The Effect of Syntax Training on "Adequacy" of Communication in Broca's Aphasia: A Social Validation Study

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Advancing the Frontier of Peacekeeping Research

The impact of United Nations (UN) peacekeeping on conflict has received a sustained amount of attention in the empirical literature. The advent of new data on UN peacekeeping and new temporal units of analysis have enabled researchers to expand the frontiers of peacekeeping research and undertake a more nuanced examination of peacekeeping effectiveness. In this special section, a series of articles examine how UN peacekeeping affects different types of violence within conflicts and leads to different types of peaceful outcomes. Factors such as the cultural affinity between peacekeepers and local communities, the size of peacekeeping operations and the specific composition of UN forces are shown to be important variables associated with lower levels of casualties and violence and also a higher likelihood of mediation and timely peaceful settlements in civil wars. In the aggregate, these articles suggest that robust peacekeeping is associated with better outcomes in many stages of conflict

Improving Project Logistics by using IoT

This Bachelor´s thesis is made on behalf of Wärtsilä Energy Solutions, Project Logistics & Transport Management department whose main task is to coordinate and ensure that materials and products are transported to the right place and on time in Project Logistics. This thesis examines how you could improve Wärtsilä´s Project Logistics by using Internet of Things. By developing IoT, there has been an increased chance to get more information about transports than before and Wärtsilä is currently looking for new solutions to use that could improve their current logistics system. The purpose of this thesis is to review new, and used, solutions on the market, and then see what could work in practice at Wärtsilä. Material to this thesis are gathered from books, web pages and articles that reviewed interesting IoT solutions and which also gave examples on different solutions that are used by other companies in the same business. The Result is two different methods that could improve Wärtsilä´s Project Logistics in different occasions. These results are intended to give tips on how IoT could improve the department´s ways of coordinating and check transports and logistics within a project.Detta examensarbete är gjort i uppdrag av Wärtsilä Energy Solutions, Project logistics & Transport Management avdelningen vars huvuduppgift är att koordinera och se till att material och produkter transporteras till rätt plats i rätt tid inom projekt logistiken. Examensarbetet behandlar hur man kunde förbättra Wärtsiläs projekt logistik genom att använda Internet of Things. Genom att IoT har utvecklats har det uppstått möjligheter att få fram mer information om transporter än tidigare och Wärtsilä söker för tillfället nya lösningar som kunde användas för att förbättra deras nuvarande logistiksystem. Syftet med arbetet är att gå igenom nya, men även redan befintliga, lösningar som används på dagens marknad - för att sedan se vad som kunde fungera i praktiken hos Wärtsilä. Material till arbetet är samlat från böcker, webbsidor och artiklar som gick igenom intressanta IoT lösningar och som också gav exempel på hur olika system fungerar och används av andra företag inom samma bransch. Slutresultatet blev två olika metoder som kunde förbättra Wärtsiläs projekt logistik vid olika tillfällen. Dessa resultat är tänkta för att ge tips på hur IoT kunde förbättra avdelningens sätt hur man koordinerar och granskar transporter och logistiken inom ett projekt

Reactive oxygen species drive proliferation in acute myeloid leukemia via the glycolytic regulator PFKFB3

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a poor clinical outcome. Previously, we showed that overproduction of reactive oxygen species (ROS), arising from constitutive activation of NOX2 oxidase, occurs in >60% of patients with AML and that ROS production promotes proliferation of AML cells. We show here that the process most significantly affected by ROS overproduction is glycolysis. Whole metabolome analysis of 20 human primary AML showed that blasts generating high levels of ROS have increased glucose uptake and correspondingly increased glucose metabolism. In support of this, exogenous ROS increased glucose consumption while inhibition of NOX2 oxidase decreased glucose consumption. Mechanistically, ROS promoted uncoupling protein 2 (UCP2) protein expression and phosphorylation of AMPK, upregulating the expression of a key regulatory glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Overexpression of PFKFB3 promoted glucose uptake and cell proliferation, whereas downregulation of PFKFB3 strongly suppressed leukemia growth both in vitro and in vivo in the NSG model. These experiments provide direct evidence that oxidase-derived ROS promotes the growth of leukemia cells via the glycolytic regulator PFKFB3. Targeting PFKFB3 may therefore present a new mode of therapy for this disease with a poor outcome. Significance: These findings show that ROS generated by NOX2 in AML cells promotes glycolysis by activating PFKFB3 and suggest PFKFB3 as a novel therapeutic target in AML

N plus 3 Advanced Concept Studies for Supersonic Commercial Transport Aircraft Entering Service in the 2030-2035 Period

Boeing, with Pratt & Whitney, General Electric, Rolls-Royce, M4 Engineering, Wyle Laboratories and Georgia Institute of Technology, conducted a study of supersonic commercial aircraft concepts and enabling technologies for the year 2030-2035 timeframe. The work defined the market and environmental/regulatory conditions that could evolve by the 2030/35 time period, from which vehicle performance goals were derived. Relevant vehicle concepts and technologies are identified that are anticipated to meet these performance and environmental goals. A series of multidisciplinary analyses trade studies considering vehicle sizing, mission performance and environmental conformity determined the appropriate concepts. Combinations of enabling technologies and the required technology performance levels needed to meet the desired goals were identified. Several high priority technologies are described in detail, including roadmaps with risk assessments that outline objectives, key technology challenges, detailed tasks and schedules and demonstrations that need to be performed. A representative configuration is provided for reference purposes, along with associated performance estimates based on these key technologies

Convergent evidence that ZNF804A is a regulator of pre-messenger RNA processing and gene expression

Genome-wide association studies have linked common variation in ZNF804A with an increased risk of schizophrenia. However, little is known about the biology of ZNF804A and its role in schizophrenia. Here, we investigate the function of ZNF804A using a variety of complementary molecular techniques. We show that ZNF804A is a nuclear protein that interacts with neuronal RNA splicing factors and RNA-binding proteins including RBFOX1, which is also associated with schizophrenia, CELF3/4, components of the ubiquitin-proteasome system and the ZNF804A paralog, GPATCH8. GPATCH8 also interacts with splicing factors and is localized to nuclear speckles indicative of a role in pre-messenger RNA (mRNA) processing. Sequence analysis showed that GPATCH8 contains ultraconserved, alternatively spliced poison exons that are also regulated by RBFOX proteins. ZNF804A knockdown in SH-SY5Y cells resulted in robust changes in gene expression and pre-mRNA splicing converging on pathways associated with nervous system development, synaptic contact, and cell adhesion. We observed enrichment (P = 1.66 × 10–9) for differentially spliced genes in ZNF804A-depleted cells among genes that contain RBFOX-dependent alternatively spliced exons. Differentially spliced genes in ZNF804A-depleted cells were also enriched for genes harboring de novo loss of function mutations in autism spectrum disorder (P = 6.25 × 10–7, enrichment 2.16) and common variant alleles associated with schizophrenia (P = .014), bipolar disorder and schizophrenia (P = .003), and autism spectrum disorder (P = .005). These data suggest that ZNF804A and its paralogs may interact with neuronal-splicing factors and RNA-binding proteins to regulate the expression of a subset of synaptic and neurodevelopmental genes

Contribution of brain size to IQ and educational underperformance in extremely preterm adolescents

OBJECTIVES:Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS:Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS:Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS:EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP

Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting

TALENs are important new tools for genome engineering. Fusions of transcription activator-like (TAL) effectors of plant pathogenic Xanthomonas spp. to the FokI nuclease, TALENs bind and cleave DNA in pairs. Binding specificity is determined by customizable arrays of polymorphic amino acid repeats in the TAL effectors. We present a method and reagents for efficiently assembling TALEN constructs with custom repeat arrays. We also describe design guidelines based on naturally occurring TAL effectors and their binding sites. Using software that applies these guidelines, in nine genes from plants, animals and protists, we found candidate cleavage sites on average every 35 bp. Each of 15 sites selected from this set was cleaved in a yeast-based assay with TALEN pairs constructed with our reagents. We used two of the TALEN pairs to mutate HPRT1 in human cells and ADH1 in Arabidopsis thaliana protoplasts. Our reagents include a plasmid construct for making custom TAL effectors and one for TAL effector fusions to additional proteins of interest. Using the former, we constructed de novo a functional analog of AvrHah1 of Xanthomonas gardneri. The complete plasmid set is available through the non-profit repository AddGene and a web-based version of our software is freely accessible online