bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodegradability, flammability, dimensional stability, and UV resistance study of green wood starch gluten nanocomposites
Authors: Baishya Prasanta , Saikia Devabrata , Mandal Manabendra , Maji Tarun K.
Published: October 2017

Biodegradable and UV resistant wood starch gluten nanocomposites (WSGNC) were prepared successfully from the natural polymers like starch and gluten, natural crosslinker and natural solvent via a green route using solution blending technique followed by compression molding. In this procedure, the starch gluten (50/50) blend was grafted with methyl methacrylate (MMA‐g‐SG) and citric acid was used to crosslink the MMA‐g‐SG with wood flour from Ipomoea carnea using water as a solvent. Later, Nano TiO2 was added in the composites to improve the properties like UV stability and flammability. The effects of TiO2 nanoparticles on biodegradability and UV stability of the composites were thoroughly investigated. The bacterial growth on the samples was analyzed by UV spectrophotometry and morphological features of the bacterial degraded samples was investigated by SEM study. The UV‐degraded samples were analyzed by FTIR and SEM study. It was observed that the incorporation of 3 phr TiO2 in the composites significantly improved the UV stability and hardness values of the composites. The flammability and dimensional stability of the nanocomposite were also improved with 3 phr nano TiO2 loading compared to TiO2‐untreated composites. POLYM. COMPOS., 40:46–55, 2019. © 2017 Society of Plastics Engineers
Who benefits from fixed‐dose combinations? Two‐year statin adherence trajectories in initiators of combined amlodipine/atorvastatin therapy
Authors: Schaffer Andrea L. , Buckley Nicholas A. , Pearson Sallie‐Anne
Published: October 2017

Purpose

We compared statin adherence in individuals initiating combined amlodipine/atorvastatin therapy as a fixed‐dose (FDC) or free combination and identified subgroups benefiting most from FDCs.

Methods

We used a 10% sample of Australian Pharmaceutical Benefits Scheme dispensing data (2005‐2015) to identify individuals initiating amlodipine and atorvastatin as an FDC (n = 3996) or free combination (n = 5434), with or without prior statin dispensing. We measured the proportion of days covered in each 30‐day period over 24 months and classified patterns of statin adherence using group‐based trajectory models. We identified predictors of adherence trajectories using logistic regression.

Results

The median age was 71 years, and 53% were female. We identified 4 patterns of statin adherence: near‐perfect adherence (n = 5383), good adherence (n = 1893), declining adherence (n = 1247), and early nonadherence (n = 907). Compared with the free combination, FDC initiators were more likely to have near‐perfect adherence if they were previously statin adherent irrespective of amlodipine dose (amlodipine 5 mg: OR = 1.61, 95% CI 1.38‐1.87; amlodipine 10 mg: OR = 2.39, 95% CI 1.63‐3.51) or they were previously statin nonadherent and initiated on the 5 mg amlodipine dose (OR = 1.87, 95% CI 1.50‐2.32). Statin‐naïve individuals initiating on the FDC with 10 mg amlodipine were less likely to have near‐perfect adherence (OR = 0.60, 95% CI 0.41‐0.88) and more likely to have early nonadherence (OR = 1.73, 95% CI 1.17‐2.55).

Conclusions

The amlodipine/atorvastatin FDC was associated with greater statin adherence among prevalent statin users, and individuals who initiated on lower amlodipine doses. The FDCs did not improve adherence in statin‐naïve individuals and in some cases resulted in poorer adherence.
Development of an Adult Physiologically Based Pharmacokinetic Model of Solithromycin in Plasma and Epithelial Lining Fluid
Authors: Salerno Sara N. , Edginton Andrea , Cohen‐Wolkowiez Michael , Hornik Christoph P. , Watt Kevin M. , Jamieson Brian D. , Gonzalez Daniel
Published: October 2017

Solithromycin is a fluoroketolide antibiotic under investigation for community‐acquired bacterial pneumonia (CABP). We developed a whole‐body physiologically based pharmacokinetic (PBPK) model for solithromycin in adults using PK‐Sim and MoBi version 6.2, which incorporated time‐dependent CYP3A4 auto‐inhibition. The model was developed and evaluated using plasma and epithelial lining fluid (ELF) concentration data from 100 healthy subjects and 22 patients with CABP (1,966 plasma, 30 ELF samples). We performed population simulations and calculated the number of observations falling outside the 90% prediction interval. For the oral regimen (800 mg on day 1 and 400 mg daily on days 2–5) that was evaluated in phase III studies, 11% and 23% of observations from healthy adults fell outside the 90% prediction interval for plasma and ELF, respectively. This regimen should be effective because ≥97% of simulated adults achieved area under the concentration vs. time curve (AUC) to minimum inhibitory concentration ratios associated with a log10 colony forming unit reduction in ELF.
Peptic ulcer risk with antidepressants and NSAIDs
Authors: Lam Y. W. Francis
Published: October 2017

Although the selective serotonin reuptake inhibitors (SSRIs) have a very good safety profile, they have been associated with spontaneous bleeding in some patients. The risk could be further increased if patients are taking concurrent nonsteroidal anti‐inflammatory drugs (NSAIDs). Investigators recently conducted a retrospective analysis to evaluate the risk of peptic ulcer disease associated with concomitant use of both classes of drugs, as compared with use of antidepressants alone, as well as to examine the differential risk among the various classes of antidepressants and individual antidepressants.
Surface analytical approaches to reliably characterize lithium ion battery electrodes
Authors: Azmi R. , Trouillet V. , Strafela M. , Ulrich S. , Ehrenberg H. , Bruns M.
Published: October 2017

Active Li‐ion battery materials are typically characterized using X‐ray photoelectron spectroscopy when regarding chemical state elucidation. This work presents a multiplet‐splitting approach comprising in minimum 3 third‐row transition metals, namely, Mn, Co, and Ni, to improve the results in comparison to peak barycenter or single symmetric Voigt profile approaches. The achieved X‐ray photoelectron spectroscopy 2p templates in particular address the complex peak structures consisting of significant photoelectron multiplet splitting, shake‐up and plasmon loss features, and additional Auger and photoelectron overlaps, inevitable also for a reliable quantification. To separate from topography effects and contributions of the electrode's binder and conductive carbon in powder electrodes, the developed procedure in a first attempt was successfully transferred to novel radio frequency magnetron sputtered Li‐Ni‐Co‐Mn‐O thin films, designed for all‐solid‐state Li‐ion batteries. In all cases, special care was taken with respect to air sensitivity, contamination during sample handling, and probable method induced sample decomposition.
Isolation and Characterisation of a Halotolerant ω‐Transaminase from a Triassic Period Salt Mine and Its Application to Biocatalysis
Authors: Kelly Stephen A. , Megaw Julianne , Caswell Jill , Scott Christopher J. , Allen Christopher C. R. , Moody Thomas S. , Gilmore Brendan F.
Published: October 2017

Chiral amines are valuable intermediates for the pharmaceutical industry, with up to 40% of current pharmaceuticals containing an amine functionality. However, their syntheses by conventional chemical methods often suffer from a number of key drawbacks. Transaminases (TAms) are pyridoxal phosphate (PLP) dependent enzymes capable of transferring an amine group to a prochiral ketone, offering a green and economically viable alternative to chiral amine production. Despite some high profile successes, TAms suffer from limited substrate scope and the ability to function under challenging conditions often required in reaction processes. Mining of untapped, extremophilic environments represents a viable approach in the search for novel enzymes. We report the cloning and expression of an (S)‐selective ω‐TAm from a Halomonas sp. (Ad2‐TAm), isolated from an extreme hypersaline environment formed during the Triassic period (circa 220 mya). Ad2‐TAm exhibits an ability to convert a range of structurally diverse aldehyde and ketone substrates, with no decrease in conversion up to 1.5 M (8.8%) NaCl. The enzyme is also tolerant to the presence of organic cosolvents up to 30% and accepts a range of amino donors. These characteristics make Ad2‐TAm a promising candidate for industrial applications, whilst also highlighting the value of extreme environments as a source of novel enzymes for the pharmaceutical industry as a whole.
Enhancing Oxygen Reduction Activity by Exposing (111) Facets of CoFe2O4 Octahedron on Graphene
Authors: Zhang Yong , Zhang Guoxin , Li Wanxi , Li Xiaoming , Uchiyama Katsumi , Chen Chengmeng
Published: October 2017

Efficient catalysts are required to promote oxygen reduction reaction (ORR) in order to implant ORR‐involved clean energy technologies such as fuel cells and metal‐air batteries. In this study, (111) facet‐exposed CoFe2O4 nano‐octahedrons crystals (NOCs) were grown on graphene via facile hydrothermal method and investigated as catalyst for ORR. The as‐made CoFe2O4 NOCs‐graphene composite exhibits very high activity towards ORR, meanwhile, excellent durability and very good tolerance to methanol were observed, which verifies the importance of exposing active facets of non‐precious metal‐based catalysts and also demonstrates its high potentials of replacing precious Pt for practical applications.
Polarity‐Dependant Intramolecular Charge Transfer Characteristics of 9‐Cyano‐10‐(1H‐pyrrol‐1‐yl)anthracene: Photophysical Investigations
Authors: Gharat Poojan Milan , Muralidharan Sukumaran , Sundararajan Mahesh , Pal Haridas , Dutta Choudhury Sharmistha
Published: October 2017

The photophysics of a newly synthesized donor‐acceptor substituted chromophore, 9‐cyano‐10‐(1H‐pyrrol‐1‐yl)anthracene (CPAN), reveals interesting features that suggest the involvement of two types of charge transfer configurations in its excited state. Dual emission bands are observed in polar and nonpolar solvents due to fluorescence from both locally excited (LE) and intramolecular charge transfer (ICT) states. From detailed analysis of the time‐resolved fluorescence data, it is proposed that by increasing the polarity of the medium the nature of the emissive ICT state is switched from a molecular conformation that is more planar (ICT1) to one that is more twisted (ICT2), compared to the ground state. Preliminary geometry optimizationsand calculated molecular parameters of CPAN in the ground and excited states, lend support to the experimental results. Qualitative potential energy diagrams are presented to substantiate the proposed model and rationalize the observed photophysics.
Direct Conversion of Glycerol to Allyl Alcohol Over Alumina‐Supported Rhenium Oxide
Authors: Kon Yoshihiro , Araque Marcia , Nakashima Takuya , Paul Sébastien , Dumeignil Franck , Katryniok Benjamin
Published: October 2017

The deoxydehydration (DODH) of glycerol was studied using several Re‐based catalysts in the liquid phase under atmospheric pressure conditions. The best performance was observed over 10 wt.% ReOx/Al2O3 with 2‐hexanol as a reductive agent giving allyl alcohol with an exceptional yield of 91%. The reaction was confirmed to be catalysed heterogeneously, since the reaction stopped upon removal of the catalyst by hot filtration. The corresponding catalyst was further successfully reused three times without any leaching of rhenium species, as shown by elemental analysis. Based on the characterisation of the fresh and the spent catalyst by XPS and Raman spectroscopy, a reaction mechanism is proposed, which involves the redox‐couple Re(V) / Re(VII).
The effect of fluoride on the structure, function, and proteome of intestinal epithelia
Authors: Amadeu de Oliveira Flávia , MacVinish Lesley J. , Amin Simran , Herath Duleni , Jeggle Pia , Mela Ioanna , Pieri Maria , Sharma Chetanya , Jarvis Gavin E. , Levy Flávia M. , Santesso Mariana R. , Khan Zohaib N. , Leite Aline L. , Oliveira Rodrigo C. , Buzalaf Marília A. R. , Edwardson J. Michael
Published: October 2017

Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride exposure. Here, we examined the effects of fluoride on the transepithelial ion transport and resistance of three intestinal epithelia. We used the Caco‐2 cell line as a model of human intestinal epithelium, and rat and mouse colonic epithelia for purposes of comparison. Fluoride caused a concentration‐dependent decline in forskolin‐induced Cl– secretion and transepithelial resistance of Caco‐2 cell monolayers, with an IC50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t1/2 of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron microscopy showed structural abnormalities in Caco‐2 cell monolayers exposed to fluoride. The Young's modulus of the epithelium was not affected by fluoride, although proteomic analysis revealed changes in expression of a number of proteins, particularly those involved in cell–cell adhesion. In line with its effects on Caco‐2 cell monolayers, fluoride, at 5 mM, also had profound effects on Cl– secretion and transepithelial resistance of both rat and mouse colonic epithelia. Our results show that treatment with fluoride has major effects on the structure, function, and proteome of intestinal epithelia, but only at concentrations considerably higher than those likely to be encountered in vivo, when much lower fluoride doses are normally ingested on a chronic basis.
Symposia in undergraduate medical education: tailoring training in competencies to students’ needs
Authors: Reefman Karin , Daelmans Hester E. M. , Ursula M. H. Klumpers Ursula M. H. , Croiset Gerda
Published: October 2017

Introduction In mastering competencies, it is a challenge to create training sessions which acknowledge individual students’ needs and are logistically feasible in the medical master’s program.

Methods Symposia were implemented in the medical master’s program to provide knowledge and training of skills in a number of topics, providing a positive contribution to students’ competencies and personal development. Each symposium contained a morning and afternoon program, structured around medical and societal themes addressing various competencies and covering current national and international events. Alternating interactive teaching methods were used. Students were asked to rate each daypart program on a 5-point Likert scale in terms of both teaching methods and content, and to comment on the best aspects of the symposium as well as areas for improvement. Scores higher than 3.5 were interpreted as a predominantly favourable outcome.

Results In 2016, 10 symposia were organized with an average of 108 attendees and a response rate of 63% (1,366 completed questionnaires). Mean overall scores on ‘teaching methods’ and ‘usefulness for professional development’ were 3.8 and 3.7, respectively. The overall results corresponded with a high level of student appreciation.

Conclusion Symposia offer a podium for training students in subject matter and competencies that is greatly appreciated. Using alternating interactive teaching methods, symposia are structured around medical and societal themes and adjusted to the latest developments and current events in healthcare. By allowing students to select the symposia they would like to participate in, a tailor-made medical master’s program in competencies is created.
Public debate on metallic hydrogen to boost high pressure research
Authors: Geng Hua Y.
Published: October 2017

Instead of praises from colleagues, the claim of observation of metallic hydrogen at 495 GPa by Dias and Silvera met much skepticism, and grew into a public debate at the International Conference on High-Pressure Science and Technology, AIRAPT26. We briefly review this debate, and extend the topic to show that this disputation could be an opportunity to benefit the whole high pressure community.
John Dalton and the origin of the atomic theory: reassessing the influence of Bryan Higgins
Authors: GROSSMAN MARK I.
Published: October 2017

During the years 1814–1819, William Higgins, an Irish chemist who worked at the Dublin Society, claimed he had anticipated John Dalton in developing the atomic theory and insinuated that Dalton was a plagiarist. This essay focuses not on William Higgins, but on his uncle Bryan Higgins, a well-known chemist of his day, who had developed his own theories of caloric and chemical combination, similar in many respects to that of Dalton. New evidence is first introduced addressing Bryan's disappearance from the scientific community after 1803. In his later years, Bryan apparently suffered from a condition resulting in a decline in his mental health, which explains why he never lodged any priority claims of his own against Dalton, or defended those of his nephew. Dalton's mention of Bryan's name in Part II ofA New System of Chemical Philosophy, his laboratory notebook entries, and a fresh look at his correspondence with chemist Thomas Charles Hope indicate that Dalton adopted a Higgins-like caloric model in 1803. Together these factors provide evidence to support the argument that Dalton learned of Bryan's theories via a meeting he had with William Allen on 10 July 1803. Existing evidence related to the origin of the atomic theory is worthy of re-examination in light of Dalton's possible prior knowledge of Bryan's work.
FURROWING PROWS: VARRO OF ATAX'SARGONAVTAEAND TRANSGRESSIVE SAILING IN VIRGIL'SAENEID
Authors: Polt Christopher B.
Published: October 2017

Discussing different types of metaphor, Isidore of Seville quotes an anonymous fragment that uses agricultural vocabulary to describe the sailing of a ship in order to illustratemetaphorae ab inanimali ad inanimale‘metaphors taken from inanimate objects and applied to inanimate objects’ (Etym.1.37.3 = inc. fr. 63 Blänsdorf):1
Mansonella ozzardiand its vectors in the New World: an update with emphasis on the current situation in Haiti
Authors: Raccurt C.P.
Published: October 2017

Mansonella ozzardi(Nematoda: Onchocercidae) is a little studied filarial nematode. This human parasite, transmitted by two families of dipteran vectors, biting midges (most of them members of the genusCulicoides) and blackflies (genusSimulium), is endemic to the Neotropical regions of the New World. With a patchy geographical distribution from southern Mexico to north-western Argentina, human infection withM. ozzardiis highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. Studies conducted in Haiti between 1974 and 1984 allowed the first complete description of the adult worm and permitted clarification of the taxonomic position of this filarial species. This paper reports the known geographical distribution ofM. ozzardiin Neotropical regions of the Americas, and focuses on the current situation in Haiti where this filariasis remains a completely neglected public health problem.
Laryngomalacia: is there an evidence base for management?
Authors: McCaffer C , Blackmore K , Flood L M
Published: October 2017

Background:

The advent of supraglottoplasty clearly has transformed the surgical management of severe laryngomalacia. The condition, however, generally runs a milder course, with spontaneous resolution the norm.

Objectives:

To identify gaps in the knowledge and identify topics for future study.

Method:

Systematic review of the literature.

Results:

The literature suggests that there is a range of abnormalities leading to the typical collapsing upper airway, and that neurological disease, other airway abnormalities, syndromes and gastroesophageal reflux all contribute to disease severity and influence outcomes. The procedures involved in supraglottoplasty are rarely specified, the indications for surgery are vaguely defined and the role of medical therapy is unclear.

Conclusion:

Every review article or survey of opinion suggests that there is still a marked variation in individual practice and a lack of consensus.
Flor do Abacate: Workers of African Descent, Dancing Associations and Nationality in Rio de Janeiro, 1898–1914
Authors: DE MIRANDA PEREIRA LEONARDO AFFONSO
Published: October 2017

From the last years of the nineteenth century until the first decades of the twentieth, the inhabitants of Rio de Janeiro witnessed a new social phenomenon: the proliferation, in every neighbourhood, of small dance clubs formed by workers. Noteworthy among them was the Flor do Abacate, a recreational society founded in 1906 by a group of men and women of African descent. Far from making any claim to ‘being African’, this association promoted balls and parades in which African cultural heritage was shown in conjunction with other cultural logics valued as modern and cosmopolitan. As a consequence, it constituted a model of recreational society, black and modern at the same time, which its members tried to associate to a national profile. The objective of this article is to analyse both the logic that explains the organisation of this dance society and the challenges that its members faced in consolidating it.
EXAMINING EVIDENCE IN U.S. PAYER COVERAGE POLICIES FOR MULTI-GENE PANELS AND SEQUENCING TESTS
Authors: Chambers James D. , Saret Cayla J. , Anderson Jordan E. , Deverka Patricia A. , Douglas Michael P. , Phillips Kathryn A.
Published: October 2017

Objectives: The aim of this study was to examine the evidence payers cited in their coverage policies for multi-gene panels and sequencing tests (panels), and to compare these findings with the evidence payers cited in their coverage policies for other types of medical interventions.

Methods: We used the University of California at San Francisco TRANSPERS Payer Coverage Registry to identify coverage policies for panels issued by five of the largest US private payers. We reviewed each policy and categorized the evidence cited within as: clinical studies, systematic reviews, technology assessments, cost-effectiveness analyses (CEAs), budget impact studies, and clinical guidelines. We compared the evidence cited in these coverage policies for panels with the evidence cited in policies for other intervention types (pharmaceuticals, medical devices, diagnostic tests and imaging, and surgical interventions) as reported in a previous study.

Results: Fifty-five coverage policies for panels were included. On average, payers cited clinical guidelines in 84 percent of their coverage policies (range, 73–100 percent), clinical studies in 69 percent (50–87 percent), technology assessments 47 percent (33–86 percent), systematic reviews or meta-analyses 31 percent (7–71 percent), and CEAs 5 percent (0–7 percent). No payers cited budget impact studies in their policies. Payers less often cited clinical studies, systematic reviews, technology assessments, and CEAs in their coverage policies for panels than in their policies for other intervention types. Payers cited clinical guidelines in a comparable proportion of policies for panels and other technology types.

Conclusions: Payers in our sample less often cited clinical studies and other evidence types in their coverage policies for panels than they did in their coverage policies for other types of medical interventions.
SECULAR FERTILITY DECLINES, BABY BOOMS, AND ECONOMIC GROWTH: INTERNATIONAL EVIDENCE
Authors: Tamura Robert , Simon Curtis
Published: October 2017

We present a model capable of explaining 200 years of declining fertility, 200 years of rising educational achievement, and a significant baby boom for the United States and twenty other industrialized market countries. We highlight the importance of secularly declining young adult mortality risk for producing secularly declining fertility and a sudden decline in housing costs after the end of the Second World War, but ending by 1970. In addition, we introduce a new puzzle for the profession: Given the magnitude of the Baby Boom, roughly equal to fertility in 1900 for many of these countries, why did schooling of the Baby Boom cohorts not fall to the 1900 level of their predecessors? In fact, not only did it not fall, but the schooling levels of these cohorts are higher than for previous cohorts. Using a quantitative model, we are able to identify the magnitude of the reduction in costs of education necessary to explain this paradoxical increase in schooling. We produce a novel data set on historical education expenditures with over 1,500 observations. We find empirical support for these cost reductions.
Evolutionary exobiology: towards the qualitative assessment of biological potential on exoplanets
Authors: Stevenson David S. , Large Sean
Published: October 2017

A planet may be defined as habitable if it has an atmosphere and is warm enough to support the existence of liquid water on its surface. Such a world has the basic set of conditions that allow it to develop life similar to ours, which is carbon-based and has water as its universal solvent. While this definition is suitably vague to allow a fairly broad range of possibilities, it does not address the question as to whether any life that does form will become either complex or intelligent. In this paper, we seek to synthesize a qualitative definition of which subset of these ‘habitable worlds’ might develop more complex and interesting life forms. We identify two key principles in determining the capacity of life to breach certain transitions on route to developing intelligence. The first is the number of potential niches a planet provides. Secondly, the complexity of life will reflect the information density of its environment, which in turn can be approximated by the number of available niches. We seek to use these criteria to begin the process of placing the evolution of terrestrial life in a mathematical framework based on environmental information content. This is currently testable on Earth and will have clear application to the worlds that we are only beginning to discover. Our model links the development of complex life to the physical properties of the planet, something which is currently lacking in all evolutionary theory.
Biggs Receives 2017 Geodesy Section Award
Authors:   AGU
Published: October 2017

Juliet Biggs will receive the 2017 Geodesy Section Award at the 2017 American Geophysical Union Fall Meeting, to be held 11–15 December in New Orleans, La. The award is given “in recognition of major advances in geodesy.”
Hudnut Receives 2017 Ivan I. Mueller Award for Distinguished Service and Leadership
Authors:   AGU
Published: October 2017

Kenneth Hudnut will receive the 2017 Ivan I. Mueller Award for Distinguished Service and Leadership at the 2017 American Geophysical Union Fall Meeting, to be held 11–15 December in New Orleans, La. The award acknowledges “major achievements in service to and/or leadership within the field of geodesy.”
Three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT)
Authors: Pégard Nicolas C. , Mardinly Alan R. , Oldenburg Ian Antón , Sridharan Savitha , Waller Laura , Adesnik Hillel
Published: October 2017

Optical methods capable of manipulating neural activity with cellular resolution and millisecond precision in three dimensions will accelerate the pace of neuroscience research. Existing approaches for targeting individual neurons, however, fall short of these requirements. Here we present a new multiphoton photo-excitation method, termed three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT), which allows precise, simultaneous photo-activation of arbitrary sets of neurons anywhere within the addressable volume of a microscope. This technique uses point-cloud holography to place multiple copies of a temporally focused disc matching the dimensions of a neuron’s cell body. Experiments in cultured cells, brain slices, and in living mice demonstrate single-neuron spatial resolution even when optically targeting randomly distributed groups of neurons in 3D. This approach opens new avenues for mapping and manipulating neural circuits, allowing a real-time, cellular resolution interface to the brain.
Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings
Authors: Lafon Belen , Henin Simon , Huang Yu , Friedman Daniel , Melloni Lucia , Thesen Thomas , Doyle Werner , Buzsáki György , Devinsky Orrin , Parra Lucas C. , A. Liu Anli
Published: October 2017

Transcranial electrical stimulation has widespread clinical and research applications, yet its effect on ongoing neural activity in humans is not well established. Previous reports argue that transcranial alternating current stimulation (tACS) can entrain and enhance neural rhythms related to memory, but the evidence from non-invasive recordings has remained inconclusive. Here, we measure endogenous spindle and theta activity intracranially in humans during low-frequency tACS and find no stable entrainment of spindle power during non-REM sleep, nor of theta power during resting wakefulness. As positive controls, we find robust entrainment of spindle activity to endogenous slow-wave activity in 66% of electrodes as well as entrainment to rhythmic noise-burst acoustic stimulation in 14% of electrodes. We conclude that low-frequency tACS at common stimulation intensities neither acutely modulates spindle activity during sleep nor theta activity during waking rest, likely because of the attenuated electrical fields reaching the cortical surface.
Microbial community-level regulation explains soil carbon responses to long-term litter manipulations
Authors: Georgiou Katerina , Abramoff Rose Z. , Harte John , Riley William J. , Torn Margaret S.
Published: October 2017

Climatic, atmospheric, and land-use changes all have the potential to alter soil microbial activity, mediated by changes in plant inputs. Many microbial models of soil organic carbon (SOC) decomposition have been proposed recently to advance prediction of climate and carbon (C) feedbacks. Most of these models, however, exhibit unrealistic oscillatory behavior and SOC insensitivity to long-term changes in C inputs. Here we diagnose the source of these problems in four archetypal models and propose a density-dependent formulation of microbial turnover, motivated by community-level interactions, that limits population sizes and reduces oscillations. We compare model predictions to 24 long-term C-input field manipulations and identify key benchmarks. The proposed formulation reproduces soil C responses to long-term C-input changes and implies greater SOC storage associated with CO2-fertilization-driven increases in C inputs over the coming century compared to recent microbial models. This study provides a simple modification to improve microbial models for inclusion in Earth System Models.
Direct observation of the nanoscale Kirkendall effect during galvanic replacement reactions
Authors: Chee See Wee , Tan Shu Fen , Baraissov Zhaslan , Bosman Michel , Mirsaidov Utkur
Published: October 2017

Galvanic replacement (GR) is a simple and widely used approach to synthesize hollow nanostructures for applications in catalysis, plasmonics, and biomedical research. The reaction is driven by the difference in electrochemical potential between two metals in a solution. However, transient stages of this reaction are not fully understood. Here, we show using liquid cell transmission electron microscopy that silver (Ag) nanocubes become hollow via the nucleation, growth, and coalescence of voids inside the nanocubes, as they undergo GR with gold (Au) ions at different temperatures. These direct in situ observations indicate that void formation due to the nanoscale Kirkendall effect occurs in conjunction with GR. Although this mechanism has been suggested before, it has not been verified experimentally until now. These experiments can inform future strategies for deriving such nanostructures by providing insights into the structural transformations as a function of Au ion concentration, oxidation state of Au, and temperature.
Phosphatidylinositol transfer protein-α in platelets is inconsequential for thrombosis yet is utilized for tumor metastasis
Authors: Zhao Liang , Thorsheim Chelsea L. , Suzuki Aae , Stalker Timothy J. , Min Sang H. , Lian Lurong , Fairn Gregory D. , Cockcroft Shamshad , Durham Amy , Krishnaswamy Sriram , Abrams Charles S.
Published: October 2017

Platelets are increasingly recognized for their contributions to tumor metastasis. Here, we show that the phosphoinositide signaling modulated by phosphatidylinositol transfer protein type α (PITPα), a protein which shuttles phosphatidylinositol between organelles, is essential for platelet-mediated tumor metastasis. PITPα-deficient platelets have reduced intracellular pools of phosphoinositides and an 80% reduction in IP3 generation upon platelet activation. Unexpectedly, mice lacking platelet PITPα form thrombi normally at sites of intravascular injuries. However, following intravenous injection of tumor cells, mice lacking PITPα develop fewer lung metastases due to a reduction of fibrin formation surrounding the tumor cells, rendering the metastases susceptible to mucosal immunity. These findings demonstrate that platelet PITPα-mediated phosphoinositide signaling is inconsequential for in vivo hemostasis, yet is critical for in vivo dissemination. Moreover, this demonstrates that signaling pathways within platelets may be segregated into pathways that are essential for thrombosis formation and pathways that are important for non-hemostatic functions.
Molecular rheotaxis directs DNA migration and concentration against a pressure-driven flow
Authors: Friedrich Sarah M. , Burke Jeffrey M. , Liu Kelvin J. , Ivory Cornelius F. , Wang Tza-Huei
Published: October 2017

In-line preconcentration techniques are used to improve the sensitivity of microfluidic DNA analysis platforms. The most common methods are electrokinetic and require an externally applied electric field. Here we describe a microfluidic DNA preconcentration technique that does not require an external field. Instead, pressure-driven flow from a fluid-filled microcapillary into a lower ionic strength DNA sample reservoir induces spontaneous DNA migration against the direction of flow. This migratory phenomenon that we call Molecular Rheotaxis initiates in seconds and results in a concentrated DNA bolus at the capillary orifice. We demonstrate the ease with which this concentration method can be integrated into a microfluidic total analysis system composed of in-line DNA preconcentration, size separation, and single-molecule detection. Paired experimental and numerical simulation results are used to delineate the parameters required to induce Molecular Rheotaxis, elucidate the underlying mechanism, and optimize conditions to achieve DNA concentration factors exceeding 10,000 fold.
Thioredoxin-1 protects against androgen receptor-induced redox vulnerability in castration-resistant prostate cancer
Authors: Samaranayake Govindi J. , Troccoli Clara I. , Huynh Mai , Lyles Rolando D. Z. , Kage Karen , Win Andrew , Lakshmanan Vishalakshi , Kwon Deukwoo , Ban Yuguang , Chen Steven Xi , Zarco Enrique Rodriguez , Jorda Merce , Burnstein Kerry L. , Rai Priyamvada
Published: October 2017

Androgen deprivation (AD) therapy failure leads to terminal and incurable castration-resistant prostate cancer (CRPC). We show that the redox-protective protein thioredoxin-1 (TRX1) increases with prostate cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1. TRX1 inhibition via shRNA or a phase I-approved inhibitor, PX-12 (untested in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-dependent counterparts. TRX1 inhibition elevates reactive oxygen species (ROS), p53 levels and cell death in androgen-deprived CRPC cells. Unexpectedly, TRX1 inhibition also elevates androgen receptor (AR) levels under AD, and AR depletion mitigates both TRX1 inhibition-mediated ROS production and cell death, suggesting that AD-resistant AR expression in CRPC induces redox vulnerability. In vivo TRX1 inhibition via shRNA or PX-12 reverses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation under systemic AD. Thus, TRX1 is an actionable CRPC therapeutic target through its protection against AR-induced redox stress.
Transformation of doped graphite into cluster-encapsulated fullerene cages
Authors: Mulet-Gas Marc , Abella Laura , Cerón Maira R. , Castro Edison , Marshall Alan G. , Rodríguez-Fortea Antonio , Echegoyen Luis , Poblet Josep M. , Dunk Paul W.
Published: October 2017

An ultimate goal in carbon nanoscience is to decipher formation mechanisms of highly ordered systems. Here, we disclose chemical processes that result in formation of high-symmetry clusterfullerenes, which attract interest for use in applications that span biomedicine to molecular electronics. The conversion of doped graphite into a C80 cage is shown to occur through bottom-up self-assembly reactions. Unlike conventional forms of fullerene, the iconic Buckminsterfullerene cage, Ih-C60, is entirely avoided in the bottom-up formation mechanism to afford synthesis of group 3-based metallic nitride clusterfullerenes. The effects of structural motifs and cluster–cage interactions on formation of compounds in the solvent-extractable C70–C100 region are determined by in situ studies of defined clusterfullerenes under typical synthetic conditions. This work establishes the molecular origin and mechanism that underlie formation of unique carbon cage materials, which may be used as a benchmark to guide future nanocarbon explorations.
Hierarchical self-entangled carbon nanotube tube networks
Authors: Schütt Fabian , Signetti Stefano , Krüger Helge , Röder Sarah , Smazna Daria , Kaps Sören , Gorb Stanislav N. , Mishra Yogendra Kumar , Pugno Nicola M. , Adelung Rainer
Published: October 2017

Three-dimensional (3D) assemblies based on carbon nanomaterials still lag behind their individual one-dimensional building blocks in terms of mechanical and electrical properties. Here we demonstrate a simple strategy for the fabrication of an open porous 3D self-organized double-hierarchical carbon nanotube tube structure with properties advantageous to those existing so far. Even though no additional crosslinking exists between the individual nanotubes, a high reinforcement effect in compression and tensile characteristics is achieved by the formation of self-entangled carbon nanotube (CNT) networks in all three dimensions, employing the CNTs in their high tensile properties. Additionally, the tubular structure causes a self-enhancing effect in conductivity when employed in a 3D stretchable conductor, together with a high conductivity at low CNT concentrations. This strategy allows for an easy combination of different kinds of low-dimensional nanomaterials in a tube-shaped 3D structure, enabling the fabrication of multifunctional inorganic-carbon-polymer hybrid 3D materials.
Diversity oriented biosynthesis via accelerated evolution of modular gene clusters
Authors: Wlodek Aleksandra , Kendrew Steve G. , Coates Nigel J. , Hold Adam , Pogwizd Joanna , Rudder Steven , Sheehan Lesley S. , Higginbotham Sarah J. , Stanley-Smith Anna E. , Warneck Tony , Nur-E-Alam Mohammad , Radzom Markus , Martin Christine J. , Overvoorde Lois , Samborskyy Markiyan , Alt Silke , Heine Daniel , Carter Guy T. , Graziani Edmund I. , Koehn Frank E. , McDonald Leonard , Alanine Alexander , Rodríguez Sarmiento Rosa María , Chao Suzan Keen , Ratni Hasane , Steward Lucinda , Norville Isobel H. , Sarkar-Tyson Mitali , Moss Steven J. , Leadlay Peter F. , Wilkinson Barrie , Gregory Matthew A.
Published: October 2017

Erythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular polyketide synthase multienzymes by an assembly-line process in which each module of enzymes in turn specifies attachment of a particular chemical unit. Although polyketide synthase encoding genes have been successfully engineered to produce novel analogues, the process can be relatively slow, inefficient, and frequently low-yielding. We now describe a method for rapidly recombining polyketide synthase gene clusters to replace, add or remove modules that, with high frequency, generates diverse and highly productive assembly lines. The method is exemplified in the rapamycin biosynthetic gene cluster where, in a single experiment, multiple strains were isolated producing new members of a rapamycin-related family of polyketides. The process mimics, but significantly accelerates, a plausible mechanism of natural evolution for modular polyketide synthases. Detailed sequence analysis of the recombinant genes provides unique insight into the design principles for constructing useful synthetic assembly-line multienzymes.
Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors
Authors: Cheng Jiqiu , Demeulemeester Jonas , Wedge David C. , Vollan Hans Kristian M. , Pitt Jason J. , Russnes Hege G. , Pandey Bina P. , Nilsen Gro , Nord Silje , Bignell Graham R. , White Kevin P. , Børresen-Dale Anne-Lise , Campbell Peter J. , Kristensen Vessela N. , Stratton Michael R. , Lingjærde Ole Christian , Moreau Yves , Van Loo Peter
Published: October 2017

Homozygous deletions are rare in cancers and often target tumour suppressor genes. Here, we build a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions, aiming to identify rare tumour suppressors. Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. We find 16 established tumour suppressors and propose 27 candidate tumour suppressors. Several of these genes (including MGMT, RAD17, and USP44) show prior evidence of a tumour suppressive function. Other candidate tumour suppressors, such as MAFTRR, KIAA1551, and IGF2BP2, are novel. Our study demonstrates how rare tumour suppressors can be identified through copy number meta-analysis.
Nonlinear photon-atom coupling with 4Pi microscopy
Authors: Chin Yue-Sum , Steiner Matthias , Kurtsiefer Christian
Published: October 2017

Implementing nonlinear interactions between single photons and single atoms is at the forefront of optical physics. Motivated by the prospects of deterministic all-optical quantum logic, many efforts are currently underway to find suitable experimental techniques. Focusing the incident photons onto the atom with a lens yielded promising results, but is limited by diffraction to moderate interaction strengths. However, techniques to exceed the diffraction limit are known from high-resolution imaging. Here we adapt a super-resolution imaging technique, 4Pi microscopy, to efficiently couple light to a single atom. We observe 36.6(3)% extinction of the incident field, and a modified photon statistics of the transmitted field–indicating nonlinear interaction at the single-photon level. Our results pave the way to few-photon nonlinear optics with individual atoms in free space.
Direct Evidence of Adult Aedes albopictus Dispersal by Car
Authors: Eritja Roger , Palmer John R. B. , Roiz David , Sanpera-Calbet Isis , Bartumeus Frederic
Published: October 2017

Whereas the Asian tiger mosquito (Aedes albopictus) has low active dispersal capabilities, its worldwide colonization has been rapid. Indirect evidence and informal reports have long implicated passive transportation in cars, but this has not previously been studied systematically given the difficulties of real-time roadside surveys. Here we report the first sampling study confirming that adult tiger mosquitoes travel with humans in cars and enabling us to estimate the frequency of these events. We combine the results with citizen science data to model the car-facilitated dispersal of Aedes albopictus at a nationwide level. During the summer of 2015, we sampled 770 cars in north-eastern Spain, discovering 4 adult female tiger mosquitoes that had entered cars prior to sampling. Our Bayesian model suggests that of the 6.5 million daily car trips in the Barcelona metropolitan area, between 13,000 and 71,500 facilitate tiger mosquito movement, and that Barcelona is the largest source of inter-province tiger mosquito transfers in Spain. Our results are supported by expert-validated citizen science data, and will contribute to better understanding the tiger mosquito’s invasion process and ultimately lead to more effective vector control strategies.
Effects of strength training and raloxifene on femoral neck metabolism and microarchitecture of aging female Wistar rats
Authors: Stringhetta-Garcia Camila Tami , Morais Samuel Rodrigues Lourenço , Fernandes Fernanda , Perez-Ueno Melise Jacon , Almeida Ricardo de Paula , Louzada Mário Jefferson Quirino , Chaves-Neto Antonio Hernandes , Ervolino Edilson , Dornelles Rita Cássia Menegati
Published: October 2017

The aim of this study was to prevent female osteoporosis using strength training (ST), raloxifene (Ral) or a combination of ST plus Ral during the natural female aging process, specifically in the periestropause period. For a total of 120 days, aging female Wistar rats at 18-21 months of age performed ST on a ladder three times per week, and Ral was administered daily by gavage (1 mg/kg/day). Bone microarchitecture, areal bone mineral density, bone strength of the femoral neck, immunohistochemistry, osteoclast and osteoblast surface were assessed. We found that the treatments modulate the bone remodeling cycle in different ways. Both ST and Ral treatment resulted in improved bone microarchitecture in the femoral neck of rats in late periestropause. However, only ST improved cortical microarchitecture and bone strength in the femoral neck. Thus, we suggest that performing ST during the late period of periestropause is a valid intervention to prevent age-associated osteoporosis in females.
Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule
Authors: Ferrandez Yann , Zhang Wenhua , Peurois François , Akendengué Lurlène , Blangy Anne , Zeghouf Mahel , Cherfils Jacqueline
Published: October 2017

Rac small GTPases and their GEFs of the DOCK family are pivotal checkpoints in development, autoimmunity and bone homeostasis, and their abnormal regulation is associated to diverse pathologies. Small molecules that inhibit their activities are therefore needed to investigate their functions. Here, we characterized the mechanism of inhibition of human DOCK5 by C21, a small molecule that inhibits mouse Dock5 in cells and blocks bone degradation in mice models of osteoporosis. We showed that the catalytic DHR2 domain of DOCK5 has a high basal GEF activity in the absence of membranes which is not regulated by a simple feedback loop. C21 blocks this activity in a non-competitive manner and is specific for DOCK5. In contrast, another Dock inhibitor, CPYPP, inhibits both DOCK5 and an unrelated GEF, Trio. To gain insight into structural features of the inhibitory mechanism of C21, we used SAXS analysis of DOCK5DHR2 and crystallographic analysis of unbound Rac1-GDP. Together, these data suggest that C21 takes advantage of intramolecular dynamics of DOCK5 and Rac1 to remodel the complex into an unproductive conformation. Based on this allosteric mechanism, we propose that diversion of intramolecular dynamics is a potent mechanism for the inhibition of multidomain regulators of small GTPases.