bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast nanoscale addressability of nitrogen-vacancy spins via coupling to a dynamic ferromagnetic vortex
Authors: Wolf M. S. , Badea R. , Berezovsky J.
Published: June 2016

The core of a ferromagnetic vortex domain creates a strong, localized magnetic field, which can be manipulated on nanosecond timescales, providing a platform for addressing and controlling individual nitrogen-vacancy centre spins in diamond at room temperature, with nanometre-scale resolution. Here, we show that the ferromagnetic vortex can be driven into proximity with a nitrogen-vacancy defect using small applied magnetic fields, inducing significant nitrogen-vacancy spin splitting. We also find that the magnetic field gradient produced by the vortex is sufficient to address spins separated by nanometre-length scales. By applying a microwave-frequency magnetic field, we drive both the vortex and the nitrogen-vacancy spins, resulting in enhanced coherent rotation of the spin state. Finally, we demonstrate that by driving the vortex on fast timescales, sequential addressing and coherent manipulation of spins is possible on ∼100 ns timescales.
Full circumpolar migration ensures evolutionary unity in the Emperor penguin
Authors: Cristofari Robin , Bertorelle Giorgio , Ancel André , Benazzo Andrea , Le Maho Yvon , Ponganis Paul J. , Stenseth Nils Chr , Trathan Phil N. , Whittington Jason D. , Zanetti Enrico , Zitterbart Daniel P. , Le Bohec Céline , Trucchi Emiliano
Published: June 2016

Defining reliable demographic models is essential to understand the threats of ongoing environmental change. Yet, in the most remote and threatened areas, models are often based on the survey of a single population, assuming stationarity and independence in population responses. This is the case for the Emperor penguin Aptenodytes forsteri, a flagship Antarctic species that may be at high risk continent-wide before 2100. Here, using genome-wide data from the whole Antarctic continent, we reveal that this top-predator is organized as one single global population with a shared demography since the late Quaternary. We refute the view of the local population as a relevant demographic unit, and highlight that (i) robust extinction risk estimations are only possible by including dispersal rates and (ii) colony-scaled population size is rather indicative of local stochastic events, whereas the species’ response to global environmental change is likely to follow a shared evolutionary trajectory.
High-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material
Authors: Loeffler Felix F. , Foertsch Tobias C. , Popov Roman , Mattes Daniela S. , Schlageter Martin , Sedlmayr Martyna , Ridder Barbara , Dang Florian-Xuan , von Bojničić-Kninski Clemens , Weber Laura K. , Fischer Andrea , Greifenstein Juliane , Bykovskaya Valentina , Buliev Ivan , Bischoff F. Ralf , Hahn Lothar , Meier Michael A. R. , Bräse Stefan , Powell Annie K. , Balaban Teodor Silviu , Breitling Frank , Nesterov-Mueller Alexander
Published: June 2016

Laser writing is used to structure surfaces in many different ways in materials and life sciences. However, combinatorial patterning applications are still limited. Here we present a method for cost-efficient combinatorial synthesis of very-high-density peptide arrays with natural and synthetic monomers. A laser automatically transfers nanometre-thin solid material spots from different donor slides to an acceptor. Each donor bears a thin polymer film, embedding one type of monomer. Coupling occurs in a separate heating step, where the matrix becomes viscous and building blocks diffuse and couple to the acceptor surface. Furthermore, we can consecutively deposit two material layers of activation reagents and amino acids. Subsequent heat-induced mixing facilitates an in situ activation and coupling of the monomers. This allows us to incorporate building blocks with click chemistry compatibility or a large variety of commercially available non-activated, for example, posttranslationally modified building blocks into the array’s peptides with >17,000 spots per cm2.
Calredoxin represents a novel type of calcium-dependent sensor-responder connected to redox regulation in the chloroplast
Authors: Hochmal Ana Karina , Zinzius Karen , Charoenwattanasatien Ratana , Gäbelein Philipp , Mutoh Risa , Tanaka Hideaki , Schulze Stefan , Liu Gai , Scholz Martin , Nordhues André , Offenborn Jan Niklas , Petroutsos Dimitris , Finazzi Giovanni , Fufezan Christian , Huang Kaiyao , Kurisu Genji , Hippler Michael
Published: June 2016

Calcium (Ca2+) and redox signalling play important roles in acclimation processes from archaea to eukaryotic organisms. Herein we characterized a unique protein from Chlamydomonas reinhardtii that has the competence to integrate Ca2+- and redox-related signalling. This protein, designated as calredoxin (CRX), combines four Ca2+-binding EF-hands and a thioredoxin (TRX) domain. A crystal structure of CRX, at 1.6 Å resolution, revealed an unusual calmodulin-fold of the Ca2+-binding EF-hands, which is functionally linked via an inter-domain communication path with the enzymatically active TRX domain. CRX is chloroplast-localized and interacted with a chloroplast 2-Cys peroxiredoxin (PRX1). Ca2+-binding to CRX is critical for its TRX activity and for efficient binding and reduction of PRX1. Thereby, CRX represents a new class of Ca2+-dependent ‘sensor-responder’ proteins. Genetically engineered Chlamydomonas strains with strongly diminished amounts of CRX revealed altered photosynthetic electron transfer and were affected in oxidative stress response underpinning a function of CRX in stress acclimation.
A new type of solar-system material recovered from Ordovician marine limestone
Authors: Schmitz B. , Yin Q. -Z. , Sanborn M. E. , Tassinari M. , Caplan C. E. , Huss G. R.
Published: June 2016

From mid-Ordovician ∼470 Myr-old limestone >100 fossil L-chondritic meteorites have been recovered, representing the markedly enhanced flux of meteorites to Earth following the breakup of the L-chondrite parent body. Recently one anomalous meteorite, Österplana 065 (Öst 65), was found in the same beds that yield L chondrites. The cosmic-ray exposure age of Öst 65 shows that it may be a fragment of the impactor that broke up the L-chondrite parent body. Here we show that in a chromium versus oxygen-isotope plot Öst 65 falls outside all fields encompassing the known meteorite types. This may be the first documented example of an ‘extinct’ meteorite, that is, a meteorite type that does not fall on Earth today because its parent body has been consumed by collisions. The meteorites found on Earth today apparently do not give a full representation of the kind of bodies in the asteroid belt ∼500 Myr ago.
Male care and life history traits in mammals
Authors: West Hannah E. R. , Capellini Isabella
Published: June 2016

Male care has energetic and opportunity costs, and is more likely to evolve when males gain greater certainty of paternity or when future mating opportunities are scarce. However, little is known about the substantial benefits that males may provide to females and offspring. Using phylogenetic comparative methods and a sample of over 500 mammalian species, we show that mammals in which males carry the offspring have shorter lactation periods, which leads to more frequent breeding events. Provisioning the female is associated with larger litters and shorter lactation. Offspring of species with male care have similar weaning mass to those without despite being supported by a shorter lactation period, implying that they grow faster. We propose that males provide an energetic contribution during the most expensive time of female reproduction, lactation, and that different male care behaviours increase female fecundity, which in turn helps males offset the costs of caring.
Polymorphism in magic-sized Au144(SR)60 clusters
Authors: Jensen Kirsten M.Ø. , Juhas Pavol , Tofanelli Marcus A. , Heinecke Christine L. , Vaughan Gavin , Ackerson Christopher J. , Billinge Simon J. L.
Published: June 2016

Ultra-small, magic-sized metal nanoclusters represent an important new class of materials with properties between molecules and particles. However, their small size challenges the conventional methods for structure characterization. Here we present the structure of ultra-stable Au144(SR)60 magic-sized nanoclusters obtained from atomic pair distribution function analysis of X-ray powder diffraction data. The study reveals structural polymorphism in these archetypal nanoclusters. In addition to confirming the theoretically predicted icosahedral-cored cluster, we also find samples with a truncated decahedral core structure, with some samples exhibiting a coexistence of both cluster structures. Although the clusters are monodisperse in size, structural diversity is apparent. The discovery of polymorphism may open up a new dimension in nanoscale engineering.
Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys
Authors: Dettmer Amanda M. , Kaburu Stefano S. K. , Simpson Elizabeth A. , Paukner Annika , Sclafani Valentina , Byers Kristen L. , Murphy Ashley M. , Miller Michelle , Marquez Neal , Miller Grace M. , Suomi Stephen J. , Ferrari Pier F.
Published: June 2016

In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency.
A Statistical Physics Characterization of the Complex Systems Dynamics: Quantifying Complexity from Spatio-Temporal Interactions
Authors: Koorehdavoudi Hana , Bogdan Paul
Published: June 2016

Biological systems are frequently categorized as complex systems due to their capabilities of generating spatio-temporal structures from apparent random decisions. In spite of research on analyzing biological systems, we lack a quantifiable framework for measuring their complexity. To fill this gap, in this paper, we develop a new paradigm to study a collective group ofNagents moving and interacting in a three-dimensional space. Our paradigm helps to identify the spatio-temporal states of the motion of the group and their associated transition probabilities. This framework enables the estimation of the free energy landscape corresponding to the identified states. Based on the energy landscape, we quantify missing information, emergence, self-organization and complexity for a collective motion. We show that the collective motion of the group of agents evolves to reach the most probable state with relatively lowest energy level and lowest missing information compared to other possible states. Our analysis demonstrates that the natural group of animals exhibit a higher degree of emergence, self-organization and complexity over time. Consequently, this algorithm can be integrated into new frameworks to engineer collective motions to achieve certain degrees of emergence, self-organization and complexity.
Multiscale approach predictions for biological outcomes in ion-beam cancer therapy
Authors: Verkhovtsev Alexey , Surdutovich Eugene , Solov’yov Andrey V.
Published: June 2016

Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects related to the ion-medium interactions on a nanometre scale. We demonstrate that the phenomenon-based MultiScale Approach to the assessment of radiation damage with ions gives a positive answer to this question. We apply this approach to numerous experiments where survival curves were obtained for different cell lines and conditions. Contrary to other, in essence empirical methods for evaluation of macroscopic effects of ionising radiation, the MultiScale Approach predicts the biodamage based on the physical effects related to ionisation of the medium, transport of secondary particles, chemical interactions, thermo-mechanical pathways of biodamage and heuristic biological criteria for cell survival. We anticipate this method to give great impetus to the practical improvement of ion-beam cancer therapy and the development of more efficient treatment protocols.
GCN2 contributes to mTORC1 inhibition by leucine deprivation through an ATF4 independent mechanism
Authors: Averous Julien , Lambert-Langlais Sarah , Mesclon Florent , Carraro Valérie , Parry Laurent , Jousse Céline , Bruhat Alain , Maurin Anne-Catherine , Pierre Philippe , Proud Christopher G. , Fafournoux Pierre
Published: June 2016

It is well known that the GCN2 and mTORC1 signaling pathways are regulated by amino acids and share common functions, in particular the control of translation. The regulation of GCN2 activity by amino acid availability relies on the capacity of GCN2 to sense the increased levels of uncharged tRNAs upon amino acid scarcity. In contrast, despite recent progress in the understanding of the regulation of mTORC1 by amino acids, key aspects of this process remain unsolved. In particular, while leucine is well known to be a potent regulator of mTORC1, the mechanisms by which this amino acid is sensed and control mTORC1 activity are not well defined. Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity, indicating that leucine and arginine exert regulation via additional mechanisms. While the mechanism by which GCN2 contributes to the initial step of mTORC1 inhibition involves the phosphorylation of eIF2α, we show that it is independent of the downstream transcription factor ATF4. These data point to a novel role for GCN2 and phosphorylation of eIF2α in the control of mTORC1 by certain amino acids.
Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury
Authors: Zhang Yu , Yang Jinhua , Zhang Peng , Liu Tao , Xu Jianwei , Fan Zhihai , Shen Yixin , Li Wenjie , Zhang Huanxiang
Published: June 2016

Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responses in vitro to CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8–37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI.
Temperature-dependent photoluminescence of surface-engineered silicon nanocrystals
Authors: Mitra Somak , Švrček Vladimir , Macias-Montero Manual , Velusamy Tamilselvan , Mariotti Davide
Published: June 2016

In this work we report on temperature-dependent photoluminescence measurements (15–300 K), which have allowed probing radiative transitions and understanding of the appearance of various transitions. We further demonstrate that transitions associated with oxide in SiNCs show characteristic vibronic peaks that vary with surface characteristics. In particular we study differences and similarities between silicon nanocrystals (SiNCs) derived from porous silicon and SiNCs that were surface-treated using a radio-frequency (RF) microplasma system.
Direct interaction of beta-amyloid with Na,K-ATPase as a putative regulator of the enzyme function
Authors: Petrushanko Irina Yu. , Mitkevich Vladimir A. , Anashkina Anastasia A. , Adzhubei Alexei A. , Burnysheva Ksenia M. , Lakunina Valentina A. , Kamanina Yulia V. , Dergousova Elena A. , Lopina Olga D. , Ogunshola Omolara O. , Bogdanova Anna Yu. , Makarov Alexander A.
Published: June 2016

By maintaining the Na+and K+transmembrane gradient mammalian Na,K-ATPase acts as a key regulator of neuronal electrotonic properties. Na,K-ATPase has an important role in synaptic transmission and memory formation. Accumulation of beta-amyloid (Aβ) at the early stages of Alzheimer’s disease is accompanied by reduction of Na,K-ATPase functional activity. The molecular mechanism behind this phenomenon is not known. Here we show that the monomeric Aβ(1-42) forms a tight (Kdof 3 μM), enthalpy-driven equimolar complex with α1β1 Na,K-ATPase. The complex formation results in dose-dependent inhibition of the enzyme hydrolytic activity. The binding site of Aβ(1-42) is localized in the “gap” between the alpha- and beta-subunits of Na,K-ATPase, disrupting the enzyme functionality by preventing the subunits from shifting towards each other. Interaction of Na,K-ATPase with exogenous Aβ(1-42) leads to a pronounced decrease of the enzyme transport and hydrolytic activity and Src-kinase activation in neuroblastoma cells SH-SY5Y. This interaction allows regulation of Na,K-ATPase activity by short-term increase of the Aβ(1-42) level. However prolonged increase of Aβ(1-42) level under pathological conditions could lead to chronical inhibition of Na,K-ATPase and disruption of neuronal function. Taken together, our data suggest the role of beta-amyloid as a novel physiological regulator of Na,K-ATPase.
Rising levels of atmospheric oxygen and evolution of Nrf2
Authors: Gacesa Ranko , Dunlap Walter C. , Barlow David J. , Laskowski Roman A. , Long Paul F.
Published: June 2016

In mammals, the master transcription regulator of antioxidant defences is provided by the Nrf2 protein. Phylogenetic analyses of Nrf2 sequences are used here to derive a molecular clock that manifests persuasive evidence that Nrf2 orthologues emerged and then diverged, at two time points that correlate with well-established geochemical and palaeobiological chronologies during progression of the ‘Great Oxygenation Event’. We demonstrate that orthologues of Nrf2 first appeared in fungi around 1.5 Ga during the Paleoproterozoic when photosynthetic oxygen was being absorbed into the oceans. A subsequent significant divergence in Nrf2 is seen during the split between fungi and the Metazoa approximately 1.0–1.2 Ga, at a time when oceanic ventilation released free oxygen to the atmosphere, but with most being absorbed by methane oxidation and oxidative weathering of land surfaces until approximately 800 Ma. Atmospheric oxygen levels thereafter accumulated giving rise to metazoan success known as the Cambrian explosion commencing at ~541 Ma. Atmospheric O2 levels then rose in the mid Paleozoic (359–252 Ma) and Nrf2 diverged once again at the division between mammals and non-mammalian vertebrates during the Permian-Triassic boundary (~252 Ma). Understanding Nrf2 evolution as an effective antioxidant response may have repercussions for improved human health.
Bax Inhibitor-1 regulates hepatic lipid accumulation via ApoB secretion
Authors: Lee Hwa Young , Lee Geum-Hwa , Bhattarai Kashi Raj , Park Byung-Hyun , Koo Seung-Hoi , Kim Hyung-Ryong , Chae Han Jung
Published: June 2016

In this study, we explored the effects of Bax Inhibitor-1 (BI-1) on ApoB aggregation in high-fat diet (HFD)-induced hepatic lipid accumulation. After 1 week on a HFD, triglycerides and cholesterol accumulated more in the liver and were not effectively secreted into the plasma, whereas after 8 weeks, lipids were highly accumulated in both the liver and plasma, with a greater effect in BI-1 KO mice compared with BI-1 WT mice. ApoB, a lipid transfer protein, was accumulated to a greater extent in the livers of HFD-BI-1 KO mice compared with HFD-BI-1 WT mice. Excessive post-translational oxidation of protein disulfide isomerase (PDI), intra-ER ROS accumulation and folding capacitance alteration were also observed in HFD-BI-1 KO mice. Higher levels of endoplasmic reticulum (ER) stress were consistently observed in KO mice compared with the WT mice. Adenovirus-mediated hepatic expression of BI-1 in the BI-1 KO mice rescued the above phenotypes. Our results suggest that BI-1-mediated enhancement of ApoB secretion regulates hepatic lipid accumulation, likely through regulation of ER stress and ROS accumulation.
Pancreatic SEC23B deficiency is sufficient to explain the perinatal lethality of germline SEC23B deficiency in mice
Authors: Khoriaty Rami , Everett Lesley , Chase Jennifer , Zhu Guojing , Hoenerhoff Mark , McKnight Brooke , Vasievich Matthew P. , Zhang Bin , Tomberg Kärt , Williams John , Maillard Ivan , Ginsburg David
Published: June 2016

In humans, loss of function mutations in SEC23B result in Congenital Dyserythropoietic Anemia type II (CDAII), a disease limited to defective erythroid development. Patients with two nonsense SEC23B mutations have not been reported, suggesting that complete SEC23B deficiency might be lethal. We previously reported that SEC23B-deficient mice die perinatally, exhibiting massive pancreatic degeneration and that mice with hematopoietic SEC23B deficiency do not exhibit CDAII. We now show that SEC23B deficiency restricted to the pancreas is sufficient to explain the lethality observed in mice with global SEC23B-deficiency. Immunohistochemical stains demonstrate an acinar cell defect but normal islet cells. Mammalian genomes contain two Sec23 paralogs, Sec23A and Sec23B. The encoded proteins share ~85% amino acid sequence identity. We generate mice with pancreatic SEC23A deficiency and demonstrate that these mice survive normally, exhibiting normal pancreatic weights and histology. Taken together, these data demonstrate that SEC23B but not SEC23A is essential for murine pancreatic development. We also demonstrate that two BAC transgenes spanning Sec23b rescue the lethality of mice homozygous for a Sec23b gene trap allele, excluding a passenger gene mutation as the cause of the pancreatic lethality, and indicating that the regulatory elements critical for Sec23b pancreatic function reside within the BAC transgenes.
Energy Landscape Topography Reveals the Underlying Link Between Binding Specificity and Activity of Enzymes
Authors: Chu Wen-Ting , Wang Jin
Published: June 2016

Enzyme activity (often quantified by kcat /Km ) is the main function of enzyme when it is active against the specific substrate. Higher or lower activities are highly desired for the design of novel enzyme and drug resistance. However, it is difficult to measure the activities of all possible variants and find the “hot-spot” within the limit of experimental time. In this study, we explore the underlying energy landscape of enzyme-substrate interactions and introduce the intrinsic specificity ratio (ISR), which reflects the landscape topography. By studying two concrete systems, we uncover the statistical correlation between the intrinsic specificity and the enzyme activity kcat /Km . This physics-based concept and method show that the energy landscape topography is valuable for understanding the relationship between enzyme specificity and activity. In addition, it can reveal the underlying mechanism of enzyme-substrate actions and has potential applications on enzyme design.
3D conductive coupling for efficient generation of prominent Fano resonances in metamaterials
Authors: Liu Zhiguang , Liu Zhe , Li Jiafang , Li Wuxia , Li Junjie , Gu Changzhi , Li Zhi-Yuan
Published: June 2016

We demonstrate a 3D conductive coupling mechanism for the efficient generation of prominent and robust Fano resonances in 3D metamaterials (MMs) formed by integrating vertical U-shape split-ring resonators (SRRs) or vertical rectangular plates along a planar metallic hole array with extraordinary optical transmission (EOT). In such a configuration, intensified vertical E-field is induced along the metallic holes and naturally excites the electric resonances of the vertical structures, which form non-radiative “dark” modes. These 3D conductive “dark” modes strongly interfere with the “bright” resonance mode of the EOT structure, generating significant Fano resonances with both prominent destructive and constructive interferences. The demonstrated 3D conductive coupling mechanism is highly universal in that both 3D MMs with vertical SRRs and vertical plates exhibit the same prominent Fano resonances despite their dramatic structural difference, which is conceptually different from conventional capacitive and inductive coupling mechanisms that degraded drastically upon small structural deviations.
Identifying a set of influential spreaders in complex networks
Authors: Zhang Jian-Xiong , Chen Duan-Bing , Dong Qiang , Zhao Zhi-Dan
Published: June 2016

Identifying a set of influential spreaders in complex networks plays a crucial role in effective information spreading. A simple strategy is to choose top-rranked nodes as spreaders according to influence ranking method such as PageRank, ClusterRank andk-shell decomposition. Besides, some heuristic methods such as hill-climbing, SPIN, degree discount and independent set based are also proposed. However, these approaches suffer from a possibility that some spreaders are so close together that they overlap sphere of influence or time consuming. In this report, we present a simply yet effectively iterative method named VoteRank to identify a set of decentralized spreaders with the best spreading ability. In this approach, all nodes vote in a spreader in each turn, and the voting ability of neighbors of elected spreader will be decreased in subsequent turn. Experimental results on four real networks show that under Susceptible-Infected-Recovered (SIR) and Susceptible-Infected (SI) models, VoteRank outperforms the traditional benchmark methods on both spreading rate and final affected scale. What’s more, VoteRank has superior computational efficiency.
Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours
Authors: Soo Ross Andrew , Syn Nicholas , Lee Soo-Chin , Wang Lingzhi , Lim Xn-Yii , Loh Marie , Tan Sing-Huang , Zee Ying-Kiat , Wong Andrea Li-Ann , Chuah Benjamin , Chan Daniel , Lim Siew-Eng , Goh Boon-Cher , Soong Richie , Yong Wei-Peng
Published: June 2016

The FDA-approved starting dosage of capecitabine is 1,250 mg/m2, and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m2. Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m2 b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m2 and 1,500 mg/m2. At 1,500 mg/m2, one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m2 b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment.
Ethnic specific association of the CAV1/CAV2 locus with primary open-angle glaucoma
Authors: Rong Shi Song , Chen Li Jia , Leung Christopher K. S. , Matsushita Kenji , Jia Liyun , Miki Atsuya , Chiang Sylvia W. Y. , Tam Pancy O. S. , Hashida Noriyasu , Young Alvin L. , Tsujikawa Motokazu , Zhang Mingzhi , Wang Ningli , Nishida Kohji , Pang Chi Pui
Published: June 2016

A single-nucleotide polymorphism (SNP) rs4236601 at the CAV1/CAV2 locus is associated with primary open-angle glaucoma (POAG). Rs4236601 is common in Caucasians but rare in East Asians. Here we conducted a haplotype-tagging SNP analysis followed by replication in a total of 848 POAG cases and 1574 controls drawn from 3 cities in China and 1 city in Japan. Two SNPs, rs4236601 (odds ratio [OR] = 6.25; P = 0.0086) and a tagging-SNP rs3801994 (OR = 1.32; P = 0.042), were associated with POAG in the Hong Kong Chinese cohort after age and gender adjustments. Rs4236601 was associated with POAG also in Shantou (OR = 6.09; P = 0.0037) and Beijing (OR = 3.92; P = 0.030) cohorts after age and gender adjustment, with a pooled-OR of 5.26 (P = 9.0 × 10−6) in Chinese; but it is non-polymorphic in the Osaka cohort. SNP rs3801994 showed a similar trend of effect in the Shantou and Beijing cohorts, with a pooled-OR of 1.23 (P = 0.022) and 1.20 (P = 0.063) in Chinese, prior to and after age and gender adjustment, respectively; but it showed a reverse effect in the Osaka cohort (OR = 0.58; P = 0.033) after the adjustments. We have thus confirmed the association of rs4236601 with POAG in different Chinese cohorts. Also, we found a common SNP rs3801994 of diverse associations with POAG between Chinese and Japanese.
An ontology-driven, case-based clinical decision support model for removable partial denture design
Authors: Chen Qingxiao , Wu Ji , Li Shusen , Lyu Peijun , Wang Yong , Li Miao
Published: June 2016

We present the initial work toward developing a clinical decision support model for specific design of removable partial dentures (RPDs) in dentistry. We developed an ontological paradigm to represent knowledge of a patient’s oral conditions and denture component parts. During the case-based reasoning process, a cosine similarity algorithm was applied to calculate similarity values between input patients and standard ontology cases. A group of designs from the most similar cases were output as the final results. To evaluate this model, the output designs of RPDs for 104 randomly selected patients were compared with those selected by professionals. An area under the curve of the receiver operating characteristic (AUC-ROC) was created by plotting true-positive rates against the false-positive rate at various threshold settings. The precision at position 5 of the retrieved cases was 0.67 and at the top of the curve it was 0.96, both of which are very high. The mean average of precision (MAP) was 0.61 and the normalized discounted cumulative gain (NDCG) was 0.74 both of which confirmed the efficient performance of our model. All the metrics demonstrated the efficiency of our model. This methodology merits further research development to match clinical applications for designing RPDs. This paper is organized as follows. After the introduction and description of the basis for the paper, the evaluation and results are presented in Section 2. Section 3 provides a discussion of the methodology and results. Section 4 describes the details of the ontology, similarity algorithm, and application.
Intracellular ROS mediates gas plasma-facilitated cellular transfection in 2D and 3D cultures
Authors: Xu Dehui , Wang Biqing , Xu Yujing , Chen Zeyu , Cui Qinjie , Yang Yanjie , Chen Hailan , Kong Michael G.
Published: June 2016

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In addition, we found that cold atmospheric plasma could transfer oligonucleotides such as siRNA and miRNA into cells even in 3D cultures, thus suggesting the potential for unique applications of CAP beyond those provided by standard transfection techniques. Together, our results suggest that cold plasma might provide an efficient technique for the delivery of siRNA and miRNA in 2D and 3D culture models.
A comparative genomic analysis of targets of Hox protein Ultrabithorax amongst distant insect species
Authors: Prasad Naveen , Tarikere Shreeharsha , Khanale Dhanashree , Habib Farhat , Shashidhara L. S.
Published: June 2016

In the fruitfly Drosophila melanogaster, the differential development of wing and haltere is dependent on the function of the Hox protein Ultrabithorax (Ubx). Here we compare Ubx-mediated regulation of wing patterning genes between the honeybee, Apis mellifera, the silkmoth, Bombyx mori and Drosophila. Orthologues of Ubx are expressed in the third thoracic segment of Apis and Bombyx, although they make functional hindwings. When over-expressed in transgenic Drosophila, Ubx derived from Apis or Bombyx could suppress wing development, suggesting evolutionary changes at the level of co-factors and/or targets of Ubx. To gain further insights into such events, we identified direct targets of Ubx from Apis and Bombyx by ChIP-seq and compared them with those of Drosophila. While majority of the putative targets of Ubx are species-specific, a considerable number of wing-patterning genes are retained, over the past 300 millions years, as targets in all the three species. Interestingly, many of these are differentially expressed only between wing and haltere in Drosophila but not between forewing and hindwing in Apis or Bombyx. Detailed bioinformatics and experimental validation of enhancer sequences suggest that, perhaps along with other factors, changes in the cis-regulatory sequences of earlier targets contribute to diversity in Ubx function.
Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59
Authors: Li Min , Dai Yingxin , Zhu Yuanjun , Fu Chih-Lung , Tan Vee Y. , Wang Yanan , Wang Xing , Hong Xufen , Liu Qian , Li Tianming , Qin Juanxiu , Ma Xiaowei , Fang Jingyuan , Otto Michael
Published: June 2016

Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin and PSMα to pathogenesis of ST59 CA-MRSA skin, lung and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants.
60-GHz Millimeter-wave Over Fiber with Directly Modulated Dual-mode Laser Diode
Authors: Tsai Cheng-Ting , Lin Chi-Hsiang , Lin Chun-Ting , Chi Yu-Chieh , Lin Gong-Ru
Published: June 2016

A directly modulated dual-mode laser diode (DMLD) with third-order intermodulation distortion (IMD3) suppression is proposed for a 60-GHz millimeter-wave over fiber (MMWoF) architecture, enabling new fiber-wireless communication access to cover 4-km single-mode-fiber (SMF) and 3-m wireless 16-QAM OFDM transmissions. By dual-mode injection-locking, the throughput degradation of the DMLD is mitigated with saturation effect to reduce its threshold, IMD3 power and relative intensity noise to 7.7 mA, −85 dBm and −110.4 dBc/Hz, respectively, providing huge spurious-free dynamic range of 85.8 dB/Hz2/3. This operation suppresses the noise floor of the DMLD carried QPSK-OFDM spectrum by 5 dB. The optical receiving power is optimized to restrict the power fading effect for improving the bit error rate to 1.9 × 10−3and the receiving power penalty to 1.1 dB. Such DMLD based hybrid architecture for 60-GHz MMW fiber-wireless access can directly cover the current optical and wireless networks for next-generation indoor and short-reach mobile communications.
Improved catalytic efficiency, thermophilicity, anti-salt and detergent tolerance of keratinase KerSMD by partially truncation of PPC domain
Authors: Fang Zhen , Zhang Juan , Du Guocheng , Chen Jian
Published: June 2016

The keratinase from Stenotrophomonas maltophilia (KerSMD) is known for its high activity and pH stability in keratin degradation. However, catalytic efficiency and detergent tolerability need to be improved in order to be used for industrial application. In this work, we obtained several keratinase variants with enhanced catalytic efficiency, thermophilicity and anti-salt and detergent tolerability by partially truncating the PPC domain of KerSMD. The variants all showed improved catalytic efficiency to synthetic substrate AAPF, with the V355 variant having the highest kcat /Km value of 143.6 s−1 mM−1. The truncation of keratinase had little effect on alkaline stability but obviously decreased collagenase activity, developing its potential application in leather treatment. The variants V380, V370 and V355 were thermophilic, with a 1.7-fold enhancement of keratinlytic activity at 60 °C when compared to the wild type. The entire truncation of PPC domain obtained the variant V355 with improved tolerance to alkalinity, salt, chaotropic agents and detergents. The V355 variant showed more than a 40% improvement in activity under 15% (w/v) NaCl or 4% (w/v) SDS solution, showing excellent stability under harsh washing and unhairing conditions. Our work investigated how protein engineering affects the function of PPC domain of KerSMD.
Volumetric (3D) bladder dose parameters are more reproducible than point (2D) dose parameters in vaginal vault high-dose-rate brachytherapy
Authors: Sapienza Lucas Gomes , Flosi Adriana , Aiza Antonio , de Assis Pellizzon Antonio Cassio , Chojniak Rubens , Baiocchi Glauco
Published: June 2016

There is no consensus on the use of computed tomography in vaginal cuff brachytherapy (VCB) planning. The purpose of this study was to prospectively determine the reproducibility of point bladder dose parameters (DICRU and maximum dose), compared with volumetric-based parameters. Twenty-two patients who were treated with high-dose-rate (HDR) VCB underwent simulation by computed tomography (CT-scan) with a Foley catheter at standard tension (position A) and extra tension (position B). CT-scan determined the bladder ICRU dose point in both positions and compared the displacement and recorded dose. Volumetric parameters (D0.1cc, D1.0cc, D2.0cc, D4.0cc and D50%) and point dose parameters were compared. The average spatial shift in ICRU dose point in the vertical, longitudinal and lateral directions was 2.91 mm (range: 0.10–9.00), 12.04 mm (range: 4.50–24.50) and 2.65 mm (range: 0.60–8.80), respectively. The DICRU ratio for positions A and B was 1.64 (p < 0.001). Moreover, a decrease in Dmax was observed (p = 0.016). Tension level of the urinary catheter did not affect the volumetric parameters. Our data suggest that point parameters (DICRU and Dmax) are not reproducible and are not the ideal choice for dose reporting.
Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert−/− mice
Authors: Zhou Q-G , Wu H-Y , Zhou H , Liu M-Y , Lee H-W , Liu X , Devkota S , Ro E J , Zhu D-Y , Suh H
Published: June 2016

The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert−/− mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert−/− mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert−/− mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert−/− mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert−/− mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert−/− mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control.
Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain
Authors: Olesen R H , Hyde T M , Kleinman J E , Smidt K , Rungby J , Larsen A
Published: June 2016

The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn2+ affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases.
Simple magnesium catalyst mediated γ-butyrolactams in desymmetrization of meso-aziridines
Authors: Li Dan , Wang Yijie , Wang Linqing , Wang Jie , Wang Pengxin , Wang Kezhou , Lin Li , Liu Dongsheng , Jiang Xianxing , Yang Dongxu
Published: June 2016

The first α-sp2-carbon of carbonyl compounds attacked catalytic desymmetrization reaction of aziridines is disclosed by employing a simple in situ generated magnesium catalyst.
Copper cobalt spinel as a high performance cathode for intermediate temperature solid oxide fuel cells
Authors: Shao Lin , Wang Qi , Fan Lishuang , Wang Pengxiang , Zhang Naiqing , Sun Kening
Published: June 2016

CuCo2O4 spinel prepared via an EDTA–citric acid process was studied as a candidate solid oxide fuel cell (SOFC) cathode material at intermediate temperatures (IT).
Exploration of magnetically separable Ag@AgxNiy core/graded-alloy-shell nanostructures
Authors: Kumar Mukesh , Soni Kiran , Satpati Biswarup , Gopinath Chinnakonda S. , Deka Sasanka
Published: June 2016

The first bimetallic core/graded-alloy-shell, i.e. a Ag NP core inside a AgxNiy shell, is explored, which shows a superior catalytic performance in the synthesis of biologically active 3-amino alkylated indoles under green reaction conditions.
Ion transfer battery: storing energy by transferring ions across liquid–liquid interfaces
Authors: Peljo Pekka , Bichon Marie , Girault Hubert H.
Published: June 2016

A battery in which the cell voltage is generated or enhanced by a Galvani potential difference between two liquid–liquid interfaces.
Multiscale modeling of aspirin dissolution: from molecular resolution to experimental scales of time and size
Authors: Greiner Maximilian , Choscz Carsten , Eder Cornelia , Elts Ekaterina , Briesen Heiko
Published: June 2016

Predicted absolute and face-specific rate constants of aspirin dissolution are incorporated in a simulation based on the equations of classical mass transfer to reproduce kinetic dissolution in experiment using a Jamin-type interferometer.
Identification of multiple conformers of the ionic liquid [emim][tf2n] in the gas phase using IR/UV action spectroscopy
Authors: Booth Ryan S. , Annesley Christopher J. , Young Justin W. , Vogelhuber Kristen M. , Boatz Jerry A. , Stearns Jaime A.
Published: June 2016

We have identified three families of conformers in gas phase ion pairs of [emim][tf2n] using IR/UV spectroscopy.
Enhanced activity for methane combustion over a Pd/Co/Al2O3 catalyst prepared by a galvanic deposition method
Authors: Mahara Yuji , Ohyama Junya , Tojo Takumi , Murata Kazumasa , Ishikawa Hiroyuki , Satsuma Atsushi
Published: June 2016

A Pd/Co/Al2O3 catalyst prepared by a galvanic deposition method exhibited notable catalytic activity for methane combustion, due to the higher reducibility of PdO nanoparticles on CoOx.
H2/D2 exchange reaction on mono-disperse Pt clusters: enhanced activity from minute O2 concentrations
Authors: Riedel Jakob Nordheim , Rötzer Marian David , Jørgensen Mikkel , Vej-Hansen Ulrik Grønbjerg , Pedersen Thomas , Sebok Bela , Schweinberger Florian Frank , Vesborg Peter Christian Kjærgaard , Hansen Ole , Schiøtz Jakob , Heiz Ulrich , Chorkendorff Ib
Published: June 2016

Hydrogen dissociation on mono-disperse platinum clusters is found to increase with minute amounts of oxygen in the gas stream.