1,004 research outputs found

    Issues Relevant to C-H Activation at Platinum(II): Comparative Studies between Cationic, Zwitterionic, and Neutral Platinum(II) Compounds in Benzene Solution

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    Cationic late metal systems are being highly scrutinized due to their propensity to mediate so-called electrophilic C-H activation reactions. This contribution compares the reactivity of highly reactive cationic platinum(II) systems with structurally related but neutral species. Our experimental design exploits isostructural neutral and cationic complexes supported by bis(phosphine) ligands amenable to mechanistic examination in benzene solution. The data presented herein collectively suggests that neutral platinum complexes can be equally if not more reactive towards benzene than their cationic counter-parts. Moreover, a number of unexpected mechanistic distinctions between the two systems arise that help to explain their respective reactivity

    Hunger in America 2014: National Report

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    Feeding America, the nation's leading domestic hunger-relief organization, has conducted the most comprehensive study of hunger in America every four years since 1993. Like the prior studies, Hunger in America 2014 (HIA 2014), the latest iteration, documents the critical role that the charitable food assistance network plays in supporting struggling families in the United States. Study results are based on surveys of food programs in the charitable food assistance network supported by Feeding America, and clients that access services through that network in 2012-2013. In addition to this report on the Feeding America national network, this study has resulted in 42 state reports and 196 food bank reports detailing network activities on local levels.The current assessment occurs in a period with historically high demand for food assistance. Unemployment and poverty rates have remained high since the Great Recession of 2008, and the number of households receiving nutrition assistance from the federal government's Supplemental Nutrition Assistance Program has increased by approximately 50 percent between 2009 and 2013.Demand for charitable food assistance has also expanded. HIA 2014 finds an increased number of individuals relying on charitable assistance to access nutritious foods for themselves and their families

    Anti-tumor necrosis factor-alpha therapy during murine Klebsiella pneumoniae bacteremia: increased mortality in the absence of liver injury.

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    Klebsiella pneumoniae is a leading cause of gram-negative bacterial pneumonia, often resulting in bacteremia concurrent with the localized pulmonary infection. The beneficial role of tumor necrosis factor (TNF)-alpha during pulmonary infection has been well documented; however, consequences of TNF-alpha production during systemic bacterial infection are controversial. A murine model of K. pneumoniae was developed to address this important issue. Liver-associated TNF-alpha mRNA was induced within 30 min after intravenous bacterial inoculation and remained elevated through 6 h before returning to near-baseline at 24 h postinfection. Intravenous K. pneumoniae infection induced liver cellular injury that was completely ablated when mice were pretreated with a neutralizing anti-TNF-alpha antibody. Interestingly, this reduction in liver injury failed to translate into improved survival. Mice receiving anti-TNF-alpha continued to succumb to the infection even out to day 10 postinfection. Bacterial clearance after TNF-alpha neutralization was significantly impaired at later time points during infection. Correlating with impaired bacterial clearance was diminished production of liver-associated MIP-2, MIP-1alpha, MCP-1, and interferon-gamma. Further evidence of diminished antibacterial immune responses was noted when the activational status of splenic natural killer cells in anti-TNF-alpha-treated mice was examined 24 h postinfection. Natural killer cells displayed decreased CD69 expression. Combined, these data indicate that the beneficial effects of TNF-alpha during systemic K. pneumoniae infection outweigh the detrimental effects of TNF-alpha-mediated hepatocyte cellular injury. Anti-TNF-alpha therapy, although preventing liver injury during blood-borne bacterial infection, results in a dampened anti-bacterial host response, resulting in decreased bacterial clearance and overall survival

    Domain specific software architectures: Command and control

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    GTE is the Command and Control contractor for the Domain Specific Software Architectures program. The objective of this program is to develop and demonstrate an architecture-driven, component-based capability for the automated generation of command and control (C2) applications. Such a capability will significantly reduce the cost of C2 applications development and will lead to improved system quality and reliability through the use of proven architectures and components. A major focus of GTE's approach is the automated generation of application components in particular subdomains. Our initial work in this area has concentrated in the message handling subdomain; we have defined and prototyped an approach that can automate one of the most software-intensive parts of C2 systems development. This paper provides an overview of the GTE team's DSSA approach and then presents our work on automated support for message processing

    Mining Microbial Communities: Exploring Symbiotic Bacteria as a Source of New Natural Products

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    As ubiquitous inhabitants of Earth, bacteria represent a diverse resource in the search for new natural products. In order for the field of natural products to progress, new and exciting sources of biodiversity must be continually accessed. Microbiomes, the community of commensal and pathogenic microorganisms that live in and on other organisms, present a unique opportunity to access new biological diversity. These symbiotic bacteria have proven to be prolific producers of natural products and represent relatively untapped resource of new secondary metabolites. Photorhabdus asymbiotica, a bacterial symbiont of an entomopathogenic nematode is an emerging health concern for humans. It engages in a bi-phasic lifestyle that switches between symbiotic and pathogenic phases. Its genome had been previously sequenced and our analysis of the secondary metabolite pathways indicated it had the genetic machinery necessary to produce multiple natural products. Extensive media screening studies were employed to induce the production of the encoded for natural products. Two known and one new proteasome inhibitors were isolated from the optimized culture conditions. The theory that P. asymbiotica’s lifestyle switch is governed in part by environmental cues was explored by injecting the bacterium into live crickets. Recovery of the bioactive natural products from the cricket corpus supported the belief that the nutrient composition of the insect gut plays a role in the life cycle switch of P. asymbiotica. The microbiomes of mammals are a rich and diverse source of bacteria. While these microbiomes are well studied in terms of populations, little is known about their ability to produce natural products. The biosynthetic potential of the microbiome of a feral hog was examined. One isolated organism, identified as a new strain of Brevibacillus latersporus, was chosen for further genomic and metabolomic characterization. Thirty two biosynthetic gene clusters were identified in the organism’s genome. Three known bioactive compounds were isolated along with two new natural products. A portion of the known and new natural products were matched up with their biosynthetic gene clusters. This work showed that symbiotic bacteria from small mammals are worthy of further investigation by natural product investigators. Finally, a method was developed to sample, isolate, and screen members of microbiome communities for biosynthetically talented and culturable organisms. By employing the use of liquid handling robots and specialized instrumentation, an efficient method for quickly evaluating organisms for secondary metabolites was created. By combining an efficient screening method and metabolomic investigations, a snap shot of the chemical products generated by microbiome members has been achieved

    Age-related changes to macrophages are detrimental to fracture healing in mice.

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    The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age-related diseases. Therefore, we investigated age-related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA-seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up-regulation of M1/pro-inflammatory genes in macrophages from old mice as well as dysregulation of other immune-related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age-matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA-seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age-related changes, and depleting infiltrating macrophages can improve fracture healing in old mice

    Facial attractiveness of patients with unilateral cleft lip and palate and of controls assessed by laypersons and professionals

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    SUMMARYOBJECTIVES: The aim of the study was to identify differences in the aesthetic evaluation of profile and frontal photographs of (1) patients treated for complete left-sided cleft lip and palate and (2) control patients by laypeople and professionals. MATERIALS, SUBJECTS, AND METHODS: Left-side profile and frontal photographs of 20 adult patients treated for complete left-sided cleft lip and palate (10 men, 10 women, mean age: 20.5 years) and of 10 control patients with a class I occlusion (five men, five women, mean age: 22.1 years) were included in the study. The post-treatment photographs were evaluated by 15 adult laypeople, 14 orthodontists, and 10 maxillofacial surgeons. Each photograph was judged on a modified visual analogue scale (VAS, 0-10; 0 ‘very unattractive' to 10 ‘very attractive'). A four-level mixed model was fitted in which the VAS score was the dependent variable; cases, profession, view, and rater were independent variables. RESULTS: Compared with laypersons, orthodontists gave higher VAS scores (+0.69, 95% confidence interval (CI) [0.53, 0.84]; P < 0.001), followed by surgeons (+0.21, 95% CI [0.03, 0.38], P = 0.02). Controls were given significantly higher scores than patients with clefts for profile and frontal photographs (+1.97, 95% CI [1.60; 2.35], P < 0.001). No significant difference was found between the scores for the frontal and lateral views (P = 0.46). CONCLUSIONS: All the different rater panels were less satisfied with the facial aesthetics of patients with clefts compared with that of control patients. Further research should evaluate whether these findings correlate with patients' self-perception and to what extent it affects the patients' psychosocial well-bein

    Brief of Feminists for Life of America, Professional Women\u27s Network, Birthright, Inc., Legal Action for Women, as Amici Curiae in Support of Respondents and Cross Petitioners - Planned Parenthood of Southeastern Pennsylvania v. Casey, 112 S. Ct. 2791 (1992)

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    Amici, representing women from all walks of life, are compelled by experience and conviction to advocate strongly that this Court reverse the vulnerable position of women caused by the lack of information given to women contemplating abortion. Amici respectfully urged this Court to affirm the ruling of the Court below, supporting the efforts of the women citizens of the Commonwealth of Pennsylvania to cause that government to exercise its police power to protect their health and safety by compelling the dissemination of the information necessary to make a fully informed decision
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