Elements of Cohesion: The Role of Business Improvement Districts in Neighborhood Cohesion

The current research examines the relationship between sense of community and business improvement districts (BIDs) in urban neighborhoods. Study 1 employed the method of imagined scenarios to distinguish sense of community ratings between hypothetical neighborhoods with and without BIDs. This study found that participants in the imagined BID neighborhood scenario reported higher sense of community than those in the imagined non-BID neighborhood scenario. In Study 2, residents of two neighborhoods in Brooklyn, New York, one with a BID and one without a BID, were surveyed on their neighborhood experience and sense of community. This study found no difference in sense of community between neighborhoods. The overall findings suggest that resources of BIDs, held in isolation, can relate to sense of community, but in a neighborhood with many additional characteristics, such as susceptibility to social change or natural disaster, the presence of a BID does not necessarily contribute directly to sense of community

Criticism to objects eulogy

Em nenhuma outra época a humanidade produziram-se tantos objetos. Sobre esta afirmação é necessário que recaia uma análise. Os reflexos deste fato sobre as noções e conceitos do pensar geográfico é o centro deste artigoIn no other time men has produced so many objects. It is necessary to analyze this affirmation. The reflection of this fact on notions and concepts of geographical thoughts are the center of this articl

Oxazolidinones as versatile scaffolds in medicinal chemistry

Oxazolidinone is a five-member heterocyclic ring with several biological applications in medicinal chemistry. Among the three possible isomers, 2-oxazolidinone is the most investigated in drug discovery. Linezolid was pioneered as the first approved drug containing an oxazolidinone ring as the pharmacophore group. Numerous analogues have been developed since its arrival on the market in 2000. Some have succeeded in reaching the advanced stages of clinical studies. However, most oxazolidinone derivatives reported in recent decades have not reached the initial stages of drug development, despite their promising pharmacological applications in a variety of therapeutic areas, including antibacterial, antituberculosis, anticancer, anti-inflammatory, neurologic, and metabolic diseases, among other areas. Therefore, this review article aims to compile the efforts of medicinal chemists who have explored this scaffold over the past decades and highlight the potential of the class for medicinal chemistry

DESVELANDO AS TRANSFORMAÇÕES DO ESPAÇO DO ALIMENTO DENTRO DOS APARTAMENTOS NA CIDADE DE VITÓRIA DURANTE A VIRADA DO SÉCULO XX

A produção da cidade vem sendo realizada a partir de diretrizes que se coadunam com a sociedade de consumo. Nela o apartamento residencial tem seu interior submetido a uma racionalidade que revela aspectos inerentes a esse espaço urbano, tal qual nossa relação com a alimentação. Este estudo visa desenvolver uma análise da cozinha como um espaço indicador de transformações urbanas na cidade de Vitória e sua relação com a sociedade de consumo. Além de autores que versam sobre o tema, utilizamos como elemento de análise as propagandas imobiliárias das décadas 1980 e 1990, período em que envolvem se profundas transformações na capital do capixaba. Ao final estabelecemos considerações indicativas de que a transformação da cozinha revela aspectos da estratégia de agentes imobiliários, que abrange um novo conceito sobre a nossa relação com o alimento

An Inexpensive, Reproducible Method to Quantify Activated Sludge Foaming Potential: Validation Through Lab-Scale Studies and Year-Long Full-Scale Sampling Campaign

Activated sludge is a conventional treatment process for biochemical oxygen demand (BOD) and total suspended solids (TSS) removal at water resource recovery facilities (WRRFs). Foaming events are a common operational issue in activated sludge and can lead to decreased treatment efficiency, maintenance issues, and potential environmental health risks. Stable foaming events are caused by biological and chemical drivers (i.e., microbes and surfactants) during the aeration process. However, foaming events are difficult to predict and quantify. We present an inexpensive and easy-to-use method that can be applied at WRRFs to quantify foaming potential. Subsequently, the method was applied over a year-long full-scale study while data on microbial community composition and functional parameters associated with foaming potential were collected from activated sludge samples at South Shore Water Reclamation Facility (WRF) (Oak Creek, WI). Results from the development of the foaming potential method using linear alkylbenzene sulfonate (LAS) showed that the method was reproducible (relative standard deviation Zoogloea, Flavobacterium, Variovorax, and Bdellovibrio. This is the first report that Variovorx and Bdellovibrio relative abundance was correlated with foaming events in activated sludge. Furthermore, the foaming potential positively correlated (ρ = 0.24) with soluble total nitrogen. Characterizing foaming events through frequent sampling and monitoring of specific genera and functional parameters may allow for predictions and preemptive mitigation efforts to avoid negative consequences in the future. Practitioner Points A reproducible method to measure foaming potential in activated sludge is available. Genera Zoogloea, Flavobacterium, Variovorax, and Bdellovibrio correlated with foaming events. A year-long sampling campaign of activated sludge measuring foaming potential and microbial community composition was conducted at South Shore Water Reclamation Facility in Oak Creek, WI. More research at other facilities with this method is needed to understand links between microbes and foamin

Interleukin-1 Stimulates β-Cell Necrosis and Release of the Immunological Adjuvant HMGB1

BACKGROUND: There are at least two phases of β-cell death during the development of autoimmune diabetes: an initiation event that results in the release of β-cell-specific antigens, and a second, antigen-driven event in which β-cell death is mediated by the actions of T lymphocytes. In this report, the mechanisms by which the macrophage-derived cytokine interleukin (IL)-1 induces β-cell death are examined. IL-1, known to inhibit glucose-induced insulin secretion by stimulating inducible nitric oxide synthase expression and increased production of nitric oxide by β-cells, also induces β-cell death. METHODS AND FINDINGS: To ascertain the mechanisms of cell death, the effects of IL-1 and known activators of apoptosis on β-cell viability were examined. While IL-1 stimulates β-cell DNA damage, this cytokine fails to activate caspase-3 or to induce phosphatidylserine (PS) externalization; however, apoptosis inducers activate caspase-3 and the externalization of PS on β-cells. In contrast, IL-1 stimulates the release of the immunological adjuvant high mobility group box 1 protein (HMGB1; a biochemical maker of necrosis) in a nitric oxide-dependent manner, while apoptosis inducers fail to stimulate HMGB1 release. The release of HMGB1 by β-cells treated with IL-1 is not sensitive to caspase-3 inhibition, while inhibition of this caspase attenuates β-cell death in response to known inducers of apoptosis. CONCLUSIONS: These findings indicate that IL-1 induces β-cell necrosis and support the hypothesis that macrophage-derived cytokines may participate in the initial stages of diabetes development by inducing β-cell death by a mechanism that promotes antigen release (necrosis) and islet inflammation (HMGB1 release)

Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi.

Hydroxymethylnitrofurazone (NFOH) is a therapeutic candidate for Chagas disease (CD). It has negligible hepatotoxicity in a murine model compared to the front-line drug benznidazole (BZN). Here, using Trypanosoma cruzi strains that express bioluminescent and/or fluorescent reporter proteins, we further investigated the in vitro and in vivo activity of NFOH to define whether the compound is trypanocidal or trypanostatic. The in vitro activity was assessed by exploiting the fluorescent reporter strain using wash-out assays and real-time microscopy. For animal experimentation, BALB/c mice were inoculated with the bioluminescent reporter strain and assessed by highly sensitive in vivo and ex vivo imaging. Cyclophosphamide treatment was used to promote parasite relapse in the chronic stage of infection. Our data show that NFOH acts by a trypanostatic mechanism, and that it is more active than BZN in vitro against the infectious trypomastigote form of Trypanosoma cruzi. We also found that it is more effective at curing experimental infections in the chronic stage, compared with the acute stage, a feature that it shares with BZN. Therefore, given its reduced toxicity, enhanced anti-trypomastigote activity, and curative properties, NFOH can be considered as a potential therapeutic option for Chagas disease, perhaps in combination with other trypanocidal agents

Poly I:C enhances cycloheximide-induced apoptosis of tumor cells through TLR3 pathway

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 3 (TLR3) is a critical component of the innate immune response to dsRNA viruses, which was considered to be mainly expressed in immune cells and some endothelial cells. In this study, we investigated the expression and proapoptotic activity of TLR3 in human and murine tumor cell lines.</p> <p>Methods</p> <p>RT-PCR and FACS analysis were used to detect expression of TLR3 in various human and murine tumor cell lines. All tumor cell lines were cultured with poly I:C, CHX, or both for 12 h, 24 h, 72 h, and then the cell viability was analyzed with CellTiter 96^®AQueous One Solution, the apoptosis was measured by FACS with Annexin V and PI staining. Production of Type I IFN in poly I:C/CHX mediated apoptosis were detected through western blotting. TLR3 antibodies and IFN-β antibodies were used in Blockade and Neutralization Assay.</p> <p>Results</p> <p>We show that TLR3 are widely expressed on human and murine tumor cell lines, and activation of TLR3 signaling in cancerous cells by poly I:C made Hela cells (human cervical cancer) and MCA38 cells (murine colon cancer) become dose-dependently sensitive to protein synthesis inhibitor cycloheximide (CHX)-induced apoptosis. Blockade of TLR3 recognition with anti-TLR3 antibody greatly attenuated the proapoptotic effects of poly I:C on tumor cells cultured with CHX. IFN-β production was induced after poly I:C/CHX treatment and neutralization of IFN-β slightly reduced poly I:C/CHX -induced apoptosis.</p> <p>Conclusion</p> <p>Our study demonstrated the proapoptotic activity of TLR3 expressed by various tumor cells, which may open a new range of clinical applications for TLR3 agonists as an adjuvant of certain cancer chemotherapy.</p

MDA5 and PTPN2, two candidate genes for type 1 diabetes, modify pancreatic β-cell responses to the viral by-product double-stranded RNA

β-Cell destruction in type 1 diabetes (T1D) is at least in part consequence of a ‘dialog’ between β-cells and immune system. This dialog may be affected by the individual's genetic background. We presently evaluated whether modulation of MDA5 and PTPN2, two candidate genes for T1D, affects β-cell responses to double-stranded RNA (dsRNA), a by-product of viral replication. These genes were selected following comparison between known candidate genes for T1D and genes expressed in pancreatic β-cells, as identified in previous array analysis. INS-1E cells and primary fluorescence-activated cell sorting-purified rat β-cells were transfected with small interference RNAs (siRNAs) targeting MDA5 or PTPN2 and subsequently exposed to intracellular synthetic dsRNA (polyinosinic–polycitidilic acid—PIC). Real-time RT–PCR, western blot and viability assays were performed to characterize gene/protein expression and viability. PIC increased MDA5 and PTPN2 mRNA expression, which was inhibited by the specific siRNAs. PIC triggered apoptosis in INS-1E and primary β-cells and this was augmented by PTPN2 knockdown (KD), although inhibition of MDA5 did not modify PIC-induced apoptosis. In contrast, MDA5 silencing decreased PIC-induced cytokine and chemokine expression, although inhibition of PTPN2 induced minor or no changes in these inflammatory mediators. These findings indicate that changes in MDA5 and PTPN2 expression modify β-cell responses to dsRNA. MDA5 regulates inflammatory signals, whereas PTPN2 may function as a defence mechanism against pro-apoptotic signals generated by dsRNA. These two candidate genes for T1D may thus modulate β-cell apoptosis and/or local release of inflammatory mediators in the course of a viral infection by acting, at least in part, at the pancreatic β-cell level