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The situation of a small-diameter liquid jet exposed to a large-diameter high-speed gas jet (gas-to-liquid nozzle area ratio of order 100 to 1000) is investigated experimentally. Flow visualization and particle-sizing techniques are employed to examine the initial jet breakup process and primary liquid atomization. Observations of the initial breakup of the liquid jet in the near-nozzle region, combined with droplet-size mea-surements, are used in an effort to elucidate the dominant mechanism of primary breakup of the liquid. It is shown that for large aerodynamic Weber numbers, the bulk of the liquid atomization is completed within a few gas-jet diameters of the nozzle exit, inside of the potential cone of the gas flow. Breakup is therefore completed within the zone of constant ambient gas velocity. It is argued that the mechanism of initial jet breakup is similar to that of a liquid drop suddenly exposed to a high-speed gas stream. A phenomenological breakup model is proposed for the initial droplet size, based upon the accelerative, secondary destabilization (via Rayleigh–Taylor instability) of the liquid wave crests resulting from the primary Kelvin–Helmholtz instability of the liquid jet surface. Primary mean droplet sizes are shown to scale well on the most unstable Rayleigh–Taylor wavelength, and the dependence of the droplet diameter on both the atomizing gas velocity and the liquid surface tension are successfully captured by the proposed breakup model.

An objective of designing molecular vehicles exhibiting virus-like transgene delivery capabilities but with low toxicity and immunogenicity continues to drive synthetic vector development. As no single step within the gene delivery pathway represents the critical limiting barrier for all vector types under all circumstances, improvements in synthetic vehicle design may be aided by quantitative analysis of the contributions of each step to the overall delivery process. To our knowledge, however, synthetic and viral gene delivery methods have not yet been explicitly compared in terms of these delivery pathway steps in a quantitative manner. As a first address of this challenge, we compare here quantitative parameters characterizing intracellular gene delivery steps for an E1/E3-deleted adenoviral vector and three polyethylenimine (PEI)-based vector formulations, as well as the liposomal transfection reagent Lipofectamine and naked DNA; the cargo is a plasmid encoding the β-galactosidase gene under a CMV promoter, and the cell host is the C3A human hepatocellular carcinoma line. The parameters were determined by applying a previously validated mathematical model to transient time-course measurements of plasmid uptake and trafficking (from whole-cell and isolated nuclei lysates, by real-time quantitative PCR), and gene expression levels, enabling discovery of those for which the adenoviral vector manifested superiority. Parameter-sensitivity analysis permitted identification of processes most critically rate-limiting for each vector. We find that the adenoviral vector advantage in delivery appears to reside partially in its import to the nuclear compartment, but that its vast superiority in transgene expression arises predominantly in our situation from postdelivery events: on the basis of per-nuclear plasmid, expression efficiency from adenovirus is superior by orders of magnitude over the PEI vectors. We find that a chemical modification of a PEI-based vector, which substantially improves its performance, appears to do so by enhancing certain trafficking rate parameters, such as binding and uptake, endosomal escape, and binding to nuclear import machinery, but leaves endosomal escape as a barrier over which transgene delivery could be most sensitively increased further for this polymer.

Stem cells share several characteristics of cancer cells including loss of contact inhibition and immortality. Therefore, stem cells represent an excellent model system in which to define the molecular mechanisms underlying cancer development and progression. Several signal transduction pathways including leukemia inhibitory factor, Wnt and FGF have been demonstrated to function in stem cell self-renewal and differentiation. However, more recently bone morphogenetic proteins (BMPs) have emerged as key regulators of stem cell fate commitment. Intriguingly, BMPs have disparate roles in regulating the biology of embryonic stem (ES) cells compared with neural crest stem cells (NCSCs). Furthermore, although BMPs block neural differentiation of ES cells from both mouse and human, they contribute to self-renewal specifically in mouse ES cells. These observations strongly suggest that combinations of extracellular factors regulate stem cells, and that crosstalk between intracellular signaling pathways precisely defines stem cell fate commitment. In this review, we focus on the role of BMP signaling in mouse and human ES cells compared with NCSCs. We then discuss how the molecular effectors of BMP signaling may contribute to cancer, and thus represent potential targets for therapeutic intervention.

Portland cement decalcification and its effects on paste microstructure and mechanical strength have been widely studied. Decalcification in alkali activated slag (AAS) pastes is still not fully understood, however. The present study therefore explored the process in AAS cement pastes, accelerated by submerging specimens in concentrated ammonium nitrate solutions (NH 4 NO 3 ) for 3–21 days to induce leaching. Two AAS pastes were prepared with slag of different origins (Spanish and Colombian) and chemical compositions. OPC pastes were used as a reference. The findings showed that decalcification has a more adverse impact on OPC than AAS pastes strength. BSEM/EDX and 29 Si MAS NMR data nonetheless confirmed that Ca leaches out of C–A–S–H gels (formed in AAS pastes) to an extent that depends on the nature of the prime material. OPC pastes were shown to generate more silica gel with a very low Ca content (Q 3 and Q 4 units). Moreover, the higher the percentage of such units, the lower was mechanical strength. Decalcification in slag with lower MgO and higher Al 2 O 3 contents leads to the formation of smaller amounts of silica gel. The resulting gel was more compact and stable due to more intense chain cross-linking a possible tri-dimensional structure.

In Ontario, Canada, the number of Salmonella Enteritidis (SE) cases increased over the years 2005–2010. A population-based case-control study was undertaken from January to August 2011 for the purpose of identifying risk factors for acquiring illness due to SE within Ontario. A total of 199 cases and 241 controls were enrolled. After adjustment for confounders, consuming any poultry meat [adjusted odds ratio (aOR) 2·24, 95% confidence interval (CI) 1·31–3·83], processed chicken (aOR 3·32, 95% CI 1·26–8·76) and not washing hands following handling of raw eggs (OR 2·82, 95% CI 1·48–5·37) were significantly associated with SE infection. The population attributable fraction was 46% for any poultry meat consumption and 10% for processed chicken. Poultry meat continues to be identified as a risk factor for SE illness. Control of SE at source, as well as proper food handling practices, are required to reduce the number of SE cases.

Background and purpose: Leukotriene B4 (LTB4), formed by the sequential actions of the 5‐lipoxygenase (5‐LO) and leukotriene A4 hydrolase (LTA4H), is a pro‐inflammatory mediator implicated in the pathogenesis of inflammatory bowel disease. However, inhibitors of 5‐LO have not proved to be consistent in their therapeutic efficacy in colitis. Another approach to inhibiting LTB4 synthesis is through the use of inhibitors of LTA4H, such as the novel, potent and selective compound, JNJ 26993135. Experimental approach: The effect of oral administration of JNJ 26993135 has been evaluated in a rat model of colitis provoked by colonic instillation of trinitrobenzenesulphonic acid (TNBS). The extent and severity of the macroscopic inflammatory response, the colonic levels of myeloperoxidase (MPO) and LTB4 and of the pro‐inflammatory cytokines, tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were measured. Key results: Oral administration of JNJ 26993135 (5, 15 and 30 mg kg−1, twice a day) dose‐dependently reduced both the extent and intensity of the colonic inflammatory damage observed 3 days after TNBS challenge. JNJ 26993135 also dose‐dependently reduced the elevated colonic levels of LTB4, as well as the inflammatory biomarkers, MPO, IL‐6 and TNF‐α. This dosing regimen was supported by the pharmacokinetic profile of JNJ 26993135, along with the demonstration of the inhibition of ex vivo production of LTB4 in whole blood following oral administration. Conclusions and implications: These results with JNJ 26993135 in the rat TNBS model support the role of LTB4 in colitis and the potential value of targeting LTA4H for the treatment of inflammatory bowel diseases. British Journal of Pharmacology (2008) 153, 983–991; doi:10.1038/sj.bjp.0707645; published online 24 December 2007

This paper reviews existing literature on sexual and reproductive health research and programming among boys and young men in sub-Saharan Africa. While there is growing body of literature on adolescent and young adult women, much less is known about male sexual and reproductive health and its potential connection to well being, and in particular the risk of contracting and spreading HIV/AIDS. The author's premise is that both societal and individual vulnerability to HIV/AIDS infection are heavily influenced by socio-cultural factors and societal norms, and that gender and sexuality are among the most powerful of these elements. In keeping with this perspective, potential gaps in the literature are identified using a modification of Dixon-Mueller's framework, which illustrates how sexuality and gender influence reproductive health outcomes. The framework focuses on several interrelated elements of sexuality - sexual partnerships, sexual acts, sexual meaning, sexual drives and enjoyment, and sexual knowledge and awareness. /// Cet article passe en revue la document.tion actuelle de la recherche et la programmation sur la santé sexuelle et reproductive chez les garçons et les jeunes hommes en Afrique subsaharienne. Alors que le corpus de la documentation sur les adolescents et les jeunes femmes adults s'accroît, on connaît très peu de la santé sexuelle et reproductive des hommes et son rapport potential avec le bien-être et surtout par rapport au risque de contracter et de propager le VIH/SIDA. L'auteur tient à affirmer que la vulnérabilité de la société et de l'individu à l'infection VIH/DISA est beaucoup influencées par les fac.teurs socio-culturels et les normes sociétales et que les sexes et la sexualité sont parmi les plus forts de ces éléments. En conformité avec cette perspective, les lacunes potentielles dans la documentation sont identifiées à l'aide du cadre Dixon-Mueller modifié qui démontre comment la sexualité et les sexes influencent les issues de la santé reproductive. Le cadre concentre sur plusieurs éléments de la sexualité qui sont étroitement liés - l'association sexuelle, les actes sexuels, la signification sexuelle, la pulsion et la jouissance sexuelles, et la connaissance et la conscience sexuelles.

Animal models have historically played a critical role in the exploration and characterization of disease pathophysiology and target identification and in the evaluation of novel therapeutic agents and treatments in vivo. Diabetes mellitus disease, commonly known as diabetes, is a group of metabolic disorders characterized by high blood glucose levels for a prolonged time. To avoid late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic symptoms, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. We overviewed the pathophysiological features of diabetes in relation to its complications in type 1 and type 2 mice along with rat models, including Zucker Diabetic Fatty (ZDF) rats, BB rats, LEW 1AR1/-iddm rats, Goto-Kakizaki rats, chemically induced diabetic models, and Nonobese Diabetic mouse, and Akita mice model. The advantages and disadvantages that these models comprise were also addressed in this review. This paper briefly reviews the wide pathophysiological and molecular mechanisms associated with type 1 and type 2 diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans.

As intracellular gene delivery pathways are highly complex combinations of multiple potentially rate-limiting cellular and molecular processes, approaches to the design of synthetic delivery vectors focusing on any single barrier individually will likely be suboptimal. We offer here an “integrative systems” approach to vector characterization and design, combining quantitative experiment and computational modeling studies of vector uptake and trafficking kinetics. This model is validated using data for delivery of a green fluorescent protein (GFP)-encoding plasmid by means of Lipofectamine, permitting specification of model parameter values. The model is then used to make a priori predictions on the effect of polymer length in polyplex vectors, with additional parameter values determined from previous independent experimental studies of plasmid release. Comparison with data on GFP expression via these polyplex vectors shows that the model successfully predicts an experimentally observed biphasic dependence of expression efficiency on polymer length and quantifies the contributions of competing effects yielding the optimal intermediate polymer length. Finally, we use the model to predict potential effects of incorporating nuclear localization sequences in these kinds of synthetic vectors, and find that the degree of benefit from these will depend on the values of other key system properties including the vector unpackaging rate constant. Thus, we demonstrate the usefulness of a bioengineering, integrative-systems modeling approach to improved vector design and analysis.