Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes

B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T‐cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non‐Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose‐dependent and time‐controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery.     

Primary explosives: electrostatic discharge initiation, additive effect and its relation to thermal and explosive characteristics

All explosives, under all conditions must be considered vulnerable to generation, accumulation and discharge of static charge. The low energy static hazards of the order as low as 2-3 mJ need to be guarded against in case of highly sensitive compounds namely primary explosives. The hazard is normally associated with manufacturing and filling operations due to discharge of static charge accumulated on a person supplying energy up to 20 mJ. To reduce the risk associated with static initiation hazard in the processing and handling of the explosives, the electrostatic sensitivity tests can provide an important input regarding electrostatic hazards. This paper presents electrostatic sensitivity data in terms of zero ignition probability data (E(SE0)) of some of the initiatory explosives such as nickel/cobalt hydrazinium nitrate, silver azide, lead azide and mercury salt of 5-nitro tetrazole. Similar data has also been presented for samples coated with polyvinyl pyrrolidone to study its effect on electrostatic sensitivity. The electrostatic spark sensitivity of some conventional and novel made to explain the increased spark sensitivity behavior on the basis of the possible primary explosives has been studied. The electrostatic spark sensitivity of primary explosives decreased in the order of AgN3 = NHN > PbN6 > MNT > CoHN > BNCP. A possible correlation of spark energy with approximation and assumption has been drawn with thermal, detonation and mechanical properties. The polyvinyl pyrrolidone coated samples followed the same order but interestingly with increased spark sensitivity. An attempt has been reasoning of dielectric nature of the materials or exothermic effects of decomposition products of PVP. The present work also reports the electrostatic spark sensitivity of cap compositions.     

Cognitive–behavioral therapy for adult anxiety disorders in clinical practice: A meta-analysis of effectiveness studies.

The efficacy of cognitive–behavioral therapy (CBT) for anxiety in adults is well established. In the present study, the authors examined whether CBT tested under well-controlled conditions generalizes to less-controlled, real-world circumstances. Fifty-six effectiveness studies of CBT for adult anxiety disorders were located and synthesized. Meta-analytic effect sizes are presented for disorder-specific symptom measures as well as symptoms of generalized anxiety and depression for each disorder, and benchmarked to results from randomized controlled trials. All pretest–posttest effect sizes for disorder-specific symptom measures were large, suggesting that CBT for adult anxiety disorders is effective in clinically representative conditions. Six studies included a control group, and between-groups comparisons yielded large effect sizes for disorder-specific symptoms in favor of CBT. Benchmarking indicated that results from effectiveness studies were in the range of those obtained in selected efficacy trials. To test whether studies that are more representative of clinical settings have smaller effect sizes, the authors coded studies for 9 criteria for clinical representativeness. Results indicate an inverse relationship between clinical representativeness and outcome, but the magnitude of the relationship is quite small. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of ethnicity in observers’ ratings of mother–child behavior.

This study examined the role of ethnicity in untrained observers’ ratings of videotaped mother–child interactions. Participants were Black, White, and Latino undergraduates (N = 109), who rated videotapes of 4 Black, 4 White, and 4 Latino mother–child dyads. Overall, participants of different ethnicities showed more similarities than differences in their ratings of parent–child behavior. There was, however, evidence that participant ethnicity and parent–child ethnicity interacted for ratings of child defiance/negative emotion. Black and White participants differed in their ratings of Black and White children’s defiance/negative emotion, with members of each ethnic group favoring children of their own ethnic group. Intergroup contact appeared to play a role in ratings of parent behavior among Black observers. Black observers who reported low intergroup contact tended to rate Black mothers high on strictness and low on permissiveness. More research is needed to better understand the role of ethnicity in observers’ ratings of parent and child behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The nature and structure of correlations among Big Five ratings: The halo-alpha-beta model.

In light of consistently observed correlations among Big Five ratings, the authors developed and tested a model that combined E. L. Thorndike’s (1920) general evaluative bias (halo) model and J. M. Digman’s (1997) higher order personality factors (alpha and beta) model. With 4 multitrait–multimethod analyses, Study 1 revealed moderate convergent validity for alpha and beta across raters, whereas halo was mainly a unique factor for each rater. In Study 2, the authors showed that the halo factor was highly correlated with a validated measure of evaluative biases in self-ratings. Study 3 showed that halo is more strongly correlated with self-ratings of self-esteem than self-ratings of the Big Five, which suggests that halo is not a mere rating bias but actually reflects overly positive self-evaluations. Finally, Study 4 demonstrated that the halo bias in Big Five ratings is stable over short retest intervals. Taken together, the results suggest that the halo-alpa-beta model integrates the main findings in structural analyses of Big Five correlations. Accordingly, halo bias in self-ratings is a reliable and stable bias in individuals’ perceptions of their own attributes. Implications of the present findings for the assessment of Big Five personality traits in monomethod studies are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social support and the well-being of persons with spinal cord injury living in the community.

100 men and 40 women (all aged 19–77 yrs) with spinal cord injury completed a social support questionnaire, the Center for Epidemiologic Studies Depression Scale, the Life Satisfaction Index Form A, and a single-item self-assessment of health status. A physician assessed the presence or absence of urinary tract infection from laboratory findings and determined the absence, presence, and severity of pressure ulcers from physical examination. Amount of social support was positively related to life satisfaction and physical well-being. Satisfaction with one's support network was associated negatively with depressive symptomatology and positively with life satisfaction. There were significant differences in the correlations between life satisfaction and total social support for men and women. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Comparison of Group Processes,Performance, and Satisfaction in Face‐to‐Face Versus Computer‐Mediated Engineering Student Design Teams

Industry often requires engineers to work in teams. Therefore, many university engineering courses require students to work in groups to complete a design project. Due to the increasingly global nature of engineering, opportunities for students to navigate the issues of distance, time, culture, language, and multiple perspectives associated with virtual teams are becoming particularly desirable. To understand students' experience with virtual teams in a graduate course on principles of lean manufacturing, a group of researchers at a midwestern university compared the project performance, selected group processes, and satisfaction of students randomly assigned to face‐to‐face and computer‐mediated communication design teams. Students in both the face‐to‐face and computer‐mediated communication design teams performed equally well on the final project, and reported similar patterns in group processes with a few exceptions. Students in face‐to‐face design teams were more satisfied with the group experience than those in the computer‐mediated communication design teams; however, all reported an overall positive experience.     

High-temperature mechanical behavior and hot rolling of AA705X

High-temperature mechanical behavior and processing performance of 705X aluminum alloys is examined, employing a combination of mechanical testing, microscopy, and computational modeling. We perform hot uniaxial compression tests over a range of temperatures and strain rates and fit the data to power-law constitutive models. These models are supported and expanded by microscopy and calorimetry, which help to elucidate the operating deformation mechanisms and examine damage evolution. The mechanical behavior constitutive relations are implemented in a finite-element code to simulate the hot rolling process. The results of the rolling simulation are used to predict final product crystallographic texture, which is compared with experimental electron backscattered diffraction measurements for model validation. Finally, we propose a parameter to characterize the development of damage during processing. This work provides a solid foundation for the design of thermomechanical processing of these alloys to maximize yield and optimize process performance.     

A test of the reactive aggression-suicidal behavior hypothesis: Is there a case for proactive aggression?

A large body of literature suggests that aggressive behavior can be classified into two subtypes--reactive aggression (RA) and proactive aggression (PA)--which differ on dimensions of emotional arousal, control, and impulsivity. A longstanding hypothesis posits that RA underlies the association between aggression and suicidal behavior, with the implicit assumption that PA is unrelated to suicidal behavior. However, no empirical study to date has specifically investigated this question. The authors examined associations of RA and PA with suicide attempts and suicidal ideation among 878 male and female patients in substance-dependence treatment programs. They also examined the moderating effects of sex. Contrary to hypotheses, PA was associated with both suicide attempts and suicidal ideation. RA was also associated with both outcomes in unadjusted analyses but became nonsignificant for suicide attempts in multivariate analyses. Moreover, sex served as a moderator, with PA showing an association with suicide attempt among men but not women. Results indicate the need for additional studies of PA and suicidal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)