A 3D Cu‐Naphthalene‐Phosphonate Metal–Organic Framework with Ultra‐High Electrical Conductivity

A conductive phosphonate metal–organic framework (MOF), [{Cu(H2O)}(2,6‐NDPA)0.5] (NDPA = naphthalenediphosphonic acid), which contains a 2D inorganic building unit (IBU) comprised of a continuous edge‐sharing sheet of copper phosphonate polyhedra is reported. The 2D IBUs are connected to each other via polyaromatic 2,6‐NDPA's, forming a 3D pillared‐layered MOF structure. This MOF, known as TUB40, has a narrow band gap of 1.42 eV, a record high average electrical conductance of 2 × 102 S m−1 at room temperature based on single‐crystal conductivity measurements, and an electrical conductance of 142 S m−1 based on a pellet measurement. Density functional theory (DFT) calculations reveal that the conductivity is due to an excitation from the highest occupied molecular orbital on the naphthalene‐building unit to the lowest unoccupied molecular orbital on the copper atoms. Temperature‐dependent magnetization measurements show that the copper atoms are antiferromagnetically coupled at very low temperatures, which is also confirmed by the DFT calculations. Due to its high conductance and thermal/chemical stability, TUB40 may prove useful as an electrode material in supercapacitors

Ultra-Rare Genetic Variation in the Epilepsies : A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA(A) receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNAIG, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.Peer reviewe

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

Majör depresyonlu hastalarda peroksizom çoğaltici-aktive edici reseptör gama 2 gen polimorfizmi, lipidler ve adipokinlerle ilişkisi

Objective: Peroxisome proliferator-activated receptor gamma (PPAR?), lipids, lipoproteins, and adipokines have recently been shown to be associated with psychiatric diseases. Our major aim is to investigate the contribution of the PPAR? gene polymorphism, adipokines, lipids, and lipoproteins to the development of major depression. Material and Methods: The frequency of Pro12Ala in exon 2 and C478T in exon 6 of the PPAR? gene, lipids and adipokines in major depression (n = 78) and control subjects (n= 64) were analyzed. Genotypes of PPARy gene polymorphisms were examined. Serum leptin, adiponectin, and resistin were studied by enzyme-linked immunosorbent assay (ELISA). Serum apo A1, apo B, and Lp(a) levels were determined by immunonephelometry. Serum total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol levels were analyzed by enzymatic methods. Results: The genotypes of exon 2 and exon 6 distribution did not differ between the control subjects and patients with major depression. Frequencies of genotypes of Pro12Ala, and Ala12Ala in exon 2 in overweight and obese patients with major depression were higher than those of overweight and obese controls. C478T polymorphism was highest in overweight and obese patients with major depression. Pro12Ala and Ala12Ala genotypes in exon 2 of PPAR? gene in patients were found to be associated with triglyceride and HDL-cholesterol. There were significant differences regarding glucose, total cholesterol, LDL-cholesterol, apo B, Lp(a), adiponectin and resistin levels between patient and control subjects. Conclusion: PPAR? exon gene polymorphisms, alterations in lipid profile and adipokines may be associated with the development of major depression. © 2011 by Türkiye Klinikleri

Proceedings of the 2002 Winter Simulation Conference

ProcessModel simulation allows the activity times of a project to be represented by a variety of distributions and further the resulting project time may also be represented by a variety of distributions. This is a significant improvement over the traditional methods of CPM and PERT. Program Evaluation and Review Technique (PERT) takes the CPM network and adds distributions to represent the activity times of the project. CPM assumes the activity times to be constant, which is not likely in the real world. PERT assumes the activity times of the project to be distributed as Beta distributions and the resulting project time to be a Normal distribution. This is better than assuming them to be constant, but these assumptions are needlessly restrictive. This paper demonstrates how simulation with ProcessModel can remove these needless restrictions