Surface Reconstructions in Organic Crystals: Simulations of the Effect of Temperature and Defectivity on Bulk and (001) Surfaces of 2,2′:6′,2″-Ternaphthalene

2,2′:6′,2″-Ternaphthalene (NNN) is a novel, blue-emitting material, suitable for preparation of organic light-emitting diodes. Its crystal structure has been solved recently, but its thermal behavior and surface properties have not yet been explored, partly due to the difficulty in obtaining high quality crystals. In the present study we use classical molecular dynamics to investigate the thermal behavior of bulk and (001) surfaces of NNN. Our bulk simulations indicate the occurrence of a phase transition at about 600 K. The transition is facilitated by the presence of a free (001) surface, since a reconstruction leading to a very similar structure occurs around 550 K in our surface models. This holds for both ideal and defective surface models, containing a small number of vacancies (one or two missing molecules in the outermost layer). In all cases, the process is triggered by thermal motion and involves the reorientation of the molecules with respect to the (001) plane. Both the bulk and surface phases share the monoclinic space group P21/a with a herringbone disposition of molecules. These findings and their implications for the use of NNN in organic electronics are discussed

Susceptibility to Melampsora leaf rust of poplar clones from diverse genetic backgrounds: effects on photochemistry and water relations

The selection of resistant genotypes is the most appropriate approach in the prevention of the reduction of biomass and mortality caused by rust infection in poplar plantations. Thus, it is pertinent that we improve our understanding of the consequences that this fungal disease has on leaf physiology. Here, we studied the susceptibility to Melampsora rust in three different poplar clones of commercial interest: Lux clone - Populus deltoides Batr. (cottonwood) and Luisa Avanzo and Adige clones - both Populus × canadensis Mönch. The most susceptible clone to the infection was L. Avanzo whereas Lux and especially Adige were only slightly affected. The propagation of the disease was very rapid in L. Avanzo; their leaves showed a high incidence and severity of the disease in early and advanced stages of infection as was clearly evidenced by the degree of infection. Infected leaves of L. Avanzo were shown to have drought impaired water relations during summer as reflected by the marked decline in the relative water content (RWC). Chlorophyll fluorescence imaging revealed heterogeneity of the effect of the pathogen in the leaves, and areas with pustules showed low maximum quantum yield (Fv/Fm) and PSII quantum yield (?PSII) values, indicative of strong photoinhibition. In L. Avanzo, with a greater pustule density, rust provoked a decline in whole leaf photochemistry as indicated by Fv/Fm and photochemical reflectance index (PRI) results. Leaf structural parameters were not affected by the disease but results in L. Avanzo and Lux showed higher leaf mass per area (LMA) and higher leaf density (D) indicating an adaptation to increasing summer drought. In all clones, the effect of the pathogen was reflected in lower leaf chlorophyll content

A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation

Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8×10−106), PRMT6 (rs17496332, 1p13.3, p = 1.4×10−11), GCKR (rs780093, 2p23.3, p = 2.2×10−16), ZBTB10 (rs440837, 8q21.13, p = 3.4×10−09), JMJD1C (rs7910927, 10q21.3, p = 6.1×10−35), SLCO1B1 (rs4149056, 12p12.1, p = 1.9×10−08), NR2F2 (rs8023580, 15q26.2, p = 8.3×10−12), ZNF652 (rs2411984, 17q21.32, p = 3.5×10−14), TDGF3 (rs1573036, Xq22.3, p = 4.1×10−14), LHCGR (rs10454142, 2p16.3, p = 1.3×10−07), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7×10−08), and UGT2B15 (rs293428, 4q13.2, p = 5.5×10−06). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5×10−08, women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance

On Infiltration and Infiltration Characteristic Times

In his seminal paper on the solution of the infiltration equation, Philip (1969), https://doi-org.proxy.library.uu.nl/10.1016/b978-1-4831-9936-8.50010-6 proposed a gravity time, tgrav, to estimate practical convergence time and the time domain validity of his infinite time series expansion, TSE, for describing the transient state. The parameter tgrav refers to a point in time where infiltration is dominated equally by capillarity and gravity as derived from the first two (dominant) terms of the TSE. Evidence suggests that applicability of the truncated two-term equation of Philip has a time limit requiring higher-order TSE terms to better describe the infiltration process for times exceeding that limit. Since the conceptual definition of tgrav is valid regardless of the infiltration model used, we opted to reformulate tgrav using the analytic implicit model proposed by Parlange et al. (1982), https://doi-org.proxy.library.uu.nl/10.1097/00010694-198206000-00001 valid for all times and related TSE. Our derived gravity times ensure a given accuracy of the approximations describing transient states, while also providing insight about the times needed to reach steady state. In addition to the roles of soil sorptivity (S) and the saturated (Ks) and initial (Ki) hydraulic conductivities, we explored the effects of a soil specific shape parameter β, involved in Parlange's model and related to the type of soil, on the behavior of tgrav. We show that the reformulated tgrav (notably urn:x-wiley:00431397:media:wrcr26009:wrcr26009-math-0001 where F(β) is a β-dependent function) is about three times larger than the classical tgrav given by urn:x-wiley:00431397:media:wrcr26009:wrcr26009-math-0002. The differences between the classical tgrav,Philip and the reformulated tgrav increase for fine-textured soils, attributed to the time needed to attain steady-state infiltration and thus i + infiltration for inferring soil hydraulic properties. Results show that the proposed tgrav is a better indicator of time domain validity than tgrav,Philip. For the attainment of steady-state infiltration, the reformulated tgrav is suitable for coarse-textured soils. Still neither the reformulated tgrav nor the classical tgrav,Philip are suitable for fine-textured soils for which tgrav is too conservative and tgrav,Philip too short. Using tgrav will improve predictions of the soil hydraulic parameters (particularly Ks) from infiltration data compared to tgrav,Philip

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) 350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.Peer reviewe

Genetic insights into biological mechanisms governing human ovarian ageing

Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease