Influence of interposed ventilation pressure upon artificial cardiac output during cardiopulmonary resuscitation in dogs

This study was conducted to determine the effects of high pressure interposed ventilations during cardiopulmonary resuscitation (CPR). Cardiac output was measured by a modified indicator dilution technique in eight anesthetized, intubated mongrel dogs. Positive pressure ventilations (12/min, 80% O2) were interposed after every five chest compressions (performed at 62/min) by a mechanical chest compressor (Thumper®). On repeated trials in the same animal, ventilation pressures from 10-50 cm of H2O were tested in randomized sequence, while the technique of chest compression was held constant. Arterial blood gases immediately after resuscitation were monitored. Increasing ventilation pressure had surprisingly little effect on cardiac output during CPR, although blood gases were profoundly altered. For ventilation pressures of 10, 20, 30, 40, and 50 cm of H2O, producing mean tidal volumes 23, 38, 61, 83, and 94 ml/kg; cardiac output remained nearly constant, averaging 21, 25, 23, 26, and 24 ml/min/kg. Corresponding mean post-resuscitation pH was 7.24, 7.41, 7.51, 7.56, and 7.53; PCO2 was 41, 26, 18, 16, and 15 torr. The post-resuscitation arterial oxygen tension was greater than 100 torr at all ventilation pressures except 10 cm of H2O. Interposed ventilations of pressure and volume more than adequate to prevent acidosis during CPR did not impair artificial cardiac output. If anything, cardiac output was slightly improved by more forceful ventilation

Relationship of blood pressure and flow during CPR to chest compression amplitude: Evidence for an effective compression threshold

This study was conducted to investigate the importance of the depth of chest compression in producing effective cardiopulmonary resuscitation (CPR) in animals, as indicated by cardiac output and mean arterial blood pressure. Cardiac output was measured by a modified indicator dilution technique in 8 anesthetized dogs, 6 to 12 kg body weight, during repeated 2-minute episodes of electrically induced ventricular fibrillation and CPR provided by a mechanical chest compressor and ventilator (Thumper®). Chest compression exceeding a threshold value (x0) between 1.5 and 3.0 cm was required in each animal to produce measurable cardiac output. In particular, cardiac output (CO) was linearly related to chest compression depth (x) by an expression of the form CO = a(x-x0) for x \u3e x0, and CO = 0 for x £ x0. The mean value of x0 was 2.3 cm. A similar threshold for measurable blood pressure was observed in 7 of the 8 dogs, with a mean value of 1.8 cm. For chest compression of 2.5 cm or greater, relatively modest increases in chest compression depth caused relatively large changes in cardiac output

An uncharged amine in the transition state of the ribosornal peptidyl transfer reaction.

The ribosome has an active site comprised of RNA that catalyzes peptide bond formation. To understand how RNA promotes this reaction requires a detailed understanding of the chemical transition state. Here, we report the Bronsted coefficient of the a-amino nucleophile with a series of puromycin derivatives. Both 50S subunit- and 70S ribosome-catalyzed reactions displayed linear free-energy relationships with slopes close to zero under conditions where chemistry is rate limiting. These results indicate that, at the transition state, the nucleophile is neutral in the ribosome-catalyzed reaction, in contrast to the substantial positive charge reported for typical uncatalyzed aminolysis reactions. This suggests that the ribosomal transition state involves deprotonation to a degree commensurate with nitrogen-carbon bond formation. Such a transition state is significantly different from that of uncatalyzed aminolysis reactions in solution

In Situ Graphene Growth Dynamics on Polycrystalline Catalyst Foils

The dynamics of graphene growth on polycrystalline Pt foils during chemical vapor deposition (CVD) are investigated using in situ scanning electron microscopy and complementary structural characterization of the catalyst with electron backscatter diffraction. A general growth model is outlined that considers precursor dissociation, mass transport, and attachment to the edge of a growing domain. We thereby analyze graphene growth dynamics at different length scales and reveal that the rate-limiting step varies throughout the process and across different regions of the catalyst surface, including different facets of an individual graphene domain. The facets that define the domain shapes lie normal to slow growth directions, which are determined by the interfacial mobility when attachment to domain edges is rate-limiting, as well as anisotropy in surface diffusion as diffusion becomes rate-limiting. Our observations and analysis thus reveal that the structure of CVD graphene films is intimately linked to that of the underlying polycrystalline catalyst, with both interfacial mobility and diffusional anisotropy depending on the presence of step edges and grain boundaries. The growth model developed serves as a general framework for understanding and optimizing the growth of 2D materials on polycrystalline catalysts.St. John’s College, Cambridge (Research Fellowship), European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie Individual Fellowship (Global) under Grant ID: ARTIST (no. 656870)), National Science Foundation (graduate research fellowship (DGE-1324585)), European Research Council (Grant ID: InsituNANO (no. 279342)), EUFP7 Work Programme (Grant ID: GRAFOL (project reference 285275)) , Engineering and Physical Sciences Research Council (Grant ID: GRAPHTED (project reference EP/K016636/1)), Strategic Capability programme of the National Measurement System of the U.K. Department of Business, Innovation, and Skills (project no. 119376

Psoriasis drug development and GWAS interpretation through in silico analysis of transcription factor binding sites

BackgroundPsoriasis is a cytokine‐mediated skin disease that can be treated effectively with immunosuppressive biologic agents. These medications, however, are not equally effective in all patients and are poorly suited for treating mild psoriasis. To develop more targeted therapies, interfering with transcription factor (TF) activity is a promising strategy.MethodsMeta‐analysis was used to identify differentially expressed genes (DEGs) in the lesional skin from psoriasis patients (n = 237). We compiled a dictionary of 2935 binding sites representing empirically‐determined binding affinities of TFs and unconventional DNA‐binding proteins (uDBPs). This dictionary was screened to identify “psoriasis response elements” (PREs) overrepresented in sequences upstream of psoriasis DEGs.ResultsPREs are recognized by IRF1, ISGF3, NF‐kappaB and multiple TFs with helix‐turn‐helix (homeo) or other all‐alpha‐helical (high‐mobility group) DNA‐binding domains. We identified a limited set of DEGs that encode proteins interacting with PRE motifs, including TFs (GATA3, EHF, FOXM1, SOX5) and uDBPs (AVEN, RBM8A, GPAM, WISP2). PREs were prominent within enhancer regions near cytokine‐encoding DEGs (IL17A, IL19 and IL1B), suggesting that PREs might be incorporated into complex decoy oligonucleotides (cdODNs). To illustrate this idea, we designed a cdODN to concomitantly target psoriasis‐activated TFs (i.e., FOXM1, ISGF3, IRF1 and NF‐kappaB). Finally, we screened psoriasis‐associated SNPs to identify risk alleles that disrupt or engender PRE motifs. This identified possible sites of allele‐specific TF/uDBP binding and showed that PREs are disproportionately disrupted by psoriasis risk alleles.ConclusionsWe identified new TF/uDBP candidates and developed an approach that (i) connects transcriptome informatics to cdODN drug development and (ii) enhances our ability to interpret GWAS findings. Disruption of PRE motifs by psoriasis risk alleles may contribute to disease susceptibility.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/1/ctm2s4016901500545-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/2/ctm2s4016901500545-sup-0018.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/3/ctm2s4016901500545-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/4/ctm2s4016901500545.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/5/ctm2s4016901500545-sup-0009.pd

Scale Development for Perceived School Climate for Girls’ Physical Activity

Objectives: To test an original scale assessing perceived school climate for girls\u27 physical activity in middle school girls. Methods: Confirmatory factor analysis (CFA) and structural equation modeling (SEM). Results: CFA retained 5 of 14 original items. A model with 2 correlated factors, perceptions about teachers\u27 and boys\u27 behaviors, respectively, fit the data well in both sixth and eighth-graders. SEM detected a positive, significant direct association of the teacher factor, but not the boy factor, with girls\u27 self-reported physical activity. Conclusions:School climate for girls\u27 physical activity is a measurable construct, and preliminary evidence suggests a relationship with physical activity

Scale Development for Perceived School Climate for Girls’ Physical Activity

Objectives: To test an original scale assessing perceived school climate for girls\u27 physical activity in middle school girls. Methods: Confirmatory factor analysis (CFA) and structural equation modeling (SEM). Results: CFA retained 5 of 14 original items. A model with 2 correlated factors, perceptions about teachers\u27 and boys\u27 behaviors, respectively, fit the data well in both sixth and eighth-graders. SEM detected a positive, significant direct association of the teacher factor, but not the boy factor, with girls\u27 self-reported physical activity. Conclusions: School climate for girls\u27 physical activity is a measurable construct, and preliminary evidence suggests a relationship with physical activity

Investigating Rumor News Using Agreement-Aware Search

Recent years have witnessed a widespread increase of rumor news generated by humans and machines. Therefore, tools for investigating rumor news have become an urgent necessity. One useful function of such tools is to see ways a specific topic or event is represented by presenting different points of view from multiple sources. In this paper, we propose Maester, a novel agreement-aware search framework for investigating rumor news. Given an investigative question, Maester will retrieve related articles to that question, assign and display top articles from agree, disagree, and discuss categories to users. Splitting the results into these three categories provides the user a holistic view towards the investigative question. We build Maester based on the following two key observations: (1) relatedness can commonly be determined by keywords and entities occurring in both questions and articles, and (2) the level of agreement between the investigative question and the related news article can often be decided by a few key sentences. Accordingly, we use gradient boosting tree models with keyword/entity matching features for relatedness detection, and leverage recurrent neural network to infer the level of agreement. Our experiments on the Fake News Challenge (FNC) dataset demonstrate up to an order of magnitude improvement of Maester over the original FNC winning solution, for agreement-aware search

Electromigration of Single-Layer Clusters

Single-layer atom or vacancy clusters in the presence of electromigration are studied theoretically assuming an isotropic medium. A variety of distinctive behaviors distinguish the response in the three standard limiting cases of periphery diffusion (PD), terrace diffusion (TD), and evaporation-condensation (EC). A general model provides power laws describing the size dependence of the drift velocity in these limits, consistent with established results in the case of PD. The validity of the widely used quasistatic limit is calculated. Atom and vacancy clusters drift in opposite directions in the PD limit but in the same direction otherwise. In absence of PD, linear stability analysis reveals a new type of morphological instability, not leading to island break-down. For strong electromigration, Monte Carlo simulations show that clusters then destabilize into slits, in contrast to splitting in the PD limit. Electromigration affects the diffusion coefficient of the cluster and morphological fluctuations, the latter diverging at the instability threshold. An instrinsic attachment-detachment bias displays the same scaling signature as PD in the drift velocity.Comment: 11 pages, 4 figure

Time and "angular" dependent backgrounds from stationary axisymmetric solutions

Backgrounds depending on time and on "angular" variable, namely polarized and unpolarized $S^1 \times S^2$ Gowdy models, are generated as the sector inside the horizons of the manifold corresponding to axisymmetric solutions. As is known, an analytical continuation of ordinary $D$-branes, $iD$-branes allows one to find $S$-brane solutions. Simple models have been constructed by means of analytic continuation of the Schwarzchild and the Kerr metrics. The possibility of studying the $i$-Gowdy models obtained here is outlined with an eye toward seeing if they could represent some kind of generalized $S$-branes depending not only on time but also on an ``angular'' variable.Comment: 24 pages, 5 figures, corrected typos, references adde