[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Very-high-frequency probes for atomic force microscopy with silicon optomechanics.

Atomic force microscopy (AFM) has been consistently supporting nanosciences and nanotechnologies for over 30 years and is used in many fields from condensed matter physics to biology. It enables the measurement of very weak forces at the nanoscale, thus elucidating the interactions at play in fundamental processes. Here, we leverage the combined benefits of micro/nanoelectromechanical systems and cavity optomechanics to fabricate a sensor for dynamic mode AFM at a frequency above 100 MHz. This frequency is two decades above the fastest commercial AFM probes, suggesting an opportunity for measuring forces at timescales unexplored thus far. The fabrication is achieved using very-large-scale integration technologies derived from photonic silicon circuits. The probe's optomechanical ring cavity is coupled to a 1.55 µm laser light and features a 130 MHz mechanical resonance mode with a quality factor of 900 in air. A limit of detection in the displacement of 3 × 10-16 m/√Hz is obtained, enabling the detection of the Brownian motion of the probe and paving the way for force sensing experiments in the dynamic mode with a working vibration amplitude in the picometer range. When inserted in a custom AFM instrument embodiment, this optomechanical sensor demonstrates the capacity to perform force-distance measurements and to maintain a constant interaction strength between the tip and sample, an essential requirement for AFM applications. Experiments indeed show a stable closed-loop operation with a setpoint of 4 nN/nm for an unprecedented subpicometer vibration amplitude, where the tip-sample interaction is mediated by a stretched water meniscus.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Analysis of Au-Pd driving forces via the effective site energy model: LRO, antisites and enthalpy of permutation.

Recently we have developed a new energetic model based on the determination of the energies on each site of random solid solutions after relaxation as a function of both the local composition and the nominal concentration. It allows to determine the main thermodynamics driving forces of disordered alloys. Here, we extend the effective site energy model to ordered alloys and illustrate the results for the Au c Pd1-c system. As a first step, we show the ability of this energetic model to reproduce the hierarchy of ordered phases. Then, we derive general mean-field analytic formulae for ordered systems and get the phase diagram. We determine the relative role of the cohesive effect, the chemical effect and the size effect and find that the chemical effect differs significantly between the disordered state and the ordered state. Finally, we link the energy formation of antisite to the permutation enthalpy and give the driving forces for the formation of antisite.

FT-IR and NMR structural markers for thiazole-based γ-peptide foldamers.

Nuclear magnetic resonance (NMR) spectroscopy has been established as a potent method for the determination of foldamer structures in solution. However, the NMR techniques could be limited by averaging, so additional experimental techniques are often needed to fully endorse the folding properties of a sequence. We have recently demonstrated that oligo-γ-peptides composed of 4-amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) adopt an original helical fold stabilized by hydrogen bonds forming C9 pseudocycles. The main objective of the present work is to reinvestigate the folding of ATC oligomer 1 in order to identify reliable FT-IR and NMR structural markers that are of value for tracking the degree of organization of ATC-based peptides.

Phase diagrams of nanoalloys: influence of size and morphology.

The size dependence of the phase diagram of nanoalloys with a tendency to phase separate is investigated. As the critical temperature may depend on both the size and the morphology of the nanoparticles, we consider nanowires with different cross-sections and also nanotubes with different circumferences. The variation of the critical temperature with the length of all these nanoparticles is systematically studied using Monte Carlo simulations based on an Ising model. A non-monotonic variation of the critical temperature is observed as a function of the length. The maximal value of the critical temperature is reached when the length and the circumference of the nanoparticles are similar. The phase diagrams obtained within two thermodynamic ensembles (the canonical ensemble and the pseudo grand canonical ensemble) are compared and discussed in terms of the behaviour of a single particle or an assembly of nanoparticles in mutual equilibrium with each other.

Ageing of out-of-equilibrium nanoalloys by a kinetic mean-field approach.

This study describes the ageing of bimetallic nanoparticles using a kinetic mean-field method which provides the time evolution of the concentration for each site. We consider the cuboctahedron of 309 atoms in the Cu-Ag system, which is a prototype of systems with a strong tendency to phase separate. Starting from an initial homogenous configuration, we investigate the evolution towards the equilibrium configuration at different temperatures. Surprisingly, at low temperature, the kinetics exhibits a first transition towards an onion-like configuration followed by a second transition towards the equilibrium core-shell configuration. An analysis of the kinetics of the formation and then of the dissolution of the onion-like structure allows us to identify the main paths of the kinetic process.

Magnetism: the driving force of order in CoPt, a first-principles study.

CoPt equiatomic alloy orders according to the tetragonal L1(0) structure which favors strong magnetic anisotropy. Conversely, magnetism can influence the chemical ordering. We present here ab initio calculations of the stability of the L1(0) and L1(2) structures of Co-Pt alloys in their paramagnetic and ferromagnetic states. They show that magnetism strongly reinforces the ordering tendencies in this system. A simple tight-binding analysis allows us to account for this behavior in terms of some pertinent parameters.

An interferometric scanning microwave microscope and calibration method for sub-fF microwave measurements.

We report on an adjustable interferometric set-up for Scanning Microwave Microscopy. This interferometer is designed in order to combine simplicity, a relatively flexible choice of the frequency of interference used for measurements as well as the choice of impedances range where the interference occurs. A vectorial calibration method based on a modified 1-port error model is also proposed. Calibrated measurements of capacitors have been obtained around the test frequency of 3.5 GHz down to about 0.1 fF. Comparison with standard vector network analyzer measurements is shown to assess the performance of the proposed system.

Exotic behavior of the outer shell of bimetallic nanoalloys.

In order to build the phase diagram of Cu-Ag nanoalloys, segregation isotherms for the different sites of the outer shell of a 405-atom cluster have been obtained by means of Monte Carlo simulations using N-body interatomic potentials. A dynamical equilibrium in phase space is observed for the (001) facets as well as for the (111) facets of the truncated octahedron. For the (001) facets, the bistability originates from a structural transition, the facets oscillating collectively between a Cu-rich square shape of coordinence 4 and an Ag-rich diamond shape of coordinence 6. For the (111) facets, the bistability is purely chemical and affects each facet individually. We thus predict the possible coexistence of Cu-pure and Ag-pure (111) facets within the same nanoparticle.

Dynamical equilibrium in nanoalloys.

Using Monte Carlo simulations on a lattice-gas model, we study the segregation isotherm of a cluster made of thousands of atoms for a system that tends to phase separate, e.g., Cu-Ag. We show that the Ag segregation involves the vertices first, then the edges and finally the (111) and (100) facets. In these facets, the segregation starts on the outer shells, leading to a heterogeneous chemical composition. When the nominal Ag concentration (or the chemical potential difference delta(mu)c between Ag and Cu), is increased a dynamical equilibrium replaces the progressive evolution of the segregation towards the core of the facets: the whole facet oscillates between one pseudo Ag-pure state and another one corresponding to a rather Cu-pure core surrounded by Ag-enriched outer shells. A remarkable consequence is that very different concentrations can be observed for facets of equivalent orientation. This dynamical equilibrium occurs in a delta(mu) range that is very close to the critical value delta(mu)c associated with the first-order phase transition of the Fowler-Guggenheim type that affects the surfaces of semi-infinite alloys. These results, which have been obtained in the grand-canonical ensemble, can also be derived in the canonical ensemble due to a sufficient number of facets that behave with each other as a reservoir.

Superficial segregation in nanoparticles: from facets to infinite surfaces.

We compare the superficial segregations of the Cu-Ag system for a nanoparticle and for surfaces that are structurally equivalent to each of its facet. Based on a lattice-gas model and within a mean-field formalism, we derive segregation isotherms at various temperatures in the canonical ensemble, i.e., for a given overall solute concentration, and in the semigrand canonical ensemble, i.e., for a given bulk solute concentration. If both processes are very similar for high temperatures, they differ substantially at lower temperatures. Due to the finite-size effect and the indirect coupling between facets and edges, the relative position of the phase transitions of the facets and the corresponding surfaces is inversed when displayed as a function of the solute bulk concentration. Moreover, we show that working in the semigrand canonical ensemble is a much more efficient way to study this phenomenon, although nanoparticles are "canonical" objects in essence.

Pinoresinol-lariciresinol reductase gene expression and secoisolariciresinol diglucoside accumulation in developing flax (Linum usitatissimum) seeds.

The transcription activity of the pinoresinol-lariciresinol reductase (PLR) gene of Linum usitatissimum (so-called LuPLR), a key gene in lignan synthesis, was studied by RT-PCR and promoter-reporter transgenesis. The promoter was found to drive transcription of a GUSint reporter gene in the seed coats during the flax seed development. This fitted well with the tissue localization monitored by semi-quantitative RT-PCR of LuPLR expression. Accumulation of the main flax lignan secoisolariciresinol diglucoside was coherent with LuPLR expression during seed development. This three-way approach demonstrated that the LuPLR gene is expressed in the seed coat of flax seeds, and that the synthesis of PLR enzyme occurs where flax main lignan is found stored in mature seeds, confirming its involvement in SDG synthesis.

[Intraspinal rib penetration in four patients in neurofibromatosis vertebral deformities]. / Pénétration intra-canalaire de côtes dans les déformations vertébrales de la neurofibromatose.

We describe the clinical and radiological features observed in four patients with neurofibromatosis-related scoliosis or kyphoscoliosis who developed rib penetration into the intervertebral foraminae. Rib penetration should be searched for on standard and elective x-rays in patients with moderate curvatures. The diagnosis can be confirmed by computed tomography or magnetic resonance imaging of the spine. In case of major deviation, x-rays must be carefully examined, with an accurate search for spinal cord compression to avoid missing the diagnosis. Surgical treatment must consist in ablation of the posterior ends of the dislocated ribs associated with anterior and posterior fusion. It should be performed early to avoid the development of spinal cord compression.

Psychobiologic responses to 4 days of increased training and recovery in cyclists.

The psychobiologic status of cyclists after 4 days of training and the kinetics of recovery were assessed by measuring the sympatho-adrenal level, the central noradrenergic activity and the cortisol/testosterone status by non-invasive methods. For this purpose, urinary excretion of methoxyamines (metanephrine [MN], normetanephrine [NMN]), which are metabolites of circulating catecholamines, 3-methoxy-4-hydroxyphenyl glycol sulfate (MHPG-S), a metabolite of brain norepinephrine, and salivary output of cortisol and testosterone were measured in twelve national cyclists (aged 19.5 +/- 4.5 years), just before (T 1 ) and at the end of the training (T 2 ), and during the three following recovery days (R 1, R 2, R 3 ). Urinary and salivary samples were also collected during a period of relative rest, in order to get reference values (T 0 ). At T 0, T 1 and T 2, mood states, as measured by the Profile of Mood States, and rating of perceived muscle soreness were assessed. The overall mood and muscle soreness levels were not affected by the training. The load increased by 187 % as an average between the first and the fourth day of training. A significant increase in NMN levels and a decrease in T:F ratio were observed at T 2, while MHPG-S excretion remained unchanged. Persistent high urinary output of NMN and MN were observed during the post-training recovery period for 24 h (R 1 ) and 48 h (R 2 ), respectively. After 72 h of recovery (R 3 ), MN levels had returned to baseline while NMN output was lower than the control level. T:F values returned to their control levels within 48 h of recovery. The strenuous training seems to induce an alteration in peripheral neuro-endocrine parameters without modifications of central factors. The hormonal status remained altered for at least 1 day of post-training recovery and seemed to be achieved within 3 days.

Wetting and structural transition induced by segregation at grain boundaries: a monte carlo study.

Wetting of the Sigma = 5 (310) <001> symmetrical tilt grain boundary (GB) close to the solubility limit in the Cu(Ag) solid solution has been observed by means of Monte Carlo simulations at T = 600 K. More precisely, a finite thickness film almost pure in Ag, separating the two initial Cu(Ag) grains, can be obtained from a critical intergranular germ induced by the strong segregation of Ag in the GB. As this film is actually a single crystal, this implies a complete rearrangement of the GB core structure. Thus the initial GB is replaced by two Cu(Ag)/Ag(Cu) interfaces. Evidence is presented for the increase of the film thickness when approaching the solubility limit, as expected in wetting phenomena.

Imaging the wave-function amplitudes in cleaved semiconductor quantum boxes

We have investigated the electronic structure of the conduction band states in InAs quantum boxes embedded in GaAs. Using cross-sectional scanning tunneling microscopy and spectroscopy, we report the direct observation of standing wave patterns in the boxes at room temperature. Electronic structure calculation of similar cleaved boxes allows the identification of the standing waves pattern as the probability density of the ground and first excited states. Their spatial distribution in the (001) plane is significantly affected by the strain relaxation due to the cleavage of the boxes.

Establishment of T-cell lines from infiltrated NOD islets by stimulation of specific T-cell receptor V beta segments.

The aims of this study were firstly to establish permanent T-cell lines from infiltrated NOD islets, by repeated stimulation of the antigen T-cell receptor with anti-V beta monoclonal antibodies (mAb) and, secondly, to characterize some of their cytotoxic and pathogenic properties. The use of anti-V beta antibodies was aimed at driving the expansion of the T cells in the absence of pancreatic antigen and, at the same time, at selecting lymphocytes expressing a given V beta gene product as an element of their TCR. Twelve lines were established as long-term cultures by regular stimulation with plastic-bound anti-V beta 6 or anti-V beta 8 mAb. The eight lines cultured with anti-V beta 6 mAb were phenotyped as early as one month after initiation and were all V beta 6+/V beta 8-. Three were CD8+ and five CD4+. Of the four lines established with anti-V beta 8 mAb, three were V beta 8+/V beta 6- and one (FD) was unexpectedly phenotyped as V beta 6+/V beta 8-. Clones derived from the FD line confirmed the expression of V beta 6. The cell-mediated cytolytic properties of the 12 lines were evaluated in two independent assays: an antibody-redirected assay to measure the lytic potential irrespective of antigen specificity and a direct cytolytic assay on YAC cells for assessing NK-like activity. The results indicate that practically all the lines (11 out of 12), irrespective of their CD4/CD8 phenotype or V beta expression, can exert cell-mediated cytotoxicity when their TCR/CD3 complex is linked to a target cell. On the other hand, anti-YAC activity is almost exclusively confined to CD8+ cell lines. Pathogenicity was evaluated in two CD4+ T cell lines, one which showed cytolytic activity in the redirected assay but not in the YAC assay (FD) and one which was totally devoid of cytotoxic activity (AH). The two lines were injected into newborn NOD mice with or without CD8+ polyclonal T cells. The results indicate that FD, the cytotoxic line, can induce severe lesions of insulitis when coinjected with polyclonal CD8+ T cells. In contrast, AH, the non-cytotoxic line, injected under the same conditions, induces no lesions. Altogether, the present data demonstrate the feasibility of establishing permanent T-cell lines on the basis of V beta expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Evidence for a preferential V beta usage by the T cells which adoptively transfer diabetes in NOD mice.

Non-obese diabetic (NOD) mice become spontaneously diabetic as a result of a genetically programmed autoimmune process mediated by autoreactive T lymphocytes and directed against beta cell antigen(s). Studies dealing with T cell receptor (TcR) variable (V) gene usage by such autoreactive T lymphocytes have given contrasted results. Various reasons may explain these discrepancies: the multiplicity of antigenic epitopes putatively recognized by T cells, the ambiguity between specifically committed T cells and passenger lymphocytes homing randomly to the pancreas, the necessarily limited size of the T cell clone panels which have been analyzed for TcR rearrangements and, last but not least, the flexibility of T cell repertoires. To circumvent some of these difficulties, we have decided to concentrate upon the T cell population present in diseased animals and capable of transferring diabetes into young naive NOD recipients. This population, composed of CD4+ and CD8+ T cells, is presumably committed against the relevant beta cell antigens and is the most likely to reveal a bias in V gene usage if such a bias does indeed exist. To find out whether certain V beta genes are more frequently used than others by such pathogenic T cells, T lymphocytes from diabetic donors have been depleted in vitro of defined V beta subsets before being reinoculated into permissive recipients. Out of four V beta families probed under such conditions, three (V beta 8, V beta 5 and V beta 11) are neutral. Their absence neither increases nor reduces the final incidence of successful transfers, indicating that these gene segments are not preferentially used. In contrast, the depletion of V beta 6-positive T cells results in a severe reduction of transfers, suggesting that V beta 6 gene is used with a relatively high frequency by diabetogenic CD4+ and/or CD8+ T cells. To define more precisely which subset uses V beta 6 gene preferentially, we have performed mixing experiments with deleted and intact subsets. The results, based on disease transfer and insulitis severity, indicate that the V beta 6 bias affects predominantly the CD4+ subset. Thus, at variance with several studies concluding that V gene usage in NOD mice is heterogeneous, our present data suggest that disease transferring T cells use a relatively restricted set of V beta genes.