The completion of the Mammalian Gene Collection (MGC)

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

A Novel Synthesis Route of Mesoporous γ-Alumina from Polyoxohydroxide Aluminum

Mesoporous gamma-aluminas (gamma-Al2O3) were synthesized starting from an unusual precursor of polyoxohydroxide aluminum (POHA). This precursor was obtained from aluminum oxidation in alkaline water-ethanol solvent in the presence of d-glucose that induces the formation of a gel, which leads to the POAH powder after ethanolic treatment Precipitated POHAs were calcined at different temperatures (300, 400, 700 and 900 degrees C) resultmg m the metastable gamma-Al(2)0(3) phase. Whereas at 300 degrees C no gamma-Al(2)0(3) phase was formed, unexpectedly, mesoporous gamma-Al(2)0(3) was obtained at 400 degrees C having a high specific surface area (282 m(2)/g) and a narrow pore size distribution At higher temperatures, the aluminas had the expected decrease in surface area 166 m(2)/g (700 degrees C) and 129 m(2)/g (900 degrees C), respectively The structural change from POHA to alumina calcined at 400 degrees C occurs directly without the need to isolate the hydroxide or oxyhydroxide aluminum precursors Both POHA and transition aluminas were characterized by Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction (XRD), N-2 sorption and Scanning Electron Microscopy (SEM) These findings show an alternative route to produce high standard aluminas.Fundacao de Apoio a Pesquisa do Estado de Sao Paulo - FAPESPCAPESCNPqUniv Sao Paulo, Dept Engn Quim DEQ, Escola Engn Lorena, Estr Municipal Campinho S-N, BR-12602810 Lorena, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Ciencias Exatas & Terra, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilUniv Fed ABC, Ctr Engn Modelagem & Ciencias Sociais Aplicadas, Santo Andre, SP, BrazilUniv Sao Paulo, Inst Quim, Ave Prof Lineu Prestes 748, BR-05508900 Sao Paulo, SP, BrazilUniv Sao Paulo, Escola Engn Lorena, Polo Ind, Dept Engn Mat DEMAR, Gleba Al-6 S-N, BR-12602810 Lorena, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Ciencias Exatas & Terra, Rua Sao Nicolau 210, BR-09913030 Diadema, SP, BrazilFAPESP: 2015/06064-6, 2013/08166-5, 2016/05496-2Web of Scienc

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

Power absorption efficiency in superconducting box-shaped optical waveguides

A very sensitive superconducting traveling wave photodetector made of a modified box-shaped waveguide, which includes two high index layers and an active superconducting layer, is studied. The optical propagation constants and the power absorption efficiency for guided modes are determined using the finite element method; the results show that by acting only on the waveguide geometry, different confinement regimes of the light in the absorption superconducting layer can be achieved and optimize

Use of real-world evidence data to evaluate the comparative effectiveness of second-line type 2 diabetes medications on chronic kidney disease

AbstractChronic kidney disease (CKD) is a common complication of type 2 diabetes mellitus (T2DM). Approximately one-third of patients with T2DM also have CKD. In clinical trial studies, several anti-diabetic medications (ADM) show evidence of preventing the progression of CKD. Biguanides (e.g., metformin) are widely accepted as the first line medication. However, the comparativeness effectiveness of second line ADMs on CKD outcomes in T2DM is unclear. In addition, results from clinical trials may not generalize into routine clinical practice. In this study, we aimed to investigate the association of second line ADMs with incident CKD and CKD hospitalization in T2DM patients using real-world data from electronic health records. Our study found that treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors was significantly associated with a lower risk of CKD incidence in both primary analysis (hazard ratio, 0.43; 95% CI, [0.22;0.87]; p-value,0.02) (SU) as a second-line ADM. Treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor was significantly associated with lower CKD incidence (hazard ratio, 0.7; 95% CI, [0.53;0.96]; p-value, 0.03) and lower CKD hospitalization events (hazard ratio, 0.6; 95% CI, [0.37; 0.96]; p-value, 0.04) in the primary analysis. However, both associations were not significant in the sensitivity analysis. We did not observe significant association between use of GLP-1, TZD, insulin and CKD incidence or hospitalization compared to use of SU as the second-line ADM.</jats:p