A survey of best practices for RNA-seq data analysis.

RNA-sequencing (RNA-seq) has a wide variety of applications, but no single analysis pipeline can be used in all cases. We review all of the major steps in RNA-seq data analysis, including experimental design, quality control, read alignment, quantification of gene and transcript levels, visualization, differential gene expression, alternative splicing, functional analysis, gene fusion detection and eQTL mapping. We highlight the challenges associated with each step. We discuss the analysis of small RNAs and the integration of RNA-seq with other functional genomics techniques. Finally, we discuss the outlook for novel technologies that are changing the state of the art in transcriptomics.This is the final published version. It first appeared at http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0881-8

Measurements, Models, Systems and Design

531 s.

Social health and subsequent cognitive functioning in people aged 50 years and older:examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. Methods: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). Findings: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001–0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000–0·002]) and in delayed recall (PIE 0·001 [0·000–0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000–0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. Interpretation: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. Funding: EU Joint Programme—Neurodegenerative Disease Research (JPND) and Alzheimer's Society. Translation: For the Swedish translation of the abstract see Supplementary Materials section.</p

Social health and subsequent cognitive functioning in people aged 50 years and older:examining the mediating roles of depressive symptoms and inflammatory biomarkers in two European longitudinal studies

Background: Social health markers, including marital status, contact frequency, network size, and social support, have been shown to be associated with cognition. However, the mechanisms underlying these associations remain poorly understood. We investigated whether depressive symptoms and inflammation mediated associations between social health and subsequent cognition. Methods: In the English Longitudinal Study of Ageing (ELSA), a nationally representative longitudinal study in England, UK, we sampled 7136 individuals aged 50 years or older living in private households without dementia at baseline or at the intermediate mediator assessment timepoint, who had recorded information on at least one social health marker and potential mediator. We used four-way decomposition to examine to what extent depressive symptoms, C-reactive protein, and fibrinogen mediated associations between social health and subsequent standardised cognition (verbal fluency and delayed and immediate recall), including cognitive change, with slopes derived from multilevel models (12-year slope). We examined whether findings were replicated in the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), a population-based longitudinal study in Sweden, in a sample of 2604 individuals aged 60 years or older living at home or in institutions in Kungsholmen (central Stockholm) without dementia at baseline or at the intermediate mediator assessment timepoint (6-year slope). Social health exposures were assessed at baseline, potential mediators were assessed at an intermediate timepoint (wave 2 in ELSA and 6-year follow-up in SNAC-K); cognitive outcomes were assessed at a single timepoint (wave 3 in ELSA and 12-year follow-up in SNAC-K), and cognitive change (between waves 3 and 9 in ELSA and between 6-year and 12-year follow-ups in SNAC-K). Findings: The study sample included 7136 participants from ELSA, of whom 3962 (55·5%) were women and 6934 (97·2%) were White; the mean baseline age was 63·8 years (SD 9·4). Replication analyses included 2604 participants from SNAC-K, of whom 1604 (61·6%) were women (SNAC-K did not collect ethnicity data); the mean baseline age was 72·3 years (SD 10·1). In ELSA, we found indirect effects via depressive symptoms of network size, positive support, and less negative support on subsequent verbal fluency, and of positive support on subsequent immediate recall (pure indirect effect [PIE] 0·002 [95% CI 0·001–0·003]). Depressive symptoms also partially mediated associations between less negative support and slower decline in immediate recall (PIE 0·001 [0·000–0·002]) and in delayed recall (PIE 0·001 [0·000–0·002]), and between positive support and slower decline in immediate recall (PIE 0·001 [0·000–0·001]). We did not observe mediation by inflammatory biomarkers. Findings of mediation by depressive symptoms in the association between positive support and verbal fluency and between positive support and change in immediate recall were replicated in SNAC-K. Interpretation: The findings of this study provide new insights into mechanisms linking social health with cognition, suggesting that associations between interactional aspects of social health, especially social support, and cognition are partly underpinned by depressive symptoms. Funding: EU Joint Programme—Neurodegenerative Disease Research (JPND) and Alzheimer's Society. Translation: For the Swedish translation of the abstract see Supplementary Materials section.</p

Evidence-based nanoscopic and molecular framework for excipient functionality in compressed orally disintegrating tablets

The work investigates the adhesive/cohesive molecular and physical interactions together with nanoscopic features of commonly used orally disintegrating tablet (ODT) excipients microcrystalline cellulose (MCC) and D-mannitol. This helps to elucidate the underlying physico-chemical and mechanical mechanisms responsible for powder densification and optimum product functionality. Atomic force microscopy (AFM) contact mode analysis was performed to measure nano-adhesion forces and surface energies between excipient-drug particles (6-10 different particles per each pair). Moreover, surface topography images (100 nm2-10 μm2) and roughness data were acquired from AFM tapping mode. AFM data were related to ODT macro/microscopic properties obtained from SEM, FTIR, XRD, thermal analysis using DSC and TGA, disintegration testing, Heckel and tabletability profiles. The study results showed a good association between the adhesive molecular and physical forces of paired particles and the resultant densification mechanisms responsible for mechanical strength of tablets. MCC micro roughness was 3 times that of D-mannitol which explains the high hardness of MCC ODTs due to mechanical interlocking. Hydrogen bonding between MCC particles could not be established from both AFM and FTIR solid state investigation. On the contrary, D-mannitol produced fragile ODTs due to fragmentation of surface crystallites during compression attained from its weak crystal structure. Furthermore, AFM analysis has shown the presence of extensive micro fibril structures inhabiting nano pores which further supports the use of MCC as a disintegrant. Overall, excipients (and model drugs) showed mechanistic behaviour on the nano/micro scale that could be related to the functionality of materials on the macro scale. © 2014 Al-khattawi et al

Computer verification of a cmos digital circuit created by subcircuits supplied by different voltages

W pracy zaprezentowano wyniki komputerowej weryfikacji cyfrowego układu CMOS utworzonego z klastrów Cn-1, Cn-2, …, Ci, … C0, z których każdy jest zasilany odpowiednio malejącymi wartościami napięć Vddn-1 > Vddn-2 > … > Vddi > … > Vdd0 . Zbiór klastrów {Ci} został utworzony przy pomocy algorytmu ECA (Evolutionary Clustering Algorithm) dla potrzeb redukcji mocy pobieranej ze źródła zasilającego. Otrzymane rozwiązanie charakteryzujące się zmniejszeniem zapotrzebowania na moc zasilającą nie powoduje pogorszenia przepustowości zaprojektowanego systemu cyfrowego CMOS.The paper presents results of a computer simulation of a CMOS digital circuit composed of Cn-1, Cn-2, …, Ci, … C0 clusters. The clusters are supplied with voltages Vddn-1 > Vddn-2 > … > Vddi > … > Vdd0, respectively. Set of clusters {Ci} was created with aid of ECA (Evolutionary Clustering Algorithm) for reduction of power dissipated. The obtained result enables for power reduction without deteriorating the throughput of the designed CMOS circuit, measured as system latency

The influence of cryogenic treatment after quenching on transformations during tempering selected tool steels. Dilatometric and DTA studies

W pracy porównano zmiany zachodzące podczas izochronicznego odpuszczania stali NC10, NC11LV i SW7M zaraz po hartowaniu oraz po hartowaniu i obróbce kriogenicznej. Zmiany badano metodą dylatometryczną i DTA. Stwierdzono, że obróbka kriogeniczna powoduje wyraźne obniżenie temperatury początku wydzielania węglików a ilość wydzielonych węglików jest większa. Wzrost zawartości węglików jest większy niż to wynika z podwyższonej wskutek obróbki kriogenicznej zawartości martenzytu .On the basis of results of dilatometric and DTA studies of isochronal tempering of quenched and quenched and cryogenic treated tool steels (NC10, NC11LV, SW7M) it was found that cryogenic treatment accelerate the tempering processes and increases accompanying them contraction. The contraction is much bigger then that resulting from the amount of martensite increase because of residual austenite transformation during cryogenic treatment. The DTA analysis supports obtained results

Energy use of textile waste as an alternative fuel to a cement plant

W niniejszym artykule zaprezentowano wyniki badań podstawowych właściwości paliwowych dla poliamidowego odpadu tekstylnego, pod kątem możliwości jego energetycznego wykorzystania w przemyśle cementowym. Wyzwaniem współczesnej cywilizacji jest przemyślana gospodarka odpadami. Rozwój gospodarczy oraz przemysłowy powoduje gwałtownie wzrastającą ilość odpadów na całym świecie. Istnieje wiele sposobów pozwalających na ich redukcję, czerpiąc tym samym korzyści gospodarcze. Jedną z możliwości wykorzystania odpadów tekstylnych jest określenie ich energetycznego potencjału. Cementownie wykorzystują paliwa z odpadów jako samodzielne paliwo bądź jako jeden z jego komponentów w zależności od ich indywidualnych wymagań.This article presents the results of research into the basic fuel properties of polyamide textile waste in terms of its potential for energy use in the cement industry. The challenge of modern civilization constitutes reasonable waste management. Economic and industrial development is causing a sharp increase in the amount of waste worldwide. There are many ways in which this can be reduced, and thus bringing economic benefits. One way of using textile waste is to identify its energy potential. Cement plants use waste fuels as an independent fuel or as one of its components, depending on their individual requirements

Conection for repair of damaged internal thread in element engine

Artykuł dotyczy nowej metody regeneracji połączeń gwintowych poprzez zastąpienie uszkodzonego gwintu wewnętrznego szpilką o specjalnej konstrukcji. Metoda regeneracji uszkodzonego połączenia gwintowanego polega na wykorzystaniu odkształcenia plastycznego zachodzącego podczas wciskania w uszkodzony gwint wewnętrzny szpilki, na której końcu wykonano nierówności trójkątne. Opracowano autorską aplikację wykorzystującą Metodę elementów skończonych (MES) w programie Ansys Workbench do analizy zjawisk fizycznych zachodzących podczas regeneracji połączenia - wciskania nowej szpilki. Przedstawiono wybrane wyniki analizy numerycznej.Article presents new method of thread regeneration through replacement damaged internal thread by a pin with special construction. Method of regeneration of a damaged threaded connection involves the use of plastic deformation occurring when pressing in the damaged threads internal a pins. At one end of the pins are made of triangular outline inequality. Developed application in Finite method elements (MES) in the program Ansys Workbench for the analysis of physical phenomena occurring during regeneration joint in new a pin. Selected results of numerical analysis are presented