The role of POLG mutations in human disease

PhD ThesisMitochondrial diseases due to mutations in the nuclear Polymerase gamma (POLG) gene, have emerged as a common group of disorders, collectively referred to as POLG-related disorders. POLG is responsible for mitochondrial DNA (mtDNA) replication and repair. Defects in POLG result in secondary mtDNA defects including mtDNA depletion and deletions, which result in respiratory chain deficiency in affected tissues. POLG-related disorders are characterised by phenotypic diversity with common neurological deficits such as epilepsy, which constitutes its predominant manifestation. Alpers’ syndrome is a severe form of POLG-related disorders and it is a rare, early-onset, progressive encephalohepatopathy characterised by: intractable seizures, developmental delay, ataxia, visual loss and liver dysfunction. It is particularly devastating as effective treatments do not currently exist, and little is known about its molecular pathophysiology downstream from POLG mutations. The aim of this work was to gain further insight into the pathogenesis of Alpers, through the characterisation of mitochondrial dysfunction in POLG-mutant fibroblasts, and neuropathological investigation of post-mortem brain tissue from affected patients. Fibroblast characterisation using quantitative methodologies, revealed no evidence of mitochondrial dysfunction in primary POLG-mutant fibroblasts derived from patients with Alpers. Neuropathological assessment of three cortical regions revealed extensive respiratory chain deficiencies in interneurons and to a lesser extent pyramidal neurons in patients with Alpers, which was associated with severe pyramidal neuron loss. A variable degree of astrogliosis, was also observed. Additionally, mtDNA depletion was found in tissue from adult patients with POLG-mutations as well as occasional mtDNA deletions. This study provides evidence that POLG mutations exert a tissue-specific effect in Alpers. Mitochondrial respiratory chain deficiencies in interneurons and pyramidal neurons, combined with extensive pyramidal neuron loss may result in altered neuronal dynamics and contribute to the underlying neuropathology and clinical manifestations of Alpers.The Ryan Stanford Appea

Testing optically stimulated luminescence dating on sand-sized quartz of deltaic deposits from the Sperchios delta plain, central Greece

This study reports on the first investigation into the potential of luminescence dating to establish a chronological framework for the depositional sequences of the Sperchios delta plain, central Greece. A series of three borehole cores (20 m deep) and two shallow cores (4 m deep), from across the delta plain, were extracted, and samples were collected for luminescence dating. The luminescence ages of sand-sized quartz grains were obtained from small aliquots of quartz, using the Single-Aliquot Regenerative-dose (SAR) protocol. The equivalent dose determination included a series of tests and the selection of the Minimum Age Model (MAM) as the most appropriate statistical model. This made it possible to confirm the applicability of quartz Optically Stimulated Luminescence (OSL) dating to establish absolute chronology for deltaic sediments from the Sperchios delta plain.Testing age results of the five cores showed that the deltaic sediments were deposited during the Holocene. A relatively rapid deposition is implied for the top ∼14 m possibly as a result of the deceleration in the rate of the sea-level rise and the transition to terrestrial conditions, while on the deeper parts, the reduced sedimentation rate may indicate a lagoonal or coastal environment

The PhanSST global database of Phanerozoic sea surface temperature proxy data

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies

The PhanSST global database of Phanerozoic sea surface temperature proxy data

Paleotemperature proxy data form the cornerstone of paleoclimate research and are integral to understanding the evolution of the Earth system across the Phanerozoic Eon. Here, we present PhanSST, a database containing over 150,000 data points from five proxy systems that can be used to estimate past sea surface temperature. The geochemical data have a near-global spatial distribution and temporally span most of the Phanerozoic. Each proxy value is associated with consistent and queryable metadata fields, including information about the location, age, and taxonomy of the organism from which the data derive. To promote transparency and reproducibility, we include all available published data, regardless of interpreted preservation state or vital effects. However, we also provide expert-assigned diagenetic assessments, ecological and environmental flags, and other proxy-specific fields, which facilitate informed and responsible reuse of the database. The data are quality control checked and the foraminiferal taxonomy has been updated. PhanSST will serve as a valuable resource to the paleoclimate community and has myriad applications, including evolutionary, geochemical, diagenetic, and proxy calibration studies

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI