Vehicle Fuel Economy and Performance Improvement via Cooled EGR, Charge Air Cooling and Thermal Parasitic Load

In recent years, stricter emissions regulations have been applied to reduce effects on the environment. Car manufacturers have to comply with these rules in order to sell cars on the market. Different solutions are researched to reduce fuel consumed; in this project a downsized engine has been considered. Effects of different EGR rate and ACT and their impact on the cooling system are analyzed. Having a higher amount of exhaust gas recirculated at a low temperature is affecting the power request on the cooling system, directly coupled to the engine. The latter should be operated at a higher load burning consequently more fuel. In this project, through engine dyno tests and 1D simulations, the increase in fuel consumption will be calculated and a procedure to reduce it will be developed. Final results showed an improvement in fuel economy up to 5% for certain conditions, without changing anything in the hardware

Giving Ideas Some Legs or Legs Some Ideas? Children's Motor Creativity Is Enhanced by Physical Activity Enrichment: Direct and Mediated Paths.

Approaches to foster motor creativity differ according to whether creative movements are assumed to be enacted creative ideas, or solutions to emerging motor problems that arise from task and environmental constraints. The twofold aim of the current study was to investigate whether (1) an enriched physical education (PE) intervention delivered with a joint constraints-led and cognitive stimulation approach fosters motor creativity, and the responsiveness to the intervention is moderated by baseline motor and cognitive skills and sex; (2) the intervention may benefit motor creativity through gains in motor coordination, executive function, and creative thinking. Ninety-five children, aged 6-9 years, participated in a 6-month group randomized trial with specialist-led enriched PE vs. generalist-led conventional PE. Before and after the intervention, Bertsch's Test of Motor Creativity, Movement Assessment Battery for Children, Random Number Generation task and Torrance Test of Creative Thinking were administered. Linear mixed models were run accounting for the random effects of data clusters. Multiple mediation analysis was performed to assess whether motor coordination, executive function and creative thinking mediated any improvement of motor creativity. Results showed that (1) specialist-led enriched PE, compared to generalist-led conventional practice, elicited a more pronounced improvement in all motor creativity dimensions (fluency, flexibility, and originality) independently of baseline levels of motor and cognitive skills and sex; and (2) improved motor creativity was partially mediated by improved motor coordination and, as regards motor flexibility, also by improved inhibitory ability. In conclusion, enriching PE with tailored manipulations of constraints and variability may enhance the ability to create multiple and original task-pertinent movements both directly and through indirect paths. The results are discussed extending to motor creativity a theoretical framework that distinguishes different creativity modes. The intervention may have fostered the generation of creative movements directly through the exposure to variation in constraints, activating the sensorimotor 'flow' mode of creativity that bypasses higher-order cognition, but also indirectly through a systematic and conscious convergence on solutions, activating the 'deliberate' mode of creativity that relies on inhibition to reject common or task-inappropriate movement categories

Hydroxytyrosol Reduces Foam Cell Formation and Endothelial Inflammation Regulating the PPARγ/LXRα/ABCA1 Pathway.

Cholesterol accumulation in macrophages leads to the formation of foam cells and increases the risk of developing atherosclerosis. We have verified whether hydroxytyrosol (HT), a phenolic compound with anti-inflammatory and antioxidant properties, can reduce the cholesterol build up in THP-1 macrophage-derived foam cells. We have also investigated the potential mechanisms. Oil Red O staining and high-performance liquid chromatography (HPLC) assays were utilized to detect cellular lipid accumulation and cholesterol content, respectively, in THP-1 macrophages foam cells treated with HT. The impact of HT on cholesterol metabolism-related molecules (SR-A1, CD36, LOX-1, ABCA1, ABCG1, PPARγ and LRX-α) in foam cells was assessed using real-time PCR (RT-qPCR) and Western blot analyses. Finally, the effect of HT on the adhesion of THP-1 monocytes to human vascular endothelial cells (HUVEC) was analyzed to study endothelial activation. We found that HT activates the PPARγ/LXRα pathway to upregulate ABCA1 expression, reducing cholesterol accumulation in foam cells. Moreover, HT significantly inhibited monocyte adhesion and reduced the levels of adhesion factors (ICAM-1 and VCAM-1) and pro-inflammatory factors (IL-6 and TNF-α) in LPS-induced endothelial cells. Taken together, our findings suggest that HT, with its ability to interfere with the import and export of cholesterol, could represent a new therapeutic strategy for the treatment of atherosclerotic disease

The effect of pharmacological treatment on ADMA in patients with heart failure.

Asymmetric dimethylarginine (ADMA) plays a crucial role in the arginine-nitric oxide (NO) pathway. NO plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The purpose of this study was to investigate the effect of pharmacological treatment on asymmetrical dimethylarginine (ADMA) plasma levels in patients with acute congestive heart failure (HF). Patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 40 percent) were included in the study. ADMA and SDMA concentrations were assessed before and after pharmacological treatment in 18 critically ill patients on the intensive care unit by high performance liquid chromatography. All patients received a complete pharmacological treatment (diuretics, digoxin, ACE-inhibitors or angiotensin receptor blockers, and nitroglicerin) for the treatment of acute congestive HF. ADMA plasma levels of critically ill patients were significantly higher after pharmacological treatment respect baseline values (pre-treatment). In critically ill patients with acute congestive HF acute renal impairment function and the modulation of NOS determine plasma ADMA/SDMA levels after therapy

Journey on VX-809-Based Hybrid Derivatives towards Drug-like F508del-CFTR Correctors: From Molecular Modeling to Chemical Synthesis and Biological Assays

open12Cystic fibrosis (CF) is a genetic disease affecting the lungs and pancreas and causing progressive damage. CF is caused by mutations abolishing the function of CFTR, a protein whose role is chloride's mobilization in the epithelial cells of various organs. Recently a therapy focused on small molecules has been chosen as a main approach to contrast CF, designing and synthesizing compounds acting as misfolding (correctors) or defective channel gating (potentiators). Multi-drug therapies have been tested with different combinations of the two series of compounds. Previously, we designed and characterized two series of correctors, namely, hybrids, which were conceived including the aminoarylthiazole (AAT) core, merged with the benzodioxole carboxamide moiety featured by VX-809. In this paper, we herein proceeded with molecular modeling studies guiding the design of a new third series of hybrids, featuring structural variations at the thiazole moiety and modifications on position 4. These derivatives were tested in different assays including a YFP functional assay on models F508del-CFTR CFBE41o-cells, alone and in combination with VX-445, and by using electrophysiological techniques on human primary bronchial epithelia to demonstrate their F508del-CFTR corrector ability. This study is aimed (i) at identifying three molecules (9b, 9g, and 9j), useful as novel CFTR correctors with a good efficacy in rescuing the defect of F508del-CFTR; and (ii) at providing useful information to complete the structure-activity study within all the three series of hybrids as possible CFTR correctors, supporting the development of pharmacophore modelling studies, taking into account all the three series of hybrids. Finally, in silico evaluation of the hybrids pharmacokinetic (PK) properties contributed to highlight hybrid developability as drug-like correctors.openParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, EnricoParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, Enric

Association of COMT, BDNF and 5-HTT functional polymorphisms with personality characteristics.

Background: The real impact of genetic factors on personality is still unknown, even if in literature about 50% of variance in personality traits are considered genetically determined. The determination of the genetic variance in personality traits could promote psychological well-being and the prevention of psychopathologies, because there are many experimental evidences showing that mental illness is associated to personality. Numerous studies have showed that Catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF) and serotonin transporter (5-HTT) are genes whose variants are associated with personality traits. This aim of this study is the investigation of the association between personality traits and 5-HTTLPR/rs255315-HTT promoter variant, COMT Val158Met and BDNF Val66Met gene polymorphisms. Methods: The sample was composed by 132 healthy female students. Genomic DNA was extracted from buccal swab, while personality was assessed with Cloninger's Temperament and Character Inventory-Revised (TCI-R). Linear discriminant analysis was used to analyze how personality characteristics can differentiate individuals in relation to their genetic polymorphisms. Results: Data showed that the temperament trait Reward Dependence discriminated individuals with different BDNF variants; Novelty Seeking and Harm Avoidance discriminated individuals with different 5HTTLPR variants; Persistence discriminated individuals with different COMT variants. Conclusions: Since these traits are connected to psychological diseases as depression, social anxiety, anorexia and obsessive-compulsive disorders of personality, the study of their genetic component can be used as intermediary issue to better define the connection between genes and predisposition toward maladaptive behavior and mental illness

Telerehabilitation proposal of mind-body technique for physical and psychological outcomes in patients with fibromyalgia

Fibromyalgia (FM) syndrome is characterized by the close correlation of chronic widespread pain and other non-pain related symptoms. Aim of this study was to investigate whether telerehabilitation that provides physical and psychological support services of the mind-body techniques can affect the clinical profile and pain relief of FM patients. The study included twenty-eight female FM patients, mean aged 56.61 +/- 8.56 years. All patients underwent a rehabilitation treatment (8 sessions, 1/week, 1 h/each) through Zoom platform, with the following principles of rehabilitation treatment: Anchoring to a positive emotion; listen and perceive your own body; conscious breathing; improve interoceptive awareness; relax. All patients then underwent clinical assessment of the physical distress and fear of movement for the Numeric Rating Scale (NRS); the Fatigue Assessment Scale (FAS); the Fear Avoidance Belief Questionnaire (FABQ); with measures of physical and mental disability for the Fibromyalgia Impact Questionnaire (FIQ); the 12-Items Short Form Survey; the Resilience Scale for Adults and the Coping Strategies Questionnaire-Revised. The evaluations were performed at T0 (baseline), T1 (after 8 weeks of treatment), and T2 (after 1 month of follow-up). The main finding was that telerehabilitation reduced physical and mental distress, fear, and disability (p < 0.001). Resilience and coping ability were less affected by the rehabilitative treatment. Our attempt of mind-body technique telerehabilitation has shown good results in the improvement of painful symptoms and quality of life for the FM patients but showed fewer positive impacts for the resilience and coping abilities aspects

Biological Effect of Licochalcone C on the Regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO Signaling Pathways in H9c2 Cells in Response to LPS Stimulation

Polyphenols compounds are a group molecules present in many plants. They have antioxidant properties and can also be helpful in the management of sepsis. Licochalcone C (LicoC), a constituent of Glycyrrhiza glabra, has various biological and pharmacological properties. In saying this, the effect of LicoC on the inflammatory response that characterizes septic myocardial dysfunction is poorly understood. The aim of this study was to determine whether LicoC exhibits anti-inflammatory properties on H9c2 cells that are stimulated with lipopolysaccharide. Our results have shown that LicoC treatment represses nuclear factor-κB (NF-κB) translocation and several downstream molecules, such as inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, LicoC has upregulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signaling pathway. Finally, 2-(4-Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), a specific PI3K inhibitor, blocked the protective effects of LicoC. These findings indicate that LicoC plays a pivotal role in cardiac dysfunction in sepsis-induced inflammation.The Italian Ministry for University and Research is acknowledged for financial support

Astaxanthin Treatment Reduced Oxidative Induced Pro-Inflammatory Cytokines Secretion in U937: SHP-1 as a Novel Biological Target

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H2O2), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H2O2, (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments

Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls

<p>Abstract</p> <p>Background</p> <p>The exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC) and 40 healthy subjects (HC) and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures.</p> <p>Results</p> <p>In the simultaneous quantification we found significantly higher levels of constitutively and LPS-induced MCP-1, MIP-1α, IL-8 and IL-18, and lower RANTES and IFNγ levels released by PBMC of SC patients compared with HC. In ten SC patients receiving therapy with risperidone, olanzapine or clozapine basal and LPS-induced production of RANTES and IL-18 was increased, while both basal and LPS-induced MCP-1 production was decreased. No statistically significant differences were detected in serum levels after therapy.</p> <p>Conclusion</p> <p>The observation that in schizophrenic patients the PBMC production of selected chemo-cytokines is dysregulated reinforces the hypothesis that the peripheral cyto-chemokine network is involved in the pathophysiology of schizophrenia. These preliminary, but promising data are supportive of the application of wider profiling approaches to the identification of biomarker as diagnostic tools for the analysis of psychiatric diseases.</p