bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in multiple breath washout measures after raised volume rapid thoracoabdominal compression maneuvers in infants
Authors: Subbarao Padmaja , Lu Zihang , Kowalik Krzysztof , Brown Meghan , Balkovec Susan , Gustafsson Per , Lou Wendy , Ratjen Felix
Published: September 2015

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of −0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of −0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies. Pediatr Pulmonol. 2016;51:183–188. © 2015 Wiley Periodicals, Inc.
Somatic MED12 mutations in prostate cancer and uterine leiomyomas promote tumorigenesis through distinct mechanisms
Authors: Kämpjärvi Kati , Kim Nam Hee , Keskitalo Salla , Clark Alison D. , von Nandelstadh Pernilla , Turunen Mikko , Heikkinen Tuomas , Park Min Ju , Mäkinen Netta , Kivinummi Kati , Lintula Susanna , Hotakainen Kristina , Nevanlinna Heli , Hokland Peter , Böhling Tom , Bützow Ralf , Böhm Jan , Mecklin Jukka‐Pekka , Järvinen Heikki , Kontro Mika , Visakorpi Tapio , Taipale Jussi , Varjosalo Markku , Boyer Thomas G. , Vahteristo Pia
Published: September 2015

BACKGROUND

Mediator is a multiprotein interface between eukaryotic gene‐specific transcription factors and RNA polymerase II. Mutations in exon 2 of the gene encoding MED12, a key subunit of the regulatory kinase module in Mediator, are extremely frequent in uterine leiomyomas, breast fibroadenomas, and phyllodes tumors. These mutations disrupt kinase module interactions and lead to diminished Mediator‐associated kinase activity. MED12 mutations in exon 26, resulting in a substitution of leucine 1224 to phenylalanine (L1224F), have been recurrently observed in prostate cancer.

METHODS

To elucidate the molecular mechanisms leading to tumorigenesis in prostate cancer, we analyzed global interaction profiles of wild‐type and L1224F mutant MED12 with quantitative affinity purification‐mass spectrometry (AP‐MS). Immunoprecipitation and kinase activity assay were used to further assess the interactions between Mediator complex subunits and kinase activity. The presence of L1224F mutation was analyzed in altogether 877 samples representing prostate hyperplasia, prostate cancer, and various tumor types in which somatic MED12 mutations have previously been observed.

RESULTS

In contrast to N‐terminal MED12 mutations observed in uterine leiomyomas, the L1224F mutation compromises neither the interaction of MED12 with kinase module subunits Cyclin C and CDK8/19 nor Mediator‐associated CDK activity. Instead, the L1224F mutation was shown to affect interactions between MED12 and other Mediator components (MED1, MED13, MED13L, MED14, MED15, MED17, and MED24). Mutation screening revealed one mutation in a Finnish (Caucasian) prostate cancer patient, whereas no mutations in any other tumor type were observed.

CONCLUSIONS

Specific somatic MED12 mutations in prostate cancer and uterine leiomyomas accumulate in two separate regions of the gene and promote tumorigenesis through clearly distinct mechanisms. Prostate 76:22–31, 2016. © 2015 Wiley Periodicals, Inc.
Chemical interaction matrices
Authors: Murphy Michelle R. , Singh Surendra K.
Published: September 2015

Despite the promulgation of the “PSM Standard” by OSHA in 1992, chemical accidents continue to occur at an alarming rate. As part of the process safety information element of the standard, OSHA requires reactivity data on the chemicals in the process. One piece of this reactivity data is a chemical interaction matrix. Several software programs provide simple approaches to generating these interaction charts for common materials using assigned reactive groups. If your process involves materials not included, you are left to determine the reactivity and incompatibilities on your own. This paper will explain a process for assigning reactive groups using chemical classification and structural analysis. This process can be used for less commonly understood materials such as additives, lubricants, mixtures, products, etc. that may come into contact with process chemicals. © 2015 American Institute of Chemical Engineers Process Saf Prog 34: 368–372, 2015
Microshear bond strength of preheated silorane‐ and methacrylate‐based composite resins to dentin
Authors: Demirbuga Sezer , Ucar Faruk Izzet , Cayabatmaz Muhammed , Zorba Yahya Orcun , Cantekin Kenan , Topçuoğlu Hüseyin Sinan , Kilinc Halil Ibrahim
Published: September 2015

The aim of this study was to investigate the effect of preheating on microshear bond strength (MSBS) of silorane and methacrylate‐based composite resins to human dentin. The teeth were randomly divided into three main groups: (1) composite resins were heated upto 68 °C; (2) cooled to 4 °C; and (3) control [room temperature (RT)]. Each group was then randomly subdivided into four subgroups according to adhesive system used [Solobond M (Voco), All Bond SE (Bisco), Clearfil SE Bond (CSE) (Kuraray), Silorane adhesive system (SAS) (3M ESPE)]. Resin composite cylinders were formed (0.9 mm diameter × 0.7 mm length) and MSBS of each specimen was tested. The preheated groups exhibited the highest MSBS (p < 0.001) and the groups cooled to 4 °C exhibited the lowest MSBS (p < 0.001). The CSE showed higher MSBS than the other adhesives (p < 0.001). This study concludes that preheating of composite resins may be an alternative way to increase the MSBS of composites on dentin. SCANNING 38:63–69, 2016. © 2015 Wiley Periodicals, Inc.
DNA Polymer Brush Patterning through Photocontrollable Surface‐Initiated DNA Hybridization Chain Reaction
Authors: Huang Fujian , Zhou Xiang , Yao Dongbao , Xiao Shiyan , Liang Haojun
Published: September 2015

The fabrication of DNA polymer brushes with spatial resolution onto a solid surface is a crucial step for biochip research and related applications, cell‐free gene expression study, and even artificial cell fabrication. Here, for the first time, a DNA polymer brush patterning method is reported based on the photoactivation of an ortho‐nitrobenzyl linker‐embedded DNA hairpin structure and a subsequent surface‐initiated DNA hybridization chain reaction (HCR). Inert DNA hairpins are exposed to ultraviolet light irradiation to generate DNA duplexes with two active sticky ends (toeholds) in a programmable manner. These activated DNA duplexes can initiate DNA HCR to generate multifunctional patterned DNA polymer brushes with complex geometrical shapes. Different multifunctional DNA polymer brush patterns can be fabricated on certain areas of the same solid surface using this method. Moreover, the patterned DNA brush surface can be used to capture target molecules in a desired manner.
My pipes say I am powerful: belonging and class as constructed through our sewers
Authors: Morales Margaret C.
Published: September 2015

This review examines the social and political roots and ongoing implications of centralized, waterborne sewerage. This system has served as a marker of class, a signal of wealth and political power, and a mechanism of social reform. As sewerage networks ballooned in the mid‐19th century throughout Europe and North America in response to a growing public health movement, their use and attendant hygiene practices served to intertwine physical and moral hygiene. The new infrastructure prioritized a felt distance between the user and their excreta, particularly signaled by the absence of odor, access to privacy, and the disassociation of users from any part of the management process beyond the flush of the toilet. Furthermore, the resource intensive system advertised affluence, and emphasized emerging notions of the networked urban space, which had the potential to tame and control Nature. This infrastructure model and its social and political underpinnings were exported to many cities under colonial influence throughout much of the 19th and 20th centuries, and were used to justify class differentiation and racialized agendas. Differential sewerage access in municipal centers of the Global South today continues to serve as a marker of class distinction, and many modern scholars explore how lack of sewerage renders the urban poor politically invisible. Ultimately, consideration of the social and political legacy of the linear sewerage system may offer new ways forward in addressing urban sanitation crises faced across the globe today, including problems posed by aging, unsustainable, and insufficient infrastructure. WIREs Water 2016, 3:63–73. doi: 10.1002/wat2.1108

This article is categorized under:

Human Water > Value of Water
Particle tracers and image analysis for surface flow observations
Authors: Tauro Flavia
Published: September 2015

Traditional observational methodologies have proved insufficient to thoroughly characterize the hydrological response of natural environments. In this context, recent efforts have fostered unprecedented observational methodologies for hydrological processes at the interface of multiple engineering and scientific fields and water science. This overview outlines latest advancements in the observation of surface flows through a novel methodology based on the combined use of high‐visibility tracer particles and digital image acquisition and processing. This low‐cost measurement system has been designed and tested in laboratory settings and natural environments, such as rill flow in natural hillslopes and riverine ecosystems. Comparison of this novel flow sensing method to traditional tracing systems has suggested that the use of multidisciplinary and unintended technology can greatly contribute to advance standard practice in environmental monitoring and to open novel research avenues in water science. WIREs Water 2016, 3:25–39. doi: 10.1002/wat2.1116

This article is categorized under:

Science of Water > Methods
Mechanisms underlying the formation of induced pluripotent stem cells
Authors: González Federico , Huangfu Danwei
Published: September 2015

Human pluripotent stem cells (hPSCs) offer unique opportunities for studying human biology, modeling diseases, and therapeutic applications. The simplest approach so far to generate human PSC lines is through reprogramming of somatic cells from an individual by defined factors, referred to simply as reprogramming. Reprogramming circumvents the ethical controversies associated with human embryonic stem cells (hESCs) and nuclear transfer hESCs (nt‐hESCs), and the resulting induced pluripotent stem cells (hiPSCs) retain the same basic genetic makeup as the somatic cell used for reprogramming. Since the first report of iPSCs by Takahashi and Yamanaka (Cell 2006, 126:663–676), the molecular mechanisms of reprogramming have been extensively investigated. A better mechanistic understanding of reprogramming is fundamental not only to iPSC biology and improving the quality of iPSCs for therapeutic use, but also to our understanding of the molecular basis of cell identity, pluripotency, and plasticity. Here, we summarize the genetic, epigenetic, and cellular events during reprogramming, and the roles of various factors identified thus far in the reprogramming process. WIREs Dev Biol 2016, 5:39–65. doi: 10.1002/wdev.206

This article is categorized under:

Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles

Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion

Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease
Enhanced Structuring of Fat with Reduced Saturates Using Mixed Molecular Compounds
Authors: Sibbald A. N. , Carney J. R. , Marangoni A. G.
Published: September 2015

Molecular compound formation between multicomponent triacylglyceride (TAG) mixtures was characterized using palm oil mid fraction enriched in sn‐1,3‐dipalmitoyl‐2‐oleoylglycerol (cPOP) and a commercial fraction enriched in sn‐1,3‐dioleyl‐2‐palmitoylglycerol containing a wide range of TAGs (cOPO). Compound formation occurred at a 1:1 (w/w) ratio of cPOP to cOPO corresponding to an equal parts ratio of two different families of TAGs. One family of TAGs consisted of a grouping of all TAGs composed of a saturated–oleic–saturated (StUSt) positioning of fatty acids. The second family consisted of a grouping of all TAGs composed of all oleic–saturated–oleic and saturated–saturated–oleic fatty acids (UStU, StStU). An increase in solid fat content, peak melting temperature, and crystalline domain size and a change in crystalline microstructure were observed at this ratio corresponding to an overall equality in the amount of cPOP to cOPO. This indicates that it is possible to achieve that same level of solid fat content and hardness as a mixture containing more saturates, simply by slightly decreasing the saturates and substituting an oleic monounsaturated fatty acid containing TAG mixture such that a molecular compound is formed. The increase in full‐width at half‐maximum indicated a decrease in crystalline order and/or decrease in crystal domain size. The characteristic spherulitic crystalline microstructure of OPO changed to small granular crystals upon addition of cPOP. This discovery may allow for the incorporation of a larger proportion of healthy monounsaturated fats into foods while decreasing the use of saturated and trans fats.
Out of Hours Emergency Computed Tomography Brain Studies: Comparison of Standard 3 Megapixel Diagnostic Workstation Monitors with the iPad 2
Authors: Salati Umer , Leong Sum , Donnellan John , Kok Hong Kuan , Buckley Orla , Torreggiani William
Published: September 2015

Purpose

The purpose was to compare performance of diagnostic workstation monitors and the Apple iPad 2 (Cupertino, CA) in interpretation of emergency computed tomography (CT) brain studies.

Methods

Two experienced radiologists interpreted 100 random emergency CT brain studies on both on-site diagnostic workstation monitors and the iPad 2 via remote access. The radiologists were blinded to patient clinical details and to each other's interpretation and the study list was randomized between interpretations on different modalities. Interobserver agreement between radiologists and intraobserver agreement between modalities was determined and Cohen kappa coefficients calculated for each. Performance with regards to urgent and nonurgent abnormalities was assessed separately.

Results

There was substantial intraobserver agreement of both radiologists between the modalities with overall calculated kappa values of 0.959 and 0.940 in detecting acute abnormalities and perfect agreement with regards to hemorrhage. Intraobserver agreement kappa values were 0.939 and 0.860 for nonurgent abnormalities. Interobserver agreement between the 2 radiologists for both diagnostic monitors and the iPad 2 was also substantial ranging from 0.821-0.860.

Conclusions

The iPad 2 is a reliable modality in the interpretation of CT brain studies in them emergency setting and for the detection of acute and chronic abnormalities, with comparable performance to standard diagnostic workstation monitors.
Children's and Parents’ Evaluations of ‘FRIENDS for Life’, an Indicated School-Based Prevention Program for Children With Symptoms of Anxiety and Depression
Authors: Zwaanswijk Marieke , Kösters Mia P.
Published: September 2015

There is evidence that the school-based program FRIENDS for Life is effective in preventing childhood anxiety and depression. Effectiveness is, however, not the only prerequisite for successful implementation. Participants’ evaluation of a prevention program may provide suggestions about how to fine-tune it to fit the needs of the target population. This study investigated children's and parents’ evaluations of the Dutch version of FRIENDS for Life. Forty-four participants of FRIENDS for Life (9–13 years) participated in online focus groups and 38 parents were interviewed in 2011–2012. Questions concerned the general opinion about the program, its perceived effectiveness and group atmosphere, and suggestions for program improvement. Most children (95.5%) and parents (65.8%) evaluated the program positively, and the majority (61.4% and 76.3%) thought that it had been useful in changing the child's behaviour. Children and parents expressed complementary views about the behaviours the child had learned. Some children (38.6%) expressed negative opinions about the program. Parents’ attendance at parent meetings was low (31.6–36.8%). Considered together with the growing evidence of the effectiveness of FRIENDS for Life, we concluded that it can be successfully implemented as an indicated prevention program in primary schools for children who show symptoms of anxiety or depression. Efforts could be made to increase parents’ involvement in the program.
The intermittency boundary in stratified plane Couette flow
Authors: Deusebio Enrico , Caulfield C. P. , Taylor J. R.
Published: September 2015

We study stratified turbulence in plane Couette flow using direct numerical simulations. Two external dimensionless parameters control the dynamics, the Reynolds number $\mathit{Re}=Uh/{\it\nu}$ and the bulk Richardson number $\mathit{Ri}=g{\it\alpha}_{V}Th/U^{2}$, where $U$ and $T$ are half the velocity and temperature difference between the two walls respectively, $h$ is the half channel depth, ${\it\nu}$ is the kinematic viscosity and $g{\it\alpha}_{V}$ is the buoyancy parameter. We focus on spatio-temporal intermittency due to stratification and we explore the boundary between fully developed turbulence and intermittent flow in the $\mathit{Re}{-}\mathit{Ri}$ plane. The structures populating the intermittent flow regime show coexistence between laminar and turbulent patches, and we demonstrate that there are qualitative differences between the previously studied low-$\mathit{Re}$ low-$\mathit{Ri}$ intermittent regime and the high-$\mathit{Re}$ high-$\mathit{Ri}$ intermittent regime. At low-$\mathit{Re}$ low-$\mathit{Ri}$, turbulent regions span the entire gap, whereas at high-$\mathit{Re}$ high-$\mathit{Ri}$, turbulence is confined vertically with complex dynamics arising from interacting turbulent layers. Consistent with a previous investigation of Flores & Riley (Boundary-Layer Meteorol., vol. 129 (2), 2010, pp. 241–259), we present evidence suggesting that intermittency in the asymptotic regime of high-$\mathit{Re}$ Couette flows appears for $L^{+}<200$, where $L^{+}=Lu_{{\it\tau}}/{\it\nu}$, with $L$ being the Monin–Obukhov length scale, $L=u_{{\it\tau}}^{3}/C_{{\it\kappa}}q_{w}$, $q_{w}$ the wall heat flux, $C_{{\it\kappa}}$ the von Kármán constant and $u_{{\it\tau}}=\sqrt{{\it\tau}_{w}/{\it\rho}_{0}}$ the friction velocity determined from the wall shear stress ${\it\tau}_{w}$, where ${\it\rho}_{0}$ is the constant background density. We also consider the mixing as quantified by various versions of the flux Richardson number $\mathit{Ri}_{f}$, defined as the ratio of the conversion rate from kinetic to potential energy to the turbulent kinetic energy injection rate due to shear. We investigate how laminar and turbulent regions separately contribute to the overall mixing. Remarkably, we find that although fluctuations are greatly suppressed in the laminar regions, $\mathit{Ri}_{f}$ does not change significantly compared with its value in turbulent regions. As we observe a tight coupling between the mean temperature and velocity fields, we demonstrate that both Monin–Obukhov self-similarity theory (Monin & Obukhov, Contrib. Geophys. Inst. Acad. Sci. USSR, vol. 151, 1954, pp. 163–187) and the explicit algebraic model of Lazeroms et al. (J. Fluid Mech., vol. 723, 2013, pp. 91–125) predict the mean profiles well. We thus use these models to trace out the boundary between fully developed turbulence and intermittency in the $\mathit{Re}{-}\mathit{Ri}$ plane.
Dynamic Stall Analysis of S809 Pitching Airfoil in Unsteady Free Stream Velocity
Authors: Karbasian H. R. , Moshizi S. A. , Maghrebi M. J.
Published: September 2015

In this paper, the dynamic stall of S809 airfoil that widely used in horizontal axis wind turbine, in different reduced frequencies is investigated. The simulation was carried out numerically handling Navier-Stokes equations. For this purpose, the segregated solver with SIMPLE algorithm was chosen to solve the momentum equations. The effect of turbulence on the flow field is taken into account using Shear Stress Transport (SST)K-ωturbulence model. The obtained numerical results are compared with experimental and a few numerical results. The results indicate that theK-ωSST model is in good agreement with experimental results for both steady and unsteady conditions. Furthermore, a non-dimensional parameter, relating the acceleration of unsteady free stream velocity and acceleration of pitch motion (known as reduced frequency), is also investigated. In addition, the results show that any increase in the reduced frequency increases the instantaneous aerodynamic characteristics of oscillating airfoil.
Vitamin D status is associated with cardiometabolic markers in 8–11-year-old children, independently of body fat and physical activity
Authors: Petersen Rikke A. , Dalskov Stine-Mathilde , Sørensen Louise B. , Hjorth Mads F. , Andersen Rikke , Tetens Inge , Krarup Henrik , Ritz Christian , Astrup Arne , Michaelsen Kim F. , Mølgaard Christian , Damsgaard Camilla T.
Published: September 2015

Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8–11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August–November. Mean serum 25(OH)D was 60·8 (sd18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (−0·3 mmHg, 95 % CI −0·6, −0·0) (P=0·02), total cholesterol (−0·07 mmol/l, 95 % CI −0·10, −0·05), LDL-cholesterol (−0·05 mmol/l, 95 % CI −0·08, −0·03), TAG (−0·02 mmol/l, 95 % CI −0·03, −0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause–effect relationship and possible long-term implications should be investigated in randomised controlled trials.
Lean and obese dietary phenotypes: differences in energy and substrate metabolism and appetite
Authors: Clamp Louise , Hehir Anthony P. J. , Lambert Estelle V. , Beglinger Christoph , Goedecke Julia H.
Published: September 2015

This study aimed to characterise lean and obese phenotypes according to diet and body composition, and to compare fasting and postprandial appetite and metabolic profiles following a high-fat test meal. A total of ten lean (BMI<25 kg/m2) high-fat (LHF), ten lean low-fat (LLF; >40 and <30 % energy from fat) and ten obese (BMI>30 kg/m2) high-fat consumers (OHF; >40 % energy from fat) were recruited. Before and following the test meal (4727 kJ (1130 kcal), 77 % fat, 20 % carbohydrate (CHO) and 3 % protein), fasting plasma glucose, insulin, leptin, ghrelin, peptide YY (PYY), RER, RMR and subjective appetite ratings (AR) were measured for 6 h. Thereafter, subjects consumed a self-selected portion of a standardised post-test meal (40 % fat, 45 % CHO and 15 % protein) and reported AR. Fasting (P=0·01) and postprandial (P<0·001) fat oxidation was significantly higher in LHF than in LLF but was not different between LHF and OHF. Although similar between the lean groups, fasting and postprandial energy expenditures were significantly higher in OHF compared with LHF (P<0·01). Despite similar AR across groups, LLF consumed a relatively greater quantity of the post-test meal than did LHF (7·87 (sd 2·96) v. 7·23 (sd 2·67) g/kg, P=0·013). The lean groups showed appropriate changes in plasma ghrelin and PYY following the test meal, whereas the OHF group showed a blunted response. In conclusion, the LHF phenotype had a greater capacity for fat oxidation, which may be protective against weight gain. OHF individuals had a blunted appetite hormone response to the high-fat test meal, which may subsequently increase energy intake, driving further weight gain.
Epidemiological features of influenza in Canadian adult intensive care unit patients
Authors: TAYLOR G. , ABDESSELAM K. , PELUDE L. , FERNANDES R. , MITCHELL R. , McGEER A. , FRENETTE C. , SUH K. N. , WONG A. , KATZ K. , WILKINSON K. , MERSEREAU T. , GRAVEL D. ,   the Canadian Nosocomial Infection Surveillance Program (CNISP)
Published: September 2015

To identify predictive factors and mortality of patients with influenza admitted to intensive care units (ICU) we carried out a prospective cohort study of patients hospitalized with laboratory-confirmed influenza in adult ICUs in a network of Canadian hospitals between 2006 and 2012. There were 626 influenza-positive patients admitted to ICUs over the six influenza seasons, representing 17·9% of hospitalized influenza patients, 3·1/10 000 hospital admissions. Variability occurred in admission rate and proportion of hospital influenza patients who were admitted to ICUs (proportion range by year: 11·7–29·4%; 21·3% in the 2009–2010 pandemic). In logistic regression models ICU patients were younger during the pandemic and post-pandemic period, and more likely to be obese than hospital non-ICU patients. Influenza B accounted for 14·2% of all ICU cases and had a similar ICU admission rate as influenza A. Influenza-related mortality was 17·8% in ICU patients compared to 2·0% in non-ICU patients.
Knowing, Learning and Teaching—How Homo Became Docens
Authors: Högberg Anders , Gärdenfors Peter , Larsson Lars
Published: September 2015

This article discusses the relation between knowing, learning and teaching in relation to early Palaeolithic technologies. We begin by distinguishing between three kinds of knowledge: knowing how, knowing what and knowing that. We discuss the relation between these types of knowledge and different forms of learning and long-term memory systems. On the basis of this analysis, we present three types of teaching: (1) helping and correcting; (2) showing; and (3) explaining. We then use this theoretical framework to suggest what kinds of teaching are required for the pre-Oldowan, the Oldowan, the early Acheulean and the late Acheulean stone-knapping technologies. As a general introductory overview to this special section, the text concludes with a brief presentation of the papers included.
Grammatical gender in bilingual Norwegian–Russian acquisition: The role of input and transparency
Authors: RODINA YULIA , WESTERGAARD MARIT
Published: September 2015

This paper investigates the role of parental input and transparency in the acquisition of two different gender systems, Norwegian and Russian, by bilingual children living in Norway. While gender in Russian is generally predictable from the morphophonological shape of the noun (with some exceptions), gender assignment in Norwegian is opaque. An experimental production study was carried out with two groups of bilinguals, children with one or two Russian-speaking parents, and monolingual controls (age 4;1–7;11). The findings show that both groups of bilinguals perform similarly to monolinguals in Norwegian, the majority language, despite the lack of transparency. In Russian, on the other hand, not only quantitative, but also qualitative differences are found in the data of the bilingual children with the least exposure to the language. These qualitative differences indicate that early age of onset is not sufficient to acquire phenomena such as gender; extensive input is necessary.
Direct-Writing of Cu Nano-Patterns with an Electron Beam
Authors: Lai Shih-En , Hong Ying-Jhan , Chen Yu-Ting , Kang Yu-Ting , Chang Pin , Yew Tri-Rung
Published: September 2015

We demonstrate direct electron beam writing of a nano-scale Cu pattern on a surface with a thin aqueous layer of CuSO4 solution. Electron beams are highly maneuverable down to nano-scales. Aqueous solutions facilitate a plentiful metal ion supply for practical industrial applications, which may require continued reliable writing of sophisticated patterns. A thin aqueous layer on a surface helps to confine the writing on the surface. For this demonstration, liquid sample holder (K-kit) for transmission electron microscope (TEM) was employed to form a sealed space in a TEM. The aqueous CuSO4 solution inside the sample holder was allowed to partially dry until a uniform thin layer was left on the surface. The electron beam thus reduced Cu ions in the solution to form the desired patterns. Furthermore, the influence of e-beam exposure time and CuSO4(aq) concentration on the Cu reduction was studied in this work. Two growth stages of Cu were shown in the plot of Cu thickness versus e-beam exposure time. The measured Cu reduction rate was found to be proportional to the CuSO4(aq) concentration.
Speckle Suppression by Decoherence in Fluctuation Electron Microscopy
Authors: Rezikyan Aram , Jibben Zechariah J. , Rock Bryan A. , Zhao Gongpu , Koeck Franz A.M. , Nemanich Robert F. , Treacy Michael M.J.
Published: September 2015

We compare experimental fluctuation electron microscopy (FEM) speckle data with electron diffraction simulations for thin amorphous carbon and silicon samples. We find that the experimental speckle intensity variance is generally more than an order of magnitude lower than kinematical scattering theory predicts for spatially coherent illumination.

We hypothesize that decoherence, which randomizes the phase relationship between scattered waves, is responsible for the anomaly. Specifically,displacement decoherencecan contribute strongly to speckle suppression, particularly at higher beam energies. Displacement decoherence arises when the local structure is rearranged significantly by interactions with the beam during the exposure. Such motions cause diffraction speckle to twinkle, some of it at observable time scales.

We also find that the continuous random network model of amorphous silicon can explain the experimental variance data if displacement decoherence and multiple scattering is included in the modeling. This may resolve the longstanding discrepancy between X-ray and electron diffraction studies of radial distribution functions, and conclusions reached from previous FEM studies.

Decoherence likely affects all quantitative electron imaging and diffraction studies. It likely contributes to the so-called Stobbs factor, where high-resolution atomic-column image intensities are anomalously lower than predicted by a similar factor to that observed here.
Examining self-verification processes in social anxiety
Authors: Howarth Mitchell P. A. , Forbes Miriam
Published: September 2015

Socially anxious individuals hold negative beliefs about their appearance, abilities and personality. These negative self-conceptions increase expectations of negative evaluation from others and, consequently increase anxiety. Self-verification theory states that individuals seek, accept and prefer feedback that is congruent with their self-conceptions. This study explored the assumptions of self-verification theory in social anxiety. This was achieved by examining the type of feedback socially anxious individuals seek and how positive and negative feedback is processed. Results from an undergraduate sample (n = 84) indicate that socially anxious individuals were no more or less likely to seek negative feedback than individuals with low social anxiety. However, participants with greater social anxiety rated positive feedback as less accurate, rated negative feedback as more accurate, and were more comfortable with negative feedback, compared to participants with low social anxiety. Greater social anxiety was also found to predict increased discomfort with positive feedback, and fear of negative evaluation fully mediated this relationship. These findings suggest that self-verification processes operate in social anxiety and highlight the need for researchers to include measures of fears of evaluation when examining self-verification theory in samples of socially anxious individuals.
Dynamical backaction cooling with free electrons
Authors: Niguès A. , Siria A. , Verlot P.
Published: September 2015

The ability to cool single ions, atomic ensembles, and more recently macroscopic degrees of freedom down to the quantum ground state has generated considerable progress and perspectives in fundamental and technological science. These major advances have been essentially obtained by coupling mechanical motion to a resonant electromagnetic degree of freedom in what is generally known as laser cooling. Here, we experimentally demonstrate the first self-induced coherent cooling mechanism that is not mediated by an electromagnetic resonance. Using a focused electron beam, we report a 50-fold reduction of the motional temperature of a nanowire. Our result primarily relies on the sub-nanometre confinement of the electron beam and generalizes to any delayed and spatially confined interaction, with important consequences for near-field microscopy and fundamental nanoscale dissipation mechanisms.
An intrinsic timer specifies distal structures of the vertebrate limb
Authors: Saiz-Lopez Patricia , Chinnaiya Kavitha , Campa Victor M. , Delgado Irene , Ros Maria A. , Towers Matthew
Published: September 2015

How the positional values along the proximo-distal axis (stylopod-zeugopod-autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein-expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb.
Enhancing S-adenosyl-methionine catabolism extends Drosophila lifespan
Authors: Obata Fumiaki , Miura Masayuki
Published: September 2015

Methionine restriction extends the lifespan of various model organisms. Limiting S-adenosyl-methionine (SAM) synthesis, the first metabolic reaction of dietary methionine, extends longevity in Caenorhabditis elegans but accelerates pathology in mammals. Here, we show that, as an alternative to inhibiting SAM synthesis, enhancement of SAM catabolism by glycine N-methyltransferase (Gnmt) extends the lifespan in Drosophila. Gnmt strongly buffers systemic SAM levels by producing sarcosine in either high-methionine or low-sams conditions. During ageing, systemic SAM levels in flies are increased. Gnmt is transcriptionally induced in a dFoxO-dependent manner; however, this is insufficient to suppress SAM elevation completely in old flies. Overexpression of gnmt suppresses this age-dependent SAM increase and extends longevity. Pro-longevity regimens, such as dietary restriction or reduced insulin signalling, attenuate the age-dependent SAM increase, and rely at least partially on Gnmt function to exert their lifespan-extending effect in Drosophila. Our study suggests that regulation of SAM levels by Gnmt is a key component of lifespan extension.
Coordination templated [2+2+2] cyclotrimerization in a porous coordination framework
Authors: Wei Yong-Sheng , Zhang Mei , Liao Pei-Qin , Lin Rui-Biao , Li Tai-Yang , Shao Guang , Zhang Jie-Peng , Chen Xiao-Ming
Published: September 2015

Controlling chemical reactions by the supramolecular confinement effects of nanopores has attracted great attention. Here we show that open metal sites in porous coordination frameworks can constitute more powerful and strict templates for precision syntheses. A Fe(III) dicarboxylate framework functionalized with triangularly arranged metal sites is used to accomplish [2+2+2] cyclotrimerization reactions for organonitrile, alkyne and alkene monomers bearing a geometrically suitable pyridyl group. In situ single-crystal X-ray diffraction facilitates the direct observation of such a coordination templated reaction, before cylcotrimerization, the monomer coordinates at the Fe(III) centre by its pyridyl donor, which forces three unsaturated groups to gather around a position very similar with that of the desired covalent cyclic trimer. After the reaction, the trimers serve as tripodal ligands to perfectly fix the Fe(III) ions and the whole crystal to generate an exceptionally rigid and porous material with large surface area coupled with guest-proof zero thermal expansion.
Suppressed phase transition and giant ionic conductivity in La2Mo2O9 nanowires
Authors: Liu Wei , Pan Wei , Luo Jian , Godfrey Andy , Ou Gang , Wu Hui , Zhang Wei
Published: September 2015

Improving the ionic conductivity of solid electrolytes at low temperatures represents a major challenge and an opportunity for enabling a variety of solid-state ionic devices for energy conversion and storage, as well as for environmental protection. Here we report a giant ionic conductivity of 0.20 Scm−1, achieved at 500 °C, in the La2Mo2O9 nanowires with a bamboo-wire morphology, corresponding to a 1000-fold enhancement in conductivity over conventional bulk material. Stabilization of the high-temperature phase is observed to account for about a 10-fold increase in the conductivity. We further demonstrate that fast surface conduction in ∼3 nm thick, partially ordered, surface ‘amorphous’ films, under strain on the curved surfaces of the nanowires (as a non-autonomous surface phase or complexion), contributes to an enhancement of the conductivity by another two orders of magnitude. Exemplified here by the study of the La2Mo2O9 nanowires, new possibilities for improvement of conductivity and for miniaturization of solid-state ionic devices by the careful use of one-dimensional nanomaterials can be envisioned.
Ultrafast multidimensional Laplace NMR for a rapid and sensitive chemical analysis
Authors: Ahola Susanna , Zhivonitko Vladimir V , Mankinen Otto , Zhang Guannan , Kantola Anu M. , Chen Hsueh-Ying , Hilty Christian , Koptyug Igor V. , Telkki Ville-Veikko
Published: September 2015

Traditional nuclear magnetic resonance (NMR) spectroscopy relies on the versatile chemical information conveyed by spectra. To complement conventional NMR, Laplace NMR explores diffusion and relaxation phenomena to reveal details on molecular motions. Under a broad concept of ultrafast multidimensional Laplace NMR, here we introduce an ultrafast diffusion-relaxation correlation experiment enhancing the resolution and information content of corresponding 1D experiments as well as reducing the experiment time by one to two orders of magnitude or more as compared with its conventional 2D counterpart. We demonstrate that the method allows one to distinguish identical molecules in different physical environments and provides chemical resolution missing in NMR spectra. Although the sensitivity of the new method is reduced due to spatial encoding, the single-scan approach enables one to use hyperpolarized substances to boost the sensitivity by several orders of magnitude, significantly enhancing the overall sensitivity of multidimensional Laplace NMR.
Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling
Authors: Kang Young Jun , Bang Bo-Ram , Han Kyung Ho , Hong Lixin , Shim Eun-Jin , Ma Jianhui , Lerner Richard A. , Otsuka Motoyuki
Published: September 2015

The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of NFAT and dephosphorylation of dynamin-related protein 1 (Drp1), a GTPase is essential for mitochondrial homoeostasis. Ripk3−/− mice show reduced NKT cell responses to metastatic tumour cells, and both deletion of RIPK3 and pharmacological inhibition of Drp1 protects mice from NKT cell-mediated induction of acute liver damage. Collectively, the results identify a crucial role for RIPK3-PGAM5-Drp1/NFAT signalling in NKT cell activation, and further suggest that RIPK3-PGAM5 signalling may mediate crosstalk between mitochondrial function and immune signalling.
Strong frequency dependence of vibrational relaxation in bulk and surface water reveals sub-picosecond structural heterogeneity
Authors: van der Post Sietse T. , Hsieh Cho-Shuen , Okuno Masanari , Nagata Yuki , Bakker Huib J. , Bonn Mischa , Hunger Johannes
Published: September 2015

Because of strong hydrogen bonding in liquid water, intermolecular interactions between water molecules are highly delocalized. Previous two-dimensional infrared spectroscopy experiments have indicated that this delocalization smears out the structural heterogeneity of neat H2O. Here we report on a systematic investigation of the ultrafast vibrational relaxation of bulk and interfacial water using time-resolved infrared and sum-frequency generation spectroscopies. These experiments reveal a remarkably strong dependence of the vibrational relaxation time on the frequency of the OH stretching vibration of liquid water in the bulk and at the air/water interface. For bulk water, the vibrational relaxation time increases continuously from 250 to 550 fs when the frequency is increased from 3,100 to 3,700 cm−1. For hydrogen-bonded water at the air/water interface, the frequency dependence is even stronger. These results directly demonstrate that liquid water possesses substantial structural heterogeneity, both in the bulk and at the surface.
miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
Authors: Chevalier Benoît , Adamiok Anna , Mercey Olivier , Revinski Diego R. , Zaragosi Laure-Emmanuelle , Pasini Andrea , Kodjabachian Laurent , Barbry Pascal , Marcet Brice
Published: September 2015

Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes
Authors: Alfano Massimo , Cinque Paola , Giusti Guido , Proietti Silvia , Nebuloni Manuela , Danese Silvio , D’Alessio Silvia , Genua Marco , Portale Federica , Lo Porto Manuela , Singhal Pravin C. , Rastaldi Maria Pia , Saleem Moin A. , Mavilio Domenico , Mikulak Joanna
Published: September 2015

Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms’ tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. Thesein vitrodata were confirmed in anin vivouPAR knock out Plaur−/−mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR.
Role of Src in Vascular Hyperpermeability Induced by Advanced Glycation End Products
Authors: Zhang Weijin , Xu Qiulin , Wu Jie , Zhou Xiaoyan , Weng Jie , Xu Jing , Wang Weiju , Huang Qiaobing , Guo Xiaohua
Published: September 2015

The disruption of microvascular barrier in response to advanced glycation end products (AGEs) stimulation contributes to vasculopathy associated with diabetes mellitus. Here, to study the role of Src and its association with moesin, VE-cadherin and focal adhesion kinase (FAK) in AGE-induced vascular hyperpermeability, we verified that AGE induced phosphorylation of Src, causing increased permeability in HUVECs. Cells over-expressed Src displayed a higher permeability after AGE treatment, accompanied with more obvious F-actin rearrangement. Activation of Src with pcDNA3/flag-SrcY530F alone duplicated these effects. Inhibition of Src with siRNA, PP2 or pcDNA3/flag-SrcK298M abolished these effects. The pulmonary microvascular endothelial cells (PMVECs) isolated from receptor for AGEs (RAGE)-knockout mice decreased the phosphorylation of Src and attenuated the barrier dysfunction after AGE-treatment. In vivo study showed that the exudation of dextran from mesenteric venules was increased in AGE-treated mouse. This was attenuated in RAGE knockout or PP2-pretreated mice. Up-regulation of Src activity induced the phosphorylation of moesin, as well as activation and dissociation of VE-cadherin, while down-regulation of Src abolished these effects. FAK was also proved to interact with Src in HUVECs stimulated with AGEs. Our studies demonstrated that Src plays a critical role in AGE-induced microvascular hyperpermeability by phosphorylating moesin, VE-cadherin and FAK respectively.