Light Commercial Vehicle ADAS-Oriented Modelling: An Optimization-Based Conversion Tool from Multibody to Real-Time Vehicle Dynamics Model

In the last few years, the number of Advanced Driver Assistance Systems (ADAS) on road vehicles has been increased with the aim of dramatically reducing road accidents. Therefore, the OEMs need to integrate and test these systems, to comply with the safety regulations. To lower the development cost, instead of experimental testing, many virtual simulation scenarios need to be tested for ADAS validation. The classic multibody vehicle approach, normally used to design and optimize vehicle dynamics performance, is not always suitable to cope with these new tasks; therefore, real-time lumped-parameter vehicle models implementation becomes more and more necessary. This paper aims at providing a methodology to convert experimentally validated light commercial vehicles (LCV) multibody models (MBM) into real-time lumped-parameter models (RTM). The proposed methodology involves the definition of the vehicle subsystems and the level of complexity required to achieve a good match between the simulation results obtained from the two models. Thus, an automatic vehicle model converter will be presented together with the assessment of its accuracy. An optimization phase is included into the conversion tool, to fine-tune uncertain vehicle parameters and to compensate for inherent modelling differences. The objective function of the optimization is based on typical performance indices used for vehicle longitudinal and lateral dynamics assessment. Finally, the simulation results from the original and converted models are compared during steady-state and transient tests, to prove the conversion fidelity

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers

Reactivation of herpes simplex virus type 1 (HSV-1) has been described in critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. In the present two-center retrospective experience, we primarily aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function. The secondary objectives were the identification of predictors for HSV-1 reactivation and the assessment of its possible prognostic impact. Overall, 41 patients met the study inclusion criteria, and 12/41 patients developed HSV-1 reactivation (29%). No independent predictors of HSV-1 reactivation were identified in the present study. No association was found between HSV-1 reactivation and mortality. Eleven out of 12 patients with HSV-1 reactivation received antiviral therapy with intravenous acyclovir. In conclusion, HSV-1 reactivation is frequently detected in intubated patients with COVID-19. An antiviral treatment in COVID-19 patients with HSV-1 reactivation and worsening respiratory function might be considered

Arranjo de semeadura para cultivares decumbentes precoces de amendoim.

O amendoim é uma cultura importante para a diversificação dos sistemas de produção agrícola no Brasil. O estado de São Paulo é o maior produtor, onde o amendoim é cultivado principalmente em áreas de renovação de canaviais. Cultivares ?Runner? precoces foram desenvolvidas recentemente, demandando estudos sobre espaçamentos e arranjos de semeadura mais adequados para estes genótipos de crescimento mais determinado que as cultivares ?Runner? tradicionais. A linhagem 2013-413 OL apresenta crescimento mais determinado e foi utilizada em um ensaio para avaliar arranjos de semeadura. O ensaio foi instalado na área experimental da Embrapa Arroz e Feijão em Santo Antônio de Goiás-GO, em blocos casualizados com quatro repetições e três tratamentos: T1: 90 cm; T2: 73 cm x 17 cm e T3: de 75 cm. Cada parcela foi composta por quatro linhas, somente as duas linhas centrais foram avaliadas. Os resultados mostraram que no espaçamento 90 cm a produtividade foi obtida foi de 3564,81 kg ha-1, no espaçamento de 73 cm x 17 cm obteve-se 3958,33 kg ha-1 e no espaçamento de 75 cm obteve-se 4511,11 kg ha-1

Temporal transcriptional response to latency reversing agents identifies specific factors regulating HIV-1 viral transcriptional switch

Background: Latent HIV-1 reservoirs are identified as one of the major challenges to achieve HIV-1 cure. Currently available strategies are associated with wide variability in outcomes both in patients and CD4+ T cell models. This underlines the critical need to develop innovative strategies to predict and recognize ways that could result in better reactivation and eventual elimination of latent HIV-1 reservoirs. Results and discussion: In this study, we combined genome wide transcriptome datasets post activation with Systems Biology approach (Signaling and Dynamic Regulatory Events Miner, SDREM analyses) to reconstruct a dynamic signaling and regulatory network involved in reactivation mediated by specific activators using a latent cell line. This approach identified several critical regulators for each treatment, which were confirmed in follow-up validation studies using small molecule inhibitors. Results indicate that signaling pathways involving JNK and related factors as predicted by SDREM are essential for virus reactivation by suberoylanilide hydroxamic acid. ERK1/2 and NF-κB pathways have the foremost role in reactivation with prostratin and TNF-aα, respectively. JAK-STAT pathway has a central role in HIV-1 transcription. Additional evaluation, using other latent J-Lat cell clones and primary T cell model, also confirmed that many of the cellular factors associated with latency reversing agents are similar, though minor differences are identified. JAK-STAT and NF-κB related pathways are critical for reversal of HIV-1 latency in primary resting T cells. Conclusion: These results validate our combinatorial approach to predict the regulatory cellular factors and pathways responsible for HIV-1 reactivation in latent HIV-1 harboring cell line models. JAK-STAT have a role in reversal of latency in all the HIV-1 latency models tested, including primary CD4+ T cells, with additional cellular pathways such as NF-κB, JNK and ERK 1/2 that may have complementary role in reversal of HIV-1 latency

Increased aortic stiffness in adults with chronic indeterminate Chagas disease

An ever-increasing number of patients with chronic indeterminate Chagas disease are diagnosed with early vascular and cardiac abnormalities, as cardiovascular imaging becomes more sensitive. However, the currently available information on aortic stiffness (a prognostic marker for adverse cardiovascular outcomes) in these patients is scarce. In this study, we consecutively recruited 21 asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease and 14 Bolivian adults, who were seronegative for Trypanosoma cruzi infection. No participants had a prior history of heart disease, hypertension, diabetes, chronic kidney disease or atrial fibrillation. Carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), carotid intima-media thickness and conventional echocardiographic measurements were recorded in all participants. Patients with chronic indeterminate Chagas disease had significantly higher cf-PWV (7.9±1.3 vs. 6.4±1.1 m/s, p = 0.003) and greater HOMA-estimated insulin resistance than subjects without Chagas disease. The two groups did not significantly differ in terms of age, sex, smoking, adiposity measures, blood pressure, plasma lipids, fasting glucose levels as well as cr-PWV, carotid intima-media thickness measurements, left ventricular mass and function. Presence of chronic indeterminate Chagas disease was significantly associated with increasing cf-PWV values (β coefficient: 1.31, 95% coefficient interval 0.44 to 2.18, p = 0.005), even after adjustment for age, sex, heart rate, systolic blood pressure and insulin resistance. In conclusion, asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease have an early and marked increase in aortic stiffness, as measured by cf-PWV, when compared to Bolivian adults who were seronegative for Trypanosoma cruzi infection

The association between Vitamin D and gut microbiota: A systematic review of human studies

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species’ richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs)

Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma

Functional rescue of NK-cells in solid tumors represents a central aim for new immunotherapeutic strategies. We have conducted a genomic, phenotypic and functional analysis of circulating NK-cells from patients with HCV-related liver cirrhosis and hepatocellular carcinoma. NK-cells were sorted from patients with HCC or liver cirrhosis and from healthy donors. Comparative mRNA gene expression profiling by whole-human-genome microarrays of sorted NK-cells was followed by phenotypic and functional characterization. To further identify possible mediators of NK-cell dysfunction, an in vitro model using media conditioned with patients’ and controls’ plasma was set up. Metabolic and cell motility defects were identified at the genomic level. Dysregulated gene expression profile has been translated into reduced cytokine production and degranulation despite a prevalent phenotype of terminally differentiated NK-cells. NKG2D-downregulation, high SMAD2 phosphorylation and other phenotypic and molecular alterations suggested TGF-β as possible mediator of this dysfunction. Blocking TGF-β could partially restore functional defects of NK-cells from healthy donors, exposed to TGF-β rich HCC patients’ plasma, suggesting that TGF-β among other molecules may represent a suitable target for immunotherapeutic intervention aimed at NK-cell functional restoration. By an unbiased approach, we have identified energy metabolism and cell motility defects of circulating NK-cells as main mechanisms responsible for functional NK-cell impairment in patients with hepatocellular carcinoma. This opens the way to test different approaches to restore NK-cell response in these patients

PATZ1 is overexpressed in pediatric glial tumors and correlates with worse event-free survival in high-grade gliomas

Glial tumors are the leading cause of cancer-related death and morbidity in children. Their diagnosis, mainly based on clinical and histopathological factors, is particularly challenging because of their high molecular heterogeneity. Thus, tumors with identical histotypes could result in variable biological behaviors and prognoses. The PATZ1 gene has been recently shown to be expressed in adult gliomas, including glioblastomas, where it correlates with the proneural subtype and with a better prognosis. Here, we analyzed the expression of PATZ1 in pediatric gliomas, first at mRNA level in a public database, and then at protein level, by immunohistochemistry, in a cohort of 52 glial brain tumors from young patients aged from 6 months to 16 years. As for adult tumors, we show that PATZ1 is enriched in glial tumors compared to the normal brain, where it correlates positively and negatively with a proneural and mesenchymal signature, respectively. Moreover, we show that PATZ1 is expressed at variable levels in our cohort of tumors. Higher expression was detected in high-grade than low-grade gliomas, suggesting a correlation with the malignancy. Among high-grade gliomas, higher levels of PATZ1 have consistently been found to correlate with worse event-free survival. Therefore, our study may imply new diagnostic opportunities for pediatric gliomas

3T DCE-MRI radiomics for prediction of complete response to neoadjuvant chemotherapy in breast cancer

Purpose: To test whether 3T MRI radiomics of breast malignant lesions improve the performance of predictive models of complete response to neoadjuvant chemotherapy when added to other clinical, histological and radiological information