Interfacial water as a “hydration fingerprint” in the noncognate complex of BamHI. Biophys

ABSTRACT The molecular code of specific DNA recognition by proteins as a paradigm in molecular biology remains an unsolved puzzle primarily because of the subtle interplay between direct protein-DNA interaction and the indirect contribution from water and ions. Transformation of the nonspecific, low affinity complex to a specific, high affinity complex is accompanied by the release of interfacial water molecules. To provide insight into the conversion from the loose to the tight form, we characterized the structure and energetics of water at the protein-DNA interface of the BamHI complex with a noncognate sequence and in the specific complex. The fully hydrated models were produced with Grand Canonical Monte Carlo simulations. Proximity analysis shows that water distributions exhibit sequence dependent variations in both complexes and, in particular, in the noncognate complex they discriminate between the correct and the star site. Variations in water distributions control the number of water molecules released from a given sequence upon transformation from the loose to the tight complex as well as the local entropy contribution to the binding free energy. We propose that interfacial waters can serve as a ''hydration fingerprint'' of a given DNA sequence

Apelin Increases Cardiac Contractility via Protein Kinase C epsilon- and Extracellular Signal-Regulated Kinase-Dependent Mechanisms

Peer reviewe

High spatial resolution imaging of methane and other trace gases with the airborne Hyperspectral Thermal Emission Spectrometer (HyTES)

Currently large uncertainties exist associated with the attribution and quantification of fugitive emissions of criteria pollutants and greenhouse gases such as methane across large regions and key economic sectors. In this study, data from the airborne Hyperspectral Thermal Emission Spectrometer (HyTES) have been used to develop robust and reliable techniques for the detection and wide-area mapping of emission plumes of methane and other atmospheric trace gas species over challenging and diverse environmental conditions with high spatial resolution that permits direct attribution to sources. HyTES is a pushbroom imaging spectrometer with high spectral resolution (256 bands from 7.5 to 12 µm), wide swath (1–2 km), and high spatial resolution (∼ 2 m at 1 km altitude) that incorporates new thermal infrared (TIR) remote sensing technologies. In this study we introduce a hybrid clutter matched filter (CMF) and plume dilation algorithm applied to HyTES observations to efficiently detect and characterize the spatial structures of individual plumes of CH_4, H_2S, NH_3, NO_2, and SO_2 emitters. The sensitivity and field of regard of HyTES allows rapid and frequent airborne surveys of large areas including facilities not readily accessible from the surface. The HyTES CMF algorithm produces plume intensity images of methane and other gases from strong emission sources. The combination of high spatial resolution and multi-species imaging capability provides source attribution in complex environments. The CMF-based detection of strong emission sources over large areas is a fast and powerful tool needed to focus on more computationally intensive retrieval algorithms to quantify emissions with error estimates, and is useful for expediting mitigation efforts and addressing critical science questions

Sample return of interstellar matter (SARIM)

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Initiator Elements Function to Determine the Activity State of BX-C Enhancers

A >300 kb cis-regulatory region is required for the proper expression of the three bithorax complex (BX-C) homeotic genes. Based on genetic and transgenic analysis, a model has been proposed in which the numerous BX-C cis-regulatory elements are spatially restricted through the activation or repression of parasegment-specific chromatin domains. Particular early embryonic enhancers, called initiators, have been proposed to control this complex process. Here, in order to better understand the process of domain activation, we have undertaken a systematic in situ dissection of the iab-6 cis-regulatory domain using a new method, called InSIRT. Using this method, we create and genetically characterize mutations affecting iab-6 function, including mutations specifically modifying the iab-6 initiator. Through our mutagenesis of the iab-6 initiator, we provide strong evidence that initiators function not to directly control homeotic gene expression but rather as domain control centers to determine the activity state of the enhancers and silencers within a cis-regulatory domain

Chromosomal organization at the level of gene complexes

Metazoan genomes primarily consist of non-coding DNA in comparison to coding regions. Non-coding fraction of the genome contains cis-regulatory elements, which ensure that the genetic code is read properly at the right time and space during development. Regulatory elements and their target genes define functional landscapes within the genome, and some developmentally important genes evolve by keeping the genes involved in specification of common organs/tissues in clusters and are termed gene complex. The clustering of genes involved in a common function may help in robust spatio-temporal gene expression. Gene complexes are often found to be evolutionarily conserved, and the classic example is the hox complex. The evolutionary constraints seen among gene complexes provide an ideal model system to understand cis and trans-regulation of gene function. This review will discuss the various characteristics of gene regulatory modules found within gene complexes and how they can be characterized

High spatial resolution imaging of methane and other trace gases with the airborne Hyperspectral Thermal Emission Spectrometer (HyTES)

Currently large uncertainties exist associated with the attribution and quantification of fugitive emissions of criteria pollutants and greenhouse gases such as methane across large regions and key economic sectors. In this study, data from the airborne Hyperspectral Thermal Emission Spectrometer (HyTES) have been used to develop robust and reliable techniques for the detection and wide-area mapping of emission plumes of methane and other atmospheric trace gas species over challenging and diverse environmental conditions with high spatial resolution that permits direct attribution to sources. HyTES is a pushbroom imaging spectrometer with high spectral resolution (256 bands from 7.5 to 12 µm), wide swath (1–2 km), and high spatial resolution (∼ 2 m at 1 km altitude) that incorporates new thermal infrared (TIR) remote sensing technologies. In this study we introduce a hybrid clutter matched filter (CMF) and plume dilation algorithm applied to HyTES observations to efficiently detect and characterize the spatial structures of individual plumes of CH_4, H_2S, NH_3, NO_2, and SO_2 emitters. The sensitivity and field of regard of HyTES allows rapid and frequent airborne surveys of large areas including facilities not readily accessible from the surface. The HyTES CMF algorithm produces plume intensity images of methane and other gases from strong emission sources. The combination of high spatial resolution and multi-species imaging capability provides source attribution in complex environments. The CMF-based detection of strong emission sources over large areas is a fast and powerful tool needed to focus on more computationally intensive retrieval algorithms to quantify emissions with error estimates, and is useful for expediting mitigation efforts and addressing critical science questions

Evaluation of Musical Creativity and Musical Metacreation Systems

The field of computational creativity, including musical metacreation, strives to develop artificial systems that are capable of demonstrating creative behavior or producing creative artefacts. But the claim of creativity is often assessed, subjectively only on the part of the researcher and not objectively at all. This article provides theoretical motivation for more systematic evaluation of musical metacreation and computationally creative systems and presents an overview of current methods used to assess human and machine creativity that may be adapted for this purpose. In order to highlight the need for a varied set of evaluation tools, a distinction is drawn among three types of creative systems: those that are purely generative, those that contain internal or external feedback, and those that are capable of reflection and self-reflection. To address the evaluation of each of these aspects, concrete examples of methods and techniques are suggested to help researchers (1) evaluate their systems' creative process and generated artefacts, and test their impact on the perceptual, cognitive, and affective states of the audience, and (2) build mechanisms for reflection into the creative system, including models of human perception and cognition, to endow creative systems with internal evaluative mechanisms to drive self-reflective processes. The first type of evaluation can be considered external to the creative system and may be employed by the researcher to both better understand the efficacy of their system and its impact and to incorporate feedback into the system. Here we take the stance that understanding human creativity can lend insight to computational approaches, and knowledge of how humans perceive creative systems and their output can be incorporated into artificial agents as feedback to provide a sense of how a creation will impact the audience. The second type centers around internal evaluation, in which the system is able to reason about its own behavior and generated output. We argue that creative behavior cannot occur without feedback and reflection by the creative/metacreative system itself. More rigorous empirical testing will allow computational and metacreative systems to become more creative by definition and can be used to demonstrate the impact and novelty of particular approaches

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223