Experimental assessment on exploiting low carbon ethanol fuel in a light-duty dual-fuel compression ignition engine

Compression ignition (CI) engines are widely used in modern society, but they are also recognized as a significative source of harmful and human hazard emissions such as particulate matter (PM) and nitrogen oxides (NOx). Moreover, the combustion of fossil fuels is related to the growing amount of greenhouse gas (GHG) emissions, such as carbon dioxide (CO2). Stringent emission regulatory programs, the transition to cleaner and more advanced powertrains and the use of lower carbon fuels are driving forces for the improvement of diesel engines in terms of overall efficiency and engine-out emissions. Ethanol, a light alcohol and lower carbon fuel, is a promising alternative fuel applicable in the dual-fuel (DF) combustion mode to mitigate CO2 and also engine-out PM emissions. In this context, this work aims to assess the maximum fuel substitution ratio (FSR) and the impact on CO2 and PM emissions of different nozzle holes number injectors, 7 and 9, in the DF operating mode. The analysis was conducted within engine working constraints and considered the influence on maximum FSR of calibration parameters, such as combustion phasing, rail pressure, injection pattern and exhaust gas recirculation (EGR). The experimental tests were carried out on a single-cylinder light-duty CI engine with ethanol introduced via port fuel injection (PFI) and direct injection of diesel in two operating points, 1500 and 2000 rpm and at 5 and 8 bar of brake mean effective pressure (BMEP), respectively. Noise and the coefficient of variation in indicated mean effective pressure (COVIMEP) limits have been chosen as practical constraints. In particular, the experimental analysis assesses for each parameter or their combination the highest ethanol fraction that can be injected. To discriminate the effect on ethanol fraction and the combustion process of each parameter, a one-at-a-time-factor approach was used. The results show that, in both operating points, the EGR reduces the maximum ethanol fraction injectable; nevertheless, the ethanol addition leads to outstanding improvement in terms of engine-out PM. The adoption of a 9 hole diesel injector, for lower load, allows reaching a higher fraction of ethanol in all test conditions with an improvement in combustion noise, on average 3 dBA, while near-zero PM emissions and a reduction can be noticed, on the average of 1 g/kWh, and CO2 compared with the fewer nozzle holes case. Increasing the load insensitivity to different holes number was observed

A single case report of granular cell tumor of the tongue successfully treated through 445 nm diode laser

Oral granular cell tumor (GCT) is a relatively rare, benign lesion that can easily be misdiagnosed. Particularly, the presence of pseudoepitheliomatous hyperplasia might, in some cases, lead to the hypothesis of squamous cell carcinoma. Surgical excision is the treatment of choice. Recurrence has been reported in up to 15% of cases treated with conventional surgery. Here, we reported a case of GCT of the tongue in a young female patient, which was successfully treated through 445 nm diode laser excision. Laser surgery might reduce bleeding and postoperative pain and may be associated with more rapid healing. Particularly, the vaporization effect on remnant tissues could eliminate GCT cells on the surgical bed, thus hypothetically leading to a lower rate of recurrence. In the present case, complete healing occurred in 1 week, and no recurrence was observed after 6 months. Laser surgery also allows the possibility to obtain second intention healing. Possible laser-induced histopathological artifacts should be carefully considered

Okadaic acid-Parthenolide combination at subtoxic doses induces potent synergistic apoptotic effects in human retinoblastoma Y79 cells by upregulating PTEN.

Retinoblastoma is the most common intraocular malignancy afflicting children. The incidence is higher in developing countries, where treatment is limited and long-term survival rates are low. Vincristine, etoposide, and carboplatin -the agents commonly used in the treatment of retinoblastoma- determine side effects causing significant morbidity to pediatric patients and significantly limiting dosing. Thus, identifying new drugs and molecular targets to facilitate the development of novel therapeutics, and finding natural drug combinations to kill cancer cells by synergistically acting at subtoxic doses, may be a good goal. Here, we investigated the effects of two natural compounds, okadaic acid (OKA) and parthenolide (PN), in human retinoblastoma Y79 cells. We showed that OKA/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by decrease in p-Akt, increase in the stabilized p53 forms and potent decrease in pS166\u2013Mdm2. We also showed the key involvement of PTEN which, after OKA/PN treatment, potently increased before p53, suggesting that p53 activation was under PTEN action. PTEN-knockdown increased p-Akt/ pS166Mdm2 over basal levels and significantly lowered p53, while OKA/PN treatment failed both to lower p-Akt and pS166\u2013Mdm2 and to increase p53 below/over their basal levels respectively. OKA/PN treatment potently increased ROS levels while decreased those of GSH. Reducing cellular GSH by butathionine-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKA/PN. The effects of OKA/PN treatment on both GSH content and cell viability were less pronounced in PTEN silenced cells than in control cells. Our study reports for the first time both a synergistic apoptotic action between OKA and PN and the involvement of PTEN as key player in the apoptotic mechanism in human retinoblastoma Y79 cells. The results provide strong suggestion for combined inhibition of the PTEN/Akt/Mdm2/p53 pathway

Global existence of solutions for the relativistic Boltzmann equation with arbitrarily large initial data on a Bianchi type I space-time

We prove, for the relativistic Boltzmann equation on a Bianchi type I space-time, a global existence and uniqueness theorem, for arbitrarily large initial data.Comment: 17 page

In human retinoblastoma Y79 cells okadaic acid\u2013parthenolide co-treatment induces synergistic apoptotic effects, with PTEN as a key player.

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. here, we investigated the effects of two natural compounds okadaic acid (OKa) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKa/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-akt levels, increasing in the stabilized forms of p53 and potent decrease in ps166-Mdm2. We also showed the key involvement of PTeN which, after OKa/PN treatment, potently increased before p53, thus suggesting that p53 activation was under PTeN action. Moreover, after PTEN-knockdown p-akt/ ps166Mdm2 increased over basal levels and p53 significantly lowered, while OKa/PN treatment failed both to lower p-akt and ps166-Mdm2 and to increase p53 below/over their basal levels respectively. OKa/PN treatment potently increased ROs levels whereas decreased those of Gsh. Reducing cellular Gsh by l-butathionine-[s,R]-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKa/ PN. Furthermore, the effects of OKa/PN treatment on both Gsh content and cell viability were less pronounced in PTeN silenced cells than in control cells. The results provide strong suggestion for combining a treatment approach that targets the PTeN/akt/Mdm2/p53 pathway

Cyclo­linopeptide A methanol solvate

Crystals of the title compound, C57H85N9O9·CH4O, the methanol solvate of a nine peptide polypeptide, cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val), were obtained after separation of the cyclic peptide from flax oil. The cyclo­linopeptide A (CLP-A) mol­ecules are linked in chains along the a axis by N—H⋯O hydrogen bonds. Each methanol O atom is hydrogen bonded to one O atom and two N—H groups in the same CLP-A mol­ecule. There are a total of eight hydrogen bonds in each CLP-A–MeOH unit

Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn's disease. An in vivo and in vitro study

Crohn's disease (CD) is notably characterized by the expansion of visceral fat with small adipocytes expressing a high proportion of anti-inflammatory genes. Conversely, visceral fat depots in ulcerative colitis (UC) patients have never been characterized. Our study aims were a) to compare adipocyte morphology and gene expression profile and bacterial translocation in omental (OM) and mesenteric (MES) adipose tissue of patients with UC and CD, and b) to investigate the effect of bacterial infection on adipocyte proliferation in vitro. Specimens of OM and MES were collected from 11 UC and 11 CD patients, processed and examined by light microscopy. Gene expression profiles were evaluated in adipocytes isolated from visceral adipose tissue using microarray and RTqPCR validations. Bacteria within adipose tissue were immuno-detected by confocal scanning laser microscopy. Adipocytes were incubated with Enterococcus faecalis and cells counted after 24 h. Morphology and molecular profile of OM and MES revealed that UC adipose tissue is less inflamed than CD adipose tissue. Genes linked to inflammation, bacterial response, chemotaxis and angiogenesis were down-regulated in adipocytes from UC compared to CD, whereas genes related to metallothioneins, apoptosis pathways and growth factor binding were up-regulated. A dense perinuclear positivity for Enterococcus faecalis was detected in visceral adipocytes from CD, whereas positivity was weak in UC. In vitro bacterial infection was associated with a five-fold increase in the proliferation rate of OM preadipocytes. Compared to UC, visceral adipose tissue from CD is more inflamed and more colonized by intestinal bacteria, which increase adipocyte proliferation. The influence of bacteria stored within adipocytes on the clinical course of IBD warrants further investigation

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells.

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involvement in promoting proliferation, invasiveness, resistance to apoptosis and stemness. By RT-PCR, methylation-specific PCR, fluorescent in situ hybridization, DNA sequence, western blot and immunofluorescence analyses, we have shown that-in comparison with parental MG63 cells where TP53 gene is hypermethylated, rearranged and in single copy-in 3AB-OS cells, TP53 is unmethylated, rearranged and in multiple copies, and mutp53 (p53-R248W/P72R) is post-translationally modified and with nuclear localization. p53-R248W/P72R-knockdown by short-interfering RNA reduced the growth and replication rate of 3AB-OS cells, markedly increasing cell cycle inhibitor levels and sensitized 3AB-OS cells to TRAIL-induced apoptosis by DR5 up-regulation; moreover, it strongly decreased the levels of stemness and invasiveness genes. We have also found that the ectopic expression of p53-R248W/P72R in MG63 cells promoted cancer stem-like features, as high proliferation rate, sphere formation, clonogenic growth, high migration and invasive ability; furthermore, it strongly increased the levels of stemness proteins. Overall, the findings suggest the involvement of p53-R248W/P72R at the origin of the aberrant characters of the 3AB-OS cells with the hypothesis that its GOF can be at the root of the dedifferentiation of MG63 cells into CSCs

Relationship between the prevalence of Dibothriocephalus latus(Cestoda: Diphyllobothriidea) and the load of Escherichia coli: New findings in a neglected fish-borne parasitic zoonosis

The sub-Alpine lakes of Switzerland, Italy and France have long been reported as an endemic area of diphyllobothriosis, a parasitic zoonosis aused by Dibothriocephalus latus. With this study, we explored the hypothesis for a relationship between the prevalence of D. latus in Perca fluviatilis and the Escherichia coli load in lake water. To do this, we identified eleven sampling sites in three areas (north, centre and south) of Lake Iseo (north Italy) to determine E. coli load and the prevalence of D. latus in P. fluviatilis. Prevalence and 95% confidence interval (CI) of D. latus infestation ranged from 0% (95% CI: 0.71–0.0) in Sarnico (southern area) to 20% (95% CI: 33.0–11.2) in Pisogne (northern area). There were significant differences in prevalence be-tween the sites (χ2= 31.12; p- value= .0006) and in E. coli load (Kruskal–Wallis test; p- value= .0005). There was decreasing gradient of E. coli load and prevalence of D. latus infestation from north to south. A significant positive correlation (r= .881; p- value= .003) was found between E. coli load and prevalence of D. latus. Also, linear regression showed a significant relationship between E. coli load and prevalence of infestation (R2= .775). Our findings offer an explanation for the link between E. coliload in water and D. latus prevalence. The potential factors in this link are the ef-ficiency of the local wastewater treatment plant, the bathymetric profile of the lake and the life cycle of D. latus, which is mainly affected by light and water temperature.KEYWORDSItaly, Lake Iseo, Perca fluviatilis, prevalence of infestation, wastewater treatment plant, the bathymetric profile of the lake and the life cycle of D. latus, which is mainly affected by light and water temperature

Aortic dilatation in Marfan syndrome: Role of arterial stiffness and fibrillin-1 variants

Objective: Marfan syndrome (MFS) is an autosomal dominant genetic disorder characterized by aortic root dilation and dissection and an abnormal fibrillin-1 synthesis. In this observational study, we evaluated aortic stiffness in MFS and its association with ascending aorta diameters and fibrillin-1 genotype. Methods: A total of 116 Marfan adult patients without history of cardiovascular surgery, and 144 age, sex, blood pressure and heart rate matched controls were enrolled. All patients underwent arterial stiffness evaluation through carotid-femoral pulse wave velocity (PWV) and central blood pressure waveform analysis (PulsePen tonometer). Fibrillin-1 mutations were classified based on the effect on the protein, into 'dominant negative' and 'haploinsufficient' mutations. Results: PWV and central pulse pressure were significantly higher in MFS patients than in controls [respectively 7.31 (6.81-7.44) vs. 6.69 (6.52-6.86)m/s, P=0.0008; 41.3 (39.1-43.5) vs. 34.0 (32.7-35.3)mmHg, P<0.0001], with a higher age-related increase of PWV in MFS (β 0.062 vs. 0.036). Pressure amplification was significantly reduced in MFS [18.2 (15.9-20.5) vs. 33.4 (31.6-35.2)%, P<0.0001]. Central pressure profile was altered even in MFS patients without aortic dilatation. Multiple linear regression models showed that PWV independently predicted aortic diameters at the sinuses of Valsalva (ß=0.243, P=0.002) and at the sinotubular junction (ß=0.186, P=0.048). PWV was higher in 'dominant negative' than 'haploinsufficient' fibrillin-1 mutations [7.37 (7.04-7.70) vs. 6.60 (5.97-7.23)m/s, P=0.035], although this difference was not significant after adjustment. Conclusion: Aortic stiffness is increased in MFS, independently from fibrillin-1 genotype and is associated with diameters of ascending aorta. Alterations in central hemodynamics are present even when aortic diameter is within normal limits. Our findings suggest an accelerated arterial aging in MFS