bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a dual-wideband monopole antenna by artificial bee colony algorithm for UMTS, WLAN, and WiMAX applications
Authors: Ustun Deniz , Akdagli Ali
Published: December 2016

In this study, a dual-wideband monopole antenna has been designed and developed for the universal mobile telecommunications system (UMTS), wireless local area network (WLAN), and worldwide interoperability for microwave access (WiMAX) applications. A novel approach integrating artificial bee colony (ABC) with the HyperLynx® 3D electromagnetic platform based on the method of moments has been employed to calculate the design parameters of the monopole antenna performance for the respective target frequencies and return loss. The proposed dual-wideband antenna operates in the dual-frequency ranges of 1.69–3.99 and 4.75–6.22 GHz applicable for the UMTS, WLAN, and WiMAX applications and it is fabricated on the flame resistant-4 substrate plate of 42 × 51 × 1.6 mm3. The performance of the presented monopole antenna is analyzed in terms of gain, radiation pattern, and s-parameter. The input reflection coefficient (S11) parameter and radiation pattern of the antenna are verified through the measurements. The measured values of the antenna parameters are found to match well within tolerable limits with the simulation results. The results illustrate that the presented dual-wideband monopole antenna obtained by using the ABC algorithm exhibits better performance in point of operating bands and s-parameter as compared with the multi-band antennas previously published in the literature.
Enduring Mistrust and Conflict Management in Southeast Asia: An Assessment of ASEAN as a Security Community
Authors: Emmers Ralf
Published: December 2016

The paper explores whether the Association of Southeast Asian Nations (ASEAN) has matured from a weak cooperative arrangement in its early days into a functioning security community by 2016. It first introduces a Deutschian and a constructivist understanding of security communities before examining ASEAN's involvement in the security realm since 1967. The paper claims that the regional body is not yet a security community, partly due to residual mistrust among its members, which undermines ASEAN's ability to address a series of ongoing inter-state disputes in Southeast Asia. While it has contributed to conflict avoidance, the Association has so far failed to conduct conflict resolution in spite of the ASEAN Political and Security Community initiative. The paper concludes that the failure to directly address and ultimately resolve sources of conflict in Southeast Asia has undermined the establishment of a security community in the region.
Democratizing Foreign-Policy Making in Indonesia and the Democratization of ASEAN: A Role Theory Analysis
Authors: Rüland Jürgen
Published: December 2016

With the resignation of President Soeharto in 1998 and subsequent democratization, Indonesia's foreign policy underwent major changes. More stakeholders than under Soeharto's New Order regime are now participating in foreign-policy making. The country seemed to make democracy promotion a hallmark of its foreign policy, especially under the presidency of Susilo Bambang Yudhoyono (2004–2014). This raises the questions of whether and, if so, to what extent Indonesian democratization changed the country's established foreign-policy role conceptions and how much impact Indonesia's democratization had on the democratization of regional governance. The paper seeks to answer these questions by developing a theoretical framework based on a constructivist version of role theory. On the basis of speeches held by Indonesian political leaders in the United Nations General Assembly and major domestic foreign-policy pronouncements, it documents changes in Indonesia's foreign-policy role concepts. It shows that, indeed, in theEra Reformasi, democracy became a major component in the country's foreign-policy role concept, although many elements of the role concept such as development orientation, Third Worldism, peace orientation, and a mediator's role remained constant. However, the litmus test for a democracy-oriented foreign policy, that is, the democratization of regional governance in Southeast Asia, remains ambiguous, and concrete policy initiatives often declaratory.
Samuel A. Bowring Receives 2016 Walter H. Bucher Medal
Authors:   AGU
Published: December 2016

Samuel A. Bowring was awarded the 2016 Walter H. Bucher Medal at the American Geophysical Union Fall Meeting Honors Ceremony, held on 14 December 2016 in San Francisco, Calif. The medal is for "original contributions to the basic knowledge of crust and lithosphere."
Major Ocean Circulation Pattern at Risk from Greenland Ice Melt
Authors: Underwood Emily
Published: December 2016

The current warming trend could mean the collapse of ocean's global conveyor belt, which would have far-reaching effects on climate around the world. But this collapse could still be avoided.
Scientists Ponder the Way Forward Under Incoming Administration
Authors: Showstack Randy
Published: December 2016

Eos asked several attendees of the American Geophysical Union's Fall Meeting for reactions to the U.S. national election. Here are their thoughts.
Insane in the membrane: a structural perspective of MLKL function in necroptosis
Authors: Petrie Emma J , Hildebrand Joanne M , Murphy James M
Published: December 2016

Necroptosis (or ‘programmed necrosis’) is a caspase‐independent cell death pathway that operates downstream of death receptors, including Tumour Necrosis Factor Receptor‐1 (TNFR1), and the Toll‐like receptors, TLR3 and TLR4. Owing to its immunogenicity, necroptosis has been attributed roles in the pathogenesis of several diseases, including inflammatory bowel disease and the tissue damage arising from ischaemic‐reperfusion injuries. Only over the past 7 years has the core machinery of this pathway, the receptor‐interacting protein kinase‐3 (RIPK3) and the pseudokinase, Mixed Lineage Kinase domain‐Like (MLKL), been defined. Our current understanding of the pathway is that RIPK3‐mediated phosphorylation activates cytoplasmic MLKL, which is the most terminal known effector in the pathway, leading to MLKL's oligomerisation, translocation to, and permeabilisation of, the plasma membrane. Here, we discuss the insights gleaned from structural and biophysical studies of MLKL and highlight the known unknowns surrounding MLKL's mechanism of action and activation.
Adoptive cellular immunotherapy for virus‐associated cancers: a new paradigm in personalized medicine
Authors: Smith Corey , Khanna Rajiv
Published: December 2016

Persistent viral infections are associated with the majority of human cancers where infectious agents have been recognized as the primary etiological agent. These viruses contribute to the malignant transformation of human cells either through the expression of oncogenic proteins or chronic inflammation. In spite of the high prevalence of these viral infections in humans, only a small proportion of these individuals who may have an underlying immune defect develop malignant disease. Furthermore, many of these viruses have evolved unique mechanisms to avoid the host immune system to successfully establish latent infection with limited gene expression. Technological advances in delineating the role of cellular immune responses in the control of viral infections and ability to rapidly expand these effector cells in vitro have provided an important platform for the development of novel immunotherapeutic strategies to treat virus‐associated cancers. While autologous T cell therapies have provided promising results, development of ‘off‐the‐shelf’ third‐party allogeneic virus‐specific T cell therapies have emerged as powerful tools to treat many of the virus‐associated diseases. It is anticipated that adoptive T cell therapy in combination with newly emerging immune checkpoint inhibitors and therapeutic vaccines will provide opportunities to successfully treat advanced metastatic virus‐associated cancers which are currently not amenable to standard therapeutic strategies.
Observing eruptions of gas-rich compressible magmas from space
Authors: Kilbride Brendan McCormick , Edmonds Marie , Biggs Juliet
Published: December 2016

Observations of volcanoes from space are a critical component of volcano monitoring, but we lack quantitative integrated models to interpret them. The atmospheric sulfur yields of eruptions are variable and not well correlated with eruption magnitude and for many eruptions the volume of erupted material is much greater than the subsurface volume change inferred from ground displacements. Up to now, these observations have been treated independently, but they are fundamentally linked. If magmas are vapour-saturated before eruption, bubbles cause the magma to become more compressible, resulting in muted ground displacements. The bubbles contain the sulfur-bearing vapour injected into the atmosphere during eruptions. Here we present a model that allows the inferred volume change of the reservoir and the sulfur mass loading to be predicted as a function of reservoir depth and the magma’s oxidation state and volatile content, which is consistent with the array of natural data.
A cell-autonomous tumour suppressor role of RAF1 in hepatocarcinogenesis
Authors: Jeric Ines , Maurer Gabriele , Cavallo Anna Lina , Raguz Josipa , Desideri Enrico , Tarkowski Bartosz , Parrini Matthias , Fischer Irmgard , Zatloukal Kurt , Baccarini Manuela
Published: December 2016

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, but its molecular heterogeneity hampers the design of targeted therapies. Currently, the only therapeutic option for advanced HCC is Sorafenib, an inhibitor whose targets include RAF. Unexpectedly, RAF1 expression is reduced in human HCC samples. Modelling RAF1 downregulation by RNAi increases the proliferation of human HCC lines in xenografts and in culture; furthermore, RAF1 ablation promotes chemical hepatocarcinogenesis and the proliferation of cultured (pre)malignant mouse hepatocytes. The phenotypes depend on increased YAP1 expression and STAT3 activation, observed in cultured RAF1-deficient cells, in HCC xenografts, and in autochthonous liver tumours. Thus RAF1, although essential for the development of skin and lung tumours, is a negative regulator of hepatocarcinogenesis. This unexpected finding highlights the contribution of the cellular/tissue environment in determining the function of a protein, and underscores the importance of understanding the molecular context of a disease to inform therapy design.
Local synthesis of dynein cofactors matches retrograde transport to acutely changing demands
Authors: Villarin Joseph M. , McCurdy Ethan P. , Martínez José C. , Hengst Ulrich
Published: December 2016

Cytoplasmic dynein mediates retrograde transport in axons, but it is unknown how its transport characteristics are regulated to meet acutely changing demands. We find that stimulus-induced retrograde transport of different cargos requires the local synthesis of different dynein cofactors. Nerve growth factor (NGF)-induced transport of large vesicles requires local synthesis of Lis1, while smaller signalling endosomes require both Lis1 and p150Glued. Lis1 synthesis is also triggered by NGF withdrawal and required for the transport of a death signal. Association of Lis1 transcripts with the microtubule plus-end tracking protein APC is required for their translation in response to NGF stimulation but not for their axonal recruitment and translation upon NGF withdrawal. These studies reveal a critical role for local synthesis of dynein cofactors for the transport of specific cargos and identify association with RNA-binding proteins as a mechanism to establish functionally distinct pools of a single transcript species in axons.
Folding of xylan onto cellulose fibrils in plant cell walls revealed by solid-state NMR
Authors: Simmons Thomas J. , Mortimer Jenny C. , Bernardinelli Oigres D. , Pöppler Ann-Christin , Brown Steven P. , deAzevedo Eduardo R. , Dupree Ray , Dupree Paul
Published: December 2016

Exploitation of plant lignocellulosic biomass is hampered by our ignorance of the molecular basis for its properties such as strength and digestibility. Xylan, the most prevalent non-cellulosic polysaccharide, binds to cellulose microfibrils. The nature of this interaction remains unclear, despite its importance. Here we show that the majority of xylan, which forms a threefold helical screw in solution, flattens into a twofold helical screw ribbon to bind intimately to cellulose microfibrils in the cell wall. 13C solid-state magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, supported by in silico predictions of chemical shifts, shows both two- and threefold screw xylan conformations are present in fresh Arabidopsis stems. The twofold screw xylan is spatially close to cellulose, and has similar rigidity to the cellulose microfibrils, but reverts to the threefold screw conformation in the cellulose-deficient irx3 mutant. The discovery that induced polysaccharide conformation underlies cell wall assembly provides new principles to understand biomass properties.
Robust fractional quantum Hall effect in the N=2 Landau level in bilayer graphene
Authors: Diankov Georgi , Liang Chi-Te , Amet François , Gallagher Patrick , Lee Menyoung , Bestwick Andrew J. , Tharratt Kevin , Coniglio William , Jaroszynski Jan , Watanabe Kenji , Taniguchi Takashi , Goldhaber-Gordon David
Published: December 2016

The fractional quantum Hall effect is a canonical example of electron–electron interactions producing new ground states in many-body systems. Most fractional quantum Hall studies have focussed on the lowest Landau level, whose fractional states are successfully explained by the composite fermion model. In the widely studied GaAs-based system, the composite fermion picture is thought to become unstable for the N≥2 Landau level, where competing many-body phases have been observed. Here we report magneto-resistance measurements of fractional quantum Hall states in the N=2 Landau level (filling factors 4<|ν|<8) in bilayer graphene. In contrast with recent observations of particle–hole asymmetry in the N=0/N=1 Landau levels of bilayer graphene, the fractional quantum Hall states we observe in the N=2 Landau level obey particle–hole symmetry within the fully symmetry-broken Landau level. Possible alternative ground states other than the composite fermions are discussed.
Multivariate time series analysis on the dynamic relationship between Class B notifiable diseases and gross domestic product (GDP) in China
Authors: Zhang Tao , Yin Fei , Zhou Ting , Zhang Xing-Yu , Li Xiao-Song
Published: December 2016

The surveillance of infectious diseases is of great importance for disease control and prevention, and more attention should be paid to the Class B notifiable diseases in China. Meanwhile, according to the International Monetary Fund (IMF), the annual growth of Chinese gross domestic product (GDP) would decelerate below 7% after many years of soaring. Under such circumstances, this study aimed to answer what will happen to the incidence rates of infectious diseases in China if Chinese GDP growth remained below 7% in the next five years. Firstly, time plots and cross-correlation matrices were presented to illustrate the characteristics of data. Then, the multivariate time series (MTS) models were proposed to explore the dynamic relationship between incidence rates and GDP. Three kinds of MTS models, i.e., vector auto-regressive (VAR) model for original series, VAR model for differenced series and error-correction model (ECM), were considered in this study. The rank of error-correction term was taken as an indicator for model selection. Finally, our results suggested that four kinds of infectious diseases (epidemic hemorrhagic fever, pertussis, scarlet fever and syphilis) might need attention in China because their incidence rates have increased since the year 2010.
The Crystal Structure of Monovalent Streptavidin
Authors: Zhang Min , Biswas Sangita , Deng Wenbin , Yu Hongjun
Published: December 2016

The strong interaction between streptavidin (SA) and biotin is widely utilized in biotechnological applications. A SA variant, monovalent SA, was developed with a single and high affinity biotin-binding site within the intact tetramer. However, its structural characterization remains undetermined. Here, we seek to determine the crystal structure of monovalent SA at 1.7-Å resolution. We show that, in contrast to its ‘close-state’ in the only wild-type subunit, the L3,4 loops of three Dead SA subunits are free from crystal packing and remain in an ‘open state’, stabilized by a consistent H-bonding network involving S52. This H-bonding network also applies to the previously reported open state of the wild-type apo-SA. These results suggest that specific substitutions (N23A/S27D/S45A) at biotin-binding sites stabilize the open state of SA L3,4 loop, thereby further reducing biotin-binding affinity. The general features of the ‘open state’ SA among different SA variants may facilitate its rational design. The structural information of monovalent SA will be valuable for its applications across a wide range of biotechnological areas.
The presence of T cell epitopes is important for induction of antibody responses against antigens directed to DEC205+ dendritic cells
Authors: Amorim Kelly N. S. , Rampazo Eline V. , Antonialli Renan , Yamamoto Marcio M. , Rodrigues Mauricio M. , Soares Irene S. , Boscardin Silvia B.
Published: December 2016

In vivo antigen targeting to dendritic cells (DCs) has been used as a way to improve immune responses. Targeting is accomplished with the use of monoclonal antibodies (mAbs) to receptors present on the DC surface fused with the antigen of interest. An anti-DEC205 mAb has been successfully used to target antigens to the DEC205+CD8α+ DC subset. The administration of low doses of the hybrid mAb together with DC maturation stimuli is able to activate specific T cells and induce production of high antibody titres for a number of different antigens. However, it is still not known if this approach would work with any fused protein. Here we genetically fused the αDEC205 mAb with two fragments (42-kDa and 19-kDa) derived from the ~200 kDa Plasmodium vivax merozoite surface protein 1 (MSP1), known as MSP142 and MSP119, respectively. The administration of two doses of αDEC-MSP142, but not of αDEC-MSP119 mAb, together with an adjuvant to two mouse strains induced high anti-MSP119 antibody titres that were dependent on CD4+ T cells elicited by peptides present in the MSP133 sequence, indicating that the presence of T cell epitopes in antigens targeted to DEC205+ DCs increases antibody responses.
Sustained Elevation of Intraocular Pressure Associated with Intravitreal Administration of Anti-vascular Endothelial Growth Factor: A Systematic Review and Meta-Analysis
Authors: Zhou Yandan , Zhou Minwen , Xia Shigang , Jing Qiancheng , Gao Ling
Published: December 2016

This study aimed to assess whether repetitive intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) cause sustained elevation of intraocular pressure (SE-IOP). We conducted a systematic review and meta-analysis based on five randomized controlled trials (RCTs) assessing 1428 subjects and 17 non-RCTs evaluating 8358 cases. In the RCTs, an increased risk of SE-IOP was found in the anti-VEGF group (summary risk ratio [RR] = 3.00, 95% confidence interval [CI]: 1.63–5.53) compared with the sham injection or laser group. The increased risk of SE-IOP was correlated with follow-up duration (RR = 2.14, 95% CI 0.69–6.57 at 6 months; RR = 3.15, 95% CI 0.99–10.09 at 12 months; RR = 3.48, 95% CI 1.38–8.78 at 23 months). The risk of SE-IOP after non-exclusion of pre-existing glaucoma patients (RR = 3.48, 95% CI 1.38–8.78) was higher than that obtained after excluding pre-existing glaucoma patients (RR = 2.6, 95% CI 1.16–5.81). In non-RCTs, the pooled prevalence of SE-IOP was 4.7% (95% CI 3.7–5.8) regardless of diagnosis criteria. In conclusion, repeated intravitreal injections of anti-VEGF agents cause a 2-fold elevation in SE-IOP risk.
The mechanism of a chitosan-collagen composite film used as biomaterial support for MC3T3-E1 cell differentiation
Authors: Wang Xiaoyan , Wang Gan , Liu Long , Zhang Dongyi
Published: December 2016

Natural composite biomaterials are good structural supports for bone cells to regenerate lost bone. Here, we report that a chitosan-collagen composite film accelerated osteoblast proliferation, differentiation and matrix mineralization in MC3T3-E1 cells. Intriguingly, we observed that the film enhanced the phosphorylation of Erk1/2. We showed that the chitosan-collagen composite film increased the transcriptional activity of Runx2, which is an important factor regulating osteoblast differentiation downstream of phosphorylated Erk1/2. Consistent with this observation, we found that the chitosan-collagen composite film increased the expression of osteoblastic marker genes, includingType I CollagenandRunx2in MC3T3-E1 cells. We conclude that this film promoted osteoblast differentiation and matrix mineralization through an Erk1/2-activated Runx2 pathway. Our findings provide new evidence that chitosan-collagen composites are promising biomaterials for bone tissue engineering in bone defect-related diseases.
Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients
Authors: Li Jing Wei , Chen Yun Dai , Chen Wei Ren , Jing Jing , Liu Jie , Yang Yong Qiang
Published: December 2016

Dipeptidyl peptidase-4 (DPP4) is an important regulator of incretins and inflammation, and it is involved in the pathophysiological process of myocardial infarction (MI). This study investigated the role of plasma DPP4 activity (DPP4a) in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone percutaneous coronary intervention (PCI). We recruited 747 consecutive PCI-treated STEMI patients from a tertiary referral center from January 2014 to October 2015. The outcomes of interest were the rates of no-reflow, in-hospital major adverse cardiac or cerebrovascular events (iMACCE), in-hospital complications (IHC) and in-hospital major bleeding. The DPP4a was lower in STEMI patients compared with the controls (p < 0.0001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with an increased rate of no-reflow events (odds ratio [OR]: 1.07; 95% CI: 1.02–1.11; p < 0.01) and a decreased rate of major bleeding events (OR: 0.90; 95% CI: 0.82–0.98; p = 0.02). There were no associations between DPP4a and either iMACCE or IHC. In conclusions, high levels of DPP4a are independently associated with an increased rate of no-reflow events and a decreased rate of major bleeding events in PCT-treated STEMI patients.
β-subunit myristoylation functions as an energy sensor by modulating the dynamics of AMP-activated Protein Kinase
Authors: Ali Nada , Ling Naomi , Krishnamurthy Srinath , Oakhill Jonathan S. , Scott John W. , Stapleton David I. , Kemp Bruce E. , Anand Ganesh Srinivasan , Gooley Paul R.
Published: December 2016

The heterotrimeric AMP-activated protein kinase (AMPK), consisting of α, β and γ subunits, is a stress-sensing enzyme that is activated by phosphorylation of its activation loop in response to increases in cellular AMP. N-terminal myristoylation of the β-subunit has been shown to suppress Thr172 phosphorylation, keeping AMPK in an inactive state. Here we use amide hydrogen-deuterium exchange mass spectrometry (HDX-MS) to investigate the structural and dynamic properties of the mammalian myristoylated and non-myristoylated inactivated AMPK (D139A) in the presence and absence of nucleotides. HDX MS data suggests that the myristoyl group binds near the first helix of the C-terminal lobe of the kinase domain similar to other kinases. Our data, however, also shows that ATP.Mg2+ results in a global stabilization of myristoylated, but not non-myristoylated AMPK, and most notably for peptides of the activation loop of the α-kinase domain, the autoinhibitory sequence (AIS) and the βCBM. AMP does not have that effect and HDX measurements for myristoylated and non-myristoylated AMPK in the presence of AMP are similar. These differences in dynamics may account for a reduced basal rate of phosphorylation of Thr172 in myristoylated AMPK in skeletal muscle where endogenous ATP concentrations are very high.
Statistically validated network of portfolio overlaps and systemic risk
Authors: Gualdi Stanislao , Cimini Giulio , Primicerio Kevin , Di Clemente Riccardo , Challet Damien
Published: December 2016

Common asset holding by financial institutions (portfolio overlap) is nowadays regarded as an important channel for financial contagion with the potential to trigger fire sales and severe losses at the systemic level. We propose a method to assess the statistical significance of the overlap between heterogeneously diversified portfolios, which we use to build a validated network of financial institutions where links indicate potential contagion channels. The method is implemented on a historical database of institutional holdings ranging from 1999 to the end of 2013, but can be applied to any bipartite network. We find that the proportion of validated links (i.e. of significant overlaps) increased steadily before the 2007–2008 financial crisis and reached a maximum when the crisis occurred. We argue that the nature of this measure implies that systemic risk from fire sales liquidation was maximal at that time. After a sharp drop in 2008, systemic risk resumed its growth in 2009, with a notable acceleration in 2013. We finally show that market trends tend to be amplified in the portfolios identified by the algorithm, such that it is possible to have an informative signal about institutions that are about to suffer (enjoy) the most significant losses (gains).
Height and prevalence of hypertension in a middle-aged and older Chinese population
Authors: Song Lulu , Shen Lijun , Li Hui , Liu Bingqing , Zheng Xiaoxuan , Liang Yuan , Yuan Jing , Wang Youjie
Published: December 2016

Evidence from epidemiological studies reported that height was inversely associated with cardiovascular diseases, but the association between height and hypertension was unclear. The purpose of this study was to explore the association between height and blood pressure or prevalence of hypertension in a middle-aged and older Chinese population. A total of 33,197 participants aged 37 to 94 years were recruited from the Dongfeng-Tongji cohort study in Hubei province, China. All participants completed baseline questionnaires, medical examinations and provided blood samples. Hypertension was define as a systolic blood pressure (SBP) over 140 mmHg or/and a diastolic blood pressure (DBP) over 90 mmHg, or current use of antihypertensive medication, or participants with self-reported physician diagnosis of hypertension. Multivariate linear and logistic regression models were used. The prevalence of hypertension was 69.1% for men and 58.0% for women. Pulse pressure (PP) and SBP, but not DBP decreased linearly with increasing height among men and women. Comparing the highest with the shortest quartile of height, the multivariate-adjusted odds ratios were 0.80 (95% confidence interval, 0.71, 0.91) for men and 0.83 (0.74, 0.92) for women. In conclusion, height was associated with reduced SBP, PP and prevalence of hypertension in a middle-aged and older Chinese population.
Plasmodium falciparum malaria importation from Africa to China and its mortality: an analysis of driving factors
Authors: Lai Shengjie , Wardrop Nicola A. , Huang Zhuojie , Bosco Claudio , Sun Junling , Bird Tomas , Wesolowski Amy , Zhou Sheng , Zhang Qian , Zheng Canjun , Li Zhongjie , Tatem Andrew J. , Yu Hongjie
Published: December 2016

Plasmodium falciparum malaria importation from Africa to China is rising with increasing Chinese overseas investment and international travel. Identifying networks and drivers of this phenomenon as well as the contributors to high case-fatality rate is a growing public health concern to enable efficient response. From 2011–2015, 8653 P. falciparum cases leading to 98 deaths (11.3 per 1000 cases) were imported from 41 sub-Saharan countries into China, with most cases (91.3%) occurring in labour-related Chinese travellers. Four strongly connected groupings of origin African countries with destination Chinese provinces were identified, and the number of imported cases was significantly associated with the volume of air passengers to China (P = 0.006), parasite prevalence in Africa (P < 0.001), and the amount of official development assistance from China (P < 0.001) with investment in resource extraction having the strongest relationship with parasite importation. Risk factors for deaths from imported cases were related to the capacity of malaria diagnosis and diverse socioeconomic factors. The spatial heterogeneity uncovered, principal drivers explored, and risk factors for mortality found in the rising rates of P. falciparum malaria importation to China can serve to refine malaria elimination strategies and the management of cases, and high risk groups and regions should be targeted.
Direct observation of atomic-scale origins of local dissolution in Al-Cu-Mg alloys
Authors: Zhang B. , Wang J. , Wu B. , Oguzie E. E. , Luo K. , Ma X. L.
Published: December 2016

Atomistic chemical inhomogeneities are anticipated to induce dissimilarities in surface potentials, which control corrosion initiation of alloys at the atomic scale. Precise understanding of corrosion is therefore hampered by lack of definite information describing how atomistic heterogeneities regulate the process. Here, using high-angle annular dark-field (HAADF) scanning transmission electron microscope (STEM) and electron energy loss spectroscopy (EELS) techniques, we systematically analyzed the Al20Cu2Mn3second phase of 2024Al and successfully observed that atomic-scale segregation of Cu at defect sites induced preferential dissolution of the adjacent zones. We define an“atomic-scale galvanic cell”, composed of zones rich in Cu and its surrounding matrix. Our findings provide vital information linking atomic-scale microstructure and pitting mechanism, particularly for Al-Cu-Mg alloys. The resolution achieved also enables understanding of dealloying mechanisms and further streamlines our comprehension of the concept of general corrosion.
Electronic Structure of the Kitaev Material α-RuCl3 Probed by Photoemission and Inverse Photoemission Spectroscopies
Authors: Sinn Soobin , Kim Choong Hyun , Kim Beom Hyun , Lee Kyung Dong , Won Choong Jae , Oh Ji Seop , Han Moonsup , Chang Young Jun , Hur Namjung , Sato Hitoshi , Park Byeong-Gyu , Kim Changyoung , Kim Hyeong-Do , Noh Tae Won
Published: December 2016

Recently, α-RuCl3 has attracted much attention as a possible material to realize the honeycomb Kitaev model of a quantum-spin-liquid state. Although the magnetic properties of α-RuCl3 have been extensively studied, its electronic structure, which is strongly related to its Kitaev physics, is poorly understood. Here, the electronic structure of α-RuCl3 was investigated by photoemission (PE) and inverse-photoemission (IPE) spectroscopies. The band gap was directly measured from the PE and IPE spectra and was found to be 1.9 eV, much larger than previously estimated values. Local density approximation (LDA) calculations showed that the on-site Coulomb interaction U could open the band gap without spin-orbit coupling (SOC). However, the SOC should also be incorporated to reproduce the proper gap size, indicating that the interplay between U and SOC plays an essential role. Several features of the PE and IPE spectra could not be explained by the results of LDA calculations. To explain such discrepancies, we performed configuration-interaction calculations for a RuCl63− cluster. The experimental data and calculations demonstrated that the 4d compound α-RuCl3 is a Jeff = 1/2 Mott insulator rather than a quasimolecular-orbital insulator. Our study also provides important physical parameters required for verifying the proposed Kitaev physics in α-RuCl3.
Structure-based rationale for differential recognition of lacto- and neolacto- series glycosphingolipids by the N-terminal domain of human galectin-8
Authors: Bohari Mohammad H. , Yu Xing , Zick Yehiel , Blanchard Helen
Published: December 2016

Glycosphingolipids are ubiquitous cell surface molecules undertaking fundamental cellular processes. Lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are the representative core structures for lacto- and neolacto-series glycosphingolipids. These glycolipids are the carriers to the blood group antigen and human natural killer antigens mainly found on blood cells, and are also principal components in human milk, contributing to infant health. The β-galactoside recognising galectins mediate various cellular functions of these glycosphingolipids. We report crystallographic structures of the galectin-8 N-terminal domain (galectin-8N) in complex with LNT and LNnT. We reveal the first example in which the non-reducing end of LNT binds to the primary binding site of a galectin, and provide a structure-based rationale for the significant ten-fold difference in binding affinities of galectin-8N toward LNT compared to LNnT, such a magnitude of difference not being observed for any other galectin. In addition, the LNnT complex showed that the unique Arg59 has ability to adopt a new orientation, and comparison of glycerol- and lactose-bound galectin-8N structures reveals a minimum atomic framework for ligand recognition. Overall, these results enhance our understanding of glycosphingolipids interactions with galectin-8N, and highlight a structure-based rationale for its significantly different affinity for components of biologically relevant glycosphingolipids.
Axonal branching in lateral olfactory tract is promoted by Nogo signaling
Authors: Iketani Masumi , Yokoyama Takaakira , Kurihara Yuji , Strittmatter Stephen M. , Goshima Yoshio , Kawahara Nobutaka , Takei Kohtaro
Published: December 2016

Mitral cells are major projection neurons of the olfactory bulb (OB) that form an axonal bundle known as the lateral olfactory tract (LOT). After axonal bundle formation, collateral branches sprout from primary axons of the LOT. Recently, we identified LOT usher substance (LOTUS) as an endogenous Nogo receptor-1 (NgR1) antagonist and demonstrated that LOTUS contributes to the formation of the LOT axonal bundle. Immunoblots revealed that the expression level of Nogo-A in the OB developmentally increased during axonal collateral formation. Next, we found that the axonal collateral branches were increased in cultured OB neurons from LOTUS-knockout (KO) mice, whereas they were decreased in cultured OB neurons from NgR1-KO mice. Knockdown of Nogo-A in cultured OB neurons reduced the number of axonal collateral branches, suggesting that endogenous Nogo-A induces axonal branching. Finally, the collateral branches of the LOT were increased in LOTUS-KO mice, whereas those in NgR1-KO mice were decreased. Moreover, the abnormal increase of axonal branching observed in LOTUS-KO mice was rescued in the double mutant of LOTUS- and NgR1-KO mice. These findings suggest that Nogo-A and NgR1 interactions may contribute to axonal branching in LOT development.
Pentacle gold–copper alloy nanocrystals: a new system for entering male germ cells in vitro and in vivo
Authors: Lin Yu , He Rong , Sun Liping , Yang Yushan , Li Wenqing , Sun Fei
Published: December 2016

Gold-based nanocrystals have attracted considerable attention for drug delivery and biological applications due to their distinct shapes. However, overcoming biological barriers is a hard and inevitable problem, which restricts medical applications of nanomaterials in vivo. Seeking for an efficient transportation to penetrate biological barriers is a common need. There are three barriers: blood-testis barrier, blood-placenta barrier, and blood-brain barrier. Here, we pay close attention to the blood-testis barrier. We found that the pentacle gold–copper alloy nanocrystals not only could enter GC-2 cells in vitro in a short time, but also could overcome the blood–testis barrier and enter male germ cells in vivo. Furthermore, we demonstrated that the entrance efficiency would become much higher in the development stages. The results also suggested that the pentacle gold–copper alloy nanocrystals could easier enter to germ cells in the pathological condition. This system could be a new method for theranostics in the reproductive system.
Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits
Authors: Ponsuksili Siriluck , Trakooljul Nares , Hadlich Frieder , Haack Fiete , Murani Eduard , Wimmers Klaus
Published: December 2016

The liver is the central metabolic organ and exhibits fundamental functions in haematological traits. Hepatic expression, haematological, plasma biochemical, and body composition traits were assessed in a porcine model (n = 297) to establish tissue-specific genetic variations that influence the function of immune-metabolism-correlated expression networks. At FDR (false discovery rate) <1%, more than 3,600 transcripts were jointly correlated (r = |0.22–0.48|) with the traits. Functional enrichment analysis demonstrated common links of metabolic and immune traits. To understand how immune and metabolic traits are affected via genetic regulation of gene expression, eQTLs were assessed. 20517 significant (FDR < 5%) eQTLs for 1401 transcripts were identified, among which 443 transcripts were associated with at least one of the examined traits and had cis-eQTL (such as ACO1 (6.52 × 10−7) and SOD1 (6.41 × 10−30). The present study establishes a comprehensive view of hepatic gene activity which links together metabolic and immune traits in a porcine model for medical research.
BTeam, a Novel BRET-based Biosensor for the Accurate Quantification of ATP Concentration within Living Cells
Authors: Yoshida Tomoki , Kakizuka Akira , Imamura Hiromi
Published: December 2016

ATP levels may represent fundamental health conditions of cells. However, precise measurement of intracellular ATP levels in living cells is hindered by the lack of suitable methodologies. Here, we developed a novel ATP biosensor termed “BTeam”. BTeam comprises a yellow fluorescent protein (YFP), the ATP binding domain of the ε subunit of the bacterial ATP synthase, and an ATP-nonconsuming luciferase (NLuc). To attain emission, BTeam simply required NLuc substrate. BTeam showed elevated bioluminescence resonance energy transfer efficiency upon ATP binding, resulted in the emission spectra changes correlating with ATP concentrations. By using values of YFP/NLuc emission ratio to represent ATP levels, BTeam achieved steady signal outputs even though emission intensities were altered. With this biosensor, we succeeded in the accurate quantification of intracellular ATP concentrations of a population of living cells, as demonstrated by detecting the slight distribution in the cytosol (3.7–4.1 mM) and mitochondrial matrix (2.4–2.7 mM) within some cultured cell lines. Furthermore, BTeam allowed continuous tracing of cytosolic ATP levels of the same cells, as well as bioluminescent imaging of cytosolic ATP dynamics within individual cells. This simple and accurate technique should be an effective method for quantitative measurement of intracellular ATP concentrations.
Identification of DEP domain-containing proteins by a machine learning method and experimental analysis of their expression in human HCC tissues
Authors: Liao Zhijun , Wang Xinrui , Zeng Yeting , Zou Quan
Published: December 2016

The Dishevelled/EGL-10/Pleckstrin (DEP) domain-containing (DEPDC) proteins have seven members. However, whether this superfamily can be distinguished from other proteins based only on the amino acid sequences, remains unknown. Here, we describe a computational method to segregate DEPDCs and non-DEPDCs. First, we examined the Pfam numbers of the known DEPDCs and used the longest sequences for each Pfam to construct a phylogenetic tree. Subsequently, we extracted 188-dimensional (188D) and 20D features of DEPDCs and non-DEPDCs and classified them with random forest classifier. We also mined the motifs of human DEPDCs to find the related domains. Finally, we designed experimental verification methods of human DEPDC expression at the mRNA level in hepatocellular carcinoma (HCC) and adjacent normal tissues. The phylogenetic analysis showed that the DEPDCs superfamily can be divided into three clusters. Moreover, the 188D and 20D features can both be used to effectively distinguish the two protein types. Motif analysis revealed that the DEP and RhoGAP domain was common in human DEPDCs, human HCC and the adjacent tissues that widely expressed DEPDCs. However, their regulation was not identical. In conclusion, we successfully constructed a binary classifier for DEPDCs and experimentally verified their expression in human HCC tissues.
Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering
Authors: Hu Fanghao , Lamprecht Michael R. , Wei Lu , Morrison Barclay , Min Wei
Published: December 2016

Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation.
Structural basis of the substrate preference towards CMP for a thymidylate synthase MilA involved in mildiomycin biosynthesis
Authors: Zhao Gong , Chen Cheng , Xiong Wei , Gao Tuling , Deng Zixin , Wu Geng , He Xinyi
Published: December 2016

Modified pyrimidine monophosphates such as methyl dCMP (mdCMP), hydroxymethyl dUMP (hmdUMP) and hmdCMP in some phages are synthesized by a large group of enzymes termed as thymidylate synthases (TS). Thymidylate is a nucleotide required for DNA synthesis and thus TS is an important drug target. In the biosynthetic pathway of the nucleoside fungicide mildiomycin isolated from Streptomyces rimofaciens ZJU5119, a cytidylate (CMP) hydroxymethylase, MilA, catalyzes the conversion of CMP into 5′-hydroxymethyl CMP (hmCMP) with an efficiency (kcat/KM) of 5-fold faster than for deoxycytidylate (dCMP). MilA is thus the first enzyme of the TS superfamily preferring CMP to dCMP. Here, we determined the crystal structures of MilA and its complexes with various substrates including CMP, dCMP and hmCMP. Comparing these structures to those of dCMP hydroxymethylase (CH) from T4 phage and TS from Escherichia coli revealed that two residues in the active site of CH and TS, a serine and an arginine, are respectively replaced by an alanine and a lysine, Ala176 and Lys133, in MilA. Mutation of A176S/K133R of MilA resulted in a reversal of substrate preference from CMP to dCMP. This is the first study reporting the evolution of the conserved TS in substrate selection from DNA metabolism to secondary nucleoside biosynthesis.
New Potassium Sodium Niobate Single Crystal with Thickness-independent High-performance for Photoacoustic Angiography of Atherosclerotic Lesion
Authors: Zhu Benpeng , Zhu Yuhang , Yang Jie , Ou-Yang Jun , Yang Xiaofei , Li Yongxiang , Wei Wei
Published: December 2016

The synthesis of (K0.45Na0.55)0.96Li0.04NbO3 (KNLN) single crystals with a <100>-orientation, using a seed-free solid state crystal growth method, is described here. With the thickness of the crystals decreasing down to the order of tens of micrometers, this new lead-free single crystal exhibits thickness-independent electrical behavior, and maintains superior piezoelectric constant (d33 = 670 pC N−1) and electromechanical coupling factor (kt = 0.55). The successful fabrication of a tiny intravascular photoacoustic probe, with a 1 mm outside diameter, is achieved using a single crystal with a thickness of around 60 μm, in combination with a 200 μm core multimode fiber. Wire phantom photoacoustic images show that the axial resolution and lateral resolution of the single crystal based probe are 60 and 220 μm, respectively. In addition, intravascular photoacoustic imaging of the atherosclerotic lesion of a human artery is presented. In the time-domain and frequency-domain images, calcified regions are clearly distinguishable from surrounding tissue. These interesting results demonstrate that KNN-based lead-free piezoelectric single crystals are a promising candidate to substitute for lead-based piezoelectric materials for photoacoustic imaging in the future.
Cpf1 Is A Versatile Tool for CRISPR Genome Editing Across Diverse Species of Cyanobacteria
Authors: Ungerer Justin , Pakrasi Himadri B.
Published: December 2016

Cyanobacteria are the ideal organisms for the production of a wide range of bioproducts as they can convert CO2 directly into the desired end product using solar energy. Unfortunately, the engineering of cyanobacteria to create efficient cell factories has been impaired by the cumbersome genetic tools that are currently available for these organisms; especially when trying to accumulate multiple modifications. We sought to construct an efficient and precise tool for generating numerous markerless modifications in cyanobacteria using CRISPR technology and the alternative nuclease, Cpf1. In this study we demonstrate rapid engineering of markerless knock-ins, knock-outs and point mutations in each of three model cyanobacteria; Synechococcus, Synechocystis and Anabaena. The markerless nature of cpf1 genome editing will allow for complex genome modification that was not possible with previously existing technology while facilitating the development of cyanobacteria as highly modified biofactories.
Angle- and Polarization-Insensitive Metamaterial Absorber using Via Array
Authors: Lim Daecheon , Lee Dongju , Lim Sungjoon
Published: December 2016

In this paper, we propose an angle- and polarization-insensitive metamaterial absorber. We design a metamaterial unit cell that is based on a split ring cross resonator (SRCR). We observe that the absorption frequency and absorption ratio are insensitive to incident angles when a via array surrounds the SRR. We demonstrate the effect of the via array using full-wave simulations by comparing the absorptivity of the SRCR with and without the via array. Because of the symmetric geometry, we also realize polarization insensitivity. We build the proposed absorber on a printed-circuit-board with 30 × 30 unit cells, and we demonstrate its performance experimentally in free space. Under normal incidence, the fabricated absorber shows 99.6% absorptivity at 11.3 GHz for all polarization angles, while for oblique incidence, the fabricated absorber maintains an absorptivity higher than 90% for incident angles up to 70° and 60° for transverse magnetic (TM) and transverse electric (TE) modes, respectively.