Forced Solid-State Interactions for the Selective “Turn-On” Fluorescence Sensing of Aluminum Ions in Water Using a Sensory Polymer Substrate

Selective and sensitive solid sensory substrates for detecting Al(III) in pure water are reported. The material is a flexible polymer film that can be handled and exhibits gel behavior and membrane performance. The film features a chemically anchored salicylaldehyde benzoylhydrazone derivative as an aluminum ion fluorescence sensor. A novel procedure for measuring Al(III) at the ppb level using a single solution drop in 20 min was developed. In this procedure, a drop was allowed to enter the hydrophilic material for 15 min before a 5 min drying period. The process forced the Al(III) to interact with the sensory motifs within the membrane before measuring the fluorescence of the system. The limit of detection of Al(III) was 22 ppm. Furthermore, a water-soluble sensory polymer containing the same sensory motifs was developed with a limit of detection of Al(III) of 1.5 ppb, which was significantly lower than the Environmental Protection Agency recommendations for drinking water.Spanish Ministerio de Economía y Competitividad-Feder (MAT2011-22544) and by the Consejería de Educación - Junta de Castilla y León (BU232U13)

Phage Display against Corneal Epithelial Cells Produced Bioactive Peptides That Inhibit Aspergillus Adhesion to the Corneas

Dissection of host-pathogen interactions is important for both understanding the pathogenesis of infectious diseases and developing therapeutics for the infectious diseases like various infectious keratitis. To enhance the knowledge about pathogenesis infectious keratitis, a random 12-mer peptide phage display library was screened against cultured human corneal epithelial cells (HCEC). Fourteen sequences were obtained and BLASTp analysis showed that most of their homologue counterparts in GenBank were for defined or putative proteins in various pathogens. Based on known or predicted functions of the homologue proteins, ten synthetic peptides (Pc-A to Pc-J) were measured for their affinity to bind cells and their potential efficacy to interfere with pathogen adhesion to the cells. Besides binding to HCEC, most of them also bound to human corneal stromal cells and umbilical endothelial cells to different extents. When added to HCEC culture, the peptides induced expression of MyD88 and IL-17 in HCEC, and the stimulated cell culture medium showed fungicidal potency to various extents. While peptides Pc-C and Pc-E inhibited Aspergillus fumigatus (A.f) adhesion to HCEC in a dose-dependent manner, the similar inhibition ability of peptides Pc-A and Pc-B required presence of their homologue ligand Alb1p on A.f. When utilized in an eyeball organ culture model and an in vivo A.f keratitis model established in mouse, Pc-C and Pc-E inhibited fungal adhesion to corneas, hence decreased corneal disruption caused by inflammatory infiltration. Affinity pull-down of HCEC membrane proteins with peptide Pc-C revealed several molecules as potential receptors for this peptide. In conclusion, besides proving that phage display-selected peptides could be utilized to interfere with adhesion of pathogens to host cells, hence could be exploited for managing infectious diseases including infectious keratitis, we also proposed that the phage display technique and the resultant peptides could be used to explore host-pathogen interactions at molecular levels

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Catalyzing Transformations to Sustainability in the World's Mountains

Mountain social‐ecological systems (MtSES) are vital to humanity, providing ecosystem services to over half the planet's human population. Despite their importance, there has been no global assessment of threats to MtSES, even as they face unprecedented challenges to their sustainability. With survey data from 57 MtSES sites worldwide, we test a conceptual model of the types and scales of stressors and ecosystem services in MtSES and explore their distinct configurations according to their primary economic orientation and land use. We find that MtSES worldwide are experiencing both gradual and abrupt climatic, economic, and governance changes, with policies made by outsiders as the most ubiquitous challenge. Mountains that support primarily subsistence‐oriented livelihoods, especially agropastoral systems, deliver abundant services but are also most at risk. Moreover, transitions from subsistence‐ to market‐oriented economies are often accompanied by increased physical connectedness, reduced diversity of cross‐scale ecosystem services, lowered importance of local knowledge, and shifting vulnerabilities to threats. Addressing the complex challenges facing MtSES and catalyzing transformations to MtSES sustainability will require cross‐scale partnerships among researchers, stakeholders, and decision makers to jointly identify desired futures and adaptation pathways, assess trade‐offs in prioritizing ecosystem services, and share best practices for sustainability. These transdisciplinary approaches will allow local stakeholders, researchers, and practitioners to jointly address MtSES knowledge gaps while simultaneously focusing on critical issues of poverty and food security

Analytical solutions for wall slip effects on magnetohydrodynamic oscillatory rotating plate and channel flows in porous media using a fractional burgers viscoelastic model

A theoretical analysis of magnetohydrodynamic (MHD) incompressible flows of Burger's fluid through a porous medium in a rotating frame of reference is presented. The constitutive model of a Burger's fluid is used based on a fractional calculus formulation. Hydrodynamic slip at the wall (plate) is incorporated and a fractional generalized Darcy model deployed to simulate porous medium drag force effects. Three different cases are considered- namely, flow induced by a general periodic oscillation at a rigid plate, periodic flow in a parallel plate channel and finally Poiseuille flow. In all cases the plate (s) boundary (ies) are electrically-non-conducting and small magnetic Reynolds is assumed, negating magnetic induction effects. The well-posed boundary value problems associated with each case are solved via Fourier transforms. Comparisons are made between the results derived with and without slip conditions. 4 special cases are retrieved from the general fractional Burgers model, viz Newtonian fluid, general Maxwell viscoelastic fluid, generalized Oldroyd-B fluid and the conventional Burger’s viscoelastic model. Extensive interpretation of graphical plots is included. We study explicitly the influence on wall slip on primary and secondary velocity evolution. The model is relevant to MHD rotating energy generators employing rheological working fluids

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Synthesis of some 4-substituted hydrazinotetrazolo[1,5-⍺] quinoxalines

1211-1213Reaction of 2,3 diketoquinoxaline in presence of phosphorus pentachloride and sodium azide in methanol gives 4-hydroxy tetrazolo[1,5-⍺]quinoxaline 3 which on reaction with phosphorous oxychloride gives 4-chloro tetrazolo[1,5-⍺]quinoxaline 4. This on treatment with hydrazine hydrate in ethanol yields 4-hydrazino tetrazolo[1,5-⍺]quinoxaline 5, which on reaction with various aldehydes in DMF gives 4-substituted hydrazinotetrazolo [1,5-⍺]quinoxalines 6a-g. The structures of compounds 6a-g have been confirmed by IR and ¹H NMR

Cloud Computing Adoption Model for Universities to Increase ICT Proficiency

Universities around the world especially those in developing countries are faced with the problem of delivering the level of information and communications technology (ICT) needed to facilitate teaching, learning, research, and development activities ideal in a typical university, which is needed to meet educational needs in-line with advancement in technology and the growing dependence on IT. This is mainly due to the high cost involved in providing and maintaining the needed hardware and software. A technology such as cloud computing that delivers on demand provisioning of IT resources on a pay per use basis can be used to address this problem. Cloud computing promises better delivery of IT services as well as availability whenever and wherever needed at reduced costs with users paying only as much as they consume through the services of cloud service providers. The cloud technology reduces complexity while increasing speed and quality of IT services provided; however, despite these benefits the challenges that come with its adoption have left many sectors especially the higher education skeptical in committing to this technology. This article identifies the reasons for the slow rate of adoption of cloud computing at university level, discusses the challenges faced and proposes a cloud computing adoption model that contains strategic guidelines to overcome the major challenges identified and a roadmap for the successful adoption of cloud computing by universities. The model was tested in one of the universities and found to be both useful and appropriate for adopting cloud computing at university level