The Landscape of Immunotherapy for Retroperitoneal Sarcoma

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this family of neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack of effective therapies. In this review, we focus on immunotherapy and its relationship with the common RPS histologic subtypes. Although initial outcomes for RPS patients with immune checkpoint inhibition alone have been somewhat disappointing, subsequent analyses on histologies, the tumor microenvironment, sarcoma immune class, tumor infiltrating lymphocytes and genetic analysis for tumor mutational burden have yielded insight into the interplay between sarcomas and immunotherapy. Such approaches have all provided critical insight into the environment and characterization of these tumors, with targets for potential immunotherapy in future clinical trials. With this insight, molecularly tailored combination treatments for improving response rates and oncologic outcomes for RPS are promising

EXAFS study of lead-free relaxor ferroelectric BaTi(1-x)Zr(x)O3 at the Zr K-edge

Extended X-ray absorption fine structure (EXAFS) experiments at the Zr K-edge were carried out on perovskite relaxor ferroelectrics BaTi(1-x)Zr(x)O3 (BTZ) (x = 0.25, 0.30, 0.35), and on BaZrO3 for comparison. Structural information up to 4.5 A around the Zr atoms is obtained, revealing that the local structure differs notably from the average Pm-3m cubic structure deduced from X-ray diffraction. In particular, our results show that the distance between Zr atoms and their first oxygen neighbors is independent of the Zr substitution rate x and equal to that measured in BaZrO3, while the X-ray cubic cell parameter increases linearly with x. Furthermore, we show that the Zr atoms tend to segregate in Zr-rich regions. We propose that the relaxor behavior in BTZ is linked to random elastic fields generated by this particular chemical arrangement, rather than to random electric fields as is the case in most relaxors.Comment: 13 pages, 12 figures, 4 tables. Submitted to Phys. Rev.

Condutância foliar e transpiração em cafeeiro irrigado de cinco anos de cultivo.

O objetivo deste trabalho foi determinar a condutância estomática e a transpiração de cafeeiro irrigado e sua relação com variáveis climáticas. O experimento foi executado em Piracicaba, SP, Brasil, em cafeeiro cultivar Mundo Novo Apuatã, com 5 anos de plantio, cultivado a pleno sol. As medições nos cinco dias estudados indicaram que a condutância estomática e a transpiração do cafeeiro responderam à variação da temperatura do ar, do saldo de radiação e do vento, sendo mais evidente no dia 24/09/2002. A condutância estomática variou de aproximadamente 0,20 cm s-1 até 0,05 cm s-1 e a transpiração de 6,0 mg m-2s-1 a 0,5 mg m-2s-1 no decorrer dos dias analisados.CBA 2009

Additive noise properties of active matrix flatâ panel imagers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134764/1/mp6721.pd

Clostridium difficile suppresses colonic vasoactive intestinal peptide associated with altered motility

We investigated whether Clostridium difficile toxin alters colonic tissue levels of vasoactive intestinal peptide (VIP) at the expense of changes in colonic motility in the isolated perfused rabbit left colon. Colonic inflammation was induced by the intracolonic administration of 10−8 M C. difflcile toxin. Strain gauge transducers were sewn onto the serosal surface of the colon to evaluate colonic motility. C. difflcile administration produced histologic changes consistent with epithelial damage. This was associated with an increased production of prostaglandin E2 and thromboxane B2. Tissue levels of VIP but not substance P were significantly reduced. This was associated with an increased number of contractions per minute and an average force of each colonic contraction. These results suggest that tissue levels of VIP are suppressed by C. difflcile and may participate in colonic dysmotility during active inflammation

Characterizing Brazilian climate zones for up-scaling the simulated crop yield potential.

ABSTRACT: Crop models are written as sets of different equations which are solved numerically. They require time series of local environmental drivers like weather conditions and constant parameters that determine sensitivity of processes to both crop state and environment. There is a hamper on the model upscaling from point to region, and the quantification of model output uncertainity at the regional scale. This paper aimed to perform a conceptual analysis of the Brazilian climate zones based on long-term uniform weather data series (air temperature, soil water deficit, rainfall and global solar radiation), were each climatic variable were spatially organized and the maps for each one were generated by a kriging interpolation. The proposed zonation seems coherent with the agroecologycal conditions observed around Brazil, and based on the biomes, there is an agreement with the main Brazilian potential vegetation types and even with the cropping systems spatial distributions. The final map might be used for ?bottom-up? upscaling approach in order to extrapolate the location specific data to a broader scale. Further work should focus in the inclusion of soil data to reach a robust zone map to support crop model outputs up-scaling, as well as in the zones validation.CBA 2013, RLAA 2013

Targeting the MDM2-p53 Pathway in Dedifferentiated Liposarcoma

Dedifferentiated liposarcoma (DDLPS) is an aggressive adipogenic cancer with poor prognosis. DDLPS tumors are only modestly sensitive to chemotherapy and radiation, and there is a need for more effective therapies. Genetically, DDLPS is characterized by a low tumor mutational burden and frequent chromosomal structural abnormalities including amplification of the 12q13-15 chromosomal region and the MDM2 gene, which are defining features of DDLPS. The MDM2 protein is an E3 ubiquitin ligase that targets the tumor suppressor, p53, for proteasomal degradation. MDM2 amplification or overexpression in human malignancies is associated with cell-cycle progression and worse prognosis. The MDM2-p53 interaction has thus garnered interest as a therapeutic target for DDLPS and other malignancies. MDM2 binds p53 via a hydrophobic protein interaction that is easily accessible with synthetic analogues. Multiple agents have been developed, including Nutlins such as RG7112 and small molecular inhibitors including SAR405838 and HDM201. Preclinical in vitro and animal models have shown promising results with MDM2 inhibition, resulting in robust p53 reactivation and cancer cell death. However, multiple early-phase clinical trials have failed to show a benefit with MDM2 pathway inhibition for DDLPS. Mechanisms of resistance are being elucidated, and novel inhibitors and combination therapies are currently under investigation. This review provides an overview of these strategies for targeting MDM2 in DDLPS

Cenários futuros para cana-de-açúcar no Estado de São Paulo baseados em projeções regionalizadas de mudanças climáticas.

Após a divulgação das projeções de mudanças climáticas globais pelo IPCC, a avaliação de impacto das mudanças climáticas sobre a agricultura para tornouse uma necessidade para a quantificação da vulnerabilidade dos sistemas agrícolas. Este trabalho teve como objetivo simular cenários futuros para a cana-de-açúcar no Estado de São Paulo em função de cenários regionalizados de projeções climáticas, utilizando um banco de dados de 78 estações meteorológicas com séries de, pelo menos, nove anos. Para cada estação meteorológica foi associado um determinado perfil do solo e todas as séries foram expandidas para 30 anos utilizando geradores de dados. As simulações foram feitas para a variedade RB72454, considerando dois cenários futuros de mudanças climáticas para 2040. Os resultados mostraram elevação na produtividade média do Estado, com ganho de até 6% de produção total no cenário pessimista para 2040. Para o cenário otimista, o efeito sobre a produção de cana-de-açúcar seria pequeno, com perspectivas de ganhos no rendimento áreas cultivadas com solos argilosos, além de uma tendência de migração para a região Sul do Estado.CBA 2009