Modeling of cooling channel flow in liquid-propellant rocket engines

Ever since the development of liquid rocket engine, there has been a need to predict the peak heat flux that affects the engine material and thus to control the wall thermal behavior of rocket engine. To prevent thermal failure, the engine is generally cooled by means of a coolant that flows in passages that line the hottest part of the engine (i.e., combustion chamber and nozzle wall). This is the fluid-cooling system. If the coolant is one of the propellants, once it passes through the cooling circuit, it can be injected into the combustion chamber or it can be dumped overboard. The former case is referred to as Regenerative cooling system while the latter as dump cooling system. In case of high performance cryogenic rocket engine (such as LO2/hydrogen and LO2/methane engines) the coolant working pressure is supercritical and thus it behaves far from a liquid or a perfect gas. The fluid-cooling system (often referred to regenerative cooling because of the limited application of the dump cooling) of cryogenic rocket engines, is the technological background of this Ph.D. thesis. It is common and well confirmed practice in industry to analyze wall thermal behaviour of liquid rocket engine by means of simple and fast tools based on semi-empirical relationships. These relationships are generally calibrated by means of data collected in experimental tests of subscale engines. Industrial tools provide reasonable results but they are not able to accurately describe many phenomena that occur in the hot-wall/coolant environment, such as three-dimensional effects, asymmetric heat flux distribution in the material and supercritical behaviour of the coolant. For that reason, to circumvent the uncertainties of the design tools, regenerative systems are often over dimensioned. Moreover, these tools are deeply related to the engine for which they have been calibrated and thus they cannot be easily extended for a new generation of engines. In last years new approaches have risen; in fact new geometry configuration (i.e., high aspect ratio cooling channels) and new coolants (such as methane) to be used in the next future, have imposed more accurate analysis tools, such as three-dimensional Navier Stokes solver to describe coolant flow and three-dimensional Fourier analysis to describe wall thermal transmission. Simplified approaches are always used since, due to the limited computer power, three-dimensional tools are not suitable as design tools. However, accurate three-dimensional analysis can be integrated with simple and fast design tool in order to better describe and comprehend the phenomena that occur in the hot-wall/coolant environment. The aim of this study is to present and provide suitable theoretical and numerical tools able to describe the thermal behaviour that occur in regenerative cooling system, with special regard to the subcritical/supercritical coolant flow inside cooling channels. This aim has been achieved in three steps: A suitable mathematical description of thermophysical properties of coolants has been adopted. According to this mathematical modeling, computer subroutines describing the thermophysics of typical coolants (such as hydrogen and methane) have been implemented; A suitable physical and mathematical model able to describe both the wall thermal behaviour and the coolant flow that occur in regeneratively cooled rocket engines has been developed and implemented in a numerical code. The model is an extension of the typical 1D-model in the sense that it is able to describe the coolant and fin thermal stratification that occurs in high aspect ratio cooling channels. For that reason this model will be referred to as a quasi-2D model. The coolant thermophysical properties have been provided by means of the above mentioned hydrogen-methane subroutines. The code has been successfully validated with respect to the literature data; At last, a Navier-Stokes solver able to describe the high Reynolds number turbulent flow of generic fluid in three-dimensional cooling channels has been developed. This numerical tool has been successfully validated by comparison with exact solutions and literature data. Furthermore three-dimensional flow fields for a cryogenic fluid (methane) have been computed to analyze the coolant behavior inside straight channels with rectangular cross section and to discuss the channel aspect ratio effect on the cooling performances

Trans-synaptic signaling at GABAergic connections: possible dysfunction in some forms of Autism Spectrum Disorders

Synapses are recognized as being highly plastic in structure and function, strongly influenced by their own histories of impulse traffic and by signals from nearby cells. Synaptic contacts are fundamental for the development, homeostasis and remodeling of complex neural circuits. Synapses are highly varied in their molecular composition. Understand this diversity is important because it sheds light on the way they function. In particular, this may be useful for understanding the mechanisms at the basis of synaptic dysfunctions associated with neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD) in order to develop properly targeted therapeutic tools. During the first part of my Phd course I characterized the functional role of gephyrin at inhibitory synapses (paper N. 1). Gephyrin is a scaffold protein essential for stabilizing glycine and GABAA receptors at inhibitory synapses. Using recombinant intrabodies against gephyrin (scFv-gephyrin) I tested the hypothesis that this protein exerts a trans-synaptic action on GABA and glutamate release. Pair recordings from interconnected hippocampal cells in culture revealed a reduced probability of GABA release in scFv-gephyrintransfected neurons compared with controls. This effect was associated with a significant decrease in VGAT, the vesicular GABA transporter, and in neuroligin 2 (NL2), a protein that, interacting with the neurexins, ensures the cross-talk between the post- and presynaptic sites. I also found that, hampering gephyrin function produced a significant reduction in VGLUT, the vesicular glutamate transporter, an effect accompanied by a significant decrease in frequency of miniature excitatory postsynaptic currents. Over-expressing NLG2 in gephyrindeprived neurons rescued GABAergic but not glutamatergic innervation, suggesting that the observed changes in the latter were not due to a homeostatic compensatory mechanism. These results suggest a key role of gephyrin in regulating trans-synaptic signaling at both inhibitory and excitatory synapses. Several lines of evidence suggest that proteins involved in synaptic function are altered in ASDs. In particular, in a small percentage of cases, ASDs have been found to be associated with single mutations in genes encoding for cell adhesion molecules of the neuroligin-neurexin families. One of these involves the postsynaptic cell adhesion molecule neuroligin (NL) 3. In the second part of my PhD, I used transgenic mice carrying the human R451C mutation of Nlgn3, to study GABAergic and glutamatergic signaling in the hippocampus early in postnatal life (paper N. 2). I performed whole cell recordings from CA3 pyramidal neurons in hippocampal slices from NL3 R451C knock-in mice and I found an enhanced frequency of Giant Depolarizing Potentials, as compared to controls. This effect was probably dependent on an increased GABAergic drive to principal cells as demonstrated by the enhanced frequency of miniature GABAAmediated (GPSCs) postsynaptic currents, but not AMPA-mediated postsynaptic currents (EPSCs). The increase in frequency of mGPSCs suggest a presynaptic 9 type of action. This was further supported by the experiments with the fast-off GABAA receptor antagonist TPMPA that, as expected for an enhanced GABA transient in the cleft, showed a reduced blocking effect on miniature events. Although an increased number of available postsynaptic GABAA receptors, if these are not saturated by the content of a single GABA containing vesicle may account for these results, this was not the case since a similar number of receptor channels was revealed with peak-scaled non-stationary fluctuation analysis in both WT and NL3R451C knock-in mice, indicating that the observed effects were not postsynaptic in origin. Presynaptic changes in GABA release can be attributed to modifications in the probability of GABA release, in the number of release sites or in the content of GABA in single synaptic vesicles. Changes in probability of GABA release seem unlikely considering that we examined miniature events generated by the release of a single quantum. Our data do not allow distinguishing between the other two possibilities (changes in the number of release sites or in vesicle GABA content). However, in agreement with previous data from S\ufcdhof group showing an enhancement of the presynaptic GABAergic marker VGAT (but not VGlut1) in the hippocampus of NL3R451C KI mice (Tabuchi et al., 2007), it is likely that an increased GABAergic innervation may contribute to the enhancement of GABA release. In additional experiments I found that changes in frequency of miniature GABAergic events were associated with an acceleration of mGPSCs decay possibly of postsynaptic origin. The increased frequency of mEPSCs detected in adult, but not young NL3 R451C mice may represent a late form of compensatory homeostatic correction to counter the excessive GABAA-mediated inhibition. Therefore, it is reasonable to assume that alterations in the excitatory/inhibitory balance, crucial for the refinement of neuronal circuits early in postnatal development, accounts for the behavioral deficits observed in ASDs patients. Although also in the present case, a modification of gephyrin expression in R451C NL 3 knock-in mice was associated with changes in GABAergic innervations suggesting the involvement of a trans-synaptic signal, the role of NL3 mutation in this effect remains to be elucidated. Finally, I contribute in writing a review article (paper N. 3) that gives an up dated picture of alterations of GABAergic signaling present in different forms of Autism Spectrum Disorders

The status of the research on the heat transfer deterioration in supercritical fluids: A review

Abstract Nowadays, both experimental and computational research on the turbulent convective heat transfer to supercritical fluids is particularly active, especially because the actual poor comprehension and prediction of the possible heat transfer deterioration is limiting the design of new promising engineering applications. In this review, such applications, among which supercritical water-cooled nuclear reactors, supercritical CO2 power generation cycles, and oxygen/methane-fuel rocket engines, are firstly introduced. Then, after a phenomenological description of the heat transfer deterioration, the status of the research is analysed in details, highlighting the major advantages and limitations of both experimental and computational studies performed so far. The review demonstrates that experimental research is mostly focused on finding simple heat transfer correlations rather than detailed models. Also detailed numerical insight of the problem is still almost unexplored. The main conclusion is that new approaches, possibly integrating extensive experiments and computations, are needed to shed new light on the problem of heat transfer to supercritical fluids

Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism

Autism Spectrum Disorders (ASDs) comprise an heterogeneous group of neuro-developmental abnormalities, mainly of genetic origin, characterized by impaired social interactions, communications deficits and stereotyped behaviors. In a small percentage of cases, ASDs have been found to be associated with single mutations in genes involved in synaptic function. One of these involves the postsynaptic cell adhesion molecule neuroligin (NL) 3. NLs interact with presynaptic neurexins (Nrxs) to ensure a correct cross talk between post and presynaptic specializations. Here, transgenic mice carrying the human R451C mutation of Nlgn3, were used to study GABAergic signaling in the hippocampus early in postnatal life. Whole cell recordings from CA3 pyramidal neurons in slices from NL3 R451C knock-in mice revealed an enhanced frequency of Giant Depolarizing Potentials, as compared to controls. This effect was probably dependent on an increased GABAergic drive to principal cells as demonstrated by the enhanced frequency of miniature GABAA-mediated (GPSCs), but not AMPA-mediated postsynaptic currents (EPSCs). Changes in frequency of mGPSCs were associated with an acceleration of their decay kinetics, in the absence of any change in unitary synaptic conductance or in the number of GABAA receptor channels, as assessed by peak scaled non-stationary fluctuation analysis. The enhanced GABAergic but not glutamatergic transmission early in postnatal life may change the excitatory/inhibitory balance known to play a key role in the construction and refinement of neuronal circuits during postnatal development. This may lead to behavioral deficits reminiscent of those observed in ASDs patients. \ua9 2013 Pizzarelli and Cherubini

Alterations of GABAergic Signaling in Autism Spectrum Disorders

Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients

Molecular imaging of tau protein: new insights and future directions

Tau is a microtubule-associated protein (MAPT) that is highly expressed in neurons and implicated in several cellular processes. Tau misfolding and self-aggregation give rise to proteinaceous deposits known as neuro-fibrillary tangles. Tau tangles play a key role in the genesis of a group of diseases commonly referred to as tauopathies; notably, these aggregates start to form decades before any clinical symptoms manifest. Advanced imaging methodologies have clarified important structural and functional aspects of tau and could have a role as diagnostic tools in clinical research. In the present review, recent progresses in tau imaging will be discussed. We will focus mainly on super-resolution imaging methods and the development of near-infrared fluorescent probes