bluuebunny/crossref_metadata_2025 huggingface dataset:
Introducing Procedural Proportionality Review in European Law
Authors: HARBO TOR-INGE
Published: December 2016

Proportionality review has emerged as a multi-purpose, best-practice standard for conflict resolution, and has for this reason been embraced by most constitutional systems worldwide. It is, however, difficult to escape the fact that proportionality review opens up room for judicial discretion. In European Union law, as well as European Convention on Human Rights law, this discretion has provided an activist judiciary with a most powerful tool for facilitating European integration through judicial adjudication. In a number of recent cases, this approach has been criticized. The critique raised reaches beyond the application of the proportionality principle in concrete cases. It also encompasses a critique of the proportionality principle as such, at least the conventional interpretation of the proportionality principle. This, in turn, raises questions concerning the concept of European law, its constitutional quest and even its very legitimacy. In this article the author discusses the legal and political implications of these challenges and proposes a revival of political power at the expense of judicial power. To this effect, the author introduces procedural proportionality review. Procedural proportionality review secures judicial deference, although not judicial abdication, in politically controversial and democratically legitimate cases.
Evolution of interfaces for the non-linear parabolic p-Laplacian type reaction–diffusion equations
Authors: ABDULLA UGUR G. , JELI ROQIA
Published: December 2016

We present a full classification of the short-time behaviour of the interfaces and local solutions to the nonlinear parabolic p-Laplacian type reaction–diffusion equation of non-Newtonian elastic filtration:
$$\begin{equation*}
u_t-\Big(|u_x|^{p-2}u_x\Big)_x+bu^{\beta}=0, \ p>2, \beta >0.
\end{equation*}$$
The interface may expand, shrink, or remain stationary as a result of the competition of the diffusion and reaction terms near the interface, expressed in terms of the parameters p, β, sign b, and asymptotics of the initial function near its support. In all cases, we prove the explicit formula for the interface and the local solution with accuracy up to constant coefficients. The methods of the proof are based on non-linear scaling laws and a barrier technique using special comparison theorems in irregular domains with characteristic boundary curves.
A Meeting That Helped Foster the Acceptance of Global Tectonics
Authors: Rampino Michael
Published: December 2016

Fifty years ago, in the United States added their heft to a theory with profound implications: Earth's ocean crust recycles itself on a global scale, and continents move across the face of the planet.
Phage-inducible islands in the Gram-positive cocci
Authors: Martínez-Rubio Roser , Quiles-Puchalt Nuria , Martí Miguel , Humphrey Suzanne , Ram Geeta , Smyth Davida , Chen John , Novick Richard P , Penadés José R
Published: December 2016

The SaPIs are a cohesive subfamily of extremely common phage-inducible chromosomal islands (PICIs) that reside quiescently at specific att sites in the staphylococcal chromosome and are induced by helper phages to excise and replicate. They are usually packaged in small capsids composed of phage virion proteins, giving rise to very high transfer frequencies, which they enhance by interfering with helper phage reproduction. As the SaPIs represent a highly successful biological strategy, with many natural Staphylococcus aureus strains containing two or more, we assumed that similar elements would be widespread in the Gram-positive cocci. On the basis of resemblance to the paradigmatic SaPI genome, we have readily identified large cohesive families of similar elements in the lactococci and pneumococci/streptococci plus a few such elements in Enterococcus faecalis. Based on extensive ortholog analyses, we found that the PICI elements in the four different genera all represent distinct but parallel lineages, suggesting that they represent convergent evolution towards a highly successful lifestyle. We have characterized in depth the enterococcal element, EfCIV583, and have shown that it very closely resembles the SaPIs in functionality as well as in genome organization, setting the stage for expansion of the study of elements of this type. In summary, our findings greatly broaden the PICI family to include elements from at least three genera of cocci.
Adaptive microwave impedance memory effect in a ferromagnetic insulator
Authors: Lee Hanju , Friedman Barry , Lee Kiejin
Published: December 2016

Adaptive electronics, which are often referred to as memristive systems as they often rely on a memristor (memory resistor), are an emerging technology inspired by adaptive biological systems. Dissipative systems may provide a proper platform to implement an adaptive system due to its inherent adaptive property that parameters describing the system are optimized to maximize the entropy production for a given environment. Here, we report that a non-volatile and reversible adaptive microwave impedance memory device can be realized through the adaptive property of the dissipative structure of the driven ferromagnetic system. Like the memristive device, the microwave impedance of the device is modulated as a function of excitation microwave passing through the device. This kind of new device may not only helpful to implement adaptive information processing technologies, but also may be useful to investigate and understand the underlying mechanism of spontaneous formation of complex and ordered structures.
Serotonergic neuronal death and concomitant serotonin deficiency curb copulation ability of Drosophila platonic mutants
Authors: Yilmazer Yasemin B. , Koganezawa Masayuki , Sato Kosei , Xu Jinhua , Yamamoto Daisuke
Published: December 2016

Drosophila platonic (plt) males court females, but fail to copulate. Here we show that plt is an allele of scribbler (sbb), a BMP signalling component. sbb knockdown in larvae leads to the loss of approximately eight serotonergic neurons, which express the sex-determinant protein Doublesex (Dsx). Genetic deprivation of serotonin (5-HT) from dsx-expressing neurons results in copulation defects. Thus, sbb+ is developmentally required for the survival of a specific subset of dsx-expressing neurons, which support the normal execution of copulation in adults by providing 5-HT. Our study highlights the conserved involvement of serotonergic neurons in the control of copulatory mechanisms and the key role of BMP signalling in the formation of a sex-specific circuitry.
Robust spin-orbit torque and spin-galvanic effect at the Fe/GaAs (001) interface at room temperature
Authors: Chen L. , Decker M. , Kronseder M. , Islinger R. , Gmitra M. , Schuh D. , Bougeard D. , Fabian J. , Weiss D. , Back C. H.
Published: December 2016

Interfacial spin-orbit torques (SOTs) enable the manipulation of the magnetization through in-plane charge currents, which has drawn increasing attention for spintronic applications. The search for material systems providing efficient SOTs, has been focused on polycrystalline ferromagnetic metal/non-magnetic metal bilayers. In these systems, currents flowing in the non-magnetic layer generate—due to strong spin–orbit interaction—spin currents via the spin Hall effect and induce a torque at the interface to the ferromagnet. Here we report the observation of robust SOT occuring at a single crystalline Fe/GaAs (001) interface at room temperature. We find that the magnitude of the interfacial SOT, caused by the reduced symmetry at the interface, is comparably strong as in ferromagnetic metal/non-magnetic metal systems. The large spin-orbit fields at the interface also enable spin-to-charge current conversion at the interface, known as spin-galvanic effect. The results suggest that single crystalline Fe/GaAs interfaces may enable efficient electrical magnetization manipulation.
Randomized phase II trial of fulvestrant alone or in combination with bortezomib in hormone receptor-positive metastatic breast cancer resistant to aromatase inhibitors: a New York Cancer Consortium trial
Authors: Adelson Kerin , Ramaswamy Bhuvaneswari , Sparano Joseph A , Christos Paul J , Wright John J , Raptis George , Han Gang , Villalona-Calero Miguel , Ma Cynthia X , Hershman Dawn , Baar Joseph , Klein Paula , Cigler Tessa , Budd G Thomas , Novik Yelena , Tan Antoinette R , Tannenbaum Susan , Goel Anupama , Levine Ellis , Shapiro Charles L , Andreopoulou Eleni , Naughton Michael , Kalinsky Kevin , Waxman Sam , Germain Doris
Published: December 2016

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A—500 mg intramuscular (i.m.) day −14, 1, 15 in cycle 1, and day 1 of additional cycles) or in combination with bortezomib (Arm B—1.6 mg/m2 intravenous (i.v.) on days 1, 8, 15 of each cycle). The study was powered to show an improvement in median progression-free survival (PFS) from 5.4 to 9.0 months and compare PFS rates at 6 and 12 months (α=0.10, β=0.10). Patients with progression on fulvestrant could cross over to the combination (arm C). Although there was no difference in median PFS (2.7 months in both arms), the hazard ratio for PFS in Arm B versus Arm A (referent) was 0.73 (95% confidence interval (CI)=0.49, 1.09, P=0.06, 1-sided log-rank test, significant at the prespecified 1-sided 0.10 α level). At 12 months, the PFS proportion in Arm A and Arm B was 13.6% and 28.1% (P=0.03, 1-sided χ2-test; 95% CI for difference (14.5%)=−0.06, 29.1%). Of 27 patients on arm A who crossed over to the combination (arm C), 5 (18%) were progression-free for at least 24 weeks. Bortezomib likely enhances the effectiveness of fulvestrant in AI-resistant, ER-positive metastatic breast cancer by reducing acquired resistance, supporting additional evaluation of proteasome inhibitors in combination with SERDs.
Correction: Corrigendum: Structural Stability and Deformation of Solvated Sm@C2(42)-C90 under High Pressure
Authors: Cui Jinxing , Yao Mingguang , Yang Hua , Liu Ziyang , Liu Shijie , Du Mingrun , Li Quanjun , Liu Ran , Cui Tian , Liu Bingbing
Published: December 2016

Scientific Reports 6: Article number: 31213; published online: 09 August 2016; updated: 14 December 2016. The original version of this Article contained an error in the title of the paper. “Structural Stability and Deformation of Solvated Sm@C2(45)-C90 under High Pressure”. should read: “Structural Stability and Deformation of Solvated Sm@C2(42)-C90 under High Pressure”.
Efficacy and safety of endoscopic ultrasonography-guided interventional treatment for refractory malignant left-sided liver tumors: a case series of 26 patients
Authors: Jiang Tian-an , Deng Zhuang , Tian Guo , Zhao Qi-yu , Wang Wei-lin
Published: December 2016

This study aimed to compare the efficacy and safety of EUS-guided ethanol injection and 125I seed brachytherapy for malignant left-sided liver tumors which were difficult for trans-abdominal intervention. The study protocol was registered at Clinicaltrials.gov (NCT02816944). Twenty-six patients were consecutively and prospectively hospitalized for EUS-guided interventional treatment of refractory malignant left-sided liver tumors between June 2014 and June 2016. Liver masses were detected using EUS in 25 of 26 (96.2%) patients. EUS-guided interventional treatment was completed uneventfully in 23 of 26 (88.5%) patients using anhydrous ethanol injection (n = 10) or iodine-125 seed implantation (n = 13). Six months later, complete response was achieved in 15 of 23 (65.2%) patients and partial response in 8 of 23 (34.8%) patients. Patients with tumor residual have second-look EUS-guided interventional treatment (n = 5), radiotherapy (n = 2) or surgical resection (n = 1). Complete response was achieved after repeated interventional treatment in 3 of 5 patients who underwent second EUS-guided intervention; 2 patients required additional surgical resection but one succeed. No significant complications occurred. Therefore EUS-guided 125I seed brachytherapy is an effective and safe treatment modality for radical operation or promising palliative control of malignant left-sided liver tumors refractory to trans-abdominal intervention.
Correction: Corrigendum: Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism
Authors: Liberato Marcelo V. , Silveira Rodrigo L. , Prates Érica T. , de Araujo Evandro A. , Pellegrini Vanessa O. A. , Camilo Cesar M. , Kadowaki Marco A. , Neto Mario de O. , Popov Alexander , Skaf Munir S. , Polikarpov Igor
Published: December 2016

Scientific Reports 6: Article number: 23473; published online: 01 April 2016; updated: 14 December 2016.
Impact of cuticle photoluminescence on the color morphism of a male damselfly Ischnura senegalensis (Rambur, 1842)
Authors: Chuang Chin-Jung , Liu Cheng-Der , Patil Ranjit A. , Wu Chi-Chung , Chang Yao-Chih , Peng Chih-Wen , Chao Ting-Kwuan , Liou Je-Wen , Liou Yung , Ma Yuan-Ron
Published: December 2016

In this study the damselfly Ischnura senegalensis (Rambur, 1842) was first found to produce strong photoluminescence (PL) emissions from various colored-body portions, such as the eighth abdominal segment of the tail. The colors of the colored-body portions can be enhanced or modified by the PL emissions for assistance in reducing intrasexual and male harassment, and improving mature mating and conspecific identity. Therefore, the PL emissions that contribute to the color modification and coloration are involved in the cuticle evolution of the damselflies. The micro-PL confocal images verify that the PL emissions can strongly influence the surface colors of the cuticle, and demonstrate why the damselfly Ischnura senegalensis is called a bluetail.
Electric-field-induced interferometric resonance of a one-dimensional spin-orbit-coupled electron
Authors: Fan Jingtao , Chen Yuansen , Chen Gang , Xiao Liantuan , Jia Suotang , Nori Franco
Published: December 2016

The efficient control of electron spins is of crucial importance for spintronics, quantum metrology, and quantum information processing. We theoretically formulate an electric mechanism to probe the electron spin dynamics, by focusing on a one-dimensional spin-orbit-coupled nanowire quantum dot. Owing to the existence of spin-orbit coupling and a pulsed electric field, different spin-orbit states are shown to interfere with each other, generating intriguing interference-resonant patterns. We also reveal that an in-plane magnetic field does not affect the interval of any neighboring resonant peaks, but contributes a weak shift of each peak, which is sensitive to the direction of the magnetic field. We find that this proposed external-field-controlled scheme should be regarded as a new type of quantum-dot-based interferometry. This interferometry has potential applications in precise measurements of relevant experimental parameters, such as the Rashba and Dresselhaus spin-orbit-coupling strengths, as well as the Landé factor.
Catalyst- and template-free low-temperature in situ growth of n-type CdS nanowire on p-type CdTe film and p-n heterojunction properties
Authors: Ma Ligang , Liu Wenchao , Cai Hongling , Zhang Fengming , Wu Xiaoshan
Published: December 2016

CdS is an important semiconductor used in optoelectronic devices. Simple techniques for growing CdS nanostructures are thus essential at a low cost. This study presents a novel method for growing single-crystal n-type CdS nanowires on p-type CdTe films by thermal annealing in an H2S/N2 mixed gas flow, which does not require the help of a catalyst or template. The formation process and growth mechanism of the nanowires are investigated. Well-dispersed whiskerlike CdS nanostructures are obtained at an appropriate annealing temperature and duration. We suggest that the stress-driving mechanism of nanowire formation may contribute to the growth of CdS nanowires, and that the evaporation of Te through the boundaries of the CdS grain seeds plays an important role in the sustainable growth of nanowire. In addition, CdS/CdTe heterojunction device is fabricated on Mo glass. The I-V characteristic of the heterojunction in dark shows typical rectifying diode behavior. The turn-on voltage can be regulated by annealing conditions. Meanwhile, the obvious photovoltaic effect is obtained on the in situ growth heterojunction prepared at low annealing temperature. Hence, this is a new fabricated method for CdTe-based materials in the field of energy conversion.
Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia
Authors: Weng Ching-Hui , Chung Fa-Po , Chen Yao-Chang , Lin Shien-Fong , Huang Po-Hsun , Kuo Terry B. J. , Hsu Wei-Hsuan , Su Wen-Cheng , Sung Yen-Ling , Lin Yenn-Jiang , Chang Shih-Lin , Lo Li-Wei , Yeh Hung-I , Chen Yi-Jen , Hong Yi-Ren , Chen Shih-Ann , Hu Yu-Feng
Published: December 2016

Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage.
Spatiotemporal analysis with a genetically encoded fluorescent RNA probe reveals TERRA function around telomeres
Authors: Yamada Toshimichi , Yoshimura Hideaki , Shimada Rintaro , Hattori Mitsuru , Eguchi Masatoshi , Fujiwara Takahiro K. , Kusumi Akihiro , Ozawa Takeaki
Published: December 2016

Telomeric repeat-containing RNA (TERRA) controls the structure and length of telomeres through interactions with numerous telomere-binding proteins. However, little is known about the mechanism by which TERRA regulates the accessibility of the proteins to telomeres, mainly because of the lack of spatiotemporal information of TERRA and its-interacting proteins. We developed a fluorescent probe to visualize endogenous TERRA to investigate its dynamics in living cells. Single-particle fluorescence imaging revealed that TERRA accumulated in a telomere-neighboring region and trapped diffusive heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), thereby inhibiting hnRNPA1 localization to the telomere. These results suggest that TERRA regulates binding of hnRNPA1 to the telomere in a region surrounding the telomere, leading to a deeper understanding of the mechanism of TERRA function.
Ultrafast laser induced local magnetization dynamics in Heusler compounds
Authors: Elliott P. , Müller T. , Dewhurst J. K. , Sharma S. , Gross E. K. U.
Published: December 2016

The overarching goal of the field of femtomagnetism is to control, via laser light, the magnetic structure of matter on a femtosecond time scale. The temporal limits to the light-magnetism interaction are governed by the fact that the electron spin interacts indirectly with light, with current studies showing a laser induced global loss in the magnetic moment on a time scale of the order of a few 100 s of femtoseconds. In this work, by means of ab-initio calculations, we show that more complex magnetic materials - we use the example of the Heusler and half-Heusler alloys - allow for purely optical excitations to cause a significant change in the local moments on the order of 5 fs. This, being purely optical in nature, represents the ultimate mechanism for the short time scale manipulation of spins. Furthermore, we demonstrate that qualitative behaviour of this rich magnetic response to laser light can be deduced from the ground-state spectrum, thus providing a route to tailoring the response of some complex magnetic materials, like the Heuslers, to laser light by the well established methods for material design from ground-state calculations.
A Novel Information-Theoretic Approach for Variable Clustering and Predictive Modeling Using Dirichlet Process Mixtures
Authors: Chen Yun , Yang Hui
Published: December 2016

In the era of big data, there are increasing interests on clustering variables for the minimization of data redundancy and the maximization of variable relevancy. Existing clustering methods, however, depend on nontrivial assumptions about the data structure. Note that nonlinear interdependence among variables poses significant challenges on the traditional framework of predictive modeling. In the present work, we reformulate the problem of variable clustering from an information theoretic perspective that does not require the assumption of data structure for the identification of nonlinear interdependence among variables. Specifically, we propose the use of mutual information to characterize and measure nonlinear correlation structures among variables. Further, we develop Dirichlet process (DP) models to cluster variables based on the mutual-information measures among variables. Finally, orthonormalized variables in each cluster are integrated with group elastic-net model to improve the performance of predictive modeling. Both simulation and real-world case studies showed that the proposed methodology not only effectively reveals the nonlinear interdependence structures among variables but also outperforms traditional variable clustering algorithms such as hierarchical clustering.
Highly efficient transduction of primary adult CNS and PNS neurons
Authors: Levin Evgeny , Diekmann Heike , Fischer Dietmar
Published: December 2016

Delivery and expression of recombinant genes, a key methodology for many applications in biological research, remains a challenge especially for mature neurons. Here, we report easy, highly efficient and well tolerated transduction of adult peripheral and central neuronal populations of diverse species in culture using VSV-G pseudo-typed, recombinant baculovirus (BacMam). Transduction rates of up to 80% were reliably achieved at high multiplicity of infection without apparent neuro-cytopathic effects. Neurons could be transduced either shortly after plating or after several days in culture. Co-incubation with two different baculoviruses attained near complete co-localization of fluorescent protein expression, indicating multigene delivery. Finally, evidence for functional protein expression is provided by means of cre-mediated genetic recombination and neurite outgrowth assays. Recombinant protein was already detected within hours after transduction, thereby enabling functional readouts even in relatively short-lived neuronal cultures. Altogether, these results substantiate the usefulness of baculovirus-mediated transduction of mature neurons for future research in neuroscience.
Clinical Association of Chemokine (C-X-C motif) Ligand 1 (CXCL1) with Interstitial Pneumonia with Autoimmune Features (IPAF)
Authors: Liang Minrui , Jiang Zhixing , Huang Qiong , Liu Lei , Xue Yu , Zhu Xiaoxia , Yu Yiyun , Wan Weiguo , Yang Haihua , Zou Hejian
Published: December 2016

The term “interstitial pneumonia with autoimmune features” (IPAF) has been recently proposed. We here investigate the clinical characteristics of IPAF and evaluate the clinical implications of CXCL1-CXCR2 axis in IPAF. An increased plasma level of CXCL1 was exhibited in IPAF compared to idiopathic interstitial pneumonia (IIP), chronic obstructive pulmonary disease (COPD), and healthy controls. Additionally, plasma CXCL1 levels were clinically associated with diffusing capacity of the lungs for carbon monoxide (DLCO), erythrocyte sedimentation rate (ESR), and involved parenchyma extension in IPAF. Furthermore, circulating CXCL1 levels were highest in IPAF patients with acute exacerbations. CXCR2, the chemokine receptor for CXCL1, was readily observed in inflammatory aggregates and endothelial cells in IPAF lungs, but was lower in IIP lungs and healthy lungs. Interestingly, increased CXCL1 concentrations in BALF paralleled neutrophil counts in IPAF. Overall, the plasma concentrations of CXCL1 indicated the disease activity and prognosis in IPAF. Thus, the CXCL1/CXCR2 axis appears to be involved in the progression of IPAF.
Invisibility cloak with image projection capability
Authors: Banerjee Debasish , Ji Chengang , Iizuka Hideo
Published: December 2016

Investigations of invisibility cloaks have been led by rigorous theories and such cloak structures, in general, require extreme material parameters. Consequently, it is challenging to realize them, particularly in the full visible region. Due to the insensitivity of human eyes to the polarization and phase of light, cloaking a large object in the full visible region has been recently realized by a simplified theory. Here, we experimentally demonstrate a device concept where a large object can be concealed in a cloak structure and at the same time any images can be projected through it by utilizing a distinctively different approach; the cloaking via one polarization and the image projection via the other orthogonal polarization. Our device structure consists of commercially available optical components such as polarizers and mirrors, and therefore, provides a significant further step towards practical application scenarios such as transparent devices and see-through displays.
The effect of standardized food intake on the association between BMI and 1H-NMR metabolites
Authors: Schutte Bianca A. M. , van den Akker Erik B. , Deelen Joris , van de Rest Ondine , van Heemst Diana , Feskens Edith J. M. , Beekman Marian , Slagboom P. Eline
Published: December 2016

Multiple studies have shown that levels of 1H-NMR metabolites are associated with disease and risk factors of disease such as BMI. While most previous investigations have been performed in fasting samples, meta-analysis often includes both cohorts with fasting and non-fasting blood samples. In the present study comprising 153 participants (mean age 63 years; mean BMI 27 kg/m2) we analyzed the effect of a standardized liquid meal (SLM) on metabolite levels and how the SLM influenced the association between metabolites and BMI. We observed that many metabolites, including glycolysis related metabolites, multiple amino acids, LDL diameter, VLDL and HDL lipid concentration changed within 35 minutes after a standardized liquid meal (SLM), similarly for all individuals. Remarkable, however, is that the correlations of metabolite levels with BMI remained highly similar before and after the SLM. Hence, as exemplified with the disease risk factor BMI, our results suggest that the applicability of 1H-NMR metabolites as disease biomarkers depends on the standardization of the fasting status rather than on the fasting status itself. Future studies are required to investigate the dependency of metabolite biomarkers for other disease risk factors on the fasting status.
Physics-driven Spatiotemporal Regularization for High-dimensional Predictive Modeling: A Novel Approach to Solve the Inverse ECG Problem
Authors: Yao Bing , Yang Hui
Published: December 2016

This paper presents a novel physics-driven spatiotemporal regularization (STRE) method for high-dimensional predictive modeling in complex healthcare systems. This model not only captures the physics-based interrelationship between time-varying explanatory and response variables that are distributed in the space, but also addresses the spatial and temporal regularizations to improve the prediction performance. The STRE model is implemented to predict the time-varying distribution of electric potentials on the heart surface based on the electrocardiogram (ECG) data from the distributed sensor network placed on the body surface. The model performance is evaluated and validated in both a simulated two-sphere geometry and a realistic torso-heart geometry. Experimental results show that the STRE model significantly outperforms other regularization models that are widely used in current practice such as Tikhonov zero-order, Tikhonov first-order and L1 first-order regularization methods.
Association between sleep duration and cardiac structure in youths at risk for metabolic syndrome
Authors: Feng Dan , Zhang Jihui , Fu Junling , Wu Heng , Wang Yonghui , Li Lujiao , Zhao Yanglu , Li Ming , Gao Shan
Published: December 2016

The evidence for a link between sleep duration and cardiovascular risk is accumulating in youths, but no study has yet investigated the relationship between sleep duration and change of cardiac structure. In this study, we recruited 559 youths aged 14–28 years from the cohort of Beijing Child and Adolescent Metabolic Syndrome Study. Questionnaire, color Doppler echocardiography, oral glucose tolerance test and blood biomarkers analyses were performed. We found that sleep duration was negatively correlated with body mass index, waist circumstance, and HbA1c (all P < 0.05), but not with adiponectin and leptin. Meanwhile, participants with shorter sleep duration (≤7 h) had larger interventricular septal diastolic thickness, left ventricular (LV) end-diastolic diameter, LV posterior wall thickness, LV mass (LVM), and LV mass index (LVMI), compared to participants in 7–9 h/night or >9 h/night group. Findings remained significant after adjustment for the major confounding factors (P < 0.05). Multivariate regression modeling revealed that each additional hour of sleep was associated with smaller LVM (β: −3.483, P < 0.0001) and LVMI (β: −0.815, P < 0.0001). Our findings suggest that short sleep has a possible direct effect on cardiac remodeling, occurring already at young ages.
Imbalanced positive selection maintains the functional divergence of duplicated DIHYDROKAEMPFEROL 4-REDUCTASE genes
Authors: Huang Bing-Hong , Chen Yi-Wen , Huang Chia-Lung , Gao Jian , Liao Pei-Chun
Published: December 2016

Gene duplication could be beneficial by functional division but might increase the risk of genetic load. The dynamics of duplicated paralogs number could involve recombination, positive selection, and functional divergence. Duplication ofDIHYDROFLAVONOL 4-REDUCTASE(DFR) has been reported in several organisms and may have been retained by escape from adaptive conflict (EAC). In this study, we screened the angiospermDFRgene focusing on a diversified genusScutellariato investigate how these duplicated genes are retained. We deduced that gene duplication involved multiple independent events in angiosperms, but the duplication ofDFRwas before the divergence ofScutellaria. Asymmetric positive selective pressures resulted in different evolutionary rates between the duplicates. Different numbers of regulatory elements, differential codon usages, radical amino acid changes, and differential gene expressions provide evidences of functional divergence between the twoDFRduplicates inScutellaria, implying adaptive subfunctionalization between duplicates. The discovery of pseudogenes accompanying a reduced replacement rate in oneDFRparalogous gene suggested possibly leading to “loss of function” due to dosage imbalance after the transient adaptive subfunctionalization in the early stage of duplication. Notwithstanding, episodic gene duplication and functional divergence may be relevant to the diversification of ecological function ofDFRgene inScutellaria.
The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression
Authors: Park Cho Rong , You Dong-Joo , Park Sumi , Mander Sunam , Jang Da-Eun , Yeom Su-Cheong , Oh Seong-Hyun , Ahn Curie , Lee Sang Heon , Seong Jae Young , Hwang Jong-Ik
Published: December 2016

Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins.
Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma
Authors: Marko Tracy A. , Shamsan Ghaidan A. , Edwards Elizabeth N. , Hazelton Paige E. , Rathe Susan K. , Cornax Ingrid , Overn Paula R. , Varshney Jyotika , Diessner Brandon J. , Moriarity Branden S. , O’Sullivan M. Gerard , Odde David J. , Largaespada David A.
Published: December 2016

Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2. Proliferation, migration, and anchorage independent growth were evaluated. RNA sequencing and immunohistochemistry of human osteosarcoma tissue samples were used to further evaluate the potential role of the Slit-Robo pathway in osteosarcoma. The effects of Srgap2 expression modulation in the murine OS cell lines support the hypothesis that SRGAP2 may have a role as a suppressor of metastases in osteosarcoma. Additionally, SRGAP2 and other genes in the Slit-Robo pathway have altered transcript levels in a subset of mouse and human osteosarcoma, and SRGAP2 protein expression is reduced or absent in a subset of primary tumor samples. SRGAP2 and other axon guidance proteins likely play a role in osteosarcoma metastasis, with loss of SRGAP2 potentially contributing to a more aggressive phenotype.
Sex differences in number processing: Differential systems for subtraction and multiplication were confirmed in men, but not in women
Authors: Pletzer Belinda
Published: December 2016

Neuroimaging studies suggest segregated neuronal systems underlying number magnitude processing (e.g. subtraction) and arithmetic fact retrieval (e.g. multiplication). While number magnitude processing is thought to rely on the intraparietal sulcus (IPS) bilaterally, arithmetic fact retrieval is thought to rely on the left angular gyrus (AG). However, evidence from brain damaged patients and brain stimulation challenges this view and suggests considerable overlap between the systems underlying number magnitude processing and arithmetic fact retrieval. This study investigates, whether sex differences in number processing can account for these conflicting findings. A subtraction and a multiplication task were administered to 40 men and 34 women in their luteal phase during functional MRI. Replicating previous studies in men, we found the IPS to be more strongly activated during subtraction than multiplication, and the AG to be more strongly activated during multiplication than subtraction. However, no differences between the two tasks were observed in women.
Effectiveness and Safety of Transcatheter Patent Foramen Ovale Closure for Migraine (EASTFORM) Trial
Authors: Xing Ying-qi , Guo Yu-Zhu , Gao Yong-Sheng , Guo Zhen-Ni , Niu Peng-Peng , Yang Yi
Published: December 2016

We evaluated the safety and effectiveness of transcatheter patent foramen ovale (PFO) closure for the treatment of migraine in a Chinese population. This non-randomized clinical trial enrolled 258 consecutive substantial or severe migraineurs with a right-to-left shunt (RLS) (grade II–IV) and grouped subjects according to their election or refusal of PFO closure. Migraine was diagnosed according to the International Classification of Headache Disorders III-beta and evaluated using the Headache Impact Test-6 (HIT-6). In total, 241 participants (125 in the transcatheter closure group and 116 in the control group) were included in the study. In general, the PFO closure procedure was found to be safe. At 1 month after closure, 76.1% of patients returned for c-TCD evaluation; of these, 85.7% were downgraded to negative status or a grade-I shunt. Residual shunts and placebo effects were thought to resolve by 12 months post-procedure, when migraine impact was reported to decrease by 73.6%. Transcatheter PFO closure was demonstrated to be effective for the treatment of migraine by comparing HIT-6 scores between the transcatheter closure and control groups (p < 0.001). Our results suggest that transcatheter PFO closure is a safe and effective approach for the treatment of migraine in the Chinese population, especially in females with constant RLS. Clinical trial no. NCT02127294 (registered on April 29, 2014).
Diagnostic test accuracy of loop-mediated isothermal amplification assay for Mycobacterium tuberculosis: systematic review and meta-analysis
Authors: Nagai Kenjiro , Horita Nobuyuki , Yamamoto Masaki , Tsukahara Toshinori , Nagakura Hideyuki , Tashiro Ken , Shibata Yuji , Watanabe Hiroki , Nakashima Kentaro , Ushio Ryota , Ikeda Misako , Narita Atsuya , Kanai Akinori , Sato Takashi , Kaneko Takeshi
Published: December 2016

Diagnostic test accuracy of the loop-mediated isothermal amplification (LAMP) assay for culture proven tuberculosis is unclear. We searched electronic databases for both cohort and case-control studies that provided data to calculate sensitivity and specificity. The index test was any LAMP assay including both commercialized kits and in-house assays. Culture-proven M. tuberculosis was considered a positive reference test. We included 26 studies on 9330 sputum samples and one study on 315 extra-pulmonary specimens. For sputum samples, 26 studies yielded the summary estimates of sensitivity of 89.6% (95% CI 85.6–92.6%), specificity of 94.0% (95% CI 91.0–96.1%), and a diagnostic odds ratio of 145 (95% CI 93–226). Nine studies focusing on Loopamp MTBC yielded the summary estimates of sensitivity of 80.9% (95% CI 76.0–85.1%) and specificity of 96.5% (95% CI 94.7–97.7%). Loopamp MTBC had higher sensitivity and lower specificity for smear-positive sputa compared to smear-negative sputa. In-house assays showed higher sensitivity and lower specificity compared to Loopamp MTBC. LAMP promises to be a useful test for the diagnosis of TB, however there is still need to improve the assay to make it simpler, cheaper and more efficient to make it competitive against other PCR methods already available.
Enhanced Lithium Storage in Hierarchically Porous Carbon Derived from Waste Tea Leaves
Authors: Choi Changhoon , Seo Seung-Deok , Kim Byung-Kook , Kim Dong-Wan
Published: December 2016

In this study, highly nanoporous carbon (HCl-TW-Car) was successfully synthesized using a facile procedure combining acid treatment with a carbonization process that uses waste tea leaves from spent tea bags as raw materials. The acid treatment not only promotes the efficient removal of unnecessary inorganic impurities but also increases the product porosity to enable synthesis of hierarchically porous carbon materials with various micro-, meso-, and macropores. When used as an anode material for lithium-ion batteries, HCl-TW-Car demonstrated a much higher discharge capacity than is theoretically possible using graphite [479 mAh g−1 after the 200th cycle at a rate of 0.2C (1C = 372 mA g−1)] and exhibited greater rate capabilities compared with those of carbonated products from tea waste without acid treatment. It was shown that the good electrochemical properties of HCl-TW-Car can be ascribed to large Brunauer–Emmett–Teller (BET) surface area, well-formed hierarchical pores, and the prevention of unexpected electrochemical reactions from the reduction of metallic atoms.
The hepatic and skeletal muscle ovine metabolomes as affected by weight loss: a study in three sheep breeds using NMR-metabolomics
Authors: Palma Mariana , Scanlon Tim , Kilminster Tanya , Milton John , Oldham Chris , Greeff Johan , Matzapetakis Manolis , Almeida André M.
Published: December 2016

Sheep are a valuable resource for meat and wool production. During the dry summer, pastures are scarce and animals face Seasonal Weight Loss (SWL), which decreases production yields. The study of breeds tolerant to SWL is important to understand the physiological mechanisms of tolerance to nutritional scarcity, and define breeding strategies. Merino, Damara and Dorper sheep breeds have been described as having different levels of tolerance to SWL. In this work, we assess their liver and muscle metabolomes, and compare the responses to feed restriction. Ram lambs from each breed were divided into growth and feed restricted groups, over 42 days. Tissue metabolomes were assessed by 1H-NMR. The Dorper restricted group showed few changes in both tissues, suggesting higher tolerance to nutritional scarcity. The Merinos exhibited more differences between treatment groups. Major differences were related to fat and protein mobilization, and antioxidant activity. Between the Damara groups, the main differences were observed in amino acid composition in muscle and in energy-related pathways in the liver. Integration of present results and previous data on the same animals support the hypothesis that, Dorper and Damara breeds are more tolerant to SWL conditions and thus, more suitable breeds for harsh environmental conditions.
Combination of dynamic transformation and dynamic recrystallization for realizing ultrafine-grained steels with superior mechanical properties
Authors: Zhao Lijia , Park Nokeun , Tian Yanzhong , Shibata Akinobu , Tsuji Nobuhiro
Published: December 2016

Dynamic recrystallization (DRX) is an important grain refinement mechanism to fabricate steels with high strength and high ductility (toughness). The conventional DRX mechanism has reached the limitation of refining grains to several microns even though employing high-strain deformation. Here we show a DRX phenomenon occurring in the dynamically transformed (DT) ferrite, by which the required strain for the operation of DRX and the formation of ultrafine grains is significantly reduced. The DRX of DT ferrite shows an unconventional temperature dependence, which suggests an optimal condition for grain refinement. We further show that new strategies for ultra grain refinement can be evoked by combining DT and DRX mechanisms, based on which fully ultrafine microstructures having a mean grain size down to 0.35 microns can be obtained without high-strain deformation and exhibit superior mechanical properties. This study will open the door to achieving optimal grain refinement to nanoscale in a variety of steels requiring no high-strain deformation in practical industrial application.
Harman Measurements for Thermoelectric Materials and Modules under Non-Adiabatic Conditions
Authors: Roh Im-Jun , Lee Yun Goo , Kang Min-Su , Lee Jae-Uk , Baek Seung-Hyub , Kim Seong Keun , Ju Byeong-Kwon , Hyun Dow-Bin , Kim Jin-Sang , Kwon Beomjin
Published: December 2016

Accuracy of the Harman measurement largely depends on the heat transfer between the sample and its surroundings, so-called parasitic thermal effects (PTEs). Similar to the material evaluations, measuring thermoelectric modules (TEMs) is also affected by the PTEs especially when measuring under atmospheric condition. Here, we study the correction methods for the Harman measurements with systematically varied samples (both bulk materials and TEMs) at various conditions. Among several PTEs, the heat transfer via electric wires is critical. Thus, we estimate the thermal conductance of the electric wires, and correct the measured properties for a certain sample shape and measuring temperature. The PTEs are responsible for the underestimation of the TEM properties especially under atmospheric conditions (10–35%). This study will be useful to accurately characterize the thermoelectric properties of materials and modules.
Modeling quorum sensing trade-offs between bacterial cell density and system extension from open boundaries
Authors: Marenda Mattia , Zanardo Marina , Trovato Antonio , Seno Flavio , Squartini Andrea
Published: December 2016

Bacterial communities undergo collective behavioural switches upon producing and sensing diffusible signal molecules; a mechanism referred to as Quorum Sensing (QS). Exemplarily, biofilm organic matrices are built concertedly by bacteria in several environments. QS scope in bacterial ecology has been debated for over 20 years. Different perspectives counterpose the role of density reporter for populations to that of local environment diffusivity probe for individual cells. Here we devise a model system where tubes of different heights contain matrix-embedded producers and sensors. These tubes allow non-limiting signal diffusion from one open end, thereby showing that population spatial extension away from an open boundary can be a main critical factor in QS. Experimental data, successfully recapitulated by a comprehensive mathematical model, demonstrate how tube height can overtake the role of producer density in triggering sensor activation. The biotic degradation of the signal is found to play a major role and to be species-specific and entirely feedback-independent.
Spatial distribution of planktonic bacterial and archaeal communities in the upper section of the tidal reach in Yangtze River
Authors: Fan Limin , Song Chao , Meng Shunlong , Qiu Liping , Zheng Yao , Wu Wei , Qu Jianhong , Li Dandan , Zhang Cong , Hu Gengdong , Chen Jiazhang
Published: December 2016

Bacterioplankton and archaeaplankton communities play key roles in the biogeochemical processes of water, and they may be affected by many factors. In this study, we used high-throughput 16S rRNA gene sequencing to profile planktonic bacterial and archaeal community compositions in the upper section of the tidal reach in Yangtze River. We found that the predominant bacterial phyla in this river section were Proteobacteria, Firmicutes, and Actinobacteria, whereas the predominant archaeal classes were Halobacteria, Methanomicrobia, and unclassified Euryarchaeota. Additionally, the bacterial and archaeal community compositions, richnesses, functional profiles, and ordinations were affected by the spatial heterogeneity related to the concentration changes of sulphate or nitrate. Notably, the bacterial community was more sensitive than the archaeal community to changes in the spatial characteristics of this river section. These findings provide important insights into the distributions of bacterial and archaeal communities in natural water habitats.