Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

Photo-chemical study and optical properties of microtips self- written on vertical laser diodes using NIR photo-polymerization.

Near infra-red (NIR) self-guided photo-polymerization is investigated in the context of micro-optics photo-fabrication on VCSELs (Vertical-Cavity Surface Emitting Lasers). We present the optimized process we have developed to allow for a collective fabrication on III-V devices wafers under real-time optical monitoring. The influence of photo-chemical parameters on final micro-elements dimensions is studied for two types of single mode 760 nm VCSELs. The difference of the resulting tip shape between the two lasers is due to the strong differences of their emissions, as they are nicely reproduced by the computed near-field profiles. The tip shapes are also compared to those produced by the light emitted by an optical fiber and differences with VCSEL tips are discussed. Also the VCSEL characteristics with fabricated tips are discussed and found in good agreement with optical modeling.

Nano-patterning photosensitive polymers using local field enhancement at the end of apertureless SNOM tips.

We show experimentally that local optical field enhancement can occur at the end of an apertureless SNOM tip illuminated by an external light source. Our approach consists in the use of a photosensitive polymer, placed in the tip near-field, to record intensity distribution in the vicinity of the tip end. The excited nanometre-size light source permits us to produce nano-patterns on the polymer surface which are then characterized by atomic force microscopy. Experimental images show the influence, on the field enhancement, of three important experimental parameters: the polarization state of the incident light, the geometry of the external illumination and the radius of curvature of the tip apex. These results are shown to be in good agreement with two-dimensional numerical calculations based on the finite-difference time-domain method. We show preliminary nanometre-size patterns created by this nano-source excited at a metallic tip extremity and discuss the potential of this approach for near-field optical lithography.

Investigation of long-term hypocoagulability in rats after intratracheal administration of unfractionated heparin.

The comparative study of intratracheal and intravenous administration of heparin on blood coagulation and mast cell population was carried out in experiments in rats. Unlike the intravenous injection of heparin which induces fast short-time inactivation of all clotting factors, single intratracheal injection of heparin inactivated the intrinsic pathway of thrombin generation. Long-term hypocoagulability after intratracheal administration of heparin was related to the accumulation of heparin in mast cell.