Brambilla et al. Reply to a Comment by J. Reinhardt et al. on "Probing the equilibrium dynamics of colloidal hard spheres above the mode-coupling glass transition"

G. Brambilla et al. Reply to a Comment by J. Reinhardt et al. questioning the existence of equilibrium dynamics above the critical volume fraction of colloidal hard spheres predicted by mode coupling theory.Comment: To appear in Phys. Rev. Lett. Reply to a Comment by J. Reinhardt et al. (see arXiv:1010.2891), which questions the existence of equilibrium dynamics above the critical volume fraction of glassy colloidal hard spheres predicted by mode coupling theor

Therapeutic Targets in Amyotrophic Lateral Sclerosis: Focus on Ion Channels and Skeletal Muscle

Amyotrophic Lateral Sclerosis is a neurodegenerative disease caused by progressive loss of motor neurons, which severely compromises skeletal muscle function. Evidence shows that muscle may act as a molecular powerhouse, whose final signals generate in patients a progressive loss of voluntary muscle function and weakness leading to paralysis. This pathology is the result of a complex cascade of events that involves a crosstalk among motor neurons, glia, and muscles, and evolves through the action of converging toxic mechanisms. In fact, mitochondrial dysfunction, which leads to oxidative stress, is one of the mechanisms causing cell death. It is a common denominator for the two existing forms of the disease: sporadic and familial. Other factors include excitotoxicity, inflammation, and protein aggregation. Currently, there are limited cures. The only approved drug for therapy is riluzole, that modestly prolongs survival, with edaravone now waiting for new clinical trial aimed to clarify its efficacy. Thus, there is a need of effective treatments to reverse the damage in this devastating pathology. Many drugs have been already tested in clinical trials and are currently under investigation. This review summarizes the already tested drugs aimed at restoring muscle-nerve cross-talk and on new treatment options targeting this tissue

FbsA-driven fibrinogen polymerization: a bacterial Deceiving Strategy.

We show that FbsA, a cell wall protein of the bacterium Streptococcus agalactiae, promotes large-scale aggregation of human plasma fibrinogen, leading to the formation of a semiflexible polymerlike network. This extensive aggregation process takes place not only in solution, but also on FbsA-functionalized colloidal particles, and leads to the formation of a thick layer on the bacterial cell wall itself, which becomes an efficient mask against phagocytosis

Statin‐induced myopathy: Translational studies from preclinical to clinical evidence

Statins are the most prescribed and effective drugs to treat cardiovascular diseases (CVD). Nevertheless, these drugs can be responsible for skeletal muscle toxicity which leads to reduced compliance. The discontinuation of therapy increases the incidence of CVD. Thus, it is essential to assess the risk. In fact, many studies have been performed at preclinical and clinical level to investigate pathophysiological mechanisms and clinical implications of statin myotoxicity. Consequently, new toxicological aspects and new biomarkers have arisen. Indeed, these drugs may affect gene transcription and ion transport and contribute to muscle function impairment. Identifying a marker of toxicity is important to prevent or to cure statin induced myopathy while assuring the right therapy for hypercholesterolemia and counteracting CVD. In this review we focused on the mechanisms of muscle damage discovered in preclinical and clinical studies and high-lighted the pathological situations in which statin therapy should be avoided. In this context, preventive or substitutive therapies should also be evaluated

Sliding drops across alternating hydrophobic and hydrophilic stripes

We perform a joint numerical and experimental study to systematically characterize the motion of 30 μl drops of pure water and of ethanol in water solutions, sliding over a periodic array of alternating hydrophobic and hydrophilic stripes with a large wettability contrast and a typical width of hundreds of microns. The fraction of the hydrophobic areas has been varied from about 20% to 80%. The effects of the heterogeneous patterning can be described by a renormalized value of the critical Bond number, i.e., the critical dimensionless force needed to depin the drop before it starts to move. Close to the critical Bond number we observe a jerky motion characterized by an evident stick-slip dynamics. As a result, dissipation is strongly localized in time, and the mean velocity of the drops can easily decrease by an order of magnitude compared to the sliding on the homogeneous surface. Lattice Boltzmann numerical simulations are crucial for disclosing to what extent the sliding dynamics can be deduced from the computed balance of capillary, viscous, and body forces by varying the Bond number, the surface composition, and the liquid viscosity. Beyond the critical Bond number, we characterize both experimentally and numerically the dissipation inside the droplet by studying the relation between the average velocity and the applied volume forces

Stick-Slip Sliding of Water Drops on Chemically Heterogeneous Surfaces

We present a comprehensive study of water drops sliding down chemically heterogeneous surfaces formed by a periodic pattern of alternating hydrophobic and hydrophilic stripes. Drops are found to undergo a stick-slip motion whose average speed is an order of magnitude smaller than that measured on a homogeneous surface having the same static contact angle. This motion is the result of the periodic deformations of the drop interface when crossing the stripes. Numerical simulations confirm this view and are used to elucidate the principles underlying the experimental observations

Optimally Managing Chemical Plant Operations: An Example Oriented by Industry 4.0 Paradigms

Updating industrial facilities to increase the level of automation and digitalization to match Industry 4.0 paradigms has become essential for many companies. Following such a trend, this paper presents a real-time optimization algorithm that plays a central role in a larger project framework devoted to highly interconnecting different network components of an Italian chemical industrial site. The proposed methodology aims at best managing the production rates of various products to fulfill a sales plan organized to satisfy numerous client requests. The considered model takes into account both batch and continuous processes as well as salable and non-storable products. The algorithm structure relies on the use of a non-linear optimization scheme and on the concepts of batch scheduling. Different features of the proposed methodology have been tested on real plant data, showing how the predicted forecast always improved the initial operation plan by considering both aspects of feasibility and economic nature. The use of the proposed algorithm assures the basis for fully integrating the control systems and the selling department of the facility in a more interactive and responsive manner

PHARMACOLOGICAL APPROACHES TO SARS-CoV-2 INFECTION: FROM DRUG REPOSITIONING FOR COVID-19 TREATMENT TO DISEASE ARREST/PREVENTION WITH MoAbs AND NOVEL ANTIVIRALS

COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the major emergencies that have affected health care systems and society in recent decades. At the end of winter 2021-2022, the number of patients infected with SARS-CoV-2 and especially those suffering from severe COVID-19 is decreasing in Europe. This is due to the protective effect of anti-SARS-CoV-2 vaccines and the increasing number of people who had COVID-19, thus developing a certain immunity. However, vaccines to prevent the disease did not appear until more than one year after the emergence of SARS-CoV-2, so the initial medical approaches to control the disease focused on the existing drugs that were considered suitable for controlling the pathological events caused by the virus as far as was known at the time. Unfortunately, due in part to the limited initial knowledge of the molecular details of the pathology of COVID-19, many of the proposed drugs fell short of expectations and were abandoned. Over time, the challenge of understanding the mechanisms behind COVID-19 has generated a large body of knowledge about how this beta-coronavirus gains control of the host during infection, a knowledge that has been used to redefine treatment strategies by repurposing existing drugs and to explore new drugs. Here, we draw a picture of the major strategies and groups of drugs studied and provide a critical overview of their efficacy and safety based on the available literature data. The main topics covered are repurposed drugs, anticoagulants, anti-cytokine agents, monoclonal antibodies against SARS-CoV-2, and small antiviral molecules

LiNbO3 integrated system for opto-microfluidic sensing

International audience; In this work, we realized and tested an integrated opto-microfluidics platform entirely made on lithium niobate (LiNbO3) crystals, able to detect the single droplet passage and estimate its size without the need of any imaging processing. It is based on the coupling of a self-aligned integrated optical stage, made of an array of optical waveguides, to a microfluidic circuit such as a T-junction or Cross-junction engraved in the same substrate. The platform presented high quality performances in terms of optical triggering, reproducibility and stability in time, allowing in real-time data analysis. The comparison with standard approaches using microscopes and fast camera imagining acquisition and relative post-processing, showed an increased capability better than 50%. The demonstrated feasibility of integration of these two stages will allow the realization of a Lab-On-a-Chip on a monolithic substrate of lithium niobate, exploiting its multiple applications for manipulation of droplets