Numerical investigation on the effects of bore reduction in a high performance turbocharged GDI engine. 3D investigation of knock tendency

Abstract Downsizing is a must for current high performance turbocharged SI engines. This is often achieved through the reduction of cylinder number, while keeping constant unit displacement and increasing boost pressure. However, the ensuing higher loads strongly increases the risk of abnormal combustion and thermo-mechanical failures. An alternative path to downsizing is the reduction of cylinder bore: this approach is more expensive, requiring a brand new design of the combustion system, but it also provides some advantages. The goal of the present paper is to explore the potential of bore reduction for achieving a challenging downsizing target, while preserving the engine knock safety margins. A current V8 GDI turbocharged sporting engine is taken as a reference, and a preliminary CFD-3D analysis is carried out in order to define the most suitable bore-to-stroke ratio. On this basis, bore is reduced by 11% at constant stroke, thus obtaining a reduction of about 20% on the engine displacement. In order to achieve the same peak power target, both engine boost and spark advance are adjusted until the knock safety margin of the original engine is met. 3D CFD tools, accurately calibrated on the reference engine, are used to address engine design and the calibration of the operating parameters

Effects on Knock Intensity and Specific Fuel Consumption of Port Water/Methanol Injection in a Turbocharged GDI Engine: Comparative Analysis

Abstract The recent rise in fuel prices, the need both to reduce ground transport-generated emissions (increasingly constrained by legislation) and to improve urban air quality have brought fuel-efficient, low-emissions powertrain technologies at the top of vehicle manufacturers' and policy makers' agenda. To these aims, engine design is now oriented towards the adoption of the so-called downsizing and down-speeding techniques, while preserving the performance target. Therefore, brake mean effective pressure is markedly increasing, leading to increased risks of knock onset and abnormal combustions in last-generation SI engines. To counterbalance the increased risks of pre-ignition, knock or mega-knock, currently made turbocharged SI engines usually operate with high fuel enrichments and delayed (sometimes negative) spark advances. The former is responsible for high fuel consumption levels, while the latter induce an even lower A/F ratio (below 11), to limit the turbine inlet temperature, with huge negative effects on BSFC. Possible solutions to increase knock resistance are investigated in the paper by means of 3D-CFD analyses: water, water/methanol emulsion and methanol are port-fuel injected to replace mixture enrichment while preserving, if not improving, indicated mean effective pressure and knock safety margins. The aim of the work is therefore the replacement of the gasoline-only rich mixture with a global stoichiometric one while avoiding power loss and improving fuel consumption. In order to maintain the same knock tendency, water, methanol or a mixture of the two is then added in the intake port to keep the same charge cooling of the original rich mixture. Different strategies in terms of methanol/water ratios of the port injected mixture are compared in order to find the best trade-off between fuel consumption, performance and knock tendency

Impact of the Primary Break-Up Strategy on the Morphology of GDI Sprays in 3D-CFD Simulations of Multi-Hole Injectors

The scientific literature focusing on the numerical simulation of fuel sprays is rich in atomization and secondary break-up models. However, it is well known that the predictive capability of even the most diused models is aected by the combination of injection parameters and operating conditions, especially backpressure. In this paper, an alternative atomization strategy is proposed for the 3D-Computational Fluid Dynamics (CFD) simulation of Gasoline Direct Injection (GDI) sprays, aiming at extending simulation predictive capabilities over a wider range of operating conditions. In particular, attention is focused on the eects of back pressure, which has a remarkable impact on both the morphology and the sizing of GDI sprays. 3D-CFD Lagrangian simulations of two dierent multi-hole injectors are presented. The first injector is a 5-hole GDI prototype unit operated at ambient conditions. The second one is the well-known Spray G, characterized by a higher back pressure (up to 0.6 MPa). Numerical results are compared against experiments in terms of liquid penetration and Phase Doppler Anemometry (PDA) data of droplet sizing/velocity and imaging. CFD results are demonstrated to be highly sensitive to spray vessel pressure, mainly because of the atomization strategy. The proposed alternative approach proves to strongly reduce such dependency. Moreover, in order to further validate the alternative primary break-up strategy adopted for the initialization of the droplets, an internal nozzle flow simulation is carried out on the Spray G injector, able to provide information on the characteristic diameter of the liquid column exiting from the nozzle

The role of ion channels in the hypoxia-induced aggressiveness of glioblastoma

The malignancy of glioblastoma multiform (GBM), the most common and aggressive form of human brain tumors, strongly correlates with the presence of hypoxic areas, but the mechanisms controlling the hypoxia-induced aggressiveness are still unclear. GBM cells express a number of ion channels whose activity supports cell volume changes and increases in the cytosolic Ca2+ concentration, ultimately leading to cell proliferation, migration or death. In several cell types it has previously been shown that low oxygen levels regulate the expression and activity of these channels, and more recent data indicate that this also occurs in GBM cells. Based on these findings, it may be hypothesized that the modulation of ion channel activity or expression by the hypoxic environment may participate in the acquisition of the aggressive phenotype observed in GBM cells residing in a hypoxic environment. If this hypothesis will be confirmed, the use of available ion channels modulators may be considered for implementing novel therapeutic strategies against these tumors.peer-reviewe

Update on the implication of potassium channels in autism : K+ channelautism spectrum disorder

Autism spectrum disorders (ASDs) are characterized by impaired ability to properly implement environmental stimuli that are essential to achieve a state of social and cultural exchange. Indeed, the main features of ASD are impairments of interpersonal relationships, verbal and non-verbal communication and restricted and repetitive behaviors. These aspects are often accompanied by several comorbidities such as motor delay, praxis impairment, gait abnormalities, insomnia, and above all epilepsy. Genetic analyses of autistic individuals uncovered deleterious mutations in several K+ channel types strengthening the notion that their intrinsic dysfunction may play a central etiologic role in ASD. However, indirect implication of K+ channels in ASD has been also reported. For instance, loss offragile X mental retardation protein (FMRP) results in K+ channels deregulation, network dysfunction and ASD-like cognitive and behavioral symptoms. This review provides an update on direct and indirect implications of K+ channels in ASDs. Owing to a mounting body of evidence associating a channelopathy pathogenesis to autism and showing that nearly 500 ion channel proteins are encoded by the human genome, we propose to classify ASDs - whose susceptibility is significantly enhanced by ion channels defects, either in a monogenic or multigenic condition - in a new category named “channelAutismSpectrumDisorder”(channelASD; cASD) and introduce a new taxonomy (e.g., Kvx.y-channelASD and likewise Navx.y-channelASD, Cavx.y-channelASD; etc.). This review also highlights some degree of clinical and genetic overlap between K+ channelASDs and K+ channelepsies, whereby such correlation suggests that a subcategory characterized by achannelASD-channelepsy phenotypemay be distinguished. Ultimately, this overview aims to further understand the different clinical subgroups and help parse out the distinct biological basis of autism that are essential to establish patient-tailored treatments.peer-reviewe

New insights into the pathogenesis and therapeutics of episodic ataxia type 1

Episodic ataxia type 1 (EA1) is a K+ channelopathy characterized by a broad spectrum of symptoms. Generally, patients may experience constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks additional symptoms may be reported such as vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. These episodes may be precipitated by anxiety, emotional stress, fatigue, startle response or sudden postural changes. Epilepsy is overrepresented in EA1. The disease is inherited in an autosomal dominant manner, and genetic analysis of several families has led to the discovery of a number of point mutations in the voltage-dependent K+ channel gene KCNA1 (Kv1.1), on chromosome 12p13. To date KCNA1 is the only gene known to be associated with EA1. Functional studies have shown that these mutations impair Kv1.1 channel function with variable effects on channel assembly, trafficking and biophysics. Despite the solid evidence obtained on the molecular mechanisms underlying EA1, how these cause dysfunctions within the central and peripheral nervous systems circuitries remains elusive. This review summarizes the main breakthrough findings in EA1, discusses the neurophysiological mechanisms underlying the disease, current therapies, future challenges and opens a window onto the role of Kv1.1 channels in central nervous system (CNS) and peripheral nervous system (PNS) functions.peer-reviewe

Reconciling the discrepancies on the involvement of large-conductance Ca2+-activated K channels in glioblastoma cell migration

Glioblastoma (GBM) is the most common and aggressive primary brain tumor, and is notable for spreading so effectively through the brain parenchyma to make complete surgical resection virtually impossible, and prospect of life dismal. Several ion channels have been involved in GBM migration and invasion, due to their critical role in supporting volume changes and Ca2+ influx occuring during the process. The large-conductance, Ca2+-activated K (BK) channels, markedly overexpressed in biopsies of patients with GBMs and in GBM cell lines, have attracted much interest and have been suggested to play a central role in cell migration and invasion as candidate channels for providing the ion efflux and consequent water extrusion that allow cell shrinkage during migration. Available experimental data on the role of BK channel in migration and invasion are not consistent though. While BK channels block typically resulted in inhibition of cell migration or in no effect, their activation would either enhance or inhibit the process. This short review reexamines the relevant available data on the topic, and presents a unifying paradigm capable of reconciling present discrepancies. According to this paradigm, BK channels would not contribute to migration under conditions where the [Ca2+]i is too low for their activation. They will instead positively contribute to migration for intermediate [Ca2+]i, insufficient as such to activate BK channels, but capable of predisposing them to cyclic activation following oscillatory [Ca2+]i increases. Finally, steadily active BK channels because of prolonged high [Ca2+]i would inhibit migration as their steady activity would be unsuitable to match the cyclic cell volume changes needed for proper cell migration.peer-reviewe

Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic vesicle pools and short-term synaptic plasticity, and can be corrected by appropriate learning training

The GDI1 gene, responsible in human for X-linked non-specific mental retardation, encodes αGDI, a regulatory protein common to all GTPases of the Rab family. Its alteration, leading to membrane accumulation of different Rab GTPases, may affect multiple steps in neuronal intracellular traffic. Using electron microscopy and electrophysiology, we now report that lack of αGDI impairs several steps in synaptic vesicle (SV) biogenesis and recycling in the hippocampus. Alteration of the SV reserve pool (RP) and a 50% reduction in the total number of SV in adult synapses may be dependent on a defective endosomal-dependent recycling and may lead to the observed alterations in short-term plasticity. As predicted by the synaptic characteristics of the mutant mice, the short-term memory deficit, observed when using fear-conditioning protocols with short intervals between trials, disappeared when the Gdi1 mutants were allowed to have longer intervals between sessions. Likewise, previously observed deficits in radial maze learning could be corrected by providing less challenging pre-training. This implies that an intact RP of SVs is necessary for memory processing under challenging conditions in mice. The possibility to correct the learning deficit in mice may have clinical implication for future studies in huma

Impact of methylmercury and other heavy metals exposure on neurocognitive function in children of 7 years old: study protocol of the follow-up

BACKGROUND: The extent to which prenatal low-level mercury (Hg) exposure through maternal fish intake and heavy metals exposure affect children neurodevelopment is controversial and may appear in long term. In 2007 a prospective cohort, the Northern Adriatic Cohort II (NAC-II), was established to investigate the association between prenatal Hg exposure from maternal fish consumption and child neurodevelopment. 900 pregnant women were enrolled. 632 and 470 children underwent neurodevelopmental evaluation, respectively, at 18 and 40 months of age. The NAC-II cohort is a part of the Mediterranean cohort in "Public health impact of long-term, low-level, mixed element exposure in susceptible population strata" project.METHODS: This protocol describes the follow-up assessment of the effects of prenatal low level Hg and other heavy metals exposure on the developing nervous system of the children born within the NAC-II and reached the age of 7 years. Child diet components are estimated through a Diet Diary. Child hair and urine are collected for determination of Hg level. In addition, levels of other potentially neurotoxic metals, namely Manganese, Cadmium, Lead, Arsenic and Selenium are also measured in the same matrices.DiscussionThis protocol extends to the first years of schooling age the evaluation of the neurotoxicant effect of Mercury and of the other heavy metals on children's neurodevelopment, adjusting for the potential confounders such as the lifestyles and the social economic status of children's families. Longitudinal analysis of neurodevelopment, assessed in different ages (18, 40 months and 7 years), are performed

Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis

Background: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. Results: We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion. Conclusion: This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in-depth molecular CFTR analysis