Theoretical And Experimental Studies On The Instability Of Charged Liquid Drops

To be able to properly predict the breakup of highly charged liquid droplets, a complete understanding of their behavior at the Rayleigh limit is necessary. An analytical model has been developed for a conductive spherical drop charged to its Rayleigh limit which predicts the final state just after the breakup for both single and multi-sibling disintegrations. The numerical analysis of this model involves scanning all the possible radii of the sibling droplets and ensuring that the solutions satisfy the conservation of energy and Rayleigh limit criteria. For a drop unaffected by any external force, the results of this model show that the most probable disintegration satisfies the single sibling breakup. The sibling, under such conditions, carries about 25% of the initial mass and 40% of the initial charge. The results also show that the difference between the final energy, calculated at different sibling mass ratios, and the minimum final energy is very small for a very wide range of sibling mass ratios (0.1 to 0.9) and thus can be easily affected by any external force to produce a multi-sibling disintegration. For the multi-sibling case, the model assumes tree-like secondary breakups which lead to a residual drop and n siblings of different sizes and charges. The results of this model show good agreement with the experimental observations of many other investigators. The numerical results also show that the single sibling exists for all the values of sibling mass ratios greater than 11.1%. For all the values less than this, the multi-sibling disintegration is favoured. This has been verified experimentally by collecting water droplets after their breakup on water sensitive paper and then examining their traces with a microscope.;Since the Rayleigh limit is only valid for spherical droplets unaffected by any external force, general equations describing the drop stability have been derived for both prolate and oblate spheroidal shapes. From the analytical evaluation of these equations, it was concluded that the Rayleigh limit is only valid for small droplet sizes (R {dollar}\u3c{dollar} 50 {dollar}\mu{dollar}m) and for very low levels of external forces. (Abstract shortened with permission of author.

FastCycle: A Message Sharing Framework for Modular Automated Driving Systems

Automated Driving Systems (ADS) have rapidly evolved in recent years and their architecture becomes sophisticated. Ensuring robustness, reliability and safety of performance is particularly important. The main challenge in building an ADS is the ability to meet certain stringent performance requirements in terms of both making safe operational decisions and finishing processing in real-time. Middlewares play a crucial role to handle these requirements in ADS. The way middlewares share data between the different system components has a direct impact on the overall performance, particularly the latency overhead. To this end, this paper presents FastCycle as a lightweight multi-threaded zero-copy messaging broker to meet the requirements of a high fidelity ADS in terms of modularity, real-time performance and security. We discuss the architecture and the main features of the proposed framework. Evaluation of the proposed framework based on standard metrics in comparison with popular middlewares used in robotics and automated driving shows the improved performance of our framework. The implementation of FastCycle and the associated comparisons with other frameworks are open sourced

Senescence and host–pathogen interactions

Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host–pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease

Characterising the senescence-like phenotype induced by the typhoid toxin of Salmonella Typhi

Cellular senescence is an innate physiological mechanism crucial in development, wound healing and tumour suppression. It is characterised by an irreversible cell cycle arrest, resistance to apoptosis, and an inflammatory secretome that remodels bystander cells, referred to as senescence-associated secretory phenotype (SASP). SASP acts in an autocrine or paracrine manner to reinforce senescence, transmit senescence to naive cells and activate immunosurveillance to remove cells of pathological potential. In ageing organisms, senescent cells accumulate, resulting in SASP-driven chronic inflammation, aberrant tissue homeostasis and immune functions, and age-related pathologies such as cancer. Ageing also comes with an increased susceptibility to infectious diseases but the cellular basis for this is unclear. Salmonella Typhi causes more than 11 million cases of drug-resistant typhoid fever cases each year that are spreading intercontinentally, making it a global health concern. The typhoid toxin of Salmonella Typhi causes DNA damage, cell cycle arrest and cell distension, which are indicative of senescence. Toxin-induced DNA damage is associated with mortality, typhoid fever symptoms and chronic Salmonella carriage in animal models, which aids in pathogen shedding and disease transmission. Therefore, dissecting the typhoid toxin virulence mechanism is of utmost importance. Using molecular and cellular biology, this thesis substantiates evidence that the typhoid toxin induces senescence in vitro marked by persistent DNA damage responses, increased senescence associated β-galactosidase, p21 activity, diminished lamin B1, and paracrine senescence via toxin-induced SASP (toxSASP). Interestingly, previous work in our lab demonstrated that toxSASP uniquely promoted Salmonella infection, while aphidicolin (APH), i.e. another senescence inducer, did not. This finding indicates that factors in the host secretome increase the susceptibility of bystander cells to Salmonella infection but the identity of the SASP factors are unknown. Using unbiased LC-MS/MS and GeneChip microarray transcriptomics, this thesis reveals toxSASP constituents which were divergent from other senescence inducers, namely APHSASP and ETPSASP. Additionally, in vitro experiments implicate potential crosstalk between TGFβ and Wnt5a signalling pathway in toxin-induced senescence phenotypes. Indeed, purified Activin A, a TGFβ ligand, and Wnt5A contributed to toxSASP paracrine senescence. Furthermore, TGFβ receptors knockdown via siRNAs ameliorated Salmonella invasion induced by toxSASP. In conclusion, this study reveals the first proteomic characterisation of a SASP induced by a bacterial toxin. The study represents a Salmonella hijacking mechanism via the TGFβ signalling pathway, which represents a novel host-pathogen interaction that may be of significance to invasive infections underlying typhoid fever and chronic carriage. This thesis is of broad significance as it reveals a way by which bacterial pathogens can reprogramme multicellular infection niches by hijacking the host secretome through DNA damage responses

Towards a Safe Real-Time Motion Planning Framework for Autonomous Driving Systems: An MPPI Approach

peer reviewedPlanning safe trajectories in Autonomous Driving Systems (ADS) is a complex problem to solve in real-time. The main challenge to solve this problem arises from the various conditions and constraints imposed by road geometry, semantics and traffic rules, as well as the presence of dynamic agents. Recently, Model Predictive Path Integral (MPPI) has shown to be an effective framework for optimal motion planning and control in robot navigation in unstructured and highly uncertain environments. In this paper, we formulate the motion planning problem in ADS as a nonlinear stochastic dynamic optimization problem that can be solved using an MPPI strategy. The main technical contribution of this work is a method to handle obstacles within the MPPI formulation safely. In this method, obstacles are approximated by circles that can be easily integrated into the MPPI cost formulation while considering safety margins. The proposed MPPI framework has been efficiently implemented in our autonomous vehicle and experimentally validated using three different primitive scenarios. Experimental results show that generated trajectories are safe, feasible and perfectly achieve the planning objective. The video results as well as the open-source implementation are available at: https://gitlab.uni.lu/360lab-public/mpp

FastCycle: A Message Sharing Framework for Modular Automated Driving Systems

Automated Driving Systems (ADS) have rapidly evolved in recent years and their architecture becomes sophisticated. Ensuring robustness, reliability and safety of performance is particularly important. The main challenge in building an ADS is the ability to meet certain stringent performance requirements in terms of both making safe operational decisions and finishing processing in real-time. Middlewares play a crucial role to handle these requirements in ADS. The way middlewares share data between the different system components has a direct impact on the overall performance, particularly the latency overhead. To this end, this paper presents FastCycle as a lightweight multi-threaded zero-copy messaging broker to meet the requirements of a high fidelity ADS in terms of modularity, real-time performance and security. We discuss the architecture and the main features of the proposed framework. Evaluation of the proposed framework based on standard metrics in comparison with popular middlewares used in robotics and automated driving shows the improved performance of our framework. The implementation of FastCycle and the associated comparisons with other frameworks are open sourced

Typhoid toxin hijacks Wnt5a to establish host senescence and Salmonella infection

Damage to our genome causes acute senescence in mammalian cells, which undergo growth arrest and release a senescence-associated secretory phenotype (SASP) that propagates the stress response to bystander cells. Thus, acute senescence is a powerful tumor suppressor. Salmonella enterica hijacks senescence through its typhoid toxin, which usurps unidentified factors in the stress secretome of senescent cells to mediate intracellular infections. Here, transcriptomics of toxin-induced senescent cells (TxSCs) and proteomics of their secretome identify the factors as Wnt5a, INHBA, and GDF15. Wnt5a establishes a positive feedback loop, driving INHBA and GDF15 expression. In fibroblasts, Wnt5a and INHBA mediate autocrine senescence in TxSCs and paracrine senescence in naive cells. Wnt5a synergizes with GDF15 to increase Salmonella invasion. Intestinal TxSCs undergo apoptosis without Wnt5a, which is required for establishing intestinal TxSCs. The study reveals how an innate defense against cancer is co-opted by a bacterial pathogen to cause widespread damage and mediate infections

Mathematical formulae for neutron self-shielding properties of media in an isotropic neutron field

The complexity of the neutron transport phenomenon throws its shadows on every physical system wherever neutron is produced or used. In the current study, an ab initio derivation of the neutron self-shielding factor to solve the problem of the decrease of the neutron flux as it penetrates into a material placed in an isotropic neutron field. We have employed the theory of steady-state neutron transport, starting from Stuart's formula. Simple formulae were derived based on the integral cross-section parameters that could be adopted by the user according to various variables, such as the neutron flux distribution and geometry of the simulation at hand. The concluded formulae of the self-shielding factors comprise an inverted sigmoid function normalized with a weight representing the ratio between the macroscopic total and scattering cross-sections of the medium. The general convex volume geometries are reduced to a set of chord lengths, while the neutron interactions probabilities within the volume are parameterized to the epithermal and thermal neutron energies. The arguments of the inverted-sigmoid function were derived from a simplified version of neutron transport formulation. Accordingly, the obtained general formulae were successful in giving the values of the experimental neutron self-shielding factor for different elements and different geometries.Comment: 14 pages, 5 figures, 1 graphical abstract, 73 references, and 2 tables, include improvement of illustration and story-telling writing styl

Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.

Salmonella Typhi activates the host DNA damage response through the typhoid toxin, facilitating typhoid symptoms and chronic infections. Here we reveal a non-canonical DNA damage response, which we call RING (response induced by a genotoxin), characterized by accumulation of phosphorylated histone H2AX (γH2AX) at the nuclear periphery. RING is the result of persistent DNA damage mediated by toxin nuclease activity and is characterized by hyperphosphorylation of RPA, a sensor of single-stranded DNA (ssDNA) and DNA replication stress. The toxin overloads the RPA pathway with ssDNA substrate, causing RPA exhaustion and senescence. Senescence is also induced by canonical γΗ2ΑΧ foci revealing distinct mechanisms. Senescence is transmitted to non-intoxicated bystander cells by an unidentified senescence-associated secreted factor that enhances Salmonella infections. Thus, our work uncovers a mechanism by which genotoxic Salmonella exhausts the RPA response by inducing ssDNA formation, driving host cell senescence and facilitating infection

Stimulated perturbation on the neutron flux distribution in the mutually-dependent source-to-absorber geometry

The complexity of the neutron transport phenomenon throws its shadows on every physical system wherever neutron is produced or absorbed. The Monte Carlo N-Particle Transport Code (MCNP) was used to investigate the flux perturbations in the neutron field caused by an absorber. The geometry of the present experiment was designed to reach a simulation of an isotopic neutron field. The neutron source was a ${}^{241}$AmBe with the production physics of neutrons is dependent only on alpha-beryllium interaction and is independent of what happened to the neutron after it was generated. The geometries have been designed to get a volume of uniform neutron densities within a spherical volume of radius 15 cm in every neutron energy group up to 10 MeV. Absorbers of different dimensions were placed within the volume to investigate the field perturbation. Different neutron absorbers were used to correlate the phenomenon to the integral cross-section of the absorber. Flux density inside and outside the absorber samples was determined, while the spatial neutron flux distribution produced by the AmBe source without an absorber was taken as a reference. This study displayed that absorbers of various dimensions perturb the neutron field in a way that is dependent on the absorption and scattering cross-sections, particularly in the neutron resonance region. Unlike the simple picture of reducing the number density of neutrons, the perturbation was found to influence the moderation of neutrons in the medium, significantly above 1 MeV.Comment: 10 pages, 13 figures, 26 reference