Registration of ‘LCS Compass’ Wheat

‘LCS Compass’ (Reg. No. CV-1149, PI 675458), a hard red winter (HRW) wheat (Triticum aestivum L.), was developed and tested as VA10HRW-13 and co-released by the Virginia Agricultural Experiment Station and Limagrain Cereal Seeds, LLC, in 2015. LCS Compass was derived from the cross ‘Vision 20’ /‘Stanof’ using a modified bulk breeding method. LCS Compass is a widely adapted, high-yielding, awned, semidwarf (Rht1) HRW wheat with early to medium maturity and resistance or moderate resistance to diseases prevalent in the mid-Atlantic and Great Plains regions of the United States. In the 2013 Uniform Bread Wheat Trial conducted over 18 locations in eastern states, LCS Compass produced an average grain yield of 4609 kg ha−1 that was similar to ‘Vision 30’ (4697 kg ha−1). In the northern Great Plains, the average grain yield of LCS Compass (4015 kg ha−1) over 44 locations in 2013 was similar to ‘Jerry’ (4013 kg ha−1). In the South Dakota crop zone 3 variety test, LCS Compass had a 3-yr (2015–2017) yield average of 5575 kg ha−1 and was one of highest-yielding cultivars among the 19 cultivars tested over the 3-yr period. LCS Compass has good end-use quality in both the eastern and Great Plains regions of the United States

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

The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas

Background: Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. Aim: To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Methods: Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. Results: All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. Conclusions: This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours

Registration of ‘LCS Compass’ Wheat

‘LCS Compass’ (Reg. No. CV-1149, PI 675458), a hard red winter (HRW) wheat (Triticum aestivum L.), was developed and tested as VA10HRW-13 and co-released by the Virginia Agricultural Experiment Station and Limagrain Cereal Seeds, LLC, in 2015. LCS Compass was derived from the cross ‘Vision 20’ /‘Stanof’ using a modified bulk breeding method. LCS Compass is a widely adapted, high-yielding, awned, semidwarf (Rht1) HRW wheat with early to medium maturity and resistance or moderate resistance to diseases prevalent in the mid-Atlantic and Great Plains regions of the United States. In the 2013 Uniform Bread Wheat Trial conducted over 18 locations in eastern states, LCS Compass produced an average grain yield of 4609 kg ha−1 that was similar to ‘Vision 30’ (4697 kg ha−1). In the northern Great Plains, the average grain yield of LCS Compass (4015 kg ha−1) over 44 locations in 2013 was similar to ‘Jerry’ (4013 kg ha−1). In the South Dakota crop zone 3 variety test, LCS Compass had a 3-yr (2015–2017) yield average of 5575 kg ha−1 and was one of highest-yielding cultivars among the 19 cultivars tested over the 3-yr period. LCS Compass has good end-use quality in both the eastern and Great Plains regions of the United States

Analogue two-dimensional semiconductor electronics

Digital electronics are ubiquitous in the modern world, but analogue electronics also play a crucial role in many devices and applications. Analogue circuits are typically manufactured using silicon as the active material. However, the desire for improved performance, new devices and flexible integration has—as for their digital counterparts—led to research into alternative materials, including the use of two-dimensional (2D) materials. Here, we show that operational amplifiers—a basic building block of analogue electronics—can be created using the 2D semiconductor molybdenum disulfide (MoS2) as the active material. The device is capable of stable operation with good performance, and we demonstrate its use in feedback circuits including inverting amplifiers, integrators, log amplifiers and transimpedance amplifiers. We also show that our 2D platform can be used to monolithically integrate an analogue signal preconditioning circuit with a MoS2 photodetector