bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships between air pollution, population density, and lichen biodiversity in the Niagara Escarpment World Biosphere Reserve
Authors: McMULLIN Richard Troy , BENNETT Lindsay L. , BJORGAN Owen J. , BOURQUE Danielle A. , BURKE Charlotte J. , CLARKE Mackenzie A. , GUTGESELL Marie K. , KRAWIEC Peter L. , MALYON Rachel , MANTIONE Annemarie , PIOTROWSKI Amanda T. , TAM Nicholas Y. , VAN NATTO Alyson C. , WIERSMA Yolanda F. , NEWMASTER Steven G.
Published: September 2016

The fragmented ecosystems along the Niagara Escarpment World Biosphere Reserve provide important habitats for biota including lichens. Nonetheless, the Reserve is disturbed by dense human populations and associated air pollution. Here we investigated patterns of lichen diversity within urban and rural sites at three different locations (Niagara, Hamilton, and Owen Sound) along the Niagara Escarpment in Ontario, Canada. Our results indicate that both lichen species richness and community composition are negatively correlated with increasing human population density and air pollution. However, our quantitative analysis of community composition using canonical correspondence analysis (CCA) indicates that human population density and air pollution is more independent than might be assumed. The CCA analysis suggests that the strongest environmental gradient (CCA1) associated with lichen community composition includes regional pollution load and climatic variables; the second gradient (CCA2) is associated with local pollution load and human population density factors. These results increase the knowledge of lichen biodiversity for the Niagara Escarpment and urban and rural fragmented ecosystems as well as along gradients of human population density and air pollution; they suggest a differential influence of regional and local pollution loads and population density factors. This study provides baseline knowledge for further research and conservation initiatives along the Niagara Escarpment World Biosphere Reserve.
Peltigera islandica, a new cyanolichen species in sectionPeltigera(‘P. caninagroup’)
Authors: MANOHARAN-BASIL Sheeba S. , MIADLIKOWSKA Jolanta , GOWARD Trevor , ANDRÉSSON Ólafur S. , MIAO Vivian P. W.
Published: September 2016

A new cyanolichen,Peltigera islandicasp. nov. in the sectionPeltigera(‘P. caninagroup’) is described from Iceland. This species is similar in general appearance toP. rufescensandP. membranacea, but may be recognized by its downturned lobe tips and narrow lobes, respectively. Most thalli are bright emerald green in colour when moist, although a dark khaki green colourmorph is also documented. Monophyly ofP. islandicas. lat. (i.e. includingP. sp. AsensuO’Brienet al., from Canada) is significantly supported based on ITS sequences and corroborated by molecular synapomorphy (absence of the ITS1 hypervariable region). Analysis of therbcLX locus indicates the cyanobiont ofP. islandica(Nostocsp.) comprises strains belonging to a pool of Icelandic genotypes, some of which are present in otherPeltigeraspecies, includingP.“neorufescens”, another taxon new to Iceland collected during this study. Association with photobionts that are shared by other local species suggestsP. islandicamay be well established in Iceland, but a review of herbarium collections as well as broader field surveys are needed to better characterize its geographical distribution.
Evaluating methods for surveying the Endangered Cuvier's gazelleGazella cuvieriin arid landscapes
Authors: Gil-Sánchez Jose María , Herrera-Sánchez F. Javier , Álvarez Begoña , Arredondo Ángel , Bautista Jesús , Cancio Inmaculada , Castillo Salvador , Díaz-Portero Miguel Ángel , de Lucas Jesús , McCain Emil , Pérez Joaquín , Rodríguez-Siles Javier , Sáez Juan Manuel , Martínez-Valderrama Jaime , Valenzuela Gerardo , Qninba Abdeljebbar , Virgós Emilio
Published: September 2016

The Endangered Cuvier's gazelleGazella cuvieriis an endemic ungulate of north-western Africa. Information on the species has been based primarily on non-systematic surveys, and the corresponding status estimates are of unknown quality. We evaluate the effectiveness and efficiency of two field methods for systematic surveys of populations of Cuvier's gazelle in arid environments: distance sampling (based on sightings) and sampling indirect sign (tracks and scats). The work was carried out in the north-western Sahara Desert, in Morocco, where what is possibly the largest population of Cuvier's gazelle persists. A logistically viable survey was conducted over a total area of c. 20.000 km2in 10 expeditions during 2011–2014. A total of 67 sites were surveyed, with 194 walking surveys (2,169 km in total). Gazelle signs were detected at 50 sites, and gazelles were sighted at 21 sites (61 individuals). We found a relationship between sightings and abundance indices based on indirect sign, which could be useful for population monitoring or ecological studies. Additionally, the data could be used in occupancy modelling. Density estimates based on distance sampling required considerable effort; however, it is possible to survey large areas during relatively short campaigns, and this proved to be the most useful approach to obtain data on the demographic structure of the population.
A study of wrist-worn activity measurement as a potential real-world biomarker for late-life depression
Authors: O'Brien J. T. , Gallagher P. , Stow D. , Hammerla N. , Ploetz T. , Firbank M. , Ladha C. , Ladha K. , Jackson D. , McNaney R. , Ferrier I. N. , Olivier P.
Published: September 2016

Background

Late-life depression (LLD) is associated with a decline in physical activity. Typically this is assessed by self-report questionnaires and, more recently, with actigraphy. We sought to explore the utility of a bespoke activity monitor to characterize activity profiles in LLD more precisely.

Method

The activity monitor was worn for 7 days by 29 adults with LLD and 30 healthy controls. Subjects underwent neuropsychological assessment and quality of life (QoL) (36-item Short-Form Health Survey) and activities of daily living (ADL) scales (Instrumental Activities of Daily Living Scale) were administered.

Results

Physical activity was significantly reduced in LLD compared with controls (t = 3.63, p < 0.001), primarily in the morning. LLD subjects showed slower fine motor movements (t = 3.49, p < 0.001). In LLD patients, activity reductions were related to reduced ADL (r = 0.61, p < 0.001), lower QoL (r = 0.65, p < 0.001), associative learning (r = 0.40, p = 0.036), and higher Montgomery–Åsberg Depression Rating Scale score (r = −0.37, p < 0.05).

Conclusions

Patients with LLD had a significant reduction in general physical activity compared with healthy controls. Assessment of specific activity parameters further revealed the correlates of impairments associated with LLD. Our study suggests that novel wearable technology has the potential to provide an objective way of monitoring real-world function.
Cumulative Inequalities over the Life-Course: Life-long Learning and Social Mobility in Britain
Authors: BUKODI ERZSÉBET
Published: September 2016

This paper examines the possibility that life-long learning promotes intergenerational class mobility. The following two research questions are asked. Is it the case that further education provides individuals coming from less advantaged origins with a second chance to improve on their educational attainment? Is it the case that the returns to further qualifications, in terms of chances of upward class career mobility, are greater for children from less advantaged backgrounds than for children from more advantaged backgrounds? The analyses – that are based on the complete educational and class histories of men and women in a British birth cohort – mainly produce negative findings. Children coming from managerial and professional backgrounds seem to benefit most from further education. More specifically, further education appears to be an effective means of career advancement for individuals of managerial and professional origins who start out in their working lives in relatively low-level class positions. Via further education they can increase or update their qualifications, and in turn enhance their chances of being counter-mobile back to their class of origin. Overall, based on the findings of this paper, we can conclude that qualifications attained through life-long learning primarily serve to maintain, rather than to narrow, inequalities attached to social origins in Britain.
HEALTH TECHNOLOGY ASSESSMENT OF MEDICAL DEVICES IN EUROPE: PROCESSES, PRACTICES, AND METHODS
Authors: Fuchs Sabine , Olberg Britta , Panteli Dimitra , Busse Reinhard
Published: September 2016

Objectives:To review and compare current Health Technology Assessment (HTA) activities for medical devices (MDs) across European HTA institutions.

Methods:A comprehensive approach was adopted to identify institutions involved in HTA in European countries. We systematically searched institutional Web sites and other online sources by using a structured tool to extract information on the role and link to decision making, structure, scope, process, methodological approach, and available HTA reports for each included institution.

Results:Information was obtained from eighty-four institutions, forty-seven of which were analyzed. Fifty-four methodological documents from twenty-three agencies in eighteen countries were identified. Only five agencies had separate documents for the assessment of MDs. A few agencies made separate provisions for the assessment of MDs in their general methods. The amount of publicly available HTA reports on MDs varied by device category and agency remit.

Conclusions:Despite growing consensus on their importance and international initiatives, such as the EUnetHTA Core Model®, specific tools for the assessment of MDs are rarely developed and implemented at the national level. Separate additional signposts incorporated in existing general methods guides may be sufficient for the evaluation of MDs.
PUBLIC AND PATIENT INVOLVEMENT IN HEALTH TECHNOLOGY ASSESSMENT: A FRAMEWORK FOR ACTION
Authors: Abelson Julia , Wagner Frank , DeJean Deirdre , Boesveld Sarah , Gauvin Franςois-Pierre , Bean Sally , Axler Renata , Petersen Stephen , Baidoobonso Shamara , Pron Gaylene , Giacomini Mita , Lavis John
Published: September 2016

Objective: As health technology assessment (HTA) organizations in Canada and around the world seek to involve the public and patients in their activities, frameworks to guide decisions about whom to involve, through which mechanisms, and at what stages of the HTA process have been lacking. The aim of this study was to describe the development and outputs of a comprehensive framework for involving the public and patients in a government agency's HTA process.

Methods: The framework was informed by a synthesis of international practice and published literature, a dialogue with local, national and international stakeholders, and the deliberations of a government agency's public engagement subcommittee in Ontario, Canada.

Results: The practice and literature synthesis failed to identify a single, optimal approach to involving the public and patients in HTA. Choice of methods should be considered in the context of each HTA stage, goals for incorporating societal and/or patient perspectives into the process, and relevant societal and/or patient values at stake. The resulting framework is structured around four actionable elements: (i) guiding principles and goals for public and patient involvement (PPI) in HTA, (ii) the establishment of a common language to support PPI efforts, (iii) a flexible array of PPI approaches, and (iv) on-going evaluation of PPI to inform adjustments over time.

Conclusions: A public and patient involvement framework has been developed for implementation in a government agency’s HTA process. Core elements of this framework may apply to other organizations responsible for HTA and health system quality improvement.
Slow increasing functions and the largest partial quotients in continued fraction expansions
Authors: CHANG JINHUA , CHEN HAIBO
Published: September 2016

Let 0 ⩽ α ⩽ ∞ and ψ be a positive function defined on (0, ∞). In this paper, we will study the level sets L(α, {ψ(n)}), B(α, {ψ(n)}) and T(α, {ψ(n)}) which are related respectively to the sequence of the largest digits among the first n partial quotients {Ln(x)}n≥1, the increasing sequence of the largest partial quotients {Bn(x)}n⩾1 and the sequence of successive occurrences of the largest partial quotients {Tn(x)}n⩾1 in the continued fraction expansion of x ∈ [0,1) ∩ ℚc. Under suitable assumptions of the function ψ, we will prove that the sets L(α, {ψ(n)}), B(α, {ψ(n)}) and T(α, {ψ(n)}) are all of full Hausdorff dimensions for any 0 ⩽ α ⩽ ∞. These results complement some limit theorems given by J. Galambos [4] and D. Barbolosi and C. Faivre [1].
Surgery on tori in the 4–sphere
Authors: LARSON KYLE
Published: September 2016

We investigate the operation of torus surgery on tori embedded inS4. Key questions include which 4–manifolds can be obtained in this way, and the uniqueness of such descriptions. As an application we construct embeddings of 3–manifolds into 4–manifolds by viewing Dehn surgery as a cross section of a surgery on a surface. In particular, we give new embeddings of homology spheres intoS4.
Dimensions of empathy in relation to language
Authors: Herlin Ilona , Visapää Laura
Published: September 2016

This article approaches the relationship between empathy and language, describing the ways in which different dimensions of empathy can be attested in naturally occurring interactional data. The authors adopt the definition of empathy as a multidimensional phenomenon: emotional contagion, as well as the cognitive and affective dimensions of empathy, are all understood to be central to the empathetic process. The article promotes the view that studying the relationship between empathy and language should be grounded in the analysis of real-life interactions. Language evolves in social interaction both phylogenetically and ontogenetically, and is not only an important product but also a means of human sociality. The authors suggest that the best approach for analyzing the empathy–language interface combines the theoretical insights of cognitive grammar with the method of conversation analysis. The paper shows that when empathy is analyzed in natural conversation, we can do sequential and linguistic analysis of the ways in which affect is shown, and through a careful analysis of grammatical devices, offer an explanation of whether the displays of affect are derived from the other person's situation. By analyzing the complex ways in which the interactants orient to the different dimensions of empathy, the paper shows how linguistic analysis can give us concrete tools for forming a deeper understanding of how empathy takes place in real-life encounters.
Mimetic schemas and shared perception through imitatives
Authors: Jääskeläinen Anni
Published: September 2016

This article examines the interplay between certain depictions of sound and certain mimetic schemas (intersubjectively shared, body-based image schemas that concern basic processes and activities). The research contributes to the study of ideophones and also demonstrates that it is beneficial to study these types of words in written everyday interaction, as well as in spoken everyday interaction. Two Finnish sound words (ideophones, imitatives),naps‘snap, pop’ andhumps(the sound of relatively soft falling) are examined and their different meanings are analysed. Some research questions of this analysis are: What causes the sound described by eithernapsorhumps? What kind of movement is described and to what mimetic schema is the sound linked? And also: What concrete, spatial processes might motivate the words’ more abstract uses? The examination indicates thatnapsandhumpsare used as concrete depictions of sounds and movements, but also more abstractly, as depictions of cognitive and emotional processes without any spatial movement or audible sound. The motivations for these more abstract uses are studied: It is argued that the basic uses ofnapsandhumpsare tied to certain bodily processes as their sounds or impressions, and that the more abstract uses ofnapsandhumpsreflect metaphorical mappings that map the mimetic schemas of these basic, bodily experiences to more abstract experiences. Grounds for this kind of use is the unique construal of imitatives: they present an imagistic, iconic depiction of a sensation and thus evoke imagery that is shared on a direct bodily level. Thus they aid in identifying with others and their experiences on a level that is directly accessible.
Université du troisième âge : les besoins en formation continue des personnes âgées francophones au Nouveau-Brunswick
Authors: Dupuis-Blanchard Suzanne , Thériault Danielle , Mazerolle Lise
Published: September 2016

Continuing education is the ideal mechanism to allow retired people to maintain their autonomy and health for as long as possible. Despite the importance of education in the development of human beings, very few studies have been identified on the need for continued education in older adults. This quantitative descriptive study allowed us to better understand the interests and the needs of seniors related to continuing education in French-speaking older adults in New Brunswick (n = 408), and to identify the perceptions of participants with regard to the benefits, the challenges and the preferences of seniors for continuing education. Study results indicate that the main interests of participants were for training in technology (computers), gardening and health matters. Given the lack of research in this domain, these results will be useful for future planning of continuing education initiatives for seniors.
Retrospective forecasting of the 2010–2014 Melbourne influenza seasons using multiple surveillance systems
Authors: MOSS R. , ZAREBSKI A. , DAWSON P. , McCAW J. M.
Published: September 2016

Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, since these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, and we have previously tailored these methods for metropolitan Melbourne (Australia) and Google Flu Trends data. Here we extend these methods to clinical observation and laboratory-confirmation data for Melbourne, on the grounds that these data sources provide more accurate characterizations of influenza activity. We show that from each of these data sources we can accurately predict the timing of the epidemic peak 4–6 weeks in advance. We also show that makingsimultaneoususe of multiple surveillance systems to improve forecast skill remains a fundamental challenge. Disparate systems provide complementary characterizations of disease activity, which may or may not be comparable, and it is unclear how a ‘ground truth’ for evaluating forecasts against these multiple characterizations might be defined. These findings are a significant step towards making optimal use of routine surveillance data for outbreak forecasting.
Evaluating the impact of two training interventions to improve diagnosis and case-management of malaria and pneumonia in Uganda
Authors: SSEBULIBA D. M. , OUIFKI R. , PRETORIUS C. , BURNETT S. M. , MBONYE M. K. , NAIKOBA S. , WILLIS K. , WEAVER M. R.
Published: September 2016

We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14–91% in reduction of disease cases.
Re-conceptualizing centrality in social networks
Authors: SCHOCH D. , BRANDES U.
Published: September 2016

In the social sciences, networks are used to represent relationships between social actors, be they individuals or aggregates. The structural importance of these actors is assessed in terms of centrality indices which are commonly defined as graph invariants. Many such indices have been proposed, but there is no unifying theory of centrality. Previous attempts at axiomatic characterization have been focused on particular indices, and the conceptual frameworks that have been proposed alternatively do not lend themselves to mathematical treatment.

We show that standard centrality indices, although seemingly distinct, can in fact be expressed in a common framework based on path algebras. Since, as a consequence, all of these indices preserve the neighbourhood-inclusion pre-order, the latter provides a conceptually clear criterion for the definition of centrality indices.
Distance to hazard: an environmental policy with income heterogeneity
Authors: Nakada Minoru
Published: September 2016

This study examines whether voting by individuals of different income levels affects the stringency of environmental policy if their residential proximity to a pollution source is considered. A location model with heterogeneous agents is extended to include a single environmentally hazardous site at the edge of a linear city and the degree of damage from pollution is assumed to depend on the distance from this emissions site. The analysis demonstrates through majority voting that the equilibrium emissions tax rate is higher when the income level of the median voter is lower, because residents with low incomes reside near the hazardous site and thus benefit more from pollution abatement than residents with higher incomes.
A Law Firm Librarian's Guide to KM
Authors: Russell Hélène
Published: September 2016

This article is written by Hélène Russell, author and teacher in the field of legal sector Knowledge Management. It presents an easy to read foundation level guide to legal sector Knowledge Management for law firm Information Professionals. It explains what Knowledge is, what Knowledge Management (KM) is, how it differs from Information Management (IM) and how law firm Information Professionals can expand their roles to help their organisations meet business goals through strategic KM as well as IM, or manage an imposed transition from IM to IM+KM.
Poverty and Participation in Twenty-First Century Multicultural Britain
Authors: Ferragina Emanuele , Tomlinson Mark , Walker Robert
Published: September 2016

Peter Townsend argued that poverty could be scientifically measured as a ‘breakpoint’ within the income distribution below which participation collapses. This paper stands on Townsend's shoulders in measuring the level of poverty and participation by: (1) broadening his original measurement of participation; (2) using Structural Equation Modelling (SEM) in conjunction with a new dataset including 40,000 households (Understanding Society, 2011; 2013); and (3) taking into account the multi-cultural/ethnic nature of British society. We find that participation – defined as lack of deprivation, social participation and trust – reduces as income falls but stops doing so among the poorest 30 per cent of individuals. This may be indicating a minimum level of participation, a floor rather than a ‘breakpoint’ as suggested by Townsend, which has to be sustained irrespective of how low income is. Respondents with an ethnic minority background manifest lower levels of participation than white respondents but the relationship has a less linear pattern. Moreover, the floor detected for the overall population is also replicated when combining all respondents from ethnic groups.
Twinning Rates in Isolates
Authors: Fellman Johan
Published: September 2016

The aim of this study was to investigate the twinning rates (TWRs) in isolates relative to the TWRs in the surrounding populations. It is not uncommon that the TWR shows extreme values (high or low rates) within isolated subpopulations. Starting from the isolated populations of the Åland Islands in Finland (high rates), we enlarged our studies to other isolated subpopulations in other countries: the island of Gotland (high rates), the county of Älvsborg located in the southwestern part of Sweden (low rates), and mountain villages in Norway. In our statistical analyses, we paid special attention to the robustness of the variance formula of the TWR and to alternative confidence intervals for the TWR. Particularly, we show how to obtain the most precise confidence intervals for the twinning rates. These statistical methods are crucial when the extreme TWRs within subpopulations are compared with the TWRs within the general population. One must decide whether the differences are real or caused by random fluctuations within the small isolates.
Nicht-suizidales selbstverletzendes Verhalten (NSSV) im Jugendalter: Klinische Leitlinie zur Diagnostik und Therapie
Authors: Plener Paul L. , Fegert Jörg M. , Kaess Michael , Kapusta Nestor D. , Brunner Romuald , Groschwitz Rebecca C. , In-Albon Tina , Resch Franz , Becker Katja
Published: September 2016

Zusammenfassung. Hintergrund: Nicht-suizidales selbstverletzendes Verhalten (NSSV) ist ein häufiges, klinisch relevantes Phänomen im Jugendalter, das sich in Zusammenhang mit verschiedenen psychischen Störungen beobachten lässt. Deutschland gehört mit einer Lebenszeitprävalenz von 25–35 % bei Jugendlichen innerhalb Europas zu den Ländern mit den höchsten Prävalenzraten an NSSV. Bislang existierte eine zuletzt im Jahr 2006 überarbeitete AWMF-Leitlinie zu selbstverletzendem Verhalten und stereotypen Bewegungsstörungen, deren Gültigkeit 2011 abgelaufen war.

Methoden: Die Leitliniengruppe setzte sich aus elf medizinisch, psychologisch bzw. psychotherapeutischen Fachgesellschaften und zwei Interessensvertretungen aus Angehörigen- bzw. Präventionsprojekten zusammen. Die Leitlinie wurde in zwei Konferenzen, darauf aufbauenden Literaturrecherchen und einer abschließenden Konsensuskonferenz erarbeitet. Der Algorithmus wurde in drei Delphi-Runden verabschiedet.

Ergebnisse: Während die Datenlage zur Epidemiologie und zur Diagnostik von NSSV gut ist, sind noch immer wenige Studien zum Langzeitverlauf und zur psychotherapeutischen sowie zum Stellenwert einer psychopharmakologischen, adjuvanten Behandlung von NSSV im Jugendalter verfügbar. Berufsgruppenübergreifend wurde auch das Vorgehen im Falle der Notwendigkeit einer somatischen Versorgung bei NSSV thematisiert.

Schlussfolgerungen: In Anbetracht der heterogenen Evidenzlage wurden, um die klinische Anwendbarkeit der Leitlinie zu gewährleisten, die wesentlichen Punkte zur Behandlung von NSSV im Jugendalter in einer Konsensuskonferenz abgestimmt. Forschungsdefizite zeigen sich sowohl im Bereich präventiver als auch klinischer Interventionen.
The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis
Authors: Duan Mubing , Hibbs Margaret L , Chen Weisan
Published: September 2016

The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro‐inflammatory repertoire of lung monocytes and monocyte‐derived dendritic cells recruited during acute inflammation. Here, we review the identity and functions of all lung macrophage and monocyte subsets during homoeostasis and acute lung inflammation, with a special focus on their contributions to influenza virus detection, clearance and the development of influenza‐induced lung pathologies. Subsequent implications for the development of new therapeutic targets against influenza‐induced lung pathologies will also be discussed.
Direct-write nanoscale printing of nanogranular tunnelling strain sensors for sub-micrometre cantilevers
Authors: Dukic Maja , Winhold Marcel , Schwalb Christian H. , Adams Jonathan D. , Stavrov Vladimir , Huth Michael , Fantner Georg E.
Published: September 2016

The sensitivity and detection speed of cantilever-based mechanical sensors increases drastically through size reduction. The need for such increased performance for high-speed nanocharacterization and bio-sensing, drives their sub-micrometre miniaturization in a variety of research fields. However, existing detection methods of the cantilever motion do not scale down easily, prohibiting further increase in the sensitivity and detection speed. Here we report a nanomechanical sensor readout based on electron co-tunnelling through a nanogranular metal. The sensors can be deposited with lateral dimensions down to tens of nm, allowing the readout of nanoscale cantilevers without constraints on their size, geometry or material. By modifying the inter-granular tunnel-coupling strength, the sensors’ conductivity can be tuned by up to four orders of magnitude, to optimize their performance. We show that the nanoscale printed sensors are functional on 500 nm wide cantilevers and that their sensitivity is suited even for demanding applications such as atomic force microscopy.
The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression
Authors: Niknafs Yashar S. , Han Sumin , Ma Teng , Speers Corey , Zhang Chao , Wilder-Romans Kari , Iyer Matthew K. , Pitchiaya Sethuramasundaram , Malik Rohit , Hosono Yasuyuki , Prensner John R. , Poliakov Anton , Singhal Udit , Xiao Lanbo , Kregel Steven , Siebenaler Ronald F. , Zhao Shuang G. , Uhl Michael , Gawronski Alexander , Hayes Daniel F. , Pierce Lori J. , Cao Xuhong , Collins Colin , Backofen Rolf , Sahinalp Cenk S. , Rae James M. , Chinnaiyan Arul M. , Feng Felix Y.
Published: September 2016

Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer.
Loss of RNA expression and allele-specific expression associated with congenital heart disease
Authors: McKean David M. , Homsy Jason , Wakimoto Hiroko , Patel Neil , Gorham Joshua , DePalma Steven R. , Ware James S. , Zaidi Samir , Ma Wenji , Patel Nihir , Lifton Richard P. , Chung Wendy K. , Kim Richard , Shen Yufeng , Brueckner Martina , Goldmuntz Elizabeth , Sharp Andrew J. , Seidman Christine E. , Gelb Bruce D. , Seidman J. G.
Published: September 2016

Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression.
Megacity pumping and preferential flow threaten groundwater quality
Authors: Khan Mahfuzur R. , Koneshloo Mohammad , Knappett Peter S. K. , Ahmed Kazi M. , Bostick Benjamin C. , Mailloux Brian J. , Mozumder Rajib H. , Zahid Anwar , Harvey Charles F. , van Geen Alexander , Michael Holly A.
Published: September 2016

Many of the world’s megacities depend on groundwater from geologically complex aquifers that are over-exploited and threatened by contamination. Here, using the example of Dhaka, Bangladesh, we illustrate how interactions between aquifer heterogeneity and groundwater exploitation jeopardize groundwater resources regionally. Groundwater pumping in Dhaka has caused large-scale drawdown that extends into outlying areas where arsenic-contaminated shallow groundwater is pervasive and has potential to migrate downward. We evaluate the vulnerability of deep, low-arsenic groundwater with groundwater models that incorporate geostatistical simulations of aquifer heterogeneity. Simulations show that preferential flow through stratigraphy typical of fluvio-deltaic aquifers could contaminate deep (>150 m) groundwater within a decade, nearly a century faster than predicted through homogeneous models calibrated to the same data. The most critical fast flowpaths cannot be predicted by simplified models or identified by standard measurements. Such complex vulnerability beyond city limits could become a limiting factor for megacity groundwater supplies in aquifers worldwide.
CARD9 negatively regulates NLRP3-induced IL-1β production on Salmonella infection of macrophages
Authors: Pereira Milton , Tourlomousis Panagiotis , Wright John , P. Monie Tom , Bryant Clare E.
Published: September 2016

Interleukin-1β (IL-1β) is a proinflammatory cytokine required for host control of bacterial infections, and its production must be tightly regulated to prevent excessive inflammation. Here we show that caspase recruitment domain-containing protein 9 (CARD9), a protein associated with induction of proinflammatory cytokines by fungi, has a negative role on IL-1β production during bacterial infection. Specifically, in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection, CARD9 negatively regulates IL-1β by fine-tuning pro-IL-1β expression, spleen tyrosine kinase (SYK)-mediated NLRP3 activation and repressing inflammasome-associated caspase-8 activity. CARD9 is suppressed during Salmonella enterica serovar Typhimurium infection, facilitating increased IL-1β production. CARD9 is, therefore, a central signalling hub that coordinates a pathogen-specific host inflammatory response.
An electrical analogy to Mie scattering
Authors: Caridad José M. , Connaughton Stephen , Ott Christian , Weber Heiko B. , Krstić Vojislav
Published: September 2016

Mie scattering is an optical phenomenon that appears when electromagnetic waves, in particular light, are elastically scattered at a spherical or cylindrical object. A transfer of this phenomenon onto electron states in ballistic graphene has been proposed theoretically, assuming a well-defined incident wave scattered by a perfectly cylindrical nanometer scaled potential, but experimental fingerprints are lacking. We present an experimental demonstration of an electrical analogue to Mie scattering by using graphene as a conductor, and circular potentials arranged in a square two-dimensional array. The tabletop experiment is carried out under seemingly unfavourable conditions of diffusive transport at room-temperature. Nonetheless, when a canted arrangement of the array with respect to the incident current is chosen, cascaded Mie scattering results robustly in a transverse voltage. Its response on electrostatic gating and variation of potentials convincingly underscores Mie scattering as underlying mechanism. The findings presented here encourage the design of functional electronic metamaterials.
Population and hierarchy of active species in gold iron oxide catalysts for carbon monoxide oxidation
Authors: He Qian , Freakley Simon J. , Edwards Jennifer K. , Carley Albert F. , Borisevich Albina Y. , Mineo Yuki , Haruta Masatake , Hutchings Graham J. , Kiely Christopher J.
Published: September 2016

The identity of active species in supported gold catalysts for low temperature carbon monoxide oxidation remains an unsettled debate. With large amounts of experimental evidence supporting theories of either gold nanoparticles or sub-nm gold species being active, it was recently proposed that a size-dependent activity hierarchy should exist. Here we study the diverging catalytic behaviours after heat treatment of Au/FeOx materials prepared via co-precipitation and deposition precipitation methods. After ruling out any support effects, the gold particle size distributions in different catalysts are quantitatively studied using aberration corrected scanning transmission electron microscopy (STEM). A counting protocol is developed to reveal the true particle size distribution from HAADF-STEM images, which reliably includes all the gold species present. Correlation of the populations of the various gold species present with catalysis results demonstrate that a size-dependent activity hierarchy must exist in the Au/FeOx catalyst.
Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration
Authors: Smid Marcel , Rodríguez-González F. Germán , Sieuwerts Anieta M. , Salgado Roberto , Prager-Van der Smissen Wendy J. C. , Vlugt-Daane Michelle van der , van Galen Anne , Nik-Zainal Serena , Staaf Johan , Brinkman Arie B. , van de Vijver Marc J. , Richardson Andrea L. , Fatima Aquila , Berentsen Kim , Butler Adam , Martin Sancha , Davies Helen R. , Debets Reno , Gelder Marion E. Meijer-Van , van Deurzen Carolien H. M. , MacGrogan Gaëtan , Van den Eynden Gert G. G. M. , Purdie Colin , Thompson Alastair M. , Caldas Carlos , Span Paul N. , Simpson Peter T. , Lakhani Sunil R. , Van Laere Steven , Desmedt Christine , Ringnér Markus , Tommasi Stefania , Eyford Jorunn , Broeks Annegien , Vincent-Salomon Anne , Futreal P. Andrew , Knappskog Stian , King Tari , Thomas Gilles , Viari Alain , Langerød Anita , Børresen-Dale Anne-Lise , Birney Ewan , Stunnenberg Hendrik G. , Stratton Mike , Foekens John A. , Martens John W. M.
Published: September 2016

A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example,TP53, PIK3CA, PTEN, CCND1andCDH1. We find thatCCND3expression levels do not correlate with amplification, while increasedGATA3expression in mutantGATA3cancers suggestsGATA3is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.
A cholinergic-sympathetic pathway primes immunity in hypertension and mediates brain-to-spleen communication
Authors: Carnevale Daniela , Perrotta Marialuisa , Pallante Fabio , Fardella Valentina , Iacobucci Roberta , Fardella Stefania , Carnevale Lorenzo , Carnevale Raimondo , De Lucia Massimiliano , Cifelli Giuseppe , Lembo Giuseppe
Published: September 2016

The crucial role of the immune system in hypertension is now widely recognized. We previously reported that hypertensive challenges couple the nervous drive with immune system activation, but the physiological and molecular mechanisms of this connection are unknown. Here, we show that hypertensive challenges activate splenic sympathetic nerve discharge to prime immune response. More specifically, a vagus-splenic nerve drive, mediated by nicotinic cholinergic receptors, links the brain and spleen. The sympathetic discharge induced by hypertensive stimuli was absent in both coeliac vagotomized mice and in mice lacking α7nAChR, a receptor typically expressed by peripheral ganglionic neurons. This cholinergic-sympathetic pathway is necessary for T cell activation and egression on hypertensive challenges. In addition, we show that selectively thermoablating the splenic nerve prevents T cell egression and protects against hypertension. This novel experimental procedure for selective splenic denervation suggests new clinical strategies for resistant hypertension.
Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia
Authors: Lang Bing , Zhang Lei , Jiang Guanyu , Hu Ling , Lan Wei , Zhao Lei , Hunter Irene , Pruski Michal , Song Ning-Ning , Huang Ying , Zhang Ling , St Clair David , McCaig Colin D. , Ding Yu-Qiang
Published: September 2016

Schizophrenia is a debilitating familial neuropsychiatric disorder which affects 1% of people worldwide. Although the heritability for schizophrenia approaches 80% only a small proportion of the overall genetic risk has been accounted for and to date only a limited number of genetic loci have been definitively implicated. We have identified recently through genetic and in vitro functional studies, a novel serine/threonine kinase gene, unc-51-like kinase 4 (ULK4), as a rare risk factor for major mental disorders including schizophrenia. Now using the approach of in utero gene transfer we have discovered that Ulk4 plays a key modulatory role in corticogenesis. Knockdown of Ulk4 leads to significantly decreased cell proliferation in germinal zones and profound deficits in radial migration and neurite ramification. These abnormalities can be reversed successfully by Ulk4 gene supplementation. Ulk4 also regulated acetylation of α-tubulin, an important post-translational modification of microtubules. We conclude that Ulk4 plays an essential role in normal brain development and when defective, the risk of neurodevelopmental disorders such as schizophrenia is increased.
Combination treatment with decitabine and ionizing radiation enhances tumor cells susceptibility of T cells
Authors: Son Cheol-Hun , Lee Hong-Rae , Koh Eun-Kyoung , Shin Dong-Yeok , Bae Jae-Ho , Yang Kwangmo , Park You-Soo
Published: September 2016

Decitabine has been found to have anti-metabolic and anti-tumor activities in various tumor cells. Recently, the use of decitabine in combination with other conventional therapies reportedly resulted in improved anti-tumor activity against various tumors. Ionizing radiation (IR) is widely used as a cancer treatment. Decitabine and IR improve immunogenicity and susceptibility of tumor cells to immune cells by up-regulating the expression of various molecules such as major histocompatibility complex (MHC) class I; natural-killer group 2, member D (NKG2D) ligands; and co-stimulatory molecules. However, the effects of combining decitabine and IR therapies are largely unknown. Our results indicate that decitabine or IR treatment upregulates MHC class I, along with various co-stimulatory molecules in target tumor cells. Furthermore, decitabine and IR combination treatment further upregulates MHC class I, along with the co-stimulatory molecules, when compared to the effect of each treatment alone. Importantly, decitabine treatment further enhanced T cell-mediated cytotoxicity and release of IFN- γ against target tumor cells which is induced by IR. Interestingly, decitabine did not affect NKG2D ligand expression or NK cell-mediated cytotoxicity in target tumor cells. These observations suggest that decitabine may be used as a useful immunomodulator to sensitize tumor cells in combination with other tumor therapies.
Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis
Authors: Liu Wei , Wu Yuan-hao , Zhang Lei , Liu Xiao-ya , Bin Xue  , Bin Liu  , Wang Yi , Ji Yang
Published: September 2016

Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with impact on axial skeleton, peripheral joints and enthuses, and it may result in severe disabilities of those parts. Tumor necrosis factor-α (TNF-α) inhibitors are considered as an effective treatment for patients with active AS. In this study, we conducted a network meta-analysis to compare the clinical outcomes of active AS patients treated with TNF-α inhibitors. Randomized controlled trials (RCTs) evaluating the efficacy and safety of TNF-α inhibitors were retrieved in literature search and selected for meta-analysis. Changes in ASAS20 response, ASAS40 response and BASDAI 50% response were regarded as efficacy outcomes; serious adverse events (SAE) and all cause withdrawals were regarded as safety outcomes. Both traditional pairwise meta-analysis and network meta-analysis were performed. The results showed that adalimumab and infliximab had better clinical outcomes. Infliximab consistently appeared to be the most effective TNF-α inhibitors with a high risk of adverse events for patients with active AS; meanwhile, adalimumab ranked highest with respect to adverse effects with efficacy secondary to infliximab. As a result, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers.
Self-Assembly of Amphiphilic Block Copolypeptoids – Micelles, Worms and Polymersomes
Authors: Fetsch Corinna , Gaitzsch Jens , Messager Lea , Battaglia Giuseppe , Luxenhofer Robert
Published: September 2016

Polypeptoids are an old but recently rediscovered polymer class with interesting synthetic, physico-chemical and biological characteristics. Here, we introduce new aromatic monomers, N-benzyl glycine N-carboxyanhydride and N-phenethyl glycine N-carboxyanhydride and their block copolymers with the hydrophilic polysarcosine. We compare their self-assembly in water and aqueous buffer with the self-assembly of amphiphilic block copolypeptoids with aliphatic side chains. The aggregates in water were investigated by dynamic light scattering and electron microscopy. We found a variety of morphologies, which were influenced by the polymer structure as well as by the preparation method. Overall, we found polymersomes, worm-like micelles and oligo-lamellar morphologies as well as some less defined aggregates of interconnected worms and vesicles. Such, this contribution may serve as a starting point for a more detailed investigation of the self-assembly behavior of the rich class of polypeptoids and for a better understanding between the differences in the aggregation behavior of non-uniform polypeptoids and uniform peptoids.