Quantum Monte Carlo and variational approaches to the Holstein model

Based on the canonical Lang-Firsov transformation of the Hamiltonian we develop a very efficient quantum Monte Carlo algorithm for the Holstein model with one electron. Separation of the fermionic degrees of freedom by a reweighting of the probability distribution leads to a dramatic reduction in computational effort. A principal component representation of the phonon degrees of freedom allows to sample completely uncorrelated phonon configurations. The combination of these elements enables us to perform efficient simulations for a wide range of temperature, phonon frequency and electron-phonon coupling on clusters large enough to avoid finite-size effects. The algorithm is tested in one dimension and the data are compared with exact-diagonalization results and with existing work. Moreover, the ideas presented here can also be applied to the many-electron case. In the one-electron case considered here, the physics of the Holstein model can be described by a simple variational approach.Comment: 18 pages, 11 Figures, v2: one typo correcte

Macrocephaly and digital anomalies expand the phenotypic spectrum of PGAP2 variants in hyperphosphatasia with impaired intellectual development syndrome 3 (HPMRS3)

Glycosylphosphatidylinositols (GPIs) anchor over 150 proteins as GPI-anchored proteins (GPI-APs) with crucial roles in diverse biological processes. The highly conserved biosynthesis of GPI-APs involves precise steps with at least 21 genes, categorized as PIG and PGAP genes. Pathogenic variants in these genes are linked to human diseases, highlighting the importance of each biosynthesis step. PGAP2 stands out among these genes due to its association with an expanded clinical spectrum of neurodevelopmental disorder (NDD) phenotypes with biallelic pathogenic variants. We present four patients from two families, one consanguineous and the other nonconsanguineous, each displaying distinct clinical presentations, including intellectual disability, hyperphosphatasia, hearing impairment, and epilepsy, as well as craniofacial and digital anomalies. Genetic analyses revealed homozygous and novel compound heterozygous missense variants in PGAP2 in four affected individuals, confirming the molecular diagnosis of hyperphosphatasia with impaired intellectual development syndrome 3 (HPMRS3). Importantly, the three amino acids affected by missense variants exhibit complete conservation in 10 vertebrate species, illuminating their crucial role in the gene’s functionality. Protein modeling provided additional evidence for the pathogenicity of the three substitutions, demonstrating their detrimental impact on protein folding and putative protein-protein interactions, ultimately leading to impaired protein function. The four patients in our study displayed common phenotypic features, such as brachydactyly, camptodactyly, and syndactyly, which have not been previously documented in individuals with PGAP2 variants. Notably, the occurrence of macrocephaly in two affected brothers from a consanguineous Pakistani family represents a novel finding. These previously unreported digital anomalies, along with macrocephaly and the identification of novel compound heterozygous variants, contribute to the expansion of the phenotypic and genotypic spectrum of HPMRS3 associated with PGAP2 variants

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990�2015: a systematic analysis for the Global Burden of Disease Study 2015

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors�the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25 over the same period. All risks jointly evaluated in 2015 accounted for 57·8 (95 CI 56·6�58·8) of global deaths and 41·2 (39·8�42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million 192·7 million to 231·1 million global DALYs), smoking (148·6 million 134·2 million to 163·1 million), high fasting plasma glucose (143·1 million 125·1 million to 163·5 million), high BMI (120·1 million 83·8 million to 158·4 million), childhood undernutrition (113·3 million 103·9 million to 123·4 million), ambient particulate matter (103·1 million 90·8 million to 115·1 million), high total cholesterol (88·7 million 74·6 million to 105·7 million), household air pollution (85·6 million 66·7 million to 106·1 million), alcohol use (85·0 million 77·2 million to 93·0 million), and diets high in sodium (83·0 million 49·3 million to 127·5 million). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens

Transformation stress induced metastable tetragonal phase in (93-92) %Pb (Zn1/3/ Nb2/3) O3 - (7-8) % PbTiO3 single crystals

10.1063/1.3460804Journal of Applied Physics1084-JAPI

Nanotwin domains in high-strain ferroelectric 89.5%Pb (Zn1/3 Nb2/3) O3 -10.5% PbTiO3 single crystal

10.1063/1.3505638Journal of Applied Physics10810-JAPI

Peroxidase isozyme patterns in the skin of maturing tomato fruit.

The cessation of tomato fruit growth is thought to be induced by an increase in the activity of enzymes which rigidify cell walls in the fruit skin. Peroxidase could catalyse such wall-stiffening reactions, and marked rises in peroxidase activity were recently reported in skin cell walls towards fruit maturity. Peroxidase isoforms in the fruit are here analysed using native gel electrophoresis. New isoforms of apparent Mr 44, 48 and 53 kDa are shown to appear in cell walls of the fruit skin at around the time of cessation of growth. It is inferred that these isozymes are present in the cell wall in vivo. Fruit from a range of non-ripening mutants were also examined. Some of these do not soften or ripen for many weeks after achieving their final size. The new isozymes were found in skin cell walls of mature fruit in each of these mutants, as in the wild-type and commercial varieties. It is concluded that the late-appearing isozymes are not associated with fruit ripening or softening, and are probably not ethylene-induced. They may act to control fruit growth by cross-linking wall polymers within the fruit skin, thus mechanically stiffening the walls and terminating growth

Formation of Mallory Body-like Inclusions and Cell Death Induced by Deregulated Expression of Keratin 18

Mallory bodies (MBs) are cytoplasmic inclusions that contain keratin 8 (K8) and K18 and are present in hepatocytes of individuals with alcoholic liver disease, nonalcoholic steatohepatitis, or benign or malignant hepatocellular neoplasia. Mice fed long term with griseofulvin are an animal model of MB formation. However, the lack of a cellular model has impeded understanding of the molecular mechanism of this process. Culture of HepG2 cells with griseofulvin has now been shown to induce both the formation of intracellular aggregates containing K18 as well as an increase in the abundance of K18 mRNA. Overexpression of K18 in HepG2, HeLa, or COS-7 cells also induced the formation of intracellular aggregates that stained with antibodies to ubiquitin and with rhodamine B (characteristics of MBs formed in vivo), eventually leading to cell death. The MB-like aggregates were deposited around centrosomes and disrupted the microtubular array. Coexpression of K8 with K18 restored the normal fibrous pattern of keratin distribution and reduced the toxicity of K18. In contrast, an NH(2)-terminal deletion mutant of K8 promoted the formation of intracellular aggregates even in the absence of K18 overexpression. Deregulated expression of K18, or an imbalance between K8 and K18, may thus be an important determinant of MB formation, which compromises the function of centrosomes and the microtubule network and leads to cell death