trieFinder: an efficient program for annotating Digital Gene Expression (DGE) tags

BACKGROUND: Quantification of a transcriptional profile is a useful way to evaluate the activity of a cell at a given point in time. Although RNA-Seq has revolutionized transcriptional profiling, the costs of RNA-Seq are still significantly higher than microarrays, and often the depth of data delivered from RNA-Seq is in excess of what is needed for simple transcript quantification. Digital Gene Expression (DGE) is a cost-effective, sequence-based approach for simple transcript quantification: by sequencing one read per molecule of RNA, this technique can be used to efficiently count transcripts while obviating the need for transcript-length normalization and reducing the total numbers of reads necessary for accurate quantification. Here, we present trieFinder, a program specifically designed to rapidly map, parse, and annotate DGE tags of various lengths against cDNA and/or genomic sequence databases. RESULTS: The trieFinder algorithm maps DGE tags in a two-step process. First, it scans FASTA files of RefSeq, UniGene, and genomic DNA sequences to create a database of all tags that can be derived from a predefined restriction site. Next, it compares the experimental DGE tags to this tag database, taking advantage of the fact that the tags are stored as a prefix tree, or “trie”, which allows for linear-time searches for exact matches. DGE tags with mismatches are analyzed by recursive calls in the data structure. We find that, in terms of alignment speed, the mapping functionality of trieFinder compares favorably with Bowtie. CONCLUSIONS: trieFinder can quickly provide the user an annotation of the DGE tags from three sources simultaneously, simplifying transcript quantification and novel transcript detection, delivering the data in a simple parsed format, obviating the need to post-process the alignment results. trieFinder is available at http://research.nhgri.nih.gov/software/trieFinder/

Experimental and numerical investigation of flexural concrete wall design details

Reinforced concrete structural walls are common in mid- to high-rise structures in high seismic regions, and are expected to have good strength and ductility characteristics if designed in accordance with ACI 318-14. However, experimental and analytical investigations of reinforced concrete structural walls and isolated boundary element prisms indicate that the existing design provisions may be insufficient to provide ductile, flexure-dominated response under cyclic loading. Walls designed with an ACI compliant boundary element length are susceptible to shear-compression failures below the maximum ACI allowable shear stress of 10Acv√fc’. Also of concern is the frequent use of thinner walls in modern design; as the wall’s cross-sectional aspect ratio increases, such brittle shear-compression failures occur at even smaller shear stress values. In regards to detailing, special boundary elements with intermediate cross-ties exhibit a minimal improvement in confinement compared to ordinary boundary elements. This response can be linked to inadequacies in multiple code design parameters, including: vertical spacing and area of confinement steel, horizontal spacing and type of restraint to longitudinal bars, and development length provided for transverse reinforcement. Recent in-field wall failures have prompted concerns related to the minimum code required vertical and horizontal web shear reinforcement, as well as the relative amount of vertical-to-horizontal web steel. This paper examines ACI 318-14 special boundary element and web reinforcement provisions and provides design recommendations intended to improve wall performance as compared with current ACI requirements

Routine activities and proactive police activity: a macro-scale analysis of police searches in London and New York City

This paper explored how city-level changes in routine activities were associated with changes in frequencies of police searches using six years of police records from the London Metropolitan Police Service and the New York City Police Department. Routine activities were operationalised through selecting events that potentially impacted on (a) the street population, (b) the frequency of crime or (c) the level of police activity. OLS regression results indicated that routine activity variables (e.g. day of the week, periods of high demand for police service) can explain a large proportion of the variance in search frequency throughout the year. A complex set of results emerged, revealing cross-national dissimilarities and the differential impact of certain activities (e.g. public holidays). Importantly, temporal frequencies in searches are not reducible to associations between searches and recorded street crime, nor changes in on-street population. Based on the routine activity approach, a theoretical police-action model is proposed

The Importance of Context and Cognitive Agency in Developing Police Knowledge: Going Beyond the Police Science Discourse

This paper argues the current exposition of police knowledge through the discourses of police science and evidenced based policing (EBP) leads to exaggerated claims about what is, and can be, known in policing. This new orthodoxy underestimates the challenges of applying knowledge within culturally-mediated police practice. The paper draws upon virtue epistemology highlighting the role cognitive agency plays in establishing knowledge claims. We challenge the assumption that it is possible to derive what works in all instances of certain aspects of policing and suggest it would be more apt to speak about what worked within a specific police context

Ductility of wide-beam RC frames as lateral resisting system

[EN] Some Mediterranean seismic codes consider wide-beam reinforced concrete moment resisting frames (WBF) as horizontal load carrying systems that cannot guarantee high ductility performances. Conversely, Eurocode 8 allows High Ductility Class (DCH) design for such structural systems. Code prescriptions related to WBF are systematically investigated. In particular, lesson learnt for previous earthquakes, historical reasons, and experimental and numerical studies underpinning specific prescriptions on wide beams in worldwide seismic codes are discussed. Local and global ductility of WBF are then analytically investigated through (1) a parametric study on chord rotations of wide beams with respect to that of deep beams, and (2) a spectral-based comparison of WBF with conventional reinforced concrete moment resisting frames (i.e. with deep beams). Results show that the set of prescriptions given by modern seismic codes provides sufficient ductility to WBF designed in DCH. In fact, global capacity of WBF relies more on the lateral stiffness of the frames and on the overstrength of columns rather than on the local ductility of wide beams, which is systematically lower with respect to that of deep beams.Gómez-Martínez, F.; Alonso Durá, A.; De Luca, F.; Verderame, GM. (2016). Ductility of wide-beam RC frames as lateral resisting system. Bulletin of Earthquake Engineering. 14(6):1545-1569. doi:10.1007/s10518-016-9891-xS15451569146ACI (1989) Building code requirements for reinforced concrete (ACI 318-89). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI (2008) Building code requirements for structural concrete (ACI 318-08) and commentary (318-08). ACI Committee 318, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (1991) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-91). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAACI-ASCE (2002) Recommendations for design of beam-column connections in monolithic reinforced concrete structures (ACI 352R-02). Joint ACI-ASCE Committee 352, American Concrete Institute, Farmington Hills, Michigan, USAArslan MH, Korkmaz HH (2007) What is to be learned from damage and failure of reinforced concrete structures during recent earthquakes in Turkey? Eng Fail Anal 14(1):1–22ASCE (2007) Seismic Rehabilitation of Existing Buildings, ASCE/SEI 41-06. American Society of Civil Engineers, RestonASCE (2010) Minimum Design Loads for Building and Other Structures, ASCE/SEI 7-10. American Society of Civil Engineers, RestonBenavent-Climent A (2007) Seismic behavior of RC side beam-column connections under dynamic loading. J Earthquake Eng 11:493–511Benavent-Climent A, Zahran R (2010) An energy-based procedure for the assessment of seismic capacity of existing frames: application to RC wide beam systems in Spain. Soil Dyn Earthq Eng 30:354–367Benavent-Climent A, Cahís X, Zahran R (2009) Exterior wide beam-column connections in existing RC frames subjected to lateral earthquake loads. Eng Struct 31:1414–1424Benavent-Climent A, Cahís X, Vico JM (2010) Interior wide beam-column connections in existing RC frames subjected to lateral earthquake loading. Bull Earthq Eng 8:401–420BHRC (2004) Iranian Code of Practice for Seismic Resistant Design of Buildings. Standard Nº 2800, 3rd edn. Building and Housing Research Center, TehranBorzi B, Elnashai AS (2000) Refined force reduction factors for seismic design. Eng Struct 22:1244–1260Borzi B, Pinho R, Crowley H (2008) Simplified pushover-based vulnerability analysis for large-scale assessment of RC buildings. Eng Struct 30:804–820BSI (2004) Eurocode 2: Design of concrete structures: Part 1-1: General rules and rules for buildings. British Standards Institutions, LondonCalvi GM (1999) A displacement-based approach for vulnerability evaluation of classes of buildings. J Earthquake Eng 3(3):411–438CDSC (1994) Seismic construction code, NCSR-94. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CDSC (2002) Seismic construction code, NCSE-02. Committee for the Development of Seismic Codes, Spanish Ministry of Construction, Madrid, Spain (in Spanish)CEN (2004) Eurocode 8: design of structures for earthquake resistance—part 1: general rules, seismic actions and rules for buildings. European Standard EN 1998-1:2003—Comité Européen de Normalisation, Brussels, BelgiumCEN (2005) Eurocode 8: design of structures for earthquake resistance—part 3: assessment and retrofitting of buildings. European Standard EN 1998-1:2005—Comité Européen de Normalisation, Brussels, BelgiumCheung PC, Paulay T, Park R (1991) Mechanisms of slab contributions in beam-column subassemblages. ACI Spec Publ 123Cosenza E, Manfredi G, Polese M, Verderame GM (2005) A multilevel approach to the capacity assessment of existing RC buildings. J Earthquake Eng 9(1):1–22Crowley H, Pinho R (2010) Revisiting Eurocode 8 formulae for periods of vibration and their employment in linear seismic analysis. Earthquake Eng Struct Dynam 39:223–235CS.LL.PP (2009) Instructions for the application of the technique code for the Constructions. Official Gazette of the Italian Republic, 47, Regular Supplement no. 27 (in Italian)De Luca F, Vamvatsikos D, Iervolino I (2013) Near-optimal piecewise linear fits of static pushover capacity curves for equivalent SDOF analysis. Earthquake Eng Struct Dynam 42(4):523–543De Luca F, Verderame GM, Gómez-Martínez F, Pérez-García A (2014) The structural role played by masonry infills on RC building performances after the 2011 Lorca, Spain, earthquake. Bull Earthq Eng 12(5):1999–2026Decanini LD, Mollaioli F (2000) Analisi di vulnerabilità sismica di edifici in cemento armato pre-normativa. In: Cosenza E (ed) Comportamento sismico di edifici in cemento armato progettati per carichi verticali. CNR—Gruppo Nazionale per la Difesa dei Terremoti, Rome (in Italian)Dolšek M, Fajfar P (2004) IN2—a simple alternative for IDA. In: Proceedings of the 13th World conference on Earthquake Engineering. August 1–6, Vancouver, Canada. Paper 3353Domínguez D, López-Almansa F, Benavent-Climent A (2014) Comportamiento para el terremoto de Lorca de 11-05-2011, de edificios de vigas planas proyectados sin tener en cuenta la acción sísmica. Informes de la Construcción 66(533):e008 (in Spanish)Domínguez D, López-Almansa F, Benavent-Climent A (2016) Would RC wide-beam buildings in Spain have survived Lorca earthquake (11-05-2011)? Eng Struct 108:134–154Dönmez C (2013) Seismic Performance of Wide-Beam Infill-Joist Block RC Frames in Turkey. J Perform Constr Facil 29(1):04014026Fadwa I, Ali TA, Nazih E, Sara M (2014) Reinforced concrete wide and conventional beam-column connections subjected to lateral load. Eng Struct 76:34–48Fardis MN (2009) Seismic design, assessment and retrofitting of concrete, Buildings edn. Springer, LondonGentry TR, Wight JK (1992) Reinforced concrete wide beam-column connections under earthquake-type loading. Report no. UMCEE 92-12. Department of Civil and Environmental Engineering, University of Michigan, Ann Arbor, Michigan, USAGómez-Martínez F (2015) FAST simplified vulnerability approach for seismic assessment of infilled RC MRF buildings and its application to the 2011 Lorca (Spain) earthquake. Ph.D. Thesis, Polytechnic University of Valencia, SpainGómez-Martínez F, Pérez García A, De Luca F, Verderame GM (2015a) Comportamiento de los edificios de HA con tabiquería durante el sismo de Lorca de 2011: aplicación del método FAST. Informes de la Construcción 67(537):e065 (in Spanish)Gómez-Martínez F, Pérez-García A, Alonso Durá A, Martínez Boquera A, Verderame GM (2015b) Eficacia de la norma NCSE-02 a la luz de los daños e intervenciones tras el sismo de Lorca de 2011. In: Proceedings of Congreso Internacional sobre Intervención en Obras Arquitectónicas tras Sismo: L’Aquila (2009), Lorca (2011) y Emilia Romagna (2012), May 13–14, Murcia, Spain (in Spanish)Gómez-Martínez F, Verderame GM, De Luca F, Pérez-García A, Alonso-Durá, A (2015c). High ductility seismic performances of wide-beam RC frames. In; XVI Convegno ANIDIS. September 13–17, L'Aquila, ItalyHawkins NM, Mitchell D (1979) Progressive collapse of flat plate structures. 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ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia

Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor. While Asxl2 was required for normal haematopoietic stem cell self-renewal, Asxl2 loss promoted AML1-ETO leukemogenesis. Moreover, ASXL2 target genes strongly overlapped with those of RUNX1 and AML1-ETO and ASXL2 loss was associated with increased chromatin accessibility at putative enhancers of key leukemogenic loci. These data reveal that Asxl2 is a critical regulator of haematopoiesis and mediates transcriptional effects that promote leukemogenesis driven by AML1-ETO

Punishing Terrorists: A Re-Examination of U.S. Federal Sentencing in the Postguidelines Era

The empirical literature on the theory and practice of sentencing politically motivated offenders such as terrorists in U.S. federal courts is limited. Thus, we know relatively little about the dealings between terrorist offenders and the criminal justice system or how these interactions may be influenced by changes in American legal or political context. This study summarizes previous findings relative to sentencing disparity among terrorists and nonterrorists in U.S. federal courts prior to the imposition of the U.S. Sentencing Guidelines. We then identify events occurring after the advent of the guidelines, including the early acts of terrorism on American soil. We evaluate the sentencing of terrorists versus nonterrorists following the confluence imposition of the guidelines and these events. We determine whether and how the sentencing disparity between terrorist and nonterrorist has changed since the implementation of the U.S. Sentencing Guidelines and the terrorist events of the early 1990s. Based on our findings, we put forth suggestions as to the possible ways these conditions may have affected sentencing outcomes.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4