Deep Histopathology Genotype-Phenotype Analysis of Focal Cortical Dysplasia Type II Differentiates Between the GATOR1-Altered Autophagocytic Subtype Iia and MTOR-Altered Migration Deficient Subtype Iib

Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype–phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin–eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype–phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration

Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA

Deep-inelastic positron-proton interactions at low values of Bjorken-x down to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons are studied with the H1 experiment at HERA. The inclusive cross section for pi^0 mesons produced at small angles with respect to the proton remnant (the forward region) is presented as a function of the transverse momentum and energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x. Measurements are also presented of the transverse energy flow in events containing a forward pi^0 meson. Hadronic final state calculations based on QCD models implementing different parton evolution schemes are confronted with the data.Comment: 27 pages, 8 figures and 3 table

Multi-Jet Event Rates in Deep Inelastic Scattering and Determination of the Strong Coupling Constant

Jet event rates in deep inelastic ep scattering at HERA are investigated applying the modified JADE jet algorithm. The analysis uses data taken with the H1 detector in 1994 and 1995. The data are corrected for detector and hadronization effects and then compared with perturbative QCD predictions using next-to-leading order calculations. The strong coupling constant alpha_S(M_Z^2) is determined evaluating the jet event rates. Values of alpha_S(Q^2) are extracted in four different bins of the negative squared momentum transfer~\qq in the range from 40 GeV2 to 4000 GeV2. A combined fit of the renormalization group equation to these several alpha_S(Q^2) values results in alpha_S(M_Z^2) = 0.117+-0.003(stat)+0.009-0.013(syst)+0.006(jet algorithm).Comment: 17 pages, 4 figures, 3 tables, this version to appear in Eur. Phys. J.; it replaces first posted hep-ex/9807019 which had incorrect figure 4

Measurement of Leading Proton and Neutron Production in Deep Inelastic Scattering at HERA

Deep--inelastic scattering events with a leading baryon have been detected by the H1 experiment at HERA using a forward proton spectrometer and a forward neutron calorimeter. Semi--inclusive cross sections have been measured in the kinematic region 2 <= Q^2 <= 50 GeV^2, 6.10^-5 <= x <= 6.10^-3 and baryon p_T <= MeV, for events with a final state proton with energy 580 <= E' <= 740 GeV, or a neutron with energy E' >= 160 GeV. The measurements are used to test production models and factorization hypotheses. A Regge model of leading baryon production which consists of pion, pomeron and secondary reggeon exchanges gives an acceptable description of both semi-inclusive cross sections in the region 0.7 <= E'/E_p <= 0.9, where E_p is the proton beam energy. The leading neutron data are used to estimate for the first time the structure function of the pion at small Bjorken--x.Comment: 30 pages, 9 figures, 2 tables, submitted to Eur. Phys.

Deep histopathology genotype–phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb

AbstractFocal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype–phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study. Clinical data were directly available from each contributing centre. Histopathological analyses were performed from formalin-fixed, paraffin-embedded tissue samples using haematoxylin–eosin and immunohistochemistry for NF-SMI32, NeuN, pS6, p62, and vimentin. Ten individuals carried loss-of-function variants in the GATOR1 complex encoding genes DEPDC5 (n = 7) and NPRL3 (n = 3), or gain-of-function variants in MTOR (n = 7). Whereas individuals with GATOR1 variants only presented with FCDIIa, i.e., lack of balloon cells, individuals with MTOR variants presented with both histopathology subtypes, FCDIIa and FCDIIb. Interestingly, 50% of GATOR1-positive cases showed a unique and predominantly vacuolizing phenotype with p62 immunofluorescent aggregates in autophagosomes. All cases with GATOR1 alterations had neurosurgery in the frontal lobe and the majority was confined to the cortical ribbon not affecting the white matter. This pattern was reflected by subtle or negative MRI findings in seven individuals with GATOR1 variants. Nonetheless, all individuals were seizure-free after surgery except four individuals carrying a DEPDC5 variant. We describe a yet underrecognized genotype–phenotype correlation of GATOR1 variants with FCDIIa in the frontal lobe. These lesions were histopathologically characterized by abnormally vacuolizing cells suggestive of an autophagy-altered phenotype. In contrast, individuals with FCDIIb and brain somatic MTOR variants showed larger lesions on MRI including the white matter, suggesting compromised neural cell migration.</jats:p

Grundwasser - Altlasten - Boden aktuell

Neun Fachbeiträge dokumentieren die Ergebnisse der aktuellen Projekt- und Forschungsarbeit des Landesamtes in den Themenbereichen Grundwasser, Altlasten und Boden

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

Measurement of the prompt J/psi and psi(2S) polarizations in pp collisions at sqrt(s) = 7 TeV

The polarizations of prompt J/psi and psi(2S) mesons are measured in proton-proton collisions at sqrt(s) = 7 TeV, using a dimuon data sample collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.9 inverse femtobarns. The prompt J/psi and psi(2S) polarization parameters lambda[theta], lambda[phi], and lambda[theta, phi], as well as the frame-invariant quantity lambda(tilde), are measured from the dimuon decay angular distributions in three different polarization frames. The J/psi results are obtained in the transverse momentum range 14 &lt; pt &lt; 70 GeV, in the rapidity intervals abs(y) &lt; 0.6 and 0.6 &lt; abs(y) &lt; 1.2. The corresponding psi(2S) results cover 14 &lt; pt &lt; 50 GeV and include a third rapidity bin, 1.2 &lt; abs(y) &lt; 1.5. No evidence of large transverse or longitudinal polarizations is seen in these kinematic regions, which extend much beyond those previously explored

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