761 research outputs found
The role of polycyclic frameworks in modulating P2X<inf>7</inf> receptor function
Herein we describe our recent attempts to target the P2X7 receptor for potential treatment of neurological disorders. This work focusses on different polycycles including carborane, adamantane or cubane, joined by either a cyanoguanidine or an amide linker to phenyl or isoquinoline moieties. We have demonstrated the superiority of the adamantyl moiety over other polycycles in terms of synthetic accessibility and biological (cellular) activity. We have also shown that an amide or cyanoguanidine linker can greatly alter the biological activity of compounds. This SAR study provides important insights into the types of functionality required to target the P2X7 receptor
A fast ILP-based Heuristic for the robust design of Body Wireless Sensor Networks
We consider the problem of optimally designing a body wireless sensor
network, while taking into account the uncertainty of data generation of
biosensors. Since the related min-max robustness Integer Linear Programming
(ILP) problem can be difficult to solve even for state-of-the-art commercial
optimization solvers, we propose an original heuristic for its solution. The
heuristic combines deterministic and probabilistic variable fixing strategies,
guided by the information coming from strengthened linear relaxations of the
ILP robust model, and includes a very large neighborhood search for reparation
and improvement of generated solutions, formulated as an ILP problem solved
exactly. Computational tests on realistic instances show that our heuristic
finds solutions of much higher quality than a state-of-the-art solver and than
an effective benchmark heuristic.Comment: This is the authors' final version of the paper published in G.
Squillero and K. Sim (Eds.): EvoApplications 2017, Part I, LNCS 10199, pp.
1-17, 2017. DOI: 10.1007/978-3-319-55849-3\_16. The final publication is
available at Springer via http://dx.doi.org/10.1007/978-3-319-55849-3_1
Pressão arterial de crianças e adolescentes de escolas públicas de Cuiabá, Mato Grosso
Deconstructing the lesbian, gay, bisexual, transgender victim of sex trafficking: Harm, exceptionality and religion–sexuality tensions
Contrary to widespread belief, sex trafficking also targets lesbian, gay, bisexual, transgender (LGBT) communities. Contemporary social and political constructions of victimhood lie at the heart of regulatory policies on sex trafficking. Led by the US Department of State, knowledge about LGBT victims of trafficking constitutes the newest frontier in the expansion of criminalization measures. These measures represent a crucial shift. From a burgeoning range of preemptive measures enacted to protect an amorphous class of ‘all potential victims’, now policies are heavily premised on the risk posed by traffickers to ‘victims of special interest’. These constructed identities, however, are at odds with established structures. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of LGBT trafficking victims. Specifically, the article argues that discourses of ‘exceptional vulnerability’ and the polarized notions of ‘innocence’ and ‘guilt’ inform hierarchies of victimhood. Based on these insights, the article argues for the need to move beyond monolithic understandings of victims, by reframing the politics of harm accordingly
Laser-induced etching of few-layer graphene synthesized by Rapid-Chemical Vapour Deposition on Cu thin films
The outstanding electrical and mechanical properties of graphene make it very
attractive for several applications, Nanoelectronics above all. However a
reproducible and non destructive way to produce high quality, large-scale area,
single layer graphene sheets is still lacking. Chemical Vapour Deposition of
graphene on Cu catalytic thin films represents a promising method to reach this
goal, because of the low temperatures (T < 900 Celsius degrees) involved during
the process and of the theoretically expected monolayer self-limiting growth.
On the contrary such self-limiting growth is not commonly observed in
experiments, thus making the development of techniques allowing for a better
control of graphene growth highly desirable. Here we report about the local
ablation effect, arising in Raman analysis, due to the heat transfer induced by
the laser incident beam onto the graphene sample.Comment: v1:9 pages, 8 figures, submitted to SpringerPlus; v2: 11 pages,
PDFLaTeX, 9 figures, revised peer-reviewed version resubmitted to
SpringerPlus; 1 figure added, figure 1 and 4 replaced,typos corrected,
"Results and discussion" section significantly extended to better explain
etching mechanism and features of Raman spectra, references adde
Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion
Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles
Dynamic pigmentary and structural coloration within cephalopod chromatophore organs
Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements
Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms
Characterization of lymphocyte populations in nonspecific interstitial pneumonia*
STUDY OBJECTIVES: Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. DESIGN: Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. RESULTS: In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. CONCLUSION: The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP
Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children
<p>Abstract</p> <p>Background</p> <p>The impact of HIV drug resistance mutations in salvage therapy has been widely investigated in adults. By contrast, data available of predictive value of resistance mutations in pediatric population is scarce.</p> <p>Methods</p> <p>A multicenter, retrospective, observational study was conducted in children who received rescue salvage antiretroviral therapy after virologic failure. CD4 counts and viral load were determined at baseline and 6 months after rescue intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed at baseline.</p> <p>Results</p> <p>A total of 33 children met the inclusion criteria and were included in the analysis. The median viral load (VL) and median percentage of CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median duration that children were taking the new rescue regimen was 24.3 weeks (23.8–30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks. When we compared the group of children who achieved virological response with those who did not, we found out that mean number of PI related mutations among the group of responders was 3.8 <it>vs</it>. 5.4 (p = 0.115). Moreover, the mean number of susceptible drugs according to virtual phenotype clinical cut-off for maximal virologic response was 1.7 <it>vs</it>. 0.8 and mean number of susceptible drugs according to virtual phenotype cut-off for minimal virlologic response was 2.7 <it>vs</it>. 1.3 (p < 0.01 in all cases). Eighteen children were rescued with a regimen containing a boosted-PI and virological response was significantly higher in those subjects compared with the others (61.1% <it>vs</it>. 28.6%, p < 0.01).</p> <p>Conclusion</p> <p>Salvage treatment containing ritonavir boosted-PIs in children with virological failure was very efficient. The use of new tools as virtual phenotype could help to improve virologic success in pediatric population.</p
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