Time Dynamics of the Down-Coupling Phenomenon in 3-D NAND Strings

We present a detailed analysis of the time dynamics of the down-coupling phenomenon (DCP) in 3-D NAND Flash memory strings. The transient time dynamics of the channel potential following the wordline (WL) bias transition fromthe pass voltage to zero is studied via numerical simulation, highlighting the existence of three temporal regimes controlledby different physical processes: electron emission from traps, hole injection from the string edges followed by capture, and propagation along the string. The impact of these processes is separately studied, followed by an analysis of the dependence of the DCP recovery time on architectural parameters. Results highlight the relevant physics and can be used as a design guideline for NAND strings with reduced sensitivity to the DCP

Are immune responses gender-related in Carabus lefebvrei (Coleoptera: Carabidae)?

The \u201clive hard, die young\u201d theory predicts the evolution of gender differences in immunocompetence, with males having a weaker immune system than females. To test this hypothesis in Carabus lefebvrei, total and basal phenoloxidase (PO) activities and lysozyme-like enzyme activity were compared among males and females of different reproductive status. The sexual dimorphism occurred only in reproductively active adults and for total and basal PO levels, while no significant differences were recorded between sexes in virgin adults. Differences were not recorded for lytic activity between sexes. Basal PO and lytic activities decreased in both males and females after mating, while the total PO value increased in males and decreased in females. Thus, resources seem to be invested to increase the humoral response in pre-reproductive phase forming a barrier against pathogens and preserving the fecundity and longevity of both sexes. Males preserve their survivorship in reproductive phase by increasing enzymatic levels in hemolymph to avoid fitness reduction due to the increased exposure to pathogen as result of mating. Females shift resources from PO and lytic activity to other physiological systems involved in reproduction in order to maximize their fitness

A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (N-cases/N-controls = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, r(g) = 0.11, P = 3.56 x 10(-06)) and systolic BP (SBP, r(g) = 0.06, P = 0.01), but not pulse pressure (PP, r(g) = -0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P <= 5 x 10(-08)), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15-1.25]/10 mmHg; P = 5.57 x 10(-25)) on migraine than SBP (1.05 [1.03-1.07]/10 mmHg; P = 2.60 x 10(-07)) and a corresponding opposite effect for PP (0.92 [0.88-0.95]/10 mmHg; P = 3.65 x 10(-07)). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine

Ultrasonic spray coating as an approach for large-area polymer OLEDs: The influence of thin film processing and surface roughness on electrical performance

In this article we present a detailed comparison of ultrasonic spray coating and spin coating for the fabrication of polymer organic light-emitting diodes (OLEDs). Single-carrier devices of hole-transporting polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4’(N-(4-sec-butylphenyl))) diphenylamine] (TFB) were fabricated by ultrasonic spray coating. Uniform reference devices using spin coating were also made. We have shown, across a range of device thicknesses from 37 nm to 138 nm, typical of those used in OLED hole-transport layers, that there is no statistical difference in the hole-injection efficiency between ultrasonic spray coating and spin coating. We have also demonstrated the importance of controlling the roughness of the films and we determine a threshold of 10 nm average roughness below which injection efficiency is not controlled by roughness. However, above 10 nm roughness we find a reduction in injection efficiency up to an 86 % loss in performance for roughnesses of the order of 40 % the thickness of the film. By optimising the deposition parameters, in order to allow the wet films to start to equilibrate, we find a wide processing window for smooth uniform films with excellent injection efficiency. This work reinforces the importance of ultrasonic spray coating as a potential route to high volume manufacturing of OLED based technology

Effects of X-ray irradiation on haemocytes of Procambarus clarkii (Arthropoda: Decapoda) males

The red swamp crayfish Procambarus clarkii is an invasive alien species spreading worldwide. The sterile male release technique (SMRT) is among the methods used to contrast the growth of P. clarkii populations within invaded areas. In this study males underwent X-ray sterilisation with a dose of 40 Gy and their immunocompetence was analysed in comparison to untreated animals to ascertain whether radiation can affect welfare parameters other than reproductive organs. The present research investigated the immune function in P. clarkii males in term of (1) morphological haemocyte characterisation by transmission electron microscopy to identify the main phagocyting haemocyte after in vivo artificial non-self challenge with latex beads; (2) total and differential haemocyte counts; and (3) basal and total phenoloxidase activities as components of the humoral defence. Three types of circulating haemocytes were characterised via transmission electron microscopy: hyaline, semigranular and granular haemocytes. The ultrastructural features of haemocyte granules allowed the characterisation of a fourth type of haemocyte, the medium granule haemocyte. In vivo artificial non-self-challenge with latex beads identified the semigranular haemocytes as primarily involved in phagocyting activity. Circulating haemocytes of males irradiated with a dose of 40 Gy, after 20 days, showed a significantly lower diameter in the granules of hyaline and semigranular haemocytes, but no other evident ultrastructural alterations in comparison with un-irradiated animals were found. Irradiated males showed a significant decrease of about 80% of circulating haemocytes and an increase in frequency of semigranular and granular haemocytes. No significant differences in basal and total phenoloxidase activity were recorded and this could, in part, explain the good survival level of irradiated males despite the drastic decline of the haemocyte number. This study represents the basis to appraise whether SMRT affects important functions, such as those of the immune system, in addition to altering the gonad tissue

A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine.

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10-06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = -0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10-08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15-1.25]/10 mmHg; P = 5.57 × 10-25) on migraine than SBP (1.05 [1.03-1.07]/10 mmHg; P = 2.60 × 10-07) and a corresponding opposite effect for PP (0.92 [0.88-0.95]/10 mmHg; P = 3.65 × 10-07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Novel Protocol for the Chemical Synthesis of Crustacean Hyperglycemic Hormone Analogues — An Efficient Experimental Tool for Studying Their Functions

The crustacean Hyperglycemic Hormone (cHH) is present in many decapods in different isoforms, whose specific biological functions are still poorly understood. Here we report on the first chemical synthesis of three distinct isoforms of the cHH of Astacus leptodactylus carried out by solid phase peptide synthesis coupled to native chemical ligation. The synthetic 72 amino acid long peptide amides, containing L- or D-Phe3 and (Glp1, D-Phe3) were tested for their biological activity by means of homologous in vivo bioassays. The hyperglycemic activity of the D-isoforms was significantly higher than that of the L-isoform, while the presence of the N-terminal Glp residue had no influence on the peptide activity. The results show that the presence of D-Phe3 modifies the cHH functionality, contributing to the diversification of the hormone pool

Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol

OBJECTIVE LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. RESEARCH DESIGN AND METHODS We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses. RESULTS A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95% CI 1.01, 1.24]) and BMI (b 5 0.07 SD units [95% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95% CI 1.01, 1.08]) with a proportion mediated of 38% of the total effect (P 5 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8% (P 5 0.04). CONCLUSIONS These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications

Genetically predicted cortisol levels and risk of venous thromboembolism

Introduction - In observational studies, venous thromboembolism (VTE) has been associated with Cushing’s syndrome and with persistent mental stress, two conditions associated with higher cortisol levels. However, it remains unknown whether high cortisol levels within the usual range are causally associated with VTE risk. We aimed to assess the association between plasma cortisol levels and VTE risk using Mendelian randomization. Methods - Three genetic variants in the SERPINA1/SERPINA6 locus (rs12589136, rs11621961 and rs2749527) were used to proxy plasma cortisol. The associations of the cortisol-associated genetic variants with VTE were acquired from the INVENT (28 907 cases and 157 243 non-cases) and FinnGen (6913 cases and 169 986 non-cases) consortia. Corresponding data for VTE subtypes were available from the FinnGen consortium and UK Biobank. Two-sample Mendelian randomization analyses (inverse-variance weighted method) were performed. Results - Genetic predisposition to higher plasma cortisol levels was associated with a reduced risk of VTE (odds ratio [OR] per one standard deviation increment 0.73, 95% confidence interval [CI] 0.62–0.87, p Conclusions - This study provides evidence that genetically predicted plasma cortisol levels in the high end of the normal range are associated with a decreased risk of VTE and that this association may be mediated by blood pressure. This study has implications for the planning of observational studies of cortisol and VTE, suggesting that blood pressure traits should be measured and accounted for