline anisotropy of our film and revealed the presence of a secondary phase which was identified as the well-known magnetite. Finally, angular analysis of the magnetic properties revealed how the presence of twins impacts their azimuthal dependence.
Intricate disorder in defect fluorite/pyrochlore: a concord of chemistry and crystallography
Authors: Simeone David , Thorogood Gordon James , Huo Da , Luneville Laurence , Baldinozzi Gianguido , Petricek Vaclav , Porcher Florence , Ribis Joel , Mazerolles Leo , Largeau Ludovic , Berar Jean Francois , Surble Suzy
Published: June 2017

Intuitively scientists accept that order can emerge from disorder and a significant amount of effort has been devoted over many years to demonstrate this. In metallic alloys and oxides, disorder at the atomic scale is the result of occupation at equivalent atomic positions by different atoms which leads to the material exhibiting a fully random or modulated scattering pattern. This arrangement has a substantial influence on the material’s properties, for example ionic conductivity. However it is generally accepted that oxides, such as defect fluorite as used for nuclear waste immobilization matrices and fuel cells, are the result of disorder at the atomic scale. To investigate how order at the atomic scale induces disorder at a larger scale length, we have applied different techniques to study the atomic composition of a homogeneous La2Zr2O7 pyrochlore, a textbook example of such a structure. Here we demonstrate that a pyrochlore, which is considered to be defect fluorite, is the result of intricate disorder due to a random distribution of fully ordered nano-domains. Our investigation provides new insight into the order disorder transformations in complex materials with regards to domain formation, resulting in a concord of chemistry with crystallography illustrating that order can induce disorder.
The role of PTEN - HCV core interaction in hepatitis C virus replication
Authors: Wu Qi , Li Zhubing , Mellor Paul , Zhou Yan , Anderson Deborah H. , Liu Qiang
Published: June 2017

Hepatitis C virus (HCV) infection leads to severe liver diseases including hepatocellular carcinoma (HCC). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumour suppressor, is frequently mutated or deleted in HCC tumors. PTEN has previously been demonstrated to inhibit HCV secretion. In this study, we determined the effects of PTEN on the other steps in HCV life cycle, including entry, translation, and replication. We showed that PTEN inhibits HCV entry through its lipid phosphatase activity. PTEN has no effect on HCV RNA translation. PTEN decreases HCV replication and the protein phosphatase activity of PTEN is essential for this function. PTEN interacts with the HCV core protein and requires R50 in domain I of HCV core and PTEN residues 1–185 for this interaction. This interaction is required for PTEN-mediated inhibition of HCV replication. This gives rise to a reduction in PTEN levels and intracellular lipid abundance, which may in turn regulate HCV replication. HCV core domain I protein increases the lipid phosphatase activity of PTEN in an in vitro assay, suggesting that HCV infection can also regulate PTEN. Taken together, our results demonstrated an important regulatory role of PTEN in the HCV life cycle.
Seabirds supply nitrogen to reef-building corals on remote Pacific islets
Authors: Lorrain Anne , Houlbrèque Fanny , Benzoni Francesca , Barjon Lucie , Tremblay-Boyer Laura , Menkes Christophe , Gillikin David P. , Payri Claude , Jourdan Hervé , Boussarie Germain , Verheyden Anouk , Vidal Eric
Published: June 2017

Seabirds concentrate nutrients from large marine areas on their nesting islands playing an important ecological role in nutrient transfer between marine and terrestrial ecosystems. Here we investigate the role of guano on corals reefs across scales by analyzing the stable nitrogen isotopic (δ15N) values of the scleractinian coralPocillopora damicornison fringing reefs around two Pacific remote islets with large seabird colonies. Marine stations closest to the seabird colonies had higher nitrate + nitrite concentrations compared to more distant stations. Coral and zooxanthellae δ15N values were also higher at these sites, suggesting that guano-derived nitrogen is assimilated into corals and contributes to their nitrogen requirements. The spatial extent of guano influence was however restricted to a local scale. Our results demonstrate that seabird-derived nutrients not only spread across the terrestrial ecosystem, but also affect components of the adjacent marine ecosystem. Further studies are now needed to assess if this nutrient input has a positive or negative effect for corals. Such studies on remote islets also open fresh perspectives to understand how nutrients affect coral reefs isolated from other anthropogenic stressors.
Exendin-4 attenuates blast traumatic brain injury induced cognitive impairments, losses of synaptophysin and in vitro TBI-induced hippocampal cellular degeneration
Authors: Rachmany Lital , Tweedie David , Rubovitch Vardit , Li Yazhou , Holloway Harold W. , Kim Dong Seok , Ratliff Whitney A. , Saykally Jessica N. , Citron Bruce A. , Hoffer Barry J. , Greig Nigel H. , Pick Chaim G.
Published: June 2017

Mild blast traumatic brain injury (B-TBI) induced lasting cognitive impairments in novel object recognition and less severe deficits in Y-maze behaviors. B-TBI significantly reduced the levels of synaptophysin (SYP) protein staining in cortical (CTX) and hippocampal (HIPP) tissues. Treatment with exendin-4 (Ex-4) delivered by subcutaneous micro-osmotic pumps 48 hours prior to or 2 hours immediately after B-TBI prevented the induction of both cognitive deficits and B-TBI induced changes in SYP staining. The effects of a series of biaxial stretch injuries (BSI) on a neuronal derived cell line, HT22 cells, were assessed in an in vitro model of TBI. Biaxial stretch damage induced shrunken neurites and cell death. Treatment of HT22 cultures with Ex-4 (25 to 100 nM), prior to injury, attenuated the cytotoxic effects of BSI and preserved neurite length similar to sham treated cells. These data imply that treatment with Ex-4 may represent a viable option for the management of secondary events triggered by blast-induced, mild traumatic brain injury that is commonly observed in militarized zones.
Optimal angle of magnetic field for magnetic bubblecade motion
Authors: Kim Duck-Ho , Moon Kyoung-Woong , Yoo Sang-Cheol , Kim Dae-Yun , Min Byoung-Chul , Hwang Chanyong , Choe Sug-Bong
Published: June 2017

Unidirectional motion of magnetic structures such as the magnetic domain and domain walls is a key concept underlying next-generation memory and logic devices. As a potential candidate of such unidirectional motion, it has been recently demonstrated that the magnetic bubblecade—the coherent unidirectional motion of magnetic bubbles—can be generated by applying an alternating magnetic field. Here we report the optimal configuration of applied magnetic field for the magnetic bubblecade. The tilted alternating magnetic field induces asymmetric expansion and shrinkage of the magnetic bubbles under the influence of the Dzyaloshinskii-Moriya interaction, resulting in continuous shift of the bubbles in time. By examining the magnetic bubblecade in Pt/Co/Pt films, we find that the bubblecade speed is sensitive to the tilt angle with a maximum at an angle, which can be explained well by a simple analytical form within the context of the domain-wall creep theory. A simplified analytic formula for the angle for maximum speed is then given as a function of the amplitude of the alternating magnetic field. The present results provide a useful guideline of optimal design for magnetic bubblecade memory and logic devices.
Quantitative modelling of hip fracture trends in 14 European countries: testing variations of a shared reversal over time
Authors: Lucas Raquel , Martins Ana , Severo Milton , Silva Poliana , Monjardino Teresa , Gaio Ana Rita , Cooper Cyrus , Barros Henrique
Published: June 2017

Qualitative similarities between hip fracture trends in different countries suggests variations of the same epidemic. We tested a single statistical shape to describe time trends in Europe, while allowing for country-level variability. Using data from 14 countries, we modelled incidence rates over time using linear mixed-effects models, including the fixed effects of calendar year and age. Random effects were tested to quantify country-level variability in background rates, timing of trend reversal and tempo of reversal. Mixture models were applied to identify clusters of countries defined by common behavioural features. A quadratic function of time, with random effects for background rates and timing of trend reversal, adjusted well to the observed data. Predicted trend reversal occurred on average in 1999 in women (peak incidence about 600 per 100 000) and 2000 in men (about 300 per 100 000). Mixture modelling of country-level effects suggested three clusters for women and two for men. In both sexes, Scandinavia showed higher rates but earlier trend reversals, whereas later trend reversals but lower peak incidences were found in Southern Europe and most of Central Europe. Our finding of a similar overall reversal pattern suggests that different countries show variations of a shared hip fracture epidemic.
Probing spermiogenesis: a digital strategy for mouse acrosome classification
Authors: Taloni Alessandro , Font-Clos Francesc , Guidetti Luca , Milan Simone , Ascagni Miriam , Vasco Chiara , Pasini Maria Enrica , Gioria Maria Rosa , Ciusani Emilio , Zapperi Stefano , La Porta Caterina A. M.
Published: June 2017

Classification of morphological features in biological samples is usually performed by a trained eye but the increasing amount of available digital images calls for semi-automatic classification techniques. Here we explore this possibility in the context of acrosome morphological analysis during spermiogenesis. Our method combines feature extraction from three dimensional reconstruction of confocal images with principal component analysis and machine learning. The method could be particularly useful in cases where the amount of data does not allow for a direct inspection by trained eye.