Synthesis of Sialyl LewisX Mimetics with E- and P-Selectin Binding Properties and Immunosuppressive Activity.

E- and P-selectins are adhesion proteins implicated in immune cell recruitment at sites of infection, making them important drug targets for diseases involving excessive and uncontrolled inflammation. In this study, we developed an efficient strategy to synthesize bicyclic galactopyranosides through a key stereoselective equatorial C4-propiolate addition and TMSCN axial C-glycosidation. The nitrile group can then be converted to the carboxyl and different bioisosteres at a late stage in the synthesis, allowing for various derivatizations to potentially enhance biological activity. The sialyl LewisX glycomimetic featuring this rigidified bicyclic galactopyranoside moiety prevents neutrophil adhesion to endothelial cells in vitro by binding to both E- and P-selectins. We show here that the axial carboxyl analogue blocks immune cell recruitment in vivo, demonstrating its potential as an immunomodulator.

Strain Rate and Stress Amplitude Effects on the Mechanical Behavior of Carbon Paste Used in the Hall-Héroult Process and Subjected to Cyclic Loadings.

Carbon products such as anodes and ramming paste must have well-defined physical, mechanical, chemical, and electrical properties to perform their functions effectively in the aluminum electrolysis cell. The physical and mechanical properties of these products are assigned during the shaping procedure in which compaction stresses are applied to the green carbon paste. The optimization of the shaping process is crucial to improving the properties of the carbon products and consequently to increasing the energy efficiency and decreasing the greenhouse gas emissions of the Hall-Héroult process. The objective of this study is to experimentally investigate the effect(s) of the strain rate, of the stress maximum amplitude, and of the unloading level on the behavior of a green carbon paste subjected to cyclic loading. To this end, experiments consisting of (1) cyclic compaction tests at different maximum stress amplitudes and strain rates, and (2) cyclic compaction tests with different unloading levels were carried out. The study obtained the following findings about the behavior of carbon paste subjected to cyclic loads. The strain rate in the studied range had no effect either on the evolution of the permanent strain as a function of the cycle number, nor on the shape of the stress-strain hysteresis during the cyclic loading. Moreover, samples of the same density that had been subjected to different maximum stress amplitudes in their loading history did not have the same shape of the stress-strain curve. On the other hand, despite having different densities, samples subjected to the same number of cycles produce the same stress-strain curve during loading even though they were subjected to different maximum stress amplitudes in their loading histories. Finally, the level of unloading during each cycle of a cyclic test proved significant; when the sample was unloaded to a lower level of stress during each cycle, the permanent strain as a function of the cycle number was higher.

Modeling of Thermo-Chemo-Mechanical Properties of Anode Mixture during the Baking Process.

In the Hall-Héroult process, prebaked carbon anodes are utilized to produce primary aluminium. The quality of the anode plays a crucial role in the efficiency of electrowinning primary aluminium. In the production of anodes, the anode baking is considered as the stage most frequently causing anode problems. During the baking process, the anode undergoes complex physicochemical transformations. Moreover, the anode at a lower position, imposed by loading pressures from upper anodes, will creep during this process. Thus, the production of high-quality anodes demands efficient control of their baking process. This paper aims to investigate the thermo-chemo-mechanical properties of the anode paste mixture at high temperatures. These properties include kinetic parameters of pitch pyrolysis such as the activation energy and the pre-exponential factor, the thermal expansion coefficient (TEC) and relevant mechanical parameters related to the elastic, the viscoelastic and the viscoplastic behaviours of the anode. For this purpose, experiments consisting of the thermogravimetric analysis, the dilatometry and the creep test were carried out. Based on the obtained results, the forementioned parameters were identified. Relevant mechanical parameters were expressed as a function of a new variable, called the shrinking index, which is related to the volatile released in open and closed pores of the anode. This variable would be used to highlight the chemo-mechanical coupling effect of the anode mixture. New insights into the phenomena such as the expansion due to the increase of the pore pressure and the chemical shrinkage of the anode during the baking process were also gained in this work. These investigations pave the way for modeling the thermo-chemo-poromechanical behaviour of the anode during the baking process.

Physical Property Evolution of the Anode Mixture during the Baking Process.

The Hall-Héroult process uses prebaked carbon anodes as electrodes. The anode's quality plays a crucial role in the efficiency of the aluminium production process. During the baking process, the anode undergoes complex physicochemical transformations. Thus, the production of high-quality anodes depends, among others, on the efficient control of their baking process. This paper aims to investigate the evolution of some physical properties of the anode paste mixture during the baking process. These properties include the mass loss fraction, real and apparent densities, the ratio of apparent volume, the permeability, and porosities. For this purpose, experiments consisting of thermogravimetric analysis, dilatometry, air permeability, and helium-pycnometric measurements were carried out. The anode permeability at high temperatures was linked to the air permeability through a permeability correlator due to experimental limitations. Moreover, the real density at high temperatures was estimated by combining real densities of the coal tar pitch and coke aggregates. Different porosities, such as the open porosity and the closed porosity related to the pitch binder, were estimated by taking the permeability at high temperatures into account. In this context, the effect of the permeability correlator, which was introduced to link the permeability at high temperatures to the air permeability, was investigated through a sensitivity analysis. These results allow an estimation of the shrinking index, a new variable introduced to reflect the baking level of the anode mixture, which is linked to the volatile that is released in both open and closed pores. Afterwards, the pore pressure inside closed pores in the coal tar pitch was estimated. The obtained results highlight some new insights related to the baking process of the anode mixture. Moreover, they pave the way for better modeling of the thermo-chemo-mechanical behavior of anodes at high temperatures.

Compaction of Cohesive Granular Material: Application to Carbon Paste.

Carbon-like materials such as the anode and the ramming paste play a crucial role in the efficiency of the Hall-Héroult process. The mechanical behavior of these materials during forming processes is complex and still ill-understood. This work aimed to investigate experimentally the mechanical behavior of a carbon paste used in the aluminum industry under different loading conditions. For this purpose, experiments consisting of (1) relaxation tests at different compaction levels, (2) quasi-static cyclic tests at several amplitudes, (3) monotonic compaction tests at varied strain rates, and (4) vibrocompaction tests at different frequencies were carried out. The obtained results highlight some fundamental aspects of the carbon paste behavior such as the strain rate's effect on the paste compressibility, the hardening-softening behavior under cyclic loadings, the effect of cycling amplitude on the stress state and the paste densification, and the frequency effect on the vibrocompaction process. These results pave the way for the development of reliable rheological models for the modeling and the numerical simulation of carbon pastes forming processes.

[Quality and determinants of anticoagulation therapy by AVK in elderly subjects: study of a continuous series of 155 patients hospitalized in geriatric medicine]. / Qualité et déterminants de l'équilibre de l'anticoagulation par AVK des sujets âgés : étude d'une série continue de 155 patients hospitalisés en gériatrie aiguë.

AVK could be prescribed in elderly patients over 75 years for the prevention of thromboembolic complications of atrial fibrillation (AF). The objective of this study was to study the quality of the anticoagulation balance by AVK and its determinants. Inclusion of all patients ≥ 75 years of age treated with AVK for an AF hospitalized in the acute geriatric department of the University hospital of Dijon. The balance of the AVK treatment was determined by the input INR and the calculation of the TTR. The last four INRs prior to admission were retrospectively collected for its calculation. Each patient had a standardized geriatric evaluation (EGS): lifestyle, MMSE, nutritional status (albumin), polypathology (Charlson), level of dependence (ADL-IADL). Bleeding complication were collected. 155 patients aged over 75 years (87±5.6 years, 88 women and 67 men) were included. The mean TTR was 55.4±31.2%. Only 46% of patients had a correct TTR (≥ 75%). The balance was significantly worse in women than in men (49.3±29.5 vs 60.1±31.8%; p=0.0326), and in case of haematological pathology (41.7±27.1 vs 57.2± 9.8; p=0.047) but better with high BMI (r=0.416, p=0.001). No EGS parameters were associated with the quality of anticoagulation. The control of AVK therapy is insufficient in geriatric elderly subjects. No modifiable explicative geriatric factor has been identified. If AVK remains a therapeutic option, direct oral anticoaulants should be considered as the first choice.