bluuebunny/crossref_metadata_2025 huggingface dataset:
DMP III: Pleistocene and Holocene palaeonvironments and prehistoric occupation of Fazzan, Libyan Sahara
Authors: Lahr Marta Mirazón , Foley Robert , Armitage Simon , Barton Huw , Crivellaro Federica , Drake Nicholas , Hounslow Mark , Maher Lisa , Mattingly David , Salem Mustapha , Stock Jay , White Kevin
Published: February 2016

The palaeoanthropological and geomorphological sub-projects of the Desert Migrations Project (DMP) focus on the Pleistocene and early Holocene environment and prehistory of Fazzan so as to assess the timing and extent of hominin and human movement across the Sahara through time. This paper reports on the findings of the 2008 field season, with a focus on the prehistoric evidence along the northern margin of the Ubari sand sea.

The geomorphological record of the area preserves evidence of at least five past episodes of lake formation. The exact chronology of these, as well as the spatial extent of these lakes, remains the focus of further study.

The archaeological record of hominin and human occupation of Fazzan prior to the establishment of the Garamantian civilisation is extraordinarily rich. Between 2007 and 2008, the DMP palaeoanthropological project surveyed thirty-five localities along the northern margin of the Ubari sand sea, recording a range of assemblages spanning all Palaeolithic industries. Most of the archaeological remains found consisted of stone-tools, while grinding stones were comparatively restricted geographically. Mode 1/Oldowan tools were found at two localities, contrasting with the widespread presence of Mode 2/Acheulean, Mode 3/Middle Stone Age and Mode 5/microlithic artefacts. This indicates that, although hominin presence in the area is probably earlier than previously thought, populations were comparatively sparse until the Middle Pleistocene. Twenty-one localities within the Ubari sand sea, as well as seven south of the Messak Settafet were also surveyed between 2007 and 2008. The detailed study of the lithics from these areas will be carried out next year, but preliminary results stress the different nature of the assemblages found within interdune corridors — very low frequency of cores, no Mode 1 and extremely rare Mode 2 lithics (found at a single locality).

The 2009 field season will focus on obtaining further samples of palaeolake sediments for dating, on the evidence of Mode 1 assemblages south of the Messak, as well as on the refining of the archaeological indicators that may distinguish the different phases of hominin and human occupation of Fazzan during the Later Pleistocene and Holocene.
EFFICIENT ESTIMATION USING THE CHARACTERISTIC FUNCTION
Authors: Carrasco Marine , Kotchoni Rachidi
Published: February 2016

The method of moments procedure proposed by Carrasco and Florens (2000) permits full exploitation of the information contained in the characteristic function and yields an estimator which is asymptotically as efficient as the maximum likelihood estimator. However, this estimation procedure depends on a regularization or tuning parameterαthat needs to be selected. The aim of the present paper is to provide a way to optimally chooseαby minimizing the approximate mean square error (AMSE) of the estimator. Following an approach similar to that of Donald and Newey (2001), we derive a higher-order expansion of the estimator from which we characterize the finite sample dependence of the AMSE onα. We propose to select the regularization parameter by minimizing an estimate of the AMSE. We show that this procedure delivers a consistent estimator ofα. Moreover, the data-driven selection of the regularization parameter preserves the consistency, asymptotic normality, and efficiency of the CGMM estimator. Simulation experiments based on a CIR model show the relevance of the proposed approach.
A variant of the Bombieri–Vinogradov theorem in short intervals and some questions of Serre
Authors: THORNER JESSE
Published: February 2016

We generalise the classical Bombieri–Vinogradov theorem for short intervals to a non-abelian setting. This leads to variants of the prime number theorem for short intervals where the primes lie in arithmetic progressions that are “twisted” by a splitting condition in a Galois extension of number fields. Using this result in conjunction with the recent work of Maynard, we prove that rational primes with a given splitting condition in a Galois extensionL/$\mathbb{Q}$exhibit bounded gaps in short intervals. We explore several arithmetic applications related to questions of Serre regarding the non-vanishing Fourier coefficients of cuspidal modular forms. One such application is that for a given modularL-functionL(s, f), the fundamental discriminantsdfor which thed-quadratic twist ofL(s, f) has a non-vanishing central critical value exhibit bounded gaps in short intervals.
Trajectories of emotional–behavioral difficulty and academic competence: A 6-year, person-centered, prospective study of affluent suburban adolescents
Authors: Ansary Nadia S. , McMahon Thomas J. , Luthar Suniya S.
Published: February 2016

This longitudinal study of affluent suburban youth (N= 319) tracked from 6th to 12th grade is parsed into two segments examining prospective associations concerning emotional–behavioral difficulties and academic achievement. In Part 1 of the investigation, markers of emotional–behavioral difficulty were used to cluster participants during 6th grade. Generalized estimating equations were then used to document between-cluster differences in academic competence from 6th to 12th grade. In Part 2 of the study, indicators of academic competence were used to cluster the same students during 6th grade, and generalized estimating equations were used to document between-cluster differences in emotional–behavioral difficulty from 6th to 12th grade. The results from Part 1 indicated that patterns of emotional–behavioral difficulty during 6th grade were concurrently associated with poorer grades and classroom adjustment with some group differences in the rate of change in classroom adjustment over time. In Part 2, patterns of academic competence during 6th grade were concurrently associated with less emotional–behavioral difficulty and some group differences in the rate of change in specific forms of emotional–behavioral difficulty over time. These results suggest that the youth sampled appeared relatively well adjusted and any emotional–behavioral–achievement difficulty that was evident at the start of middle school was sustained through the end of high school.
Vulnerable Populations in Hospital and Health Care Emergency Preparedness Planning: A Comprehensive Framework for Inclusion
Authors: Kreisberg Debra , Thomas Deborah S.K. , Valley Morgan , Newell Shannon , Janes Enessa , Little Charles
Published: February 2016

Introduction

As attention to emergency preparedness becomes a critical element of health care facility operations planning, efforts to recognize and integrate the needs of vulnerable populations in a comprehensive manner have lagged. This not only results in decreased levels of equitable service, but also affects the functioning of the health care system in disasters. While this report emphasizes the United States context, the concepts and approaches apply beyond this setting.

Objective

This report: (1) describes a conceptual framework that provides a model for the inclusion of vulnerable populations into integrated health care and public health preparedness; and (2) applies this model to a pilot study.

Methods

The framework is derived from literature, hospital regulatory policy, and health care standards, laying out the communication and relational interfaces that must occur at the systems, organizational, and community levels for a successful multi-level health care systems response that is inclusive of diverse populations explicitly. The pilot study illustrates the application of key elements of the framework, using a four-pronged approach that incorporates both quantitative and qualitative methods for deriving information that can inform hospital and health facility preparedness planning.

Conclusions

The conceptual framework and model, applied to a pilot project, guide expanded work that ultimately can result in methodologically robust approaches to comprehensively incorporating vulnerable populations into the fabric of hospital disaster preparedness at levels from local to national, thus supporting best practices for a community resilience approach to disaster preparedness.

KreisbergD, ThomasDSK, ValleyM, NewellS, JanesE, LittleC. Vulnerable populations in hospital and health care emergency preparedness planning: a comprehensive framework for inclusion. Prehosp Disaster Med. 2016;31(2):211–219.
Women, Physical Activity, and Quality of Life: Self-concept as a Mediator
Authors: Gonzalo Silvestre Tamara , Ubillos Landa Silvia
Published: February 2016

The objectives of this research are: (a) analyze the incremental validity of physical activity’s (PA) influence on perceived quality of life (PQL); (b) determine if PA’s predictive power is mediated by self-concept; and (c) study if results vary according to a unidimensional or multidimensional approach to self-concept measurement. The sample comprised 160 women from Burgos, Spain aged 18 to 45 years old. Non-probability sampling was used. Two three-step hierarchical regression analyses were applied to forecast PQL. The hedonic quality-of-life indicators, self-concept, self-esteem, and PA were included as independent variables. The first regression analysis included global self-concept as predictor variable, while the second included its five dimensions. Two mediation analyses were conducted to see if PA’s ability to predict PQL was mediated by global and physical self-concept. Results from the first regression shows that self-concept, satisfaction with life, and PA were significant predictors. PA slightly but significantly increased explained variance in PQL (2.1%). In the second regression, substituting global self-concept with its five constituent factors, only the physical dimension and satisfaction with life predicted PQL, while PA ceased to be a significant predictor. Mediation analysis revealed that only physical self-concept mediates the relationship between PA and PQL (z = 1.97, p < .050), and not global self-concept. Physical self-concept was the strongest predictor and approximately 32.45 % of PA’s effect on PQL was mediated by it. This study’s findings support a multidimensional view of self-concept, and represent a more accurate image of the relationship between PQL, PA, and self-concept.
Frequency comb transferred by surface plasmon resonance
Authors: Geng Xiao Tao , Chun Byung Jae , Seo Ji Hoon , Seo Kwanyong , Yoon Hana , Kim Dong-Eon , Kim Young-Jin , Kim Seungchul
Published: February 2016

Frequency combs, millions of narrow-linewidth optical modes referenced to an atomic clock, have shown remarkable potential in time/frequency metrology, atomic/molecular spectroscopy and precision LIDARs. Applications have extended to coherent nonlinear Raman spectroscopy of molecules and quantum metrology for entangled atomic qubits. Frequency combs will create novel possibilities in nano-photonics and plasmonics; however, its interrelation with surface plasmons is unexplored despite the important role that plasmonics plays in nonlinear spectroscopy and quantum optics through the manipulation of light on a subwavelength scale. Here, we demonstrate that a frequency comb can be transformed to a plasmonic comb in plasmonic nanostructures and reverted to the original frequency comb without noticeable degradation of <6.51 × 10−19 in absolute position, 2.92 × 10−19 in stability and 1 Hz in linewidth. The results indicate that the superior performance of a well-defined frequency comb can be applied to nanoplasmonic spectroscopy, quantum metrology and subwavelength photonic circuits.
Rapid and continuous activity-dependent plasticity of olfactory sensory input
Authors: Cheetham Claire E. J. , Park Una , Belluscio Leonardo
Published: February 2016

Incorporation of new neurons enables plasticity and repair of circuits in the adult brain. Adult neurogenesis is a key feature of the mammalian olfactory system, with new olfactory sensory neurons (OSNs) wiring into highly organized olfactory bulb (OB) circuits throughout life. However, neither when new postnatally generated OSNs first form synapses nor whether OSNs retain the capacity for synaptogenesis once mature, is known. Therefore, how integration of adult-born OSNs may contribute to lifelong OB plasticity is unclear. Here, we use a combination of electron microscopy, optogenetic activation and in vivo time-lapse imaging to show that newly generated OSNs form highly dynamic synapses and are capable of eliciting robust stimulus-locked firing of neurons in the mouse OB. Furthermore, we demonstrate that mature OSN axons undergo continuous activity-dependent synaptic remodelling that persists into adulthood. OSN synaptogenesis, therefore, provides a sustained potential for OB plasticity and repair that is much faster than OSN replacement alone.
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
Authors: Sancho-Martinez Ignacio , Nivet Emmanuel , Xia Yun , Hishida Tomoaki , Aguirre Aitor , Ocampo Alejandro , Ma Li , Morey Robert , Krause Marie N. , Zembrzycki Andreas , Ansorge Olaf , Vazquez-Ferrer Eric , Dubova Ilir , Reddy Pradeep , Lam David , Hishida Yuriko , Wu Min-Zu , Esteban Concepcion Rodriguez , O’Leary Dennis , Wahl Geoffrey M. , Verma Inder M. , Laurent Louise C. , Izpisua Belmonte Juan Carlos
Published: February 2016

Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis.
Wavefront shaping through emulated curved space in waveguide settings
Authors: Sheng Chong , Bekenstein Rivka , Liu Hui , Zhu Shining , Segev Mordechai
Published: February 2016

The past decade has witnessed remarkable progress in wavefront shaping, including shaping of beams in free space, of plasmonic wavepackets and of electronic wavefunctions. In all of these, the wavefront shaping was achieved by external means such as masks, gratings and reflection from metasurfaces. Here, we propose wavefront shaping by exploiting general relativity (GR) effects in waveguide settings. We demonstrate beam shaping within dielectric slab samples with predesigned refractive index varying so as to create curved space environment for light. We use this technique to construct very narrow non-diffracting beams and shape-invariant beams accelerating on arbitrary trajectories. Importantly, the beam transformations occur within a mere distance of 40 wavelengths, suggesting that GR can inspire any wavefront shaping in highly tight waveguide settings. In such settings, we demonstrate Einstein’s Rings: a phenomenon dating back to 1936.
Understanding cachexia as a cancer metabolism syndrome
Authors: Porporato P E
Published: February 2016

Metabolic reprogramming occurs in tumors to foster cancer cell proliferation, survival and metastasis, but as well at a systemic level affecting the whole organism, eventually leading to cancer cachexia. Indeed, as cancer cells rely on external sources of nitrogen and carbon skeleton to grow, systemic metabolic deregulation promoting tissue wasting and metabolites mobilization ultimately supports tumor growth. Cachectic patients experience a wide range of symptoms affecting several organ functions such as muscle, liver, brain, immune system and heart, collectively decreasing patients’ quality of life and worsening their prognosis. Moreover, cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The main aspect of cachexia syndrome is the unstoppable skeletal muscle and fat storage wasting, even with an adequate caloric intake, resulting in nutrient mobilization – both directly as lipid and amino acids and indirectly as glucose derived from the exploitation of liver gluconeogenesis – that reaches the tumor through the bloodstream. From a metabolic standpoint, cachectic host develops a wide range of dysfunctions, from increased insulin and IGF-1 resistance to induction of mitochondrial uncoupling proteins and fat tissue browning resulting in an increased energy expenditure and heat generation, even at rest. For a long time, cachexia has been merely considered an epiphenomenon of end-stage tumors. However, in specific tumor types, such as pancreatic cancers, it is now clear that patients present markers of tissue wasting at a stage in which tumor is not yet clinically detectable, and that host amino acid supply is required for tumor growth. Indeed, tumor cells actively promote tissue wasting by secreting specific factors such as parathyroid hormone-related protein and micro RNAs. Understanding the molecular and metabolic mediators of cachexia will not only advance therapeutic approaches against cancer, but also improve patients’ quality of life.
PAX6 Isoforms, along with Reprogramming Factors, Differentially Regulate the Induction of Cornea-specific Genes
Authors: Sasamoto Yuzuru , Hayashi Ryuhei , Park Sung-Joon , Saito-Adachi Mihoko , Suzuki Yutaka , Kawasaki Satoshi , Quantock Andrew J. , Nakai Kenta , Tsujikawa Motokazu , Nishida Kohji
Published: February 2016

PAX6 is the key transcription factor involved in eye development in humans, but the differential functions of the two PAX6 isoforms, isoform-a and isoform-b, are largely unknown. To reveal their function in the corneal epithelium, PAX6 isoforms, along with reprogramming factors, were transduced into human non-ocular epithelial cells. Herein, we show that the two PAX6 isoforms differentially and cooperatively regulate the expression of genes specific to the structure and functions of the corneal epithelium, particularly keratin 3 (KRT3) and keratin 12 (KRT12). PAX6 isoform-a induced KRT3 expression by targeting its upstream region. KLF4 enhanced this induction. A combination of PAX6 isoform-b, KLF4 and OCT4 induced KRT12 expression. These new findings will contribute to furthering the understanding of the molecular basis of the corneal epithelium specific phenotype.
Universality in boundary domain growth by sudden bridging
Authors: Saberi A. A. , Rahbari S. H. Ebrahimnazhad , Dashti-Naserabadi H. , Abbasi A. , Cho Y. S. , Nagler J.
Published: February 2016

We report on universality in boundary domain growth in cluster aggregation in the limit of maximum concentration. Maximal concentration means that the diffusivity of the clusters is effectively zero and, instead, clusters merge successively in a percolation process, which leads to a sudden growth of the boundary domains. For two-dimensional square lattices of linear dimension L, independent of the models studied here, we find that the maximum of the boundary interface width, the susceptibility χ, exhibits the scaling χ ~ Lγ with the universal exponent γ = 1. The rapid growth of the boundary domain at the percolation threshold, which is guaranteed to occur for almost any cluster percolation process, underlies the universal scaling of χ.
In silico selection of an aptamer to estrogen receptor alpha using computational docking employing estrogen response elements as aptamer-alike molecules
Authors: Ahirwar Rajesh , Nahar Smita , Aggarwal Shikha , Ramachandran Srinivasan , Maiti Souvik , Nahar Pradip
Published: February 2016

Aptamers, the chemical-antibody substitute to conventional antibodies, are primarily discovered through SELEX technology involving multi-round selections and enrichment. Circumventing conventional methodology, here we report anin silicoselection of aptamers to estrogen receptor alpha (ERα) using RNA analogs of human estrogen response elements (EREs). The inverted repeat nature of ERE and the ability to form stable hairpins were used as criteria to obtain aptamer-alike sequences. Near-native RNA analogs of selected single stranded EREs were modelled and their likelihood to emerge as ERα aptamer was examined using AutoDock Vina, HADDOCK and PatchDock docking. Thesein silicopredictions were validated by measuring the thermodynamic parameters of ERα -RNA interactions using isothermal titration calorimetry. Based on thein silicoandin vitroresults, we selected a candidate RNA (ERaptR4; 5′-GGGGUCAAGGUGACCCC-3′) having a binding constant (Ka) of 1.02 ± 0.1 × 108 M−1as an ERα-aptamer. Target-specificity of the selected ERaptR4 aptamer was confirmed through cytochemistry and solid-phase immunoassays. Furthermore, stability analyses identified ERaptR4 resistant to serum and RNase A degradation in presence of ERα. Taken together, an efficient ERα-RNA aptamer is identified using a non-SELEX procedure of aptamer selection. The high-affinity and specificity can be utilized in detection of ERα in breast cancer and related diseases.
Comparative Proteomic Study of Fatty Acid-treated Myoblasts Reveals Role of Cox-2 in Palmitate-induced Insulin Resistance
Authors: Chen Xiulan , Xu Shimeng , Wei Shasha , Deng Yaqin , Li Yiran , Yang Fuquan , Liu Pingsheng
Published: February 2016

Accumulated studies demonstrate that saturated fatty acids (FAs) such as palmitic acid (PA) inhibit insulin signaling in skeletal muscle cells and monounsaturated fatty acids such as oleic acid (OA) reverse the effect of PA on insulin signaling. The detailed molecular mechanism of these opposite effects remains elusive. Here we provide a comparative proteomic study of skeletal myoblast cell line C2C12 that were untreated or treated with PA, and PA plus OA. A total of 3437 proteins were quantified using SILAC in this study and 29 proteins fall into the pattern that OA reverses PA effect. Expression of some these proteins were verified using qRT-PCR and Western blot. The most significant change was cyclooxygenase-2 (Cox-2). In addition to whole cell comparative proteomic study, we also compared lipid droplet (LD)-associated proteins and identified that Cox-2 was one of three major altered proteins under the FA treatment. This finding was then confirmed using immunofluorescence. Finally, Cox-2 selective inhibitor, celecoxib protected cells from PA-reduced insulin signaling Akt phosphorylation. Together, these results not only provide a dataset of protein expression change in FA treatment but also suggest that Cox-2 and lipid droplets (LDs) are potential players in PA- and OA-mediated cellular processes.
Tailoring electromagnetically induced transparency with different coupling mechanisms
Authors: Li Hai-ming , Liu Shao-bin , Wang Shen-yun , Liu Si-yuan , Hu Yan , Li Hai-bin
Published: February 2016

Tailoring electromagnetically induced transparency with two different coupling mechanisms has been numerically demonstrated. The results show that EIT based on simultaneous electric resonance and magnetic resonance has relatively larger coupling distance compared with that based on electric resonance near field coupling to magnetic resonance. The relatively large coupling distance is due to the relatively small susceptibility change. For EIT based on simultaneous electric resonance and magnetic resonance, not only incident electric field but also the incident magnetic field pays a role on the susceptibility of system. The influence of the incident magnetic field leads to relatively smaller susceptibility change compared with that based on electric resonance near field coupling to magnetic resonance.
Soil organic carbon dynamics under long-term fertilization in a black soil of China: Evidence from stable C isotopes
Authors: Dou Xiaolin , He Ping , Zhu Ping , Zhou Wei
Published: February 2016

Effects of different fertilizers on organic carbon (C) storage and turnover of soil fractions remains unclear. We combined soil fractionation with isotope analyses to examine soil organic carbon (SOC) dynamics after 25 years of fertilization. Five types of soil samples including the initial level (CK) and four fertilization treatments (inorganic nitrogen fertilizer, N; balanced inorganic fertilizer, NPK; inorganic fertilizer plus farmyard manure, MNPK; inorganic fertilizer plus corn straw residue, SNPK) were separated into four aggregate sizes (>2000 μm, 2000–250 μm, 250–53 μm, and <53 μm), and three density fractions: free light fraction (LF), intra-aggregate particulate organic matter (iPOM), and mineral-associated organic matter (mSOM). Physical fractionation showed the iPOM fraction of aggregates dominated C storage, averaging 76.87% of SOC storage. Overall, application of N and NPK fertilizers cannot significantly increase the SOC storage but enhanced C in mSOM of aggregates, whereas MNPK fertilizer resulted in the greatest amount of SOC storage (about 5221.5 g C m2) because of the enhanced SOC in LF, iPOM and mSOM of each aggregate. The SNPK fertilizer increased SOC storage in >250 μm aggregates but reduced SOC storage in <250 μm aggregates due to SOC changes in LF and iPOM.
Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
Authors: Vignaroli Giulia , Calandro Pierpaolo , Zamperini Claudio , Coniglio Federica , Iovenitti Giulia , Tavanti Matteo , Colecchia David , Dreassi Elena , Valoti Massimo , Schenone Silvia , Chiariello Mario , Botta Maurizio
Published: February 2016

Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1–4) on the base of their anti-neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and ζ-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility.
Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata
Authors: Zahari Azeana , Ablat Abdulwali , Omer Noridayu , Nafiah Mohd Azlan , Sivasothy Yasodha , Mohamad Jamaludin , Khan Mohammad Niyaz , Awang Khalijah
Published: February 2016

The UV-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The pKa values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a pKa value of 9.16 and 10.44. All of the alkaloids 1–3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host.
Transport of pyruvate into mitochondria is involved in methylmercury toxicity
Authors: Lee Jin-Yong , Ishida Yosuke , Takahashi Tsutomu , Naganuma Akira , Hwang Gi-Wook
Published: February 2016

We have previously demonstrated that the overexpression of enzymes involved in the production of pyruvate, enolase 2 (Eno2) and D-lactate dehydrogenase (Dld3) renders yeast highly sensitive to methylmercury and that the promotion of intracellular pyruvate synthesis may be involved in intensifying the toxicity of methylmercury. In the present study, we showed that the addition of pyruvate to culture media in non-toxic concentrations significantly enhanced the sensitivity of yeast and human neuroblastoma cells to methylmercury. The results also suggested that methylmercury promoted the transport of pyruvate into mitochondria and that the increased pyruvate concentrations in mitochondria were involved in intensifying the toxicity of methylmercury without pyruvate being converted to acetyl-CoA. Furthermore, in human neuroblastoma cells, methylmercury treatment alone decreased the mitochondrial membrane potential and the addition of pyruvate led to a further significant decrease. In addition, treatment with N-acetylcysteine (an antioxidant) significantly alleviated the toxicity of methylmercury and significantly inhibited the intensification of methylmercury toxicity by pyruvate. Based on these data, we hypothesize that methylmercury exerts its toxicity by raising the level of pyruvate in mitochondria and that mitochondrial dysfunction and increased levels of reactive oxygen species are involved in the action of pyruvate.
Chemical Vapor Deposition of Monolayer Mo1−xWxS2 Crystals with Tunable Band Gaps
Authors: Wang Ziqian , Liu Pan , Ito Yoshikazu , Ning Shoucong , Tan Yongwen , Fujita Takeshi , Hirata Akihiko , Chen Mingwei
Published: February 2016

Band gap engineering of monolayer transition metal dichalcogenides, such as MoS2 and WS2, is essential for the applications of the two-dimensional (2D) crystals in electronic and optoelectronic devices. Although it is known that chemical mixture can evidently change the band gaps of alloyed Mo1−xWxS2 crystals, the successful growth of Mo1−xWxS2 monolayers with tunable Mo/W ratios has not been realized by conventional chemical vapor deposition. Herein, we developed a low-pressure chemical vapor deposition (LP-CVD) method to grow monolayer Mo1−xWxS2 (x = 0–1) 2D crystals with a wide range of Mo/W ratios. Raman spectroscopy and high-resolution transmission electron microscopy demonstrate the homogeneous mixture of Mo and W in the 2D alloys. Photoluminescence measurements show that the optical band gaps of the monolayer Mo1−xWxS2 crystals strongly depend on the Mo/W ratios and continuously tunable band gap can be achieved by controlling the W or Mo portion by the LP-CVD.
Reactive oxygen species regulate leaf pulvinus abscission zone cell separation in response to water-deficit stress in cassava
Authors: Liao Wenbin , Wang Gan , Li Yayun , Wang Bin , Zhang Peng , Peng Ming
Published: February 2016

Cassava (Manihot esculenta Crantz) plant resists water-deficit stress by shedding leaves leading to adaptive water-deficit condition. Transcriptomic, physiological, cellular, molecular, metabolic and transgenic methods were used to study the mechanism of cassava abscission zone (AZ) cell separation under water-deficit stress. Microscopic observation indicated that AZ cell separation initiated at the later stages during water-deficit stress. Transcriptome profiling of AZ suggested that differential expression genes of AZ under stress mainly participate in reactive oxygen species (ROS) pathway. The key genes involved in hydrogen peroxide biosynthesis and metabolism showed significantly higher expression levels in AZ than non-separating tissues adjacent to the AZ under stress. Significantly higher levels of hydrogen peroxide correlated with hydrogen peroxide biosynthesis related genes and AZ cell separation was detected by microscopic observation, colorimetric detection and GC-MS analyses under stress. Co-overexpression of the ROS-scavenging proteins SOD and CAT1 in cassava decreased the levels of hydrogen peroxide in AZ under water-deficit stress. The cell separation of the pulvinus AZ also delayed in co-overexpression of the ROS-scavenging proteins SOD and CAT1 plants both in vitro and at the plant level. Together, the results indicated that ROS play an important regulatory role in the process of cassava leaf abscission under water-deficit stress.
CdS-Nanowires Flexible Photo-detector with Ag-Nanowires Electrode Based on Non-transfer Process
Authors: Pei Yanli , Pei Ruihan , Liang Xiaoci , Wang Yuhao , Liu Ling , Chen Haibiao , Liang Jun
Published: February 2016

In this study, UV-visible flexible resistivity-type photo-detectors were demonstrated with CdS-nanowires (NWs) percolation network channel and Ag-NWs percolation network electrode. The devices were fabricated on Mixed Cellulose Esters (MCE) membrane using a lithographic filtration method combined with a facile non-transfer process. The photo-detectors demonstrated strong adhesion, fast response time, fast decay time, and high photo sensitivity. The high performance could be attributed to the high quality single crystalline CdS-NWs, encapsulation of NWs in MCE matrix and excellent interconnection of the NWs. Furthermore, the sensing performance was maintained even the device was bent at an angle of 90°. This research may pave the way for the facile fabrication of flexible photo-detectors with high performances.
Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells
Authors: Huang Yu-Ja , Hoffmann Gwendolyn , Wheeler Benjamin , Schiapparelli Paula , Quinones-Hinojosa Alfredo , Searson Peter
Published: February 2016

Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments.
Full Valley and Spin Polarizations in Strained Graphene with Rashba Spin Orbit Coupling and Magnetic Barrier
Authors: Wu Qing-Ping , Liu Zheng-Fang , Chen Ai-Xi , Xiao Xian-Bo , Liu Zhi-Min
Published: February 2016

We propose a graphene-based full valley- and spin-polarization device based on strained graphene with Rashba spin orbit coupling and magnetic barrier. The underlying mechanism is the coexistence of the valley and single spin band gaps in a certain Fermi energy. By aligning the Fermi energy in the valley and single spin band gaps, remarkable valley- and spin-polarization currents can be accessed.
Long distance dispersal and vertical gene flow in the Caribbean brooding coral Porites astreoides
Authors: Serrano Xaymara M. , Baums Iliana B. , Smith Tyler B. , Jones Ross J. , Shearer Tonya L. , Baker Andrew C.
Published: February 2016

To date, most assessments of coral connectivity have emphasized long-distance horizontal dispersal of propagules from one shallow reef to another. The extent of vertical connectivity, however, remains largely understudied. Here, we used newly-developed and existing DNA microsatellite loci for the brooding coral Porites astreoides to assess patterns of horizontal and vertical connectivity in 590 colonies collected from three depth zones (≤10 m, 15–20 m and ≥25 m) at sites in Florida, Bermuda and the U.S. Virgin Islands (USVI). We also tested whether maternal transmission of algal symbionts (Symbiodinium spp.) might limit effective vertical connectivity. Overall, shallow P. astreoides exhibited high gene flow between Florida and USVI, but limited gene flow between these locations and Bermuda. In contrast, there was significant genetic differentiation by depth in Florida (Upper Keys, Lower Keys and Dry Tortugas), but not in Bermuda or USVI, despite strong patterns of depth zonation in algal symbionts at two of these locations. Together, these findings suggest that P. astreoides is effective at dispersing both horizontally and vertically despite its brooding reproductive mode and maternal transmission of algal symbionts. In addition, these findings might help explain the ecological success reported for P. astreoides in the Caribbean in recent decades.
Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells
Authors: Venturelli Leonardo , Nappini Silvia , Bulfoni Michela , Gianfranceschi Giuseppe , Dal Zilio Simone , Coceano Giovanna , Del Ben Fabio , Turetta Matteo , Scoles Giacinto , Vaccari Lisa , Cesselli Daniela , Cojoc Dan
Published: February 2016

The mesenchymal state in cancer is usually associated with poor prognosis due to the metastatic predisposition and the hyper-activated metabolism. Exploiting cell glucose metabolism we propose a new method to detect mesenchymal-like cancer cells. We demonstrate that the uptake of glucose-coated magnetic nanoparticles (MNPs) by mesenchymal-like cells remains constant when the glucose in the medium is increased from low (5.5 mM) to high (25 mM) concentration, while the MNPs uptake by epithelial-like cells is significantly reduced. These findings reveal that the glucose-shell of MNPs plays a major role in recognition of cells with high-metabolic activity. By selectively blocking the glucose transporter 1 channels we showed its involvement in the internalization process of glucose-coated MNPs. Our results suggest that glucose-coated MNPs can be used for metabolic-based assays aimed at detecting cancer cells and that can be used to selectively target cancer cells taking advantage, for instance, of the magnetic-thermotherapy.
Mammalian interspecies substitution of immune modulatory alleles by genome editing
Authors: Lillico Simon G. , Proudfoot Chris , King Tim J. , Tan Wenfang , Zhang Lei , Mardjuki Rachel , Paschon David E. , Rebar Edward J. , Urnov Fyodor D. , Mileham Alan J. , McLaren David G. , Whitelaw C. Bruce A.
Published: February 2016

We describe a fundamentally novel feat of animal genetic engineering: the precise and efficient substitution of an agronomic haplotype into a domesticated species. Zinc finger nuclease in-embryo editing of the RELA locus generated live born domestic pigs with the warthog RELA orthologue, associated with resilience to African Swine Fever. The ability to efficiently achieve interspecies allele introgression in one generation opens unprecedented opportunities for agriculture and basic research.
Ultrasound triggered image-guided drug delivery to inhibit vascular reconstruction via paclitaxel-loaded microbubbles
Authors: Zhu Xu , Guo Jun , He Cancan , Geng Huaxiao , Yu Gengsheng , Li Jinqing , Zheng Hairong , Ji Xiaojuan , Yan Fei
Published: February 2016

Paclitaxel (PTX) has been recognized as a promising drug for intervention of vascular reconstructions. However, it is still difficult to achieve local drug delivery in a spatio-temporally controllable manner under real-time image guidance. Here, we introduce an ultrasound (US) triggered image-guided drug delivery approach to inhibit vascular reconstruction via paclitaxel (PTX)-loaded microbubbles (PLM) in a rabbit iliac balloon injury model. PLM was prepared through encapsulating PTX in the shell of lipid microbubbles via film hydration and mechanical vibration technique. Our results showed PLM could effectively deliver PTX when exposed to US irradiation and result in significantly lower viability of vascular smooth muscle cells. Ultrasonographic examinations revealed the US signals from PLM in the iliac artery were greatly increased after intravenous administration of PLM, making it possible to identify the restenosis regions of iliac artery. The in vivo anti-restenosis experiments with PLM and US greatly inhibited neointimal hyperplasia at the injured site, showing an increased lumen area and reduced the ratio of intima area and the media area (I/M ratio). No obvious functional damages to liver and kidney were observed for those animals. Our study provided a promising approach to realize US triggered image-guided PTX delivery for therapeutic applications against iliac restenosis.
Computer-aided multiple-head 3D printing system for printing of heterogeneous organ/tissue constructs
Authors: Jung Jin Woo , Lee Jung-Seob , Cho Dong-Woo
Published: February 2016

Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries.
Microfluidic model of the platelet-generating organ: beyond bone marrow biomimetics
Authors: Blin Antoine , Le Goff Anne , Magniez Aurélie , Poirault-Chassac Sonia , Teste Bruno , Sicot Géraldine , Nguyen Kim Anh , Hamdi Feriel S. , Reyssat Mathilde , Baruch Dominique
Published: February 2016

We present a new, rapid method for producing blood platelets in vitro from cultured megakaryocytes based on a microfluidic device. This device consists in a wide array of VWF-coated micropillars. Such pillars act as anchors on megakaryocytes, allowing them to remain trapped in the device and subjected to hydrodynamic shear. The combined effect of anchoring and shear induces the elongation of megakaryocytes and finally their rupture into platelets and proplatelets. This process was observed with megakaryocytes from different origins and found to be robust. This original bioreactor design allows to process megakaryocytes at high throughput (millions per hour). Since platelets are produced in such a large amount, their extensive biological characterisation is possible and shows that platelets produced in this bioreactor are functional.
Interactive effects between gaze direction and facial expression on attentional resources deployment: the task instruction and context matter
Authors: Ricciardelli Paola , Lugli Luisa , Pellicano Antonello , Iani Cristina , Nicoletti Roberto
Published: February 2016

In three experiments, we tested whether the amount of attentional resources needed to process a face displaying neutral/angry/fearful facial expressions with direct or averted gaze depends on task instructions and face presentation. To this end, we used a Rapid Serial Visual Presentation paradigm in which participants in Experiment 1 were first explicitly asked to discriminate whether the expression of a target face (T1) with direct or averted gaze was angry or neutral and then to judge the orientation of a landscape (T2). Experiment 2 was identical to Experiment 1 except that participants had to discriminate the gender of the face of T1 and fearful faces were also presented randomly inter-mixed within each block of trials. Experiment 3 differed from Experiment 2 only because angry and fearful faces were never presented within the same block. The findings indicated that the presence of the attentional blink (AB) for face stimuli depends on specific combinations of gaze direction and emotional facial expressions and crucially revealed that the contextual factors (e.g., explicit instruction to process the facial expression and the presence of other emotional faces) can modify and even reverse the AB, suggesting a flexible and more contextualized deployment of attentional resources in face processing.
An automated framework for 3D serous pigment epithelium detachment segmentation in SD-OCT images
Authors: Sun Zhuli , Chen Haoyu , Shi Fei , Wang Lirong , Zhu Weifang , Xiang Dehui , Yan Chenglin , Li Liang , Chen Xinjian
Published: February 2016

Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorioretinal diseases, which can cause loss of central vision. In this paper, an automated framework is proposed to segment serous PED in SD-OCT images. The proposed framework consists of four main steps: first, a multi-scale graph search method is applied to segment abnormal retinal layers; second, an effective AdaBoost method is applied to refine the initial segmented regions based on 62 extracted features; third, a shape-constrained graph cut method is applied to segment serous PED, in which the foreground and background seeds are obtained automatically; finally, an adaptive structure elements based morphology method is applied to remove false positive segmented regions. The proposed framework was tested on 25 SD-OCT volumes from 25 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 90.08%, 0.22%, 91.20% and 92.62%, respectively. The proposed framework can provide clinicians with accurate quantitative information, including shape, size and position of the PED region, which can assist clinical diagnosis and treatment.