Encapsulated Cell Therapy for The Treatment of Epilepsy

Contemporary antiepileptic drugs are ineffective in approximately 30% of the patients. These patients continue to experience seizures and, in many cases, seizures increase in frequency and are associated with significant cognitive decline and psychiatric disorders. The delivery of trophic factors such as glial cell-derived neurotrophic factor (GDNF) to the CNS has tremendous potential for treating a range of diseases including epilepsy. We have recently tested a clinically-validated, implantable cell encapsulation system (EC) that delivers high levels of GDNF in a selective, long-term and stable manner to the epileptogenic area of pilocarpine treated rats. As such, this therapeutic technology platform combines the potency of de novo in situ synthesis of cell-derived GDNF with the safety of an implantable, biocompatible, and retrievable medical device. The de novo synthetized source of very high levels of GDNF in the brain region of interest proved able to significantly reduce generalized seizures frequency, improved cognitive performance and normalized anatomical alterations associated with chronic epilepsy

Conormal distributions in the Shubin calculus of pseudodifferential operators

We characterize the Schwartz kernels of pseudodifferential operators of Shubin type by means of an FBI transform. Based on this we introduce as a generalization a new class of tempered distributions called Shubin conormal distributions. We study their transformation behavior, normal forms and microlocal properties.Comment: 23 page

Long-term, stable, targeted biodelivery and efficacy of GDNF from encapsulated cells in the rat and Goettingen miniature pig brain

Delivering glial cell line-derived neurotrophic factor (GDNF) to the brain is a potential treatment for Parkinson'sDisease (PD). Here we use an implantable encapsulated cell technology that uses modified human clonal ARPE-19cells to deliver of GDNF to the brain. In vivostudies demonstrated sustained delivery of GDNF to the rat striatumover 6 months. Anatomical benefits and behavioral efficacy were shown in 6-OHDA lesioned rats where nigraldopaminergic neurons were preserved in neuroprotection studies and dopaminergicfibers were restored inneurorecovery studies. When larger, clinical-sized devices were implanted for 3 months into the putamen ofG\u20acottingen minipigs, GDNF was widely distributed throughout the putamen and caudate producing a significantupregulation of tyrosine hydroxylase immunohistochemistry. These results are thefirst to provide clear evidencethat implantation of encapsulated GDNF-secreting cells deliver efficacious and biologically relevant amounts ofGDNF in a sustained and targeted manner that is scalable to treat the large putamen in patients with Parkinson'sdiseas

Measurement of the charge asymmetry in top quark pair production in pp collisions at √s = 7 TeV using the ATLAS detector

A measurement of the top-antitop production charge asymmetry AC is presented using data corresponding to an integrated luminosity of 1.04 fb−1 of pp collisions at √s = 7 TeV collected by the ATLAS detector at the LHC. Events are selected with a single lepton (electron or muon), missing transverse momentum and at least four jets of which at least one jet is identified as coming from a b-quark. A kinematic fit is used to reconstruct the t ̄t event topology. After background subtraction, a Bayesian unfolding procedure is performed to correct for acceptance and detector effects. The measured value of AC is AC = −0.019±0.028 (stat.)±0.024 (syst.), consistent with the prediction from the MC@NLO Monte Carlo generator of AC = 0.006 ± 0.002. Measurements of AC in two ranges of invariant mass of the top-antitop pair are also shown.Facultad de Ciencias Exacta

Measurement of the charge asymmetry in top quark pair production in pp collisions at √s = 7 TeV using the ATLAS detector

A measurement of the top-antitop production charge asymmetry AC is presented using data corresponding to an integrated luminosity of 1.04 fb−1 of pp collisions at √s = 7 TeV collected by the ATLAS detector at the LHC. Events are selected with a single lepton (electron or muon), missing transverse momentum and at least four jets of which at least one jet is identified as coming from a b-quark. A kinematic fit is used to reconstruct the t ̄t event topology. After background subtraction, a Bayesian unfolding procedure is performed to correct for acceptance and detector effects. The measured value of AC is AC = −0.019±0.028 (stat.)±0.024 (syst.), consistent with the prediction from the MC@NLO Monte Carlo generator of AC = 0.006 ± 0.002. Measurements of AC in two ranges of invariant mass of the top-antitop pair are also shown.Facultad de Ciencias Exacta

Search for vector-boson resonances decaying to a top quark and bottom quark in the lepton plus jets final state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for new charged massive gauge bosons, W', is performed with the ATLAS detector at the LHC. Data were collected in proton–proton collisions at a center-of-mass energy of √s = 13 TeV and correspond to an integrated luminosity of 36.1 fb−1. This analysis searches for W' bosons in the W' → t ̄ b decay channel in final states with an electron or muon plus jets. The search covers resonance masses between 0.5 and 5.0 TeV and considers right-handed W' bosons. No significant deviation from the Standard Model (SM) expectation is observed and upper limits are set on the W' → t ̄ b cross section times branching ratio and the W' boson effective couplings as a function of the W' boson mass. For right-handed W' bosons with coupling to the SM particles equal to the SM weak coupling constant, masses below 3.15 TeV are excluded at the 95% confidence level. This search is also combined with a previously published ATLAS result for W' → t ̄ b in the fully hadronic final state. Using the combined searches, right-handed W bosons with masses below 3.25 TeV are excluded at the 95% confidence level.Facultad de Ciencias Exacta

Search for vector-boson resonances decaying to a top quark and bottom quark in the lepton plus jets final state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for new charged massive gauge bosons, W', is performed with the ATLAS detector at the LHC. Data were collected in proton–proton collisions at a center-of-mass energy of √s = 13 TeV and correspond to an integrated luminosity of 36.1 fb−1. This analysis searches for W' bosons in the W' → t ̄ b decay channel in final states with an electron or muon plus jets. The search covers resonance masses between 0.5 and 5.0 TeV and considers right-handed W' bosons. No significant deviation from the Standard Model (SM) expectation is observed and upper limits are set on the W' → t ̄ b cross section times branching ratio and the W' boson effective couplings as a function of the W' boson mass. For right-handed W' bosons with coupling to the SM particles equal to the SM weak coupling constant, masses below 3.15 TeV are excluded at the 95% confidence level. This search is also combined with a previously published ATLAS result for W' → t ̄ b in the fully hadronic final state. Using the combined searches, right-handed W bosons with masses below 3.25 TeV are excluded at the 95% confidence level.Facultad de Ciencias Exacta