Singlet-triplet gaps in large multireference systems: spin-flip-driven alternatives for bioinorganic modelling

The proper description of low-spin states of open-shell systems, which are commonly encountered in the field of bioinorganic chemistry, rigorously requires using multireference ab initio methodologies. Such approaches are unfortunately very CPU-time consuming as dynamic correlation effects also have to be taken into account. The broken-symmetry unrestricted (spin-polarized) density functional theory (DFT) technique has been widely employed up to now to bypass that drawback, but despite a number of relative successes in the determination of singlet-triplet gaps, this framework cannot be considered as entirely satisfactory. In this contribution, we investigate some alternative ways relying on the spin-flip time-dependent DFT approach [Y. Shao et al. J. Chem. Phys. 118, 4807 (2003)]. Taking a few well-documented copper-dioxygen adducts as examples, we show that spin-flip (SF)-DFT computed singlet-triplet gaps compare very favorably to either experimental results or large-scale CASMP2 computations. Moreover, it is shown that this approach can be used to optimize geometries at a DFT level including some multireference effects. Finally, a clear-cut added value of the SF-DFT computations is drawn: if pure ab initio data are required, then the electronic excitations revealed by SF-DFT can be considered in designing dramatically reduced zeroth-order variational spaces to be used in subsequent multireference configuration interaction or multireference perturbation treatments

Azoospermie non obstructive : auto-immunité, génétique, histologie testiculaire et résultats d’une prise en charge endocrinienne dans une série prospective de 29 patients

peer reviewedIntroduction : L’azoospermie non obstructive (NOA) est l’absence de spermatozoïdes dans l’éjaculat, secondaire à une anomalie de la spermatogenèse. L’étiologie de cette atteinte est souvent méconnue. Patients et Méthodes : Depuis 2020, nous suivons une série de 29 hommes( (32 ans) avec NOA, consultant pour une infertilité primaire. Ils ont bénéficié d’un bilan endocrinien et urologique, incluant une échographie testiculaire, un spermogramme, une bactériologie et une sérologie virales. Une première étude du caryotype, CFTR et micro délétions AZF(29 patients) a été suivie d’un panel de 130 gènes d’hypogonadisme (10 patients). Résultats : Une auto-immunité thyroïdienne a été retrouvée chez 14/29. Des anomalies génétiques sont présentes chez 11/29 cas incluant : XXY (1cas), délétion AZF (2cas), CFTR (2 cas), une mutation hétérozygote connexine 30-26, associant une surdité congénitale (1 cas), 2 mutations non décrites du récepteur aux androgènes, une mutation SRD5A2, maladie de Wilson (1cas), CYP21A2 (1cas). L’histologie testiculaire retrouve un arrêt de la spermatogenèse chez 11/14 cas et un Sertoli only syndrome chez 3/14 cas, avec une orchite localisée (auto-immune ?) chez 2 cas. Après stimulation de 3 à 6 mois par clomifène 50 mg/j (26 cas), létrozol 2.5mg/j (5 cas), et supplémentation par hydrocortisone (1 cas) ou lévothyroxine (13 cas), on observe à ce jour une faible production de spermatozoïdes chez 6/29 patients. Conclusions : L’auto-immunité et les causes génétiques incluant la voie des androgènes sont des mécanismes sous-estimés chez les patients avec NOA. Une prise en charge endocrinienne est susceptible d’améliorer la fertilité chez des patients soigneusement étudiés.Introduction: Non-obstructive azoospermia (NOA) is the absence of spermatozoa in the ejaculate, secondary to an abnormality of spermatogenesis. The etiology of this disease is often unknown. Patients and Methods: Since 2020, we followed a series of 29 men (with NOA, consultant for primary infertility). They underwent an endocrine and urological assessment, including testicular ultrasound, spermogram, bacteriology and viral serology. A first study of karyotype, CFTR and AZF microdeletions (29 patients) was followed by a panel of 130 hypogonadism genes (10 patients). Results: Thyroid autoimmunity was found in 14/29 patients. Genetic abnormalities were present in 11/29 cases including: XXY (1 case), AZF deletion (2 cases), CFTR (2 cases), a heterozygous connectin 30-26 mutation, associating congenital deafness (1 case), 2 undescribed androgen receptor mutations, an SRD5A2 mutation, Wilson's disease (1 case), CYP21A2 (1 case). Testicular histology showed arrest of spermatogenesis in 11/14 cases and Sertoli only syndrome in 3/14 cases, with localized orchitis (autoimmune?) in 2 cases. After stimulation of 3 to 6 months with clomiphene 50 mg/day (26 cases), letrozol 2.5 mg/day (5 cases), and supplementation with hydrocortisone (1 case) or levothyroxine (13 cases), low sperm production has been observed to date in 6/29 patients. Conclusions: Autoimmunity and genetic causes including the androgen pathway are underestimated mechanisms in patients with NOA. Endocrine management has the potential to improve fertility in patients who have been carefully studied

Microchannel-patterned and heparin micro-contact-printed biodegradable composite membranes for tissue-engineering applications

Microchannel-patterned starch–poly(capro-lactone)/hydydroxyapatite (SPCL–HA) and starch– poly(lactic acid) (SPLA) composite membranes were produced for use as a laminated tissueengineering scaffold that incorporates both physical and biochemical patterns. For this purpose, SPCL (30% starch) blended with inorganic hydroxyl apatite (50%) and SPLA (50% starch) membranes were made with compressive moulding. Consequently, the microchannel structures (width 102 μm, 174 μm intervals) were developed on the composite membranes by means of micro-patterned metal mould(s) and hydraulic pressing. An elastomer poly(dimetylsiloxane) stamp was used to transfer heparin as a biochemical cue over the microchannel surfaces by micro-contact printing (μCP). Toluidine blue staining of developed capillaries and heparin μCP-coated membranes showed that heparin was transferred predominantly over the microchannel surfaces. Fibroblast cell culture over the microchannel-formed and heparin μCP-modified SPCL–HA and SPLA membranes showed distinct growth patterns. In contrast to the uniform cell layer formed on unmodified microchannels, the cells were bridging across the grooves of heparin-printed microchannels. At extended culture periods, the heparin-printed microchannels were covered with a layer of fibroblast cells without cellular ingrowths inside. This study indicated that the topographical pattern could induce an organization of fibroblasts only with the biochemical cue and the cells’ functions can be controlled spatially over the microchannels by using both cues.E. T. Baran thanks the Portuguese Foundation for Science and Technology (FCT) for providing a post-doctoral scholarship (No. SFRH/BPD/30768/2006). This work was partially supported by the FCT through funds from the POCTI and/or FEDER programmes and also by the European Union-funded STREP Project HIPPOCRATES (Grant No. NMP3-CT-2003-505758)

Novel Sulfated Polysaccharides Disrupt Cathelicidins, Inhibit RAGE and Reduce Cutaneous Inflammation in a Mouse Model of Rosacea

Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases

QUBIC: the Q&U Bolometric Interferometer for Cosmology

The primordial B-mode polarisation of the Cosmic Microwave Background is the imprints of the gravitational wave background generated by inflation. Observing the B-mode is up to now the most direct way to constrain the physics of the primordial Universe, especially inflation. To detect these B-modes, high sensitivity is required as well as an exquisite control of systematics effects. To comply with these requirements, we propose a new instrument called QUBIC (Q and U Bolometric Interferometer for Cosmology) based on bolometric interferometry. The control of systematics is obtained with a close-packed interferometer while bolometers cooled to very low temperature allow for high sensitivity. We present the architecture of this new instrument, the status of the project and the self-calibration technique which allows accurate measurement of the instrumental systematic effects

Synthesis and catalytic chemistry of a new generation of aminophosphine ligands

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Le port de Collioure et la défense du Roussillon (XVIe-XVIIIe siècle)

Parisel Reynald. Le port de Collioure et la défense du Roussillon (XVIe-XVIIIe siècle). In: Défense des côtes et cartographie historique. Actes du 124e Congrès national des sociétés historiques et scientifiques, « Milieu littoral et estuaires », Nantes, 1999. Paris : Editions du CTHS, 2002. pp. 109-127. (Actes du Congrès national des sociétés savantes, 124