bluuebunny/crossref_metadata_2025 huggingface dataset:
Equipping future doctors: incorporating management and leadership into medical curriculums in the United Kingdom
Authors: Sonsale Aniket , Bharamgoudar Reshma
Published: February 2017

Throughout their careers, doctors are likely to come across complex management and leadership scenarios that many would not have had prior training in. Expectations of doctors are rising and it is becoming increasingly necessary to be able to astutely handle a variety of situations. Medical curricula must reflect this change and adapt to include the teaching of key management and leadership skills. Despite budgeting pressures, the National Health Service continues to spend vast sums of money on external management consultants. The 2013 Francis Report stressed the need for better management skills and leadership, especially in doctors who were identified as the spearheads of change. This view is backed up by senior professionals who stress that by incorporating it into undergraduate curricula, doctors will be equipped with the skills to flourish in the future. The challenges of doing so must be highlighted, since the teaching of managerial and leadership concepts must effectively combine theoretical approaches with practical applications. Empowering students of today will enable them as tomorrow’s doctors to tackle the challenges of modern medicine
The link between operational leanness and credit ratings
Authors: Bendig David , Strese Steffen , Brettel Malte
Published: February 2017

Although there is rich literature documenting the positive relationship between operational leanness and financial performance, recent research indicates that the effects of leanness may be more complex than is typically assumed. We explore the impact of two kinds of leanness, relative inventory leanness and relative PPE leanness, on credit ratings. We thus use an alternative lens to explore the financial implications of leanness. We analyze secondary U.S. data from 1985 to 2012, with 11,197 firm‐year observations of manufacturing firms. Using panel data analysis, we show that inventory leanness is positively associated with credit ratings in a concave relationship. This is consistent with previous research that has looked at the impact of relative inventory leanness on equity performance. Conversely, we find that PPE leanness is negatively related with credit ratings in a concave relationship—in contrast to prior studies addressing the impact of PPE leanness on equity performance.
Laboratory modeling of hydrate formation in rock specimens (a review)
Authors: Manakov A. Yu. , Duchkov A.D.
Published: February 2017

We present a review of the literature on the methods of modeling of sedimentary rocks containing gas hydrates with the aim of a subsequent study of their physical and mechanical properties. The attention is focused mainly on the non-Russian researches carried out in the last 15 years. The review includes description of corresponding setups and modeling techniques. The dependence of the morphology of hydrate present in the specimen on the specimen preparation technique is reviewed in detail. In addition, the structure and texture of synthetic and natural hydrate-containing rock specimens are briefly reported, as well as the regularities of formation and dissociation of gas hydrates in the Earth’s crust.
Physical and mathematical modeling of transient electromagnetic soundings over salt-dome structures
Authors: Bobrov N.Yu. , Krylov S.S. , Antonov E.Yu. , Shein A.N. , Smilevets N.P.
Published: February 2017

This paper presents the results of physical and mathematical modeling performed to evaluate the potential of transient electromagnetic sounding in areas of salt-dome tectonics. Two geoelectric arrays are considered: an array with an inductive source (a horizontal loop) and an array with a mixed-type source (a horizontal current line). It is shown that the transient electromagnetic method provides important information on the relief of the top of salt deposits.
Beyond Bunker and Vaccine: The DNC Hack as a Conflict of Laws
Issue
Authors: Johns Fleur , Riles Annelise
Published: February 2017

Who was responsible for the cyberincursions upon the Democratic National Committee
(DNC) that took place during the U.S. presidential campaign? Russia's “senior most officials”? A “
a tattooed 26-year-old” running a server rental company
in western Siberia? U.S. political party leaders and other insiders disinclined to
implement “best in class” cybersecurity measures? Or does
responsibility lie elsewhere?
On the genesis and evolution of barchan dunes: morphodynamics
Authors: Khosronejad A. , Sotiropoulos F.
Published: February 2017

Barchan dunes are crescent-shaped formations of sand that can dominate both desert and subaqueous landscapes when the supply of sand is scarce. Because of the complexity and scale of the underlying phenomena, the mechanisms governing the entire process from the genesis to the long-term evolution of barchan fields still remain to be better understood. Herein, we attempt to present a description of this process in a subaqueous environment by employing a large-eddy simulation approach that couples turbulent flow and sand-bed morphodynamics. We show that the seeds of the emergent structure in barchan fields are random turbulent flow motions near the initially flat bed. We also provide high-resolution insights into phenomena such as barchan migration and merging, and show how transverse sand waves are formed and migrate over the barchan horns. Furthermore, the transverse sand waves over the barchan horns are shown to be the seeds of the newly born barchans at the end points of the two horns of a barchan through the process known as calving. To show this, we examine the celerity, wavelength and amplitude of the transverse sand waves over the barchan as they approach the end of its horn. The celerity and wavelength of these transverse sand waves are shown to be the defining factors in determining the frequency of the calving process. The amplitude of the newly born barchans (through calving) is also shown to be associated with the amplitude of the transverse waves near the end of the horn. The simulation data also show that the wavelength of the newly born barchans (the distance between individual dunes) is closely related to that of the transverse sand waves over their maternal barchan. Finally, we use the simulation results to discuss past conclusions derived from theory, conventional models and field observations.
Ritual Observance: Colonial Representations of Afro-Caribbean Spiritual Practices in the Eighteenth and Nineteenth Century French Caribbean
Authors: Leonard Ray
Published: February 2017

Over the eighteenth century and into the nineteenth century, colonial observers repeatedly recorded Afro-Caribbean spiritual practices in the French Caribbean. “Ritual Observances” charts four such records; the 1698 journal of Jean Baptiste Labat, trial records from 1784, Moreau de-Saint Merie’s 1794Description Topographique, and Drouin De Bercy’sDe Saint Domingue. Although these records span distinct historical periods and textual mediums, they all employ a set of recognizable forms to express the convergence of disgust and desire that have historically attended colonial observations of Afro-Caribbean agency. I argue, however, that the significance of this ambivalence is constitutive of the historical moment in which it appears and that these observations are connected by more than a “shared” ambivalence. Instead, we might categorize these records asthemselvesritualistic. The termritual observancegestures to the act of observing a ritual, but also the way in which the observation is itself ritualistic. The repeated and sequential forms, or “actions” as I term them, of the ritual observance work to inscribe a legible history over the turbulence of eighteenth- and nineteenth-century French colonialism.
Proton fire hose instabilities in the expanding solar wind
Authors: Hellinger Petr
Published: February 2017

Using two-dimensional hybrid expanding box simulations we study the competition between the continuously driven parallel proton temperature anisotropy and fire hose instabilities in collisionless homogeneous plasmas. For a quasi-radial ambient magnetic field the expansion drives $T_{p\Vert }>T_{p\bot }$ and the system becomes eventually unstable with respect to the dominant parallel fire hose instability. This instability is generally unable to counteract the induced anisotropization and the system typically becomes unstable with respect to the oblique fire hose instability later on. The oblique instability efficiently reduces the anisotropy and the system rapidly stabilizes, while a significant part of the generated electromagnetic fluctuations is damped to protons. As long as the magnetic field is in the quasi-radial direction, this evolution repeats itself and the electromagnetic fluctuations accumulate. For a sufficiently oblique magnetic field the expansion drives $T_{p\bot }>T_{p\Vert }$ and brings the system to the stable region with respect to the fire hose instabilities.
Validation of the Calakmul–Laguna de Terminos corridor for jaguarsPanthera oncain south-eastern Mexico
Authors: Hidalgo-Mihart Mircea G. , Contreras-Moreno Fernando M. , Jesús de la Cruz Alejandro , Juárez-López Rugieri
Published: February 2017

The fragmentation of jaguarPanthera oncapopulations as a result of habitat loss is considered to be one of the main challenges for the conservation of the species. Corridors have been proposed as a means of maintaining connectivity and the long-term viability of jaguar populations. The corridor that connects the jaguar conservation units of Calakmul and Laguna de Terminos in Mexico has been considered to be a link for the movement of individuals between these units but its functionality had yet to be verified. During 2012–2014 we divided the corridor into four sections, where we used camera traps to verify the corridor's functionality. We obtained 106 photographs of jaguars, proving the presence of jaguars (including resident jaguars and females) in three of the corridor sections. We did not record any individuals in more than one section of the corridor. The presence of several resident jaguars and females throughout the corridor suggests that portions of the corridor should be incorporated into the Calakmul and Laguna de Terminos jaguar conservation units. Nevertheless, to confirm that the corridor is fully functional it is necessary to obtain evidence of movement of jaguars among the various sections of the corridor. Our results suggest that the area should be included in regional conservation strategies.
Why Study History? On Its Epistemic Benefits and Its Relation to the Sciences
Authors: Grimm Stephen R.
Published: February 2017

I try to return the focus of the philosophy of history to the nature of understanding, with a particular emphasis on Louis Mink's project of exploring how historical understanding compares to the understanding we find in the natural sciences. On the whole, I come to a conclusion that Mink almost certainly would not have liked: that the understanding offered by history has a very similar epistemic profile to the understanding offered by the sciences, a similarity that stems from the fact that both are concerned with grasping how the objects of their study are structured, or how the various elements of the things they study depend upon and relate to one another. At the same time, however, I claim that historical inquiry naturally puts us in a position to acquire further epistemic goods, including the old-fashioned epistemic good of wisdom, which is plausibly constituted by knowledge of how to live well. This is something the natural sciences cannot offer, and it is part of the reason why history is such an important form of inquiry.
Pricing American-style Parisian up-and-out call options
Authors: LU XIAOPING , LE NHAT-TAN , ZHU SONG PING , CHEN WENTING
Published: February 2017

In this paper, we propose an integral equation approach for pricing an American-style Parisian up-and-out call option under the Black–Scholes framework. The main difficulty of pricing this option lies in the determination of its optimal exercise price, which is a three-dimensional surface, instead of a two-dimensional (2-D) curve as is the case for a “one-touch” barrier option. In our approach, we first reduce the 3-D pricing problem to a 2-D one by using the “moving window” technique developed by Zhu and Chen (2013, Pricing Parisian and Parasian options analytically. Journal of Economic Dynamics and Control, 37(4): 875-896), then apply the Fourier sine transform to the 2-D problem to obtain two coupled integral equations in terms of two unknown quantities: the option price at the asset barrier and the optimal exercise price. Once the integral equations are solved numerically by using an iterative procedure, the calculation of the option price and the hedging parameters is straightforward from their integral representations. Our approach is validated by a comparison between our results and those of the trusted finite difference method. Numerical results are also provided to show some interesting features of the prices of American-style Parisian up-and-out call options and the behaviour of the associated optimal exercise boundaries.
A NEW SPECIES OF ETLINGERA (ZINGIBERACEAE) FROM BOUGAINVILLE ISLAND, PAPUA NEW GUINEA
Authors: Poulsen A. D. , Bau B. B.
Published: February 2017

A new species, Etlingera frederikii, is described and illustrated, and is the first record of the genus in the Bougainville Region. Etlingera frederikii and E. cevuga, which occurs in Fiji and Samoa, are the two most easterly species in the distribution range of the genus. The new species differs from Etlingera cevuga in its much larger leaves, with a conspicuously silky-haired band on the ligule; the smaller, narrowly ovoid to cylindrical inflorescence with pale brown bracts (not hemiglobose with reddish brown bracts); and fewer, smaller flowers.
Approach to atypical Alzheimer’s disease and case studies of the major subtypes
Authors: Dickerson Bradford C. , McGinnis Scott M. , Xia Chenjie , Price Bruce H. , Atri Alireza , Murray Melissa E. , Mendez Mario F. , Wolk David A.
Published: February 2017

Alzheimer’s disease (AD) has long been recognized as a heterogeneous illness, with a common clinical presentation of progressive amnesia and less common “atypical” clinical presentations, including syndromes dominated by visual, aphasic, “frontal,” or apraxic symptoms. Our knowledge of atypical clinical phenotypes of AD comes from clinicopathologic studies, but with the growing use of in vivo molecular biomarkers of amyloid and tau pathology, we are beginning to recognize that these syndromes may not be as rare as once thought. When a clinician is evaluating a patient whose clinical phenotype is dominated by progressive aphasia, complex visual impairment, or other neuropsychiatric symptoms with relative sparing of memory, the differential diagnosis may be broader and a confident diagnosis of an atypical form of AD may require the use of molecular biomarkers. Despite the evolving sophistication in our diagnostic tools, and the acknowledgment of atypical AD syndromes in the 2011 revised diagnostic criteria for AD, the assessment of such patients still poses substantial challenges. We use a case-based approach to review the clinical and imaging phenotypes of a series of patients with typical and atypical AD, and discuss our current approach to their evaluation. One day, we hope that regardless of whether a patient exhibits typical or atypical symptoms of AD pathology, we will be able to identify the condition at a prodromal phase and institute a combination of symptomatic and disease-modifying therapies to support cognitive processes, function, and behavior, and slow or halt progression to dementia.
A comparative dosimetric study comparing dose to the carotid artery using 3D conformal radiotherapy and intensity-modulated radiotherapy for T1-T2 glottic cancer at Gharbia Cancer Society, Egypt
Authors: Mahmoud Mohamed , Elfaramawy Safa , Mokhtar Maha H.
Published: February 2017

Purpose

This is a dosimetric study to compare the feasibility of carotid artery sparing as a primary objective, as well as planning target volume coverage and dose to spinal cord as a secondary objective, by using 3D conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) for patients with early glottis cancer.

Patients and methods

Six patients who had been treated for early stage glottic carcinoma (stage T1-2 N0M0) were included in this study. All patients were immobilised in the supine position with a thermoplastic mask and treatment planning computed tomography scans were obtained from the top of the skull to the top of aortic arch with a 3-mm slice thickness. Two plans were created for every patient, one using 3DCRT and the second using IMRT. Comparison between the two plans was undertaken and analysis was made regarding the dose to the carotids arteries, target coverage and doses to the organs at risk.

Results

For target coverage, theV95%for both plans was the same with no significant difference, hot spots were the highest in 3DCRT withp=0·002, the homogeneity index for IMRT plan was better than 3DCRT (p=0·0001). Regarding the dose to the carotids, it was significantly lower in the IMRT plan compared with the 3DCRT plan (p=0·01). The spinal cord dose was significantly higher in the IMRT plan.

Conclusion

IMRT significantly reduces the radiation dose to the carotid arteries compared with 3DCRT while maintaining clinical target volume coverage. Such a results assists in decreasing the incidence of radiation-induced carotid stenosis, thus improving the quality of life for patients.
State intervention in the lives of people with disabilities: the case for a disability-neutral framework
Authors: Flynn Eilionóir , Arstein-Kerslake Anna
Published: February 2017

People with disabilities continue to experience a disproportionately high level of state intervention in their private lives. Many disabled people's organisations have long sought to challenge this discriminatory approach and, in recent times, have relied upon the provisions of the UN Convention on the Rights of Persons with Disabilities in support of their claims. In this paper, we argue for the abolition of disability-specific legal bases for state intervention in the private lives of adults. We also argue for the introduction of a narrower disability-neutral legislative framework for state intervention in the lives of all adults – based on risk of imminent and serious harm to the individual's life, health or safety, while providing greater respect for the person's legal capacity as expressed through her will and preferences.
Tempering Hard Times: Integrating Well-Being Metrics Into Utility Analysis
Authors: Tziner Aharon , Fein Erich C. , Birati Assa
Published: February 2017

This article highlights the virtue of integrating well-being metrics (e.g., psychological well-being, perceived meaning) into aspects of utility analysis for the purpose of enhancing human resource management strategies and worker performance. We present the reader with a review of conceptual and practical developments in this field and examples of utility analysis calculations, while we advocate for the necessity of including well-being metrics in utility analysis for the 21st century. The basic thrust of this effort is to encourage the greater employment by managers of quantitative models that allow decision makers to generate all the factors needed to estimate long-term financial gains and/or losses before any intervention strategy is implemented in the workplace. As indicated, the use of quantitative models to estimate the net financial gains of using particular intervention strategies, accompanied with the value estimation of certain types of employee states (e.g., psychological well-being) and worker behaviors (e.g., employee turnover), can ultimately save companies from making gross tactical errors and, more positively, can assist management in promoting the organization's long-term economic goals in conjunction with the enhanced well-being of employees.
Rational Extremism: Understanding Terrorism in the Twenty-first Century
Authors: Lake David A.
Published: February 2017

In the last decade, the field of international relations has undergone a revolution in conflict studies. Where earlier approaches attempted to identify the attributes of individuals, states, and systems that produced conflict, the “rationalist approach to war” now explains violence as the product of private information with incentives to misrepresent, problems of credible commitment, and issue indivisibilities. In this new approach, war is understood as a bargaining failure that leaves both sides worse off than had they been able to negotiate an efficient solution. This rationalist framework has proven remarkably general—being applied to civil wars, ethnic conflicts, and interstate wars—and fruitful in understanding not only the causes of war but also war termination and conflict management. Interstate war is no longer seen as sui generis, but as a particular form within a single, integrated theory of conflict.
The Globalization of Informal Violence, Theories of World Politics, and the “Liberalism of Fear”
Authors: Keohane Robert O.
Published: February 2017

The attacks on the United States on 11 September 2001 have incalculable consequences for domestic politics and world affairs. Reliable predictions about these consequences are impossible. However, it may be worthwhile, even at this early point, to reflect on what these acts of violence reveal about the adequacy of our theories of world politics. In what respects have our assumptions and our analytical models helped us to understand these events and responses to them? And in what ways have we been misled by our theories?
September 11 in Comparative Perspective: The Antiterrorism Campaigns of Germany and Japan
Authors: Katzenstein Peter J.
Published: February 2017

For the United States, September 11 is a turning point.; For Japan and Germany it brought a sense of déjà vu. The United States’ experience with terrorism is not unique, but it is distinctive. How other states, here Japan and Germany, have dealt with terrorism may help put the events of September 11 and their aftermath into perspective. Japan and Germany were not as successful in stemming terrorism as their governments and people would have liked. An analysis of their policies sheds new light on this turn in world politics.
Hyperspectral infrared nanoimaging of organic samples based on Fourier transform infrared nanospectroscopy
Authors: Amenabar Iban , Poly Simon , Goikoetxea Monika , Nuansing Wiwat , Lasch Peter , Hillenbrand Rainer
Published: February 2017

Infrared nanospectroscopy enables novel possibilities for chemical and structural analysis of nanocomposites, biomaterials or optoelectronic devices. Here we introduce hyperspectral infrared nanoimaging based on Fourier transform infrared nanospectroscopy with a tunable bandwidth-limited laser continuum. We describe the technical implementations and present hyperspectral infrared near-field images of about 5,000 pixel, each one covering the spectral range from 1,000 to 1,900 cm−1. To verify the technique and to demonstrate its application potential, we imaged a three-component polymer blend and a melanin granule in a human hair cross-section, and demonstrate that multivariate data analysis can be applied for extracting spatially resolved chemical information. Particularly, we demonstrate that distribution and chemical interaction between the polymer components can be mapped with a spatial resolution of about 30 nm. We foresee wide application potential of hyperspectral infrared nanoimaging for valuable chemical materials characterization and quality control in various fields ranging from materials sciences to biomedicine.
No saturation in the accumulation of alien species worldwide
Authors: Seebens Hanno , Blackburn Tim M. , Dyer Ellie E. , Genovesi Piero , Hulme Philip E. , Jeschke Jonathan M. , Pagad Shyama , Pyšek Petr , Winter Marten , Arianoutsou Margarita , Bacher Sven , Blasius Bernd , Brundu Giuseppe , Capinha César , Celesti-Grapow Laura , Dawson Wayne , Dullinger Stefan , Fuentes Nicol , Jäger Heinke , Kartesz John , Kenis Marc , Kreft Holger , Kühn Ingolf , Lenzner Bernd , Liebhold Andrew , Mosena Alexander , Moser Dietmar , Nishino Misako , Pearman David , Pergl Jan , Rabitsch Wolfgang , Rojas-Sandoval Julissa , Roques Alain , Rorke Stephanie , Rossinelli Silvia , Roy Helen E. , Scalera Riccardo , Schindler Stefan , Štajerová Kateřina , Tokarska-Guzik Barbara , van Kleunen Mark , Walker Kevin , Weigelt Patrick , Yamanaka Takehiko , Essl Franz
Published: February 2017

Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970–2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.
Selective sulfur dioxide adsorption on crystal defect sites on an isoreticular metal organic framework series
Authors: Rodríguez-Albelo L. Marleny , López-Maya Elena , Hamad Said , Ruiz-Salvador A. Rabdel , Calero Sofia , Navarro Jorge A.R.
Published: February 2017

The widespread emissions of toxic gases from fossil fuel combustion represent major welfare risks. Here we report the improvement of the selective sulfur dioxide capture from flue gas emissions of isoreticular nickel pyrazolate metal organic frameworks through the sequential introduction of missing-linker defects and extra-framework barium cations. The results and feasibility of the defect pore engineering carried out are quantified through a combination of dynamic adsorption experiments, X-ray diffraction, electron microscopy and density functional theory calculations. The increased sulfur dioxide adsorption capacities and energies as well as the sulfur dioxide/carbon dioxide partition coefficients values of defective materials compared to original non-defective ones are related to the missing linkers enhanced pore accessibility and to the specificity of sulfur dioxide interactions with crystal defect sites. The selective sulfur dioxide adsorption on defects indicates the potential of fine-tuning the functional properties of metal organic frameworks through the deliberate creation of defects.
Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension
Authors: Kopeć Grzegorz , Waligóra Marcin , Tyrka Anna , Jonas Kamil , Pencina Michael J. , Zdrojewski Tomasz , Moertl Deddo , Stokwiszewski Jakub , Zagożdżon Paweł , Podolec Piotr
Published: February 2017

Low-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26–0.74, p = 0.002) after a median follow-up time of 33(21–36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1–3.2] to 4.0[2.8–4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2–2.7] vs 2.3[2.1–2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels.
Eu3+-doped Bi4Si3O12 red phosphor for solid state lighting: microwave synthesis, characterization, photoluminescence properties and thermal quenching mechanisms
Authors: Zhang Yan , Xu Jiayue , Cui Qingzhi , Yang Bobo
Published: February 2017

Europium-doped bismuth silicate (Bi4Si3O12) phosphor has been prepared by microwave irradiation method and its crystal structure is determined using Rietveld method. As-prepared phosphor consists of spherical, monodispersed particles with few agglomeration, high crystallinity, and narrow grain size distribution. The phosphor can be efficiently excited in the wavelength range of 260–400 nm, which matched well with the emission wavelengths of NUV LED chips. The photoluminescence spectra exhibit the highest emission peak at 703 nm originating from 5D0 → 7F4 transition of Eu3+ under NUV excitation. The luminescence lifetime for Bi4Si3O12: 2 at% Eu3+ phosphor decreases from 2.11 to 1.86 ms with increasing temperature from 10 to 498 K. This behavior of decays is discussed in terms of radiative and nonradiative decays dependence on temperature. The thermal quenching mechanism of 5D0 emission of Eu3+ in Bi4Si3O12 phosphor is a crossover process from the 5D0 level of Eu3+ to a ligand-to-europium (O2− → Eu3+) charge transfer state. The quantum efficiency of the phosphor under 393 nm excitation is found to be 14.5%, which is higher than that of the commercial red phosphors Y2O3: Eu3+, Y2O2S: Eu3+. The temperature effect on CIE coordinate was discussed in order to further investigate the potential applications.
The secondary resistome of multidrug-resistant Klebsiella pneumoniae
Authors: Jana Bimal , Cain Amy K. , Doerrler William T. , Boinett Christine J. , Fookes Maria C. , Parkhill Julian , Guardabassi Luca
Published: February 2017

Klebsiella pneumoniae causes severe lung and bloodstream infections that are difficult to treat due to multidrug resistance. We hypothesized that antimicrobial resistance can be reversed by targeting chromosomal non-essential genes that are not responsible for acquired resistance but essential for resistant bacteria under therapeutic concentrations of antimicrobials. Conditional essentiality of individual genes to antimicrobial resistance was evaluated in an epidemic multidrug-resistant clone of K. pneumoniae (ST258). We constructed a high-density transposon mutant library of >430,000 unique Tn5 insertions and measured mutant depletion upon exposure to three clinically relevant antimicrobials (colistin, imipenem or ciprofloxacin) by Transposon Directed Insertion-site Sequencing (TraDIS). Using this high-throughput approach, we defined three sets of chromosomal non-essential genes essential for growth during exposure to colistin (n = 35), imipenem (n = 1) or ciprofloxacin (n = 1) in addition to known resistance determinants, collectively termed the “secondary resistome”. As proof of principle, we demonstrated that inactivation of a non-essential gene not previously found linked to colistin resistance (dedA) restored colistin susceptibility by reducing the minimum inhibitory concentration from 8 to 0.5 μg/ml, 4-fold below the susceptibility breakpoint (S ≤ 2 μg/ml). This finding suggests that the secondary resistome is a potential target for developing antimicrobial “helper” drugs that restore the efficacy of existing antimicrobials.
High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-β1-induced epithelia-to-mesenchymal transition
Authors: Wu Yanxia , Shen Zhihua , Wang Keke , Ha Yanping , Lei Hong , Jia Yanan , Ding Ranran , Wu Dongmei , Gan Siyuan , Li Rujia , Luo Botao , Jiang Hanguo , Jie Wei
Published: February 2017

Formin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples. In vitro experiments showed that FMNL3 expression was inversely related to NPC cell differentiation status. Overexpression of FMNL3 led to epithelial-to-mesenchymal transition (EMT) in well differentiated CNE1 cells. TGF-β1-treated poorly differentiated CNE2 cells showed changes in EMT accompanied by enhanced FMNL3 expression and cell migration. On the contrary, knockdown of FMNL3 partially attenuated the TGF-β1-promoted CNE2 cell migration, together with associated changes in EMT markers. Finally, knockdown of FMNL3 also weakened EMT in tumours in xenographs. Our study indicates for the first time that TGF-β1/FMNL3 signalling may be a novel mechanism mediating EMT in NPC, which is closely associated with NPC metastasis.
Dual Electrophoresis Detection System for Rapid and Sensitive Immunoassays with Nanoparticle Signal Amplification
Authors: Zhang Fangfang , Ma Junjie , Watanabe Junji , Tang Jinlong , Liu Huiyu , Shen Heyun
Published: February 2017

An electrophoretic technique was combined with an enzyme-linked immunosorbent assay (ELISA) system to achieve a rapid and sensitive immunoassay. A cellulose acetate filter modified with polyelectrolyte multilayer (PEM) was used as a solid substrate for three-dimensional antigen-antibody reactions. A dual electrophoresis process was used to induce directional migration and local condensation of antigens and antibodies at the solid substrate, avoiding the long diffusion times associated with antigen-antibody reactions in conventional ELISAs. The electrophoretic forces drove two steps in the ELISA process, namely the adsorption of antigen, and secondary antibody-labelled polystyrene nanoparticles (NP-Ab). The total time needed for dual electrophoresis-driven detection was just 4 min, nearly 2 h faster than a conventional ELISA system. Moreover, the rapid NP-Ab electrophoresis system simultaneously achieved amplification of the specific signal and a reduction in noise, leading to a more sensitive NP-Ab immunoassay with a limit of detection (LOD) of 130 fM, and wide range of detectable concentrations from 0.13 to 130 pM. These results suggest that the combination of dual electrophoresis detection and NP-Ab signal amplification has great potential for future immunoassay systems.
Identification of Methylation-Driven, Differentially Expressed STXBP6 as a Novel Biomarker in Lung Adenocarcinoma
Authors: Lenka Govinda , Tsai Mong-Hsun , Lin Hsin-Chieh , Hsiao Jen-Hao , Lee Yi-Ching , Lu Tzu-Pin , Lee Jang-Ming , Hsu Chung-Ping , Lai Liang-Chuan , Chuang Eric Y.
Published: February 2017

DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ −0.5), corresponding to 17 genes. Examining the endogenous expression in lung cancer cell lines, five of the genes were found to be significantly down-regulated. Furthermore, in tumor cells alone, 5-aza-2′-deoxycytidine treatment increased the expression levels of STXBP6 in a dose dependent manner and pyrosequencing showed higher percentage of methylation in STXBP6 promoter. Functional analysis revealed that overexpressed STXBP6 in A549 and H1299 cells significantly decreased cell proliferation, colony formation, and migration, and increased apoptosis. Finally, significantly lower survival rates (P < 0.05) were observed when expression levels of STXBP6 were low. Our results provide a basis for the genetic etiology of lung adenocarcinoma by demonstrating the possible role of hypermethylation of STXBP6 in poor clinical outcomes in lung cancer patients.
Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction
Authors: Elmonem Mohamed A. , Khalil Ramzi , Khodaparast Ladan , Khodaparast Laleh , Arcolino Fanny O. , Morgan Joseph , Pastore Anna , Tylzanowski Przemko , Ny Annelii , Lowe Martin , de Witte Peter A. , Baelde Hans J. , van den Heuvel Lambertus P. , Levtchenko Elena
Published: February 2017

The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis.
TaWRKY70 transcription factor in wheat QTL-2DL regulates downstream metabolite biosynthetic genes to resist Fusarium graminearum infection spread within spike
Authors: Kage Udaykumar , Yogendra Kalenahalli N. , Kushalappa Ajjamada C.
Published: February 2017

A semi-comprehensive metabolomics was used to identify the candidate metabolites and genes to decipher mechanisms of resistance in wheat near-isogenic lines (NILs) containingQTL-2DLagainstFusarium graminearum (Fg). Metabolites, with high fold-change in abundance, belonging tohydroxycinnamic acid amides (HCAAs): such as coumaroylagmatine, coumaroylputrescine andFatty acids: phosphatidic acids (PAs) were identified as resistance related induced (RRI) metabolites in rachis of resistant NIL (NIL-R), inoculated withFg.A WRKY like transcription factor (TF) was identified within theQTL-2DLregion, along with three resistance genes that biosynthesized RRI metabolites. Sequencing andin-silicoanalysis ofWRKYconfirmed it to be wheatTaWRKY70. Quantitative real time-PCR studies showed a higher expression ofTaWRKY70in NIL-R as compared to NIL-S afterFginoculation. Further, the functional validation ofTaWRKY70based on virus induced gene silencing (VIGS) in NIL-R, not only confirmed an increased fungal biomass but also decreased expressions of downstream resistance genes:TaACT, TaDGKandTaGLI1,along with decreased abundances of RRI metabolites biosynthesized by them. Among more than 200 FHB resistance QTL identified in wheat, this is the first QTL from which a TF was identified, and its downstream target genes as well as the FHB resistance functions were deciphered.
Risk of other Cancers in Families with Melanoma: Novel Familial Links
Authors: Frank Christoph , Sundquist Jan , Hemminki Akseli , Hemminki Kari
Published: February 2017

A family history of cutaneous melanoma (‘melanoma’) is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.
Therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) mice
Authors: Li Jia , Chen Ying , Chen Zhibo , Huang Yuanyuan , Yang Dehao , Su Zhongqian , Weng Yiyun , Li Xiang , Zhang Xu
Published: February 2017

This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels. Transplantation of hADSCs significantly alleviated the body weight loss and neurological function impairment of EAE mice. Inflammatory cell infiltration and demyelination were significantly increased, which were relieved by hADSC transplantation. Moreover, the Th17 cells and the ROR-γt mRNA level were significantly elevated, while the Treg cells and the Foxp3 mRNA level were significantly declined, resulting in significantly increased Th17/Treg ratio. This was reversed by the transplantation of hADSCs. Furthermore, serum levels of IL-17A, IL-6, IL-23, and TGF-β, were significantly increased, which could be influenced by the hADSC transplantation. Transplantation of hADSCs alleviates the neurological function impairment and histological changes, and reduces the inflammatory cell infiltration and demyelination in EAE mice, which might be associated with the regulation of Th17/Treg balance.
Increased nutrient availability in dense breast tissue of postmenopausal women in vivo
Authors: Abrahamsson Annelie , Rzepecka Anna , Dabrosin Charlotta
Published: February 2017

Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.
A cyclometalated iridium(III) complex used as a conductor for the electrochemical sensing of IFN-γ
Authors: Miao Xiangmin , Ko Chung-Nga , Vellaisamy Kasipandi , Li Zongbing , Yang Guanjun , Leung Chung-Hang , Ma Dik-Lung
Published: February 2017

A novel iridium(III) complex was prepared and used as a conductor for sensitive and enzyme-free electrochemical detection of interferon gamma (IFN-γ). This assay is based on a dual signal amplification mechanism involving positively charged gold nanoparticles ((+)AuNPs) and hybridization chain reaction (HCR). To construct the sensor, nafion (Nf) and (+)AuNPs composite membrane was first immobilized onto the electrode surface. Subsequently, a loop-stem structured capture probe (CP) containing a special IFN-γ interact strand was modified onto the (+)AuNP surface via the formation of Au-S bonds. Upon addition of IFN-γ, the loop-stem structure of CP was opened, and the newly exposed “sticky” region of CP then hybridized with DNA hairpin-1 (H1), which in turn opened its hairpin structure for hybridizing with DNA hairpin-2 (H2). Happen of HCR between H1 and H2 thus generated a polymeric duplex DNA (dsDNA) chain. Meanwhile, the iridium(III) complex could interact with the grooves of the dsDNA polymer, producing a strong current signal that was proportional to IFN-γ concentration. Thus, sensitive detection of IFN-γ could be realized with a detection limit down to 16.3 fM. Moreover, satisfied results were achieved by using this method for the detection of IFN-γ in human serum samples.
A Simple Method for Noninvasive Quantification of Pressure Gradient Across the Pulmonary Valve
Authors: Zhou Xueying , Xing Changyang , Feng Yang , Duan Yunyou , Zheng Qiangsun , Wang Zuojun , Liu Jie , Cao Tiesheng , Yuan Lijun
Published: February 2017

Pressure gradient across the pulmonary valve (PVPG) is an important hemodynamic variable used in the management of patients with cardiovascular and pulmonary disease. However, a reliable noninvasive method is unavailable. We hypothesized that a progressive Muller maneuver would elicit the pulmonary valve premature opening (PVPO) in diastole and that this event would be detectable by Doppler echocardiography. The intrathoracic pressure (ITP) decrease during this maneuver equals PVPG, which may be assessed with a custom airway pressure measurement device. A total of 102 subjects were enrolled in the study. At the earliest appearance of PVPO, the ITP decrease was recorded as the PVPG. PVPG was also simultaneously measured and compared by other two methods: right heart catheterization in 43 subjects, and routine Doppler echocardiography (pulmonary regurgitation jet) in the other 59 subjects. The results measured by different approaches were compared using the Bland-Altman analysis. PVPG assessed via PVPO showed strong agreement with PVPG measured by catheterization or routine Doppler echocardiography methods, with Lin concordance correlation coefficients of 0.91 and 0.70, respectively. In conclusion, PVPO provides a new noninvasive method of quantification of PVPG.