Quantum electrodynamics of relativistic bound states with cutoffs

We consider an Hamiltonian with ultraviolet and infrared cutoffs, describing the interaction of relativistic electrons and positrons in the Coulomb potential with photons in Coulomb gauge. The interaction includes both interaction of the current density with transversal photons and the Coulomb interaction of charge density with itself. We prove that the Hamiltonian is self-adjoint and has a ground state for sufficiently small coupling constants.Comment: To appear in "Journal of Hyperbolic Differential Equation

Bipotential mouse embryonic liver (BMEL) cells spontaneously express Pdx1 and Ngn3 but do not undergo further pancreatic differentiation upon Hes1 down-regulation

<p>Abstract</p> <p>Background</p> <p>Liver-to-pancreas conversion offers new possibilities for β-cell engineering for type 1 diabetes therapy. Among conceivable sources of liver cells, we focused on BMEL cells. These untransformed mouse embryonic liver cells have been reproducibly isolated from different inbred mice strains and have the potential to differentiate into hepatocytes and cholangiocytes <it>in vitro </it>and <it>in vivo</it>.</p> <p>Findings</p> <p>Strikingly, we find here that adherent BMEL cells display functional similarities with multipotent pancreatic precursor cells, namely Pdx1 and Ngn3 expression, and further express <it>Hnf6 </it>in floating aggregate culture. Hes1, a direct repressor of Ngn3 and pancreatic endocrine commitment, is expressed in adherent BMEL cells and decreases with time in aggregate culture. However, Hes1 decrease fails to initiate activation of late-stage pancreatic endocrine transcription factors.</p> <p>Conclusion</p> <p>Here we report that BMEL cells present features of pancreatic endocrine progenitor cells. In the field of diabetes research, BMEL cells are of potential interest for the study of inductive signals critical for in vitro β-cell maturation in-liver-to-pancreas conversion.</p

Type 1 diabetes: from the identification of a crucial autoantigenic epitope to a targeted therapeutic approach

The characterisation of CD8 epitopes is essential to understand the role of autoreactive CD8 T lymphocytes in the development of type 1 diabetes, and will eventually lead to testing new targeted therapeutic approaches. To identify GAD (Glutamic Acid Decarboxylase)-derived CD8 T epitopes, we administered a GAD65-coding plasmid (pc-GAD) to NOD female mice. The pc-GAD plasmidic immunisation activates CD8 T lymphocytes specific of the GAD 90-98 epitope (p90). These lymphocytes are Tc1 cells secreting the cytokines IFNg and TNFa, often associated with autoimmune diabetes. NOD mice developed spontaneously a p90-specific CD8 T cell reaction, as early as 4 weeks of age. Moreover, these lymphocytes were also able to destroy pancreatic islet cells in vitro and can cause diabetes in NOD scid mouse. We present here the initial results of p90 administration to NOD mice, which we hope may prevent the onset of diabetes if administered before its spontaneous activation.La caractérisation d'épitopes T CD8 est déterminante pour mieux comprendre le rôle des lymphocytes T CD8 autoréactifs dans la pathogénie du diabète de type 1 (DT1) et devrait permettre de tester de nouvelles approches thérapeutiques ciblées. Afin d'identifier des épitopes T CD8 relevant de l'autoantigène « Décarboxylase de l'Acide Glutamique » (GAD), nous avons administré à des souris NOD femelles, un plasmide codant pour la GAD65 (pc-GAD). L'immunisation plasmidique pc-GAD induit l'activation de lymphocytes T CD8 spécifiques de l'épitope GAD 90-98 (p90). Ces lymphocytes sont de sous-type Tc1, sécrétant de l'IFNγ et du TNFa, cytokines très souvent associées au développement d'un diabète autoimmun. Spontanément, les souris NOD présentent une réaction lymphocytaire T CD8 Tc1 spécifique de p90 très précoce, dès l'âge de 4 semaines. De plus, les lymphocytes T CD8 spécifiques de p90 attaquent les cellules d'îlots pancréatiques in vitro et induisent un diabète chez la souris NOD scid. Enfin, nous présentons ici les premiers résultats de protocoles d'administration de p90 à des souris NOD. Une telle administration pourrait prévenir l'apparition de la maladie si elle est effectuée avant son activation spontannée

Quantitative estimates on the Hydrogen ground state energy in non-relativistic QED

In this paper, we determine the exact expression for the hydrogen binding energy in the Pauli-Fierz model up to the order $O(\alpha^5\log\alpha^{-1})$, where $\alpha$ denotes the finestructure constant, and prove rigorous bounds on the remainder term of the order $o(\alpha^5\log\alpha^{-1})$. As a consequence, we prove that the binding energy is not a real analytic function of $\alpha$, and verify the existence of logarithmic corrections to the expansion of the ground state energy in powers of $\alpha$, as conjectured in the recent literature.Comment: AMS Latex, 51 page

Pdx-1 or Pdx-1-VP16 protein transduction induces β-cell gene expression in liver-stem WB cells

<p>Abstract</p> <p>Background</p> <p>Pancreatic duodenal homeobox-1 (<it>Pdx-1</it>) or <it>Pdx-1-VP16 </it>gene transfer has been shown to induce <it>in vitro </it>rat liver-stem WB cell conversion into pancreatic endocrine precursor cells. High glucose conditions were necessary for further differentiation into functional insulin-producing cells. Pdx-1 has the ability to permeate different cell types due to an inherent protein transduction domain (PTD). In this study, we evaluated liver-to-pancreas conversion of WB cells following Pdx-1 or Pdx-1-VP16 protein transduction.</p> <p>Findings</p> <p>WB cells were grown in high glucose medium containing Pdx-1 or Pdx-1-VP16 recombinant proteins for two weeks. β-like cell commitment was analysed by RT-PCR of pancreatic endocrine genes. We found that WB cells in high glucose culture spontaneously express pancreatic endocrine genes (<it>Pdx-1, Ngn3, Nkx2.2, Kir6.2</it>). Their further differentiation into β-like cells expressing genes related to endocrine pancreas development (<it>Ngn3, NeuroD, Pax4, Nkx2.2, Nkx6.1, Pdx-1</it>) and β-cell function (<it>Glut-2, Kir6.2, insulin</it>) was achieved only in the presence of Pdx-1(-VP16) protein.</p> <p>Conclusion</p> <p>These results demonstrate that Pdx-1(-VP16) protein transduction is instrumental for <it>in vitro </it>liver-to-pancreas conversion and is an alternative to gene therapy for β-cell engineering for diabetes cell therapy.</p

Spectral theory for a mathematical model of the weak interaction: The decay of the intermediate vector bosons W+/-, II

We do the spectral analysis of the Hamiltonian for the weak leptonic decay of the gauge bosons W+/-. Using Mourre theory, it is shown that the spectrum between the unique ground state and the first threshold is purely absolutely continuous. Neither sharp neutrino high energy cutoff nor infrared regularization are assumed.Comment: To appear in Ann. Henri Poincar\'

Generation of cattle knockout for galactose‐α1,3‐galactose and N‐glycolylneuraminic acid antigens

Two well-characterized carbohydrate epitopes are absent in humans but present in other mammals. These are galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) which are introduced by the activities of two enzymes including α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Gc hydroxylase (encoded by the CMAH gene) that are inactive in humans but present in cattle. Hence, bovine-derived products are antigenic in humans who receive bioprosthetic heart valves (BHVs) or those that suffer from red meat syndrome. Using programmable nucleases, we disrupted (knockout, KO) GGTA1 and CMAH genes encoding for the enzymes that catalyse the synthesis of αGal and Neu5Gc, respectively, in both male and female bovine fibroblasts. The KO in clonally selected fibroblasts was detected by polymerase chain reaction (PCR) and confirmed by Sanger sequencing. Selected fibroblasts colonies were used for somatic cell nuclear transfer (SCNT) to produce cloned embryos that were implanted in surrogate recipient heifers. Fifty-three embryos were implanted in 33 recipients heifers; 3 pregnancies were carried to term and delivered 3 live calves. Primary cell cultures were established from the 3 calves and following molecular analyses confirmed the genetic deletions. FACS analysis showed the double-KO phenotype for both antigens confirming the mutated genotypes. Availability of such cattle double-KO model lacking both αGal and Neu5Gc offers a unique opportunity to study the functionality of BHV manufactured with tissues of potentially lower immunogenicity, as well as a possible new clinical approaches to help patients with red meat allergy syndrome due to the presence of these xenoantigens in the diet

A comparison of treatment-seeking behavioral addiction patients with and without parkinson's disease

The administration of dopaminergic medication to treat the symptoms of Parkinson's disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions

A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson's Disease

The administration of dopaminergic medication to treat the symptoms of Parkinson's disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions

Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018): A Position Statement of the International Society for Extracellular Vesicles and Update of the MISEV2014 Guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points