Entrepreneurial Community Development - Exploring Earned Income Activities and Strategic Alliances for Community Development Nonprofits

This paper examines social entrepreneurship from a community-development perspective. The target audience is community-development nonprofit organizations. The paper begins by contextualizing social entrepreneurship in community development and creating an analytical framework in which to think about efforts of organizations to integrate entrepreneurial and businesslike thinking. The paper presents key findings regarding both earned-income activities and strategic alliances as options for these organizations, as well as 10 key issues that arose as factors that impact their successful implementation. Information was gathered through a literature review, 29 interviews of practitioners, policymakers and academics and a survey of 59 community-development nonprofit organizations

A study of trace contaminant identification by microwave double resonance spectroscopy

Trace contaminant identification using microwave double resonance spectroscop

Lola

https://digitalcommons.library.umaine.edu/mmb-vp/3804/thumbnail.jp

Computing Specificity

This note reports on an effort to implement a version of Poole\u27s rule for specificity. Relatively, efficient implementation relies on correcting and improving a pruning lemma of Simari-Loui [92]. This in turn requires revision of Poole\u27s specificity concept. The resulting system is a usable knowledge representation system with first-order-language and defeasible reasoning. Sample input and output are included in an appendix. It is a good candidate for multiple inheritance applications; it is useful for planning, but limited by the underlying search for plans

Transcriptome analysis reveals a major impact of JAK protein tyrosine kinase 2 (Tyk2) on the expression of interferon-responsive and metabolic genes

<p>Abstract</p> <p>Background</p> <p>Tyrosine kinase 2 (Tyk2), a central component of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, has major effects on innate immunity and inflammation. Mice lacking Tyk2 are resistant to endotoxin shock induced by lipopolysaccharide (LPS), and Tyk2 deficient macrophages fail to efficiently induce interferon α/β after LPS treatment. However, how Tyk2 globally regulates transcription of downstream target genes remains unknown. Here we examine the regulatory role of Tyk2 in basal and inflammatory transcription by comparing gene expression profiles of peritoneal macrophages from Tyk2 mutant and wildtype control mice that were either kept untreated or exposed to LPS for six hours.</p> <p>Results</p> <p>Untreated Tyk2-deficient macrophages exhibited reduced expression of immune response genes relative to wildtype, in particular those that contain interferon response elements (IRF/ISRE), whereas metabolic genes showed higher expression. Upon LPS challenge, IFN-inducible genes (including those with an IRF/ISRE transcription factor binding-site) were strongly upregulated in both Tyk2 mutant and wildtype cells and reached similar expression levels. In contrast, metabolic gene expression was strongly decreased in wildtype cells upon LPS treatment, while in Tyk2 mutant cells the expression of these genes remained relatively unchanged, which exaggerated differences already present at the basal level. We also identified several 5'UR transcription factor binding-sites and 3'UTR regulatory elements that were differentially induced between Tyk2 deficient and wildtype macrophages and that have not previously been implicated in immunity.</p> <p>Conclusions</p> <p>Although Tyk2 is essential for the full LPS response, its function is mainly required for baseline expression but not LPS-induced upregulation of IFN-inducible genes. Moreover, Tyk2 function is critical for the downregulation of metabolic genes upon immune challenge, in particular genes involved in lipid metabolism. Together, our findings suggest an important regulatory role for Tyk2 in modulating the relationship between immunity and metabolism.</p

Synchronous versus sequential updating in the three-state Ising neural network with variable dilution

The three-state Ising neural network with synchronous updating and variable dilution is discussed starting from the appropriate Hamiltonians. The thermodynamic and retrieval properties are examined using replica mean-field theory. Capacity-temperature phase diagrams are derived for several values of the pattern activity and different gradations of dilution, and the information content is calculated. The results are compared with those for sequential updating. The effect of self-coupling is established. Also the dynamics is studied using the generating function technique for both synchronous and sequential updating. Typical flow diagrams for the overlap order parameter are presented. The differences with the signal-to-noise approach are outlined.Comment: 21 pages Latex, 12 eps figures and 1 ps figur

Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases