bluuebunny/crossref_metadata_2025 huggingface dataset:
Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer
Authors: Hermanson David L. , Bendzick Laura , Pribyl Lee , McCullar Valarie , Vogel Rachel Isaksson , Miller Jeff S. , Geller Melissa A. , Kaufman Dan S.
Published: October 2015

Natural killer (NK) cells can provide effective immunotherapy for ovarian cancer. Here, we evaluated the ability of NK cells isolated from peripheral blood (PB) and NK cells derived from induced pluripotent stem cell (iPSC) to mediate killing of ovarian cancer cells in a mouse xenograft model. A mouse xenograft model was used to evaluate the intraperitoneal delivery of three different NK cell populations: iPSC-derived NK cells, PB-NK cells that had been activated and expanded in long-term culture, and overnight activated PB-NK cells that were isolated through CD3/CD19 depletion of PB B and T cells. Bioluminescent imaging was used to monitor tumor burden of luciferase expressing tumor lines. Tumors were allowed to establish prior to administering NK cells via intraperitoneal injection. These studies demonstrate a single dose of any of the three NK cell populations significantly reduced tumor burden. When mice were given three doses of either iPSC-NK cells or expanded PB-NK cells, the median survival improved from 73 days in mice untreated to 98 and 97 days for treated mice, respectively. From these studies, we conclude iPSC-derived NK cells mediate antiovarian cancer killing at least as well as PB-NK cells, making these cells a viable resource for immunotherapy for ovarian cancer. Due to their ability to be easily differentiated into NK cells and their long-term expansion potential, iPSCs can be used to produce large numbers of well-defined NK cells that can be banked and used to treat a large number of patients including treatment with multiple doses if necessary.
An observer‐based controller for a class of polynomial fuzzy systems with disturbance
Authors: Han Hugang
Published: October 2015

In this paper, a new observer‐based controller for a class of polynomial fuzzy systems with disturbance is proposed. First, by some appropriate equivalence transformation of the polynomial fuzzy model, the first output‐sized states can be obtained directly from the output, which eventually enables us to obtain the feedback control gain and observer‐related parameters together without considering the so‐called separation principle. Second, with the disturbance in mind, a PI‐type observer is suggested. Finally, the sum of squares for the stability of the closed‐loop observer‐based control system is provided. © 2015 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Shrieking, Just False and Exclusion
Authors: Young Gareth ,   Philosophy Documentation Center
Published: October 2015

In a recent paper (2013), Jc Beall has employed what he calls ‘shriek rules’ in a putative solution to the long-standing ‘just false’ problem for glut theory.The purpose of this paper is twofold: firstly, I distinguish the ‘just false’ problem from another problem, with which it is often conflated, which I will call the ‘exclusion problem’. Secondly, I argue that shriek rules do not help glut theorists with either problem.
Terrestrial Laser Scanning for Plot-Scale Forest Measurement
Authors: Newnham Glenn J. , Armston John D. , Calders Kim , Disney Mathias I. , Lovell Jenny L. , Schaaf Crystal B. , Strahler Alan H. , Danson F. Mark
Published: October 2015

Plot-scale measurements have been the foundation for forest surveys and reporting for over 200 years. Through recent integration with airborne and satellite remote sensing, manual measurements of vegetation structure at the plot scale are now the basis for landscape, continental and international mapping of our forest resources. The use of terrestrial laser scanning (TLS) for plot-scale measurement was first demonstrated over a decade ago, with the intimation that these instruments could replace manual measurement methods. This has not yet been the case, despite the unparalleled structural information that TLS can capture. For TLS to reach its full potential, these instruments cannot be viewed as a logical progression of existing plot-based measurement. TLS must be viewed as a disruptive technology that requires a rethink of vegetation surveys and their application across a wide range of disciplines. We review the development of TLS as a plot-scale measurement tool, including the evolution of both instrument hardware and key data processing methodologies. We highlight two broad data modelling approaches of gap probability and geometrical modelling and the basic theory that underpins these. Finally, we discuss the future prospects for increasing the utilisation of TLS for plot-scale forest assessment and forest monitoring.
Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy
Authors: Śledzińska Anna , Menger Laurie , Bergerhoff Katharina , Peggs Karl S. , Quezada Sergio A.
Published: October 2015

The term ‘inhibitory checkpoint’ refers to the broad spectrum of co‐receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self‐tolerance. Co‐inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti‐tumour immunity. Recent studies demonstrate that manipulation of these co‐inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co‐inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA‐4 and PD‐1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co‐inhibitory receptors on different T cells subsets, emphasising differences between CD4+ and CD8+ T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.
The united innovation process: integrating science, design, and entrepreneurship as sub-processes
Authors: Luo Jianxi
Published: October 2015

‘Innovation’ has become a buzzword in academic papers, news articles, and book titles, but it is variously defined and is often referred to as ‘invention’ or ‘design’. A consensus of understanding the interrelationships of the concepts and activities pertaining to innovation is needed to guide collective action for innovation. This paper proposes a united view of the innovation process, which advocates uniting the complementary (1) science, (2) design, and (3) entrepreneurship sub-processes of innovation. The shared creative, uncertain, and costly nature of these three processes also implies an opportunity to leverage design science to understand and guide the science and entrepreneurship processes. This paper describes the benefits, major challenges, and actionable strategies for uniting science, design, and entrepreneurship as sub-processes of innovation, with a few detailed real life examples. The variety of the cases and examples shows that science, design, and entrepreneurship sub-processes can be effectively united to different extents, within and across organizations and innovation ecosystems.
Classification of Healthcare-Associated Staphylococcus aureus Bacteremia: Influence of Different Definitions on Prevalence, Patient Characteristics, and Outcome
Authors: Smit Jesper , Søgaard Mette , Schønheyder Henrik Carl , Nielsen Henrik , Thomsen Reimar Wernich
Published: October 2015

We investigated whether different definitions of healthcare-associated infection influenced the prevalence, characteristics, and mortality of patients with Staphylococcus aureus bacteremia. With different definitions, the proportion of patients classified as having healthcare-associated S. aureus bacteremia varied substantially and the distribution of patient characteristics was influenced, whereas 30-day mortality remained robust.

Infect. Control Hosp. Epidemiol. 2016;37(2):208–211
A Fractional Calculus Approach to the Prediction of Free Recovery Behaviors of Amorphous Shape Memory Polymers
Authors: Fang C.-Q. , Sun H.-Y. , Gu J.-P.
Published: October 2015

A fractional model generalized from the Zener model is proposed for the prediction of temperature-dependent free recovery behaviors of amorphous shape memory polymers (SMPs). This model differs from the Zener model in that it involves nonlinear differential equations of fractional, not integer, order. The theoretical solution based on this fractional model is utilized to simulate the isothermal and nonisothermal free recovery of an amorphous SMP compared with the one based on the Zener model. The results show a reasonable improvement in the prediction of the strain recovery response of SMP by the fractional calculus method.
The ichneumon fly and the equilibration of British natural economies in the eighteenth century
Authors: WILLE SHEILA
Published: October 2015

The parasitic ichneumon fly, discovered by European natural philosophers in the seventeenth century, remained largely unstudied until it captured the attention of Enlightenment-era natural historians. Although this sudden surge of interest has been explained as an effort to understand the natural ‘evil’ of parasitism, the heyday of ichneumon studies was actually inspired by the political and agricultural context of late eighteenth-century Britain. British naturalists were captivated by this insect for reasons both philosophical and practical. In the providentially self-equilibrating qualities of ‘natural’ ichneumon economies, they saw solutions to political problems of famine, dearth, national wealth, governance and excess population, in addition to finding reassurance that Enlightened confidence in nature's inherent stability and fruitfulness was not unfounded.
Generation of relative commutator subgroups in Chevalley groups
Authors: Hazrat R. , Vavilov N. , Zhang Z.
Published: October 2015

Let Φ be a reduced irreducible root system of rank greater than or equal to 2, let R be a commutative ring and let I, J be two ideals of R. In the present paper we describe generators of the commutator groups of relative elementary subgroups [E(Φ,R,I),E(Φ,R,J)] both as normal subgroups of the elementary Chevalley group E(Φ,R), and as groups. Namely, let xα(ξ), α ∈ Φ ξ ∈ R, be an elementary generator of E(Φ,R). As a normal subgroup of the absolute elementary group E(Φ,R), the relative elementary subgroup is generated by xα(ξ), α ∈ Φ, ξ ∈ I. Classical results due to Stein, Tits and Vaserstein assert that as a group E(Φ,R,I) is generated by zα(ξ,η), where α ∈ Φ, ξ ∈ I, η ∈ R. In the present paper, we prove the following birelative analogues of these results. As a normal subgroup of E(Φ,R) the relative commutator subgroup [E(Φ,R,I),E(Φ,R,J)] is generated by the following three types of generators: (i) [xα(ξ),zα(ζ,η)], (ii) [xα(ξ),x_α(ζ)] and (iii) xα(ξζ), where α ∈ Φ, ξ ∈ I, ζ ∈ J, η ∈ R. As a group, the generators are essentially the same, only that type (iii) should be enlarged to (iv) zα(ξζ,η). For classical groups, these results, with many more computational proofs, were established in previous papers by the authors. There is already an amazing application of these results in the recent work of Stepanov on relative commutator width.
The demography of a dominant Amazon liana species exhibits little environmental sensitivity
Authors: Franci Luciana de Campos , Svenning Jens-Christian , Balslev Henrik , Martins Fernando Roberto , Nabe-Nielsen Jacob
Published: October 2015

Despite its high plant diversity, the Amazon forest is dominated by a limited number of highly abundant, oligarchic tree and liana species. The high diversity can be related to specific habitat requirements in many of the less common species, but fewer studies have investigated the characteristics of the dominant species. To test how environmental variation may contribute to the success of dominant species we investigated whether the vital rates of the abundant lianaMachaerium cuspidatumis sensitive to canopy height, topographic steepness, vegetation density, soil components and floristic composition across an Ecuadorian Amazon forest. The population was inventoried in 1998 and in 2009. Plants were divided into seedling-sized individuals, non-climbers and climbers. Out of 448 seedling-sized plants 421 died, 539 of 732 non-climbers died, and 107 of 198 climbers died. There was weak positive effect of dense understorey on the relative growth rate of climbers. The mortality of seedling-sized plants was higher in areas with intermediate slope, but for larger plants mortality was not related to environmental variation. The limited sensitivity of the vital rates to environmental gradients in the area suggests that ecological generalism contributes to the success of this dominant Amazonian liana.
Spatial patterns of primary seed dispersal and adult tree distributions: Genipa americana dispersed by Cebus capucinus – CORRIGENDUM
Authors: Valenta Kim , Hopkins Mariah E. , Meeking Melanie , Chapman Colin A. , Fedigan Linda M.
Published: October 2015

Within the second paragraph of page 494 incorrect language was used to characterize the summary characteristics used. Sentences 3–11 of this paragraph should have read:

Second, we calculated three univariate summary characteristics: the nearest neighbour distribution function D(r), the pair-correlation function g(r) and the K-function K(r). The use of multiple summary characteristics holds increased power to characterize variation in spatial patterns (Wiegand et al. 2013). The univariate nearest neighbour distribution function D(r) can be interpreted as the probability that the typical adult tree has its nearest neighbouring adult tree within radius r (or alternatively, the probability that the typical defecation has its nearest neighbouring defecation within radius r). The univariate pair-correlation function g(r) is a non-cumulative normalized neighbourhood density function that gives the expected number of points within rings of radius r and width w centred on a typical point, divided by the mean density of points λ in the study region (Wiegand et al. 2009). We applied g(r) to trees and defecation point patterns separately, using a ring width of 10 m. The K-function K(r) provides a cumulative counterpart to the non-cumulative pair-correlation function g(r) by analysing dispersion and aggregation up to distance r rather than at distance r (Weigand & Moloney 2004). The K-function can be defined as the number of expected points (i.e. either trees or defecations) within circles of radius r extending from a typical point, divided by the mean density of points λ within the study region. Here, we apply the square root transformation L(r) to the K-function to remove scale dependence and stabilize the variance: $L( r ) = \scriptstyle\sqrt {\frac{{K( r )}}{\pi }} - r$ (Besag 1977, Wiegand & Moloney 2014).
An explicit Baker-type lower bound of exponential values
Authors: Ernvall-Hytönen Anne-Maria , Leppälä Kalle , Matala-aho Tapani
Published: October 2015

Let 𝕀 denote an imaginary quadratic field or the field ℚ of rational numbers and let ℤ𝕀denote its ring of integers. We shall prove a new explicit Baker-type lower bound for a ℤ𝕀-linear form in the numbers 1, eα1, . . . , eαm,m⩾ 2, whereα0= 0,α1, . . . ,αmarem+ 1 different numbers from the field 𝕀. Our work gives substantial improvements on the existing explicit versions of Baker’s work about exponential values at rational points. In particular, dependencies onmare improved.
Building phonological lexical representations
Authors: van der Feest Suzanne V. H. , Fikkert Paula
Published: October 2015

This paper contributes to the ongoing debate on how much detail young children's word representations contain. We investigate early representations of place of articulation and voicing contrasts, inspired by previously attested asymmetrical patterns in children's early word productions. We tested Dutch-learning 20- and 24-month-olds’ perception of these fundamentally different contrasts in a mispronunciation-detection paradigm. Our results show that different kinds and directions of phonological changes yield different effects. Both 20- and 24-month-olds noticed coronal mispronunciations of labials, but notvice versa. The 24-month-olds noticed voiced mispronunciations of voiceless stops, but notvice versa, while the 20-month-olds failed to notice any voicing mispronunciations. We argue that early lexical representations are specified in very systematic ways, that not all phonological contrasts are encoded at the same time and that the phonological system of a language determines which contrasts are specified first in the representations of early words.
Tonal association in Tashlhiyt Berber: evidence from polar questions and contrastive statements
Authors: Grice Martine , Ridouane Rachid , Roettger Timo B.
Published: October 2015

The placement of F0 peaks in Tashlhiyt Berber is highly variable, both within and across speakers, even across repetitions of the same target sentence. We show that peak placement is determined by a number of competing factors: in addition to a general tendency for the peak to be placed on the rightmost syllable – a tendency that is stronger in questions than in statements – the peak is attracted to the syllable with the most sonorous nucleus and preferentially to heavy syllables. Moreover, in words consisting entirely of obstruents, there are three possible intonation patterns: no F0 peak at all, an anticipated peak (before the target word) or a peak on a vocoid between two obstruents. The F0 peak is analysed phonologically as a H tone that is either associated with a postlexically determined syllable or, if the syllable is not tone-bearing, aligned with the edge of the larger domain.
Does Gokana really have syllables? A postscript
Authors: Hyman Larry M.
Published: October 2015

After years of searching for evidence for the syllable in Gokana, I presented a possible argument in Hyman (2011) that the prosodic stem consists at most of two bimoraic syllables. In this note I show that there is an alternative account not involving syllables. Either way, Gokana makes very little reference to syllable structure, if at all.
Long-term monitoring of landbirds on Aldabra Atoll indicates increasing population trends
Authors: VAN DE CROMMENACKER JANSKE , RICHARDS HEATHER , ONEZIA CATHERINA , MAHOUNE TERENCE , HAUPT PHILIP , ACCOUCHE WILNA , FLEISCHER-DOGLEY FRAUKE , BUNBURY NANCY
Published: October 2015

Long-term survey data can provide important information on temporal and spatial changes in bird populations and are needed for conservation management. We investigate population indices of seven landbird species using an 11-year dataset from the UNESCO World Heritage Site of Aldabra Atoll. We analysed the associations of location, season and habitat with abundance, assessed population trends, and examined the influence of monitoring circumstances on results. Populations of all species except for the Aldabra Drongo Dicrurus aldabranus increased over this period. Abundance was associated with season and habitat, and interactions were found between season and location that differed for each species. Bird count results were affected by the timing of monitoring, number of observers and weather conditions. We use the results to review the strengths and weaknesses of the current monitoring programme and make recommendations for improvements. Overall our results indicate no immediate cause for conservation concern for the Aldabra landbird species monitored.
Perfect Packings in Quasirandom Hypergraphs II
Authors: LENZ JOHN , MUBAYI DHRUV
Published: October 2015

For each of the notions of hypergraph quasirandomness that have been studied, we identify a large class of hypergraphsFso that every quasirandom hypergraphHadmits a perfectF-packing. An informal statement of a special case of our general result for 3-uniform hypergraphs is as follows. Fix an integerr⩾ 4 and 0 <p< 1. Suppose thatHis ann-vertex triple system withr|nand the following two properties:

•

for every graphGwithV(G) =V(H), at leastpproportion of the triangles inGare also edges ofH,

•

for every vertexxofH, the link graph ofxis a quasirandom graph with density at leastp.

ThenHhas a perfectKr(3)-packing. Moreover, we show that neither of the hypotheses above can be weakened, so in this sense our result is tight. A similar conclusion for this special case can be proved by Keevash's Hypergraph Blow-up Lemma, with a slightly stronger hypothesis onH.
Kit ligand promotes the transition from primordial to primary follicles afterin vitroculture of ovine ovarian tissue
Authors: Cavalcante A.Y.P. , Gouveia B.B. , Barberino R.S. , Lins T.L.B.G. , Santos L.P. , Gonçalves R.J.S. , Celestino J.J.H. , Matos M.H.T.
Published: October 2015

This study evaluated the effects of kit ligand (KL) on the morphology and development of ovine preantral follicles (fresh control) and after 7 days ofin vitroculture in α-Minimal Essential Medium (α-MEM; control medium) or the presence of KL (1, 10, 50, 100 or 200 ng/ml). There was an increase in the percentage of primary follicles at the concentration of 100 ng/ml KL, compared with the fresh control, control medium (α-MEM) and the other KL concentrations. Follicle diameter was significantly higher than the control medium only at concentrations of 50 and 100 ng/ml KL. In conclusion, 100 ng/ml KL promoted the transition from primordial to primary follicles (follicular activation) afterin vitroculture of ovine ovarian tissue.
Book Review: Asian Expansions: The historical experiences of polity expansion in Asia, Edited by Geoff Wade. pp. xii, 259. Abingdon, Routledge, 2015. - ERRATUM
Authors: Stoll Viktor M.
Published: October 2015

In this book review published in the October 2015 print issue of the JRAS, and online, Viktor M. Stoll has been incorrectly listed as an Honorary Fellow of the University of Cambridge, he is currently a doctoral candidate at that university. The publisher apologises for this error.
Vitamin D fortification and seasonality of birth in type 1 diabetic cases: D-tect study
Authors: Jacobsen R. , Moldovan M. , Vaag A. A. , Hypponen E. , Heitmann B. L.
Published: October 2015

Fortification of margarine with vitamin D was mandatory in Denmark during 1961–1985. The aim of the study was to assess whether gestational and early infancy exposure to margarine fortification was associated with seasonality of birth in Danish type 1 diabetes (T1D) patients. The risks of T1D in Danes born during various exposure periods around margarine fortification termination in 1985 were analyzed. As expected, the T1D hazards in males unexposed to margarine fortification and born in spring were higher than in males born in autumn: relevant hazard ratios (95% confidence intervals) in various exposure groups ranged from 1.74 (1.112/2.708) to 37.43 (1.804/776.558). There were no indications of seasonality of birth in males exposed to fortification, nor in both exposed and unexposed females. The study suggests that early life exposure to low-dose vitamin D from fortified food eliminates seasonality of birth in T1D male patients. Further studies are required to investigate the identified gender differences.
Perspectives of Suicidal Veterans on Safety Planning
Authors: Kayman Deborah J. , Goldstein Marjorie F. , Dixon Lisa , Goodman Marianne
Published: October 2015

Abstract. Aims: Individual interviews were conducted and analyzed to learn about the engagement of suicidal veterans in safety planning. Method: Twenty suicidal veterans who had recently constructed safety plans were recruited at two VA hospitals. In semistructured interviews, they discussed how they felt about constructing and using the plan and suggested changes in plan content and format that might increase engagement. Results: The veterans’ experiences varied widely, from reviewing plans often and noting symptom improvement to not using them at all and doubting that they would think of doing so when deeply depressed. Conclusion: The veterans suggested ways to enrich safety planning encounters and identified barriers to plan use. Their ideas were specific and practical. Safety planning was most meaningful and helpful to them when they experienced the clinician as a partner in exploring their concerns (e.g., fear of discussing and attending to warning signs) and collaborating with them to devise solutions.
Integrating Carbon Cycle Research into Decision-Making Processes
Authors: Vargas Rodrigo , Alin Simone , Shrestha Gyami
Published: October 2015

North American Carbon Program Principal Investigators Meeting; Washington, D.C., 26–29 January 2015
Large-scale climatic anomalies affect marine predator foraging behaviour and demography
Authors: Bost Charles A. , Cotté Cedric , Terray Pascal , Barbraud Christophe , Bon Cécile , Delord Karine , Gimenez Olivier , Handrich Yves , Naito Yasuhiko , Guinet Christophe , Weimerskirch Henri
Published: October 2015

Determining the links between the behavioural and population responses of wild species to environmental variations is critical for understanding the impact of climate variability on ecosystems. Using long-term data sets, we show how large-scale climatic anomalies in the Southern Hemisphere affect the foraging behaviour and population dynamics of a key marine predator, the king penguin. When large-scale subtropical dipole events occur simultaneously in both subtropical Southern Indian and Atlantic Oceans, they generate tropical anomalies that shift the foraging zone southward. Consequently the distances that penguins foraged from the colony and their feeding depths increased and the population size decreased. This represents an example of a robust and fast impact of large-scale climatic anomalies affecting a marine predator through changes in its at-sea behaviour and demography, despite lack of information on prey availability. Our results highlight a possible behavioural mechanism through which climate variability may affect population processes.
Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug
Authors: Marschallinger Julia , Schäffner Iris , Klein Barbara , Gelfert Renate , Rivera Francisco J. , Illes Sebastian , Grassner Lukas , Janssen Maximilian , Rotheneichner Peter , Schmuckermair Claudia , Coras Roland , Boccazzi Marta , Chishty Mansoor , Lagler Florian B. , Renic Marija , Bauer Hans-Christian , Singewald Nicolas , Blümcke Ingmar , Bogdahn Ulrich , Couillard-Despres Sebastien , Lie D. Chichung , Abbracchio Maria P. , Aigner Ludwig
Published: October 2015

As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.
Holographic acoustic elements for manipulation of levitated objects
Authors: Marzo Asier , Seah Sue Ann , Drinkwater Bruce W. , Sahoo Deepak Ranjan , Long Benjamin , Subramanian Sriram
Published: October 2015

Sound can levitate objects of different sizes and materials through air, water and tissue. This allows us to manipulate cells, liquids, compounds or living things without touching or contaminating them. However, acoustic levitation has required the targets to be enclosed with acoustic elements or had limited manoeuvrability. Here we optimize the phases used to drive an ultrasonic phased array and show that acoustic levitation can be employed to translate, rotate and manipulate particles using even a single-sided emitter. Furthermore, we introduce the holographic acoustic elements framework that permits the rapid generation of traps and provides a bridge between optical and acoustical trapping. Acoustic structures shaped as tweezers, twisters or bottles emerge as the optimum mechanisms for tractor beams or containerless transportation. Single-beam levitation could manipulate particles inside our body for applications in targeted drug delivery or acoustically controlled micro-machines that do not interfere with magnetic resonance imaging.
Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug
Authors: Miller Miles A. , Zheng Yao-Rong , Gadde Suresh , Pfirschke Christina , Zope Harshal , Engblom Camilla , Kohler Rainer H. , Iwamoto Yoshiko , Yang Katherine S. , Askevold Bjorn , Kolishetti Nagesh , Pittet Mikael , Lippard Stephen J. , Farokhzad Omid C. , Weissleder Ralph
Published: October 2015

Therapeutic nanoparticles (TNPs) aim to deliver drugs more safely and effectively to cancers, yet clinical results have been unpredictable owing to limited in vivo understanding. Here we use single-cell imaging of intratumoral TNP pharmacokinetics and pharmacodynamics to better comprehend their heterogeneous behaviour. Model TNPs comprising a fluorescent platinum(IV) pro-drug and a clinically tested polymer platform (PLGA-b-PEG) promote long drug circulation and alter accumulation by directing cellular uptake toward tumour-associated macrophages (TAMs). Simultaneous imaging of TNP vehicle, its drug payload and single-cell DNA damage response reveals that TAMs serve as a local drug depot that accumulates significant vehicle from which DNA-damaging Pt payload gradually releases to neighbouring tumour cells. Correspondingly, TAM depletion reduces intratumoral TNP accumulation and efficacy. Thus, nanotherapeutics co-opt TAMs for drug delivery, which has implications for TNP design and for selecting patients into trials.
Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels
Authors: Jin Peng , Wang Tifeng , Liu Nana , Dupont Sam , Beardall John , Boyd Philip W. , Riebesell Ulf , Gao Kunshan
Published: October 2015

Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.
Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations
Authors: Ronstedt Katharina , Sternberg Damien , Detro-Dassen Silvia , Gramkow Thomas , Begemann Birgit , Becher Toni , Kilian Petra , Grieschat Matthias , Machtens Jan-Philipp , Schmalzing Günther , Fischer Martin , Fahlke Christoph
Published: October 2015

Mutations in the muscle chloride channel gene (CLCN1) cause myotonia congenita, an inherited condition characterized by muscle stiffness upon sudden forceful movement. We here studied the functional consequences of four disease-causing mutations that predict amino acid substitutions Q43R, S70L, Y137D and Q160H. Wild-type (WT) and mutant hClC-1 channels were heterologously expressed as YFP or CFP fusion protein in HEK293T cells and analyzed by whole-cell patch clamp and fluorescence recordings on individual cells. Q43R, Y137D and Q160H, but not S70L reduced macroscopic current amplitudes, but left channel gating and unitary current amplitudes unaffected. We developed a novel assay combining electrophysiological and fluorescence measurements at the single-cell level in order to measure the probability of ion channel surface membrane insertion. With the exception of S70L, all tested mutations significantly reduced the relative number of homodimeric hClC-1 channels in the surface membrane. The strongest effect was seen for Q43R that reduced the surface insertion probability by more than 99% in Q43R homodimeric channels and by 92 ± 3% in heterodimeric WT/Q43R channels compared to homodimeric WT channels. The new method offers a sensitive approach to investigate mutations that were reported to cause channelopathies, but display only minor changes in ion channel function.
A geometric network model of intrinsic grey-matter connectivity of the human brain
Authors: Lo Yi-Ping , O’Dea Reuben , Crofts Jonathan J. , Han Cheol E. , Kaiser Marcus
Published: October 2015

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability and that such gains are consistent with (and enhanced by) the presence of short-cut connections.
Simultaneous demultiplexing and steering of multiple orbital angular momentum modes
Authors: Li Shuhui , Wang Jian
Published: October 2015

We present a simple scheme to perform simultaneous demultiplexing and steering of multiple orbital angular momentum (OAM) modes using a single complex phase mask. By designing the phase mask, the propagation directions of demultiplexed beams can be arbitrarily steered. System experiments using orthogonal frequency-division multiplexing 32-ary quadrature amplitude modulation (OFDM-32QAM) signals over two OAM modes are carried out by using a two-mode complex phase mask. Moreover, demultiplexing of sixteen OAM modes and arbitrary demultiplexed beam steering are also demonstrated in the experiment.
Strong odd-frequency correlations in fully gapped Zeeman-split superconductors
Authors: Linder Jacob , Robinson Jason W. A.
Published: October 2015

It is now well established that at a superconductor/ferromagnet (S/F) interface an unconventional superconducting state arises in which the pairing is odd-frequency. The hallmark signature of this superconducting state is generally understood to be an enhancement of the electronic density of states (DoS) at subgap energies close to the S/F interface. However, here we show that an odd frequency state can be present even if the DoS is fully gapped. As an example, we show that this is the case in the pioneering S/FI (where FI is a insulating ferromagnet) tunneling experiments of Meservey and Tedrow and we derive a generalized analytical criterium to describe the effect of odd-frequency pairing on the DoS. Finally, we propose a simple experiment in which odd-frequency pairing in a Zeeman-split superconductor can be unambiguously detected via the application of an external magnetic field.
Annual periodicity in planktonic bacterial and archaeal community composition of eutrophic Lake Taihu
Authors: Li Junfeng , Zhang Junyi , Liu Liyang , Fan Yucai , Li Lianshuo , Yang Yunfeng , Lu Zuhong , Zhang Xuegong
Published: October 2015

Bacterioplankton plays a key role in nutrient cycling and is closely related to water eutrophication and algal bloom. We used high-throughput 16S rRNA gene sequencing to profile archaeal and bacterial community compositions in the surface water of Lake Taihu. It is one of the largest lakes in China and has suffered from recurring cyanobacterial bloom. A total of 81 water samples were collected from 9 different sites in 9 different months of 2012. We found that temporal variation of the microbial community was significantly greater than spatial variation (adonis, n = 9999, P < 1e−4). The composition of bacterial community in December was similar to that in January and so was the archaeal community, suggesting potential annual periodicity. Unsupervised K-means clustering was used to identify the synchrony of abundance variations between different taxa. We found that the cluster consisting mostly of ACK-M1, C111 (members of acIV), Pelagibacteraceae (alfV-A) and Synechococcaceae showed relatively higher abundance in autumn. On the contrary, the cluster of Comamonadaceae and Methylophilaceae (members of lineage betI and betIV) had higher abundance in spring. The co-occurrence relationships between taxa were greatly altered during the cyanobacterial bloom according to our further network module analysis.
Multifunctional Single-Phase Photocatalysts: Extended Near Infrared Photoactivity and Reliable Magnetic Recyclability
Authors: Li Xiaoning , Zhu Zhu , Li Feng , Huang Yan , Hu Xiang , Huang Haoliang , Peng Ranran , Zhai XiaoFang , Fu Zhengping , Lu Yalin
Published: October 2015

A practical photocatalyst should be able to integrate together various functions including the extended solar conversion, a feasible and economic recyclability and above the room temperature operation potential, et al., in order to fulfill the spreading application needs in nowadays. In this report, a multifunctional single-phase photocatalyst which possesses a high photoactivity extended into the near infrared region, an easy magnetic recyclability and the high temperature stability was developed by doping Co into a new layer-structured Bi7Fe3Ti3O21 material. Light absorption and photocatalytic activity of the resulted Bi7Fe3-xCoxTi3O21 photocatalyst were extended to the long wavelength as far as 800 nm. Its strong ferromagnetism above the room temperature enables the nanopowders fully recyclable in viscous solutions simply with a magnet bar in an experimental demonstration. Furthermore, such photoactivity and magnetic recyclability were heavily tested under high-temperature and high-viscosity conditions, which was intended to simulate the actual industrial environments. This work brings the bright light to a full availability of a new multifunctional photocatalyst, via integrating the much enhanced ferromagnetic, ferroelectric, optoelectronic properties, most importantly, into a single-phase structure.
The spatial range of peripheral collinear facilitation
Authors: Maniglia Marcello , Pavan Andrea , Aedo-Jury Felipe , Trotter Yves
Published: October 2015

Contrast detection thresholds for a central Gabor patch (target) can be modulated by the presence of co-oriented and collinear high contrast Gabors flankers. In foveal vision collinear facilitation can be observed for target-to-flankers relative distances beyond two times the wavelength (λ) of the Gabor’s carrier, while for shorter relative distances (<2λ) there is suppression. These modulatory influences seem to disappear after 12λ. In this study, we measured contrast detection thresholds for different spatial frequencies (1, 4 and 6 cpd) and target-to-flankers relative distances ranging from 6 to 16λ, but with collinear configurations presented in near periphery at 4° of eccentricity. Results showed that in near periphery collinear facilitation extends beyond 12λ for the higher spatial frequencies tested (4 and 6 cpd), while it decays already at 10λ for the lowest spatial frequency used (i.e., 1 cpd). In addition, we found that increasing the spatial frequency the peak of collinear facilitation shifts towards larger target-to-flankers relative distances (expressed as multiples of the stimulus wavelength), an effect never reported neither for near peripheral nor for central vision. The results suggest that the peak and the spatial extent of collinear facilitation in near periphery depend on the spatial frequency of the stimuli used.
Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography
Authors: Kennedy Kelsey M. , Chin Lixin , McLaughlin Robert A. , Latham Bruce , Saunders Christobel M. , Sampson David D. , Kennedy Brendan F.
Published: October 2015

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties. To overcome this limitation, we present quantitative micro-elastography, which combines compression OCE with a compliant stress sensor to image tissue elasticity. The sensor consists of a layer of translucent silicone with well-characterized stress-strain behaviour. The measured strain in the sensor is used to estimate the two-dimensional stress distribution applied to the sample surface. Elasticity is determined by dividing the stress by the strain in the sample. We show that quantification of elasticity can improve the ability of compression OCE to distinguish between tissues, thereby extending the potential for inter-sample comparison and longitudinal studies of tissue elasticity. We validate the technique using tissue-mimicking phantoms and demonstrate the ability to map elasticity of freshly excised malignant and benign human breast tissues.
Mechanical versus manual chest compressions for out-of-hospital cardiac arrest: a meta-analysis of randomized controlled trials
Authors: Tang Lu , Gu Wan-Jie , Wang Fei
Published: October 2015

Recent evidence regarding mechanical chest compressions in out-of-hospital cardiac arrest (OHCA) is conflicting. The objective of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the effect of mechanical versus manual chest compressions on resuscitation outcomes in OHCA. PubMed, Embase, the Cochrane Central Register of Controlled Trials and the ClinicalTrials.gov registry were searched. In total, five RCTs with 12,510 participants were included. Compared with manual chest compressions, mechanical chest compressions did not significantly improve survival with good neurological outcome to hospital discharge (relative risks (RR) 0.80, 95% CI 0.61–1.04, P = 0.10; I2 = 65%), return of spontaneous circulation (RR 1.02, 95% CI 0.95–1.09, P = 0.59; I2 = 0%), or long-term (≥6 months) survival (RR 0.96, 95% CI 0.79–1.16, P = 0.65; I2 = 16%). In addition, mechanical chest compressions were associated with worse survival to hospital admission (RR 0.94, 95% CI 0.89–1.00, P = 0.04; I2 = 0%) and to hospital discharge (RR 0.88, 95% CI 0.78–0.99, P = 0.03; I2 = 0%). Based on the current evidence, widespread use of mechanical devices for chest compressions in OHCA cannot be recommended.
Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent
Authors: Winham Stacey J. , Preuss Ulrich W. , Geske Jennifer R. , Zill Peter , Heit John A. , Bakalkin Georgy , Biernacka Joanna M. , Karpyak Victor M.
Published: October 2015

We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p  =  0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific.
PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet
Authors: Lorenzo Petra I. , Fuente-Martín Esther , Brun Thierry , Cobo-Vuilleumier Nadia , Jimenez-Moreno Carmen María , G. Herrera Gomez Irene , López Noriega Livia , Mellado-Gil José Manuel , Martin-Montalvo Alejandro , Soria Bernat , Gauthier Benoit R.
Published: October 2015

PAX4 is a key regulator of pancreatic islet development whilst in adult acute overexpression protects β-cells against stress-induced apoptosis and stimulates proliferation. Nonetheless, sustained PAX4 expression promotes β-cell dedifferentiation and hyperglycemia, mimicking β-cell failure in diabetic patients. Herein, we study mechanisms that allow stringent PAX4 regulation endowing favorable β-cell adaptation in response to changing environment without loss of identity. To this end, PAX4 expression was monitored using a mouse bearing the enhanced green fluorescent protein (GFP) and cre recombinase construct under the control of the islet specific pax4 promoter. GFP was detected in 30% of islet cells predominantly composed of PAX4-enriched β-cells that responded to glucose-induced insulin secretion. Lineage tracing demonstrated that all islet cells were derived from PAX4+ progenitor cells but that GFP expression was confined to a subpopulation at birth which declined with age correlating with reduced replication. However, this GFP+ subpopulation expanded during pregnancy, a state of active β-cell replication. Accordingly, enhanced proliferation was exclusively detected in GFP+ cells consistent with cell cycle genes being stimulated in PAX4-overexpressing islets. Under stress conditions, GFP+ cells were more resistant to apoptosis than their GFP- counterparts. Our data suggest PAX4 defines an expandable β-cell sub population within adult islets.