A positron trap and beam apparatus for atomic and molecular scattering experiments

An instrument has been designed and constructed to provide new insights into fundamental, low energy positron scattering processes. The design is based on the Surko trap system and produces a pulsed positron beam with an energy resolution of as good as 54 meV. The design and operation of the apparatus is explained, while the first experimental results from this apparatus have been demonstrated in recent publications.The authors would like to acknowledge the Australian Research Council for funding support, through the Centre of Excellence program, as well as the LIEF and Discovery funding programs

(2-Aminobenzothiazole)-Methyl-1,1-bisphosphonic acids: Targeting matrix metalloproteinase 13 inhibition to the bone

Matrix Metalloproteinases (MMPs) are a family of secreted and membrane-bound enzymes, of which 24 isoforms are known in humans. These enzymes degrade the proteins of the extracellular matrix and play a role of utmost importance in the physiological remodeling of all tissues. However, certain MMPs, such as MMP-2, -9, and -13, can be overexpressed in pathological states, including cancer and metastasis. Consequently, the development of MMP inhibitors (MMPIs) has been explored for a long time as a strategy to prevent and hinder metastatic growth, but the important side effects linked to promiscuous inhibition of MMPs prevented the clinical use of MMPIs. Therefore, several strategies were proposed to improve the therapeutic profile of this pharmaceutical class, including improved selectivity toward specific MMP isoforms and targeting of specific organs and tissues. Combining both approaches, we conducted the synthesis and preliminary biological evaluation of a series of (2-aminobenzothiazole)-methyl-1,1-bisphosphonic acids active as selective inhibitors of MMP-13 via in vitro and in silico studies, which could prove useful for the treatment of bone metastases thanks to the bone-targeting capabilities granted by the bisphosphonic acid group

Stokes-parameter representation for Compton scattering of entangled and classically correlated two-photon systems

A Stokes parameter representation for two-photon systems is developed to calculate cross sections for both entangled and classically correlated mixed states scattering off unpolarized and polarized Compton electrons. The cross section of Compton scattering for pairs of maximally entangled annihilation photons, generated by the disintegration of para-positronium, is compared with classical analogs. An analysis of the symmetrical properties and basis independence of these systems is conducted to elucidate the observed differences. We propose a method to establish an upper bound for identifying correlations influenced by entanglement. Furthermore, we calculate the cross section for Compton scattering of annihilation photons from spin-polarized electrons. A qualitative analysis reveals a contradiction to the contemporary assumption that Compton scattering acts as an entanglement kill switch. These findings contribute to a broader understanding of photon systems and their behavior in various scattering scenarios. Although the primary focus of this article is on Compton scattering, the formalism can be adapted to other interactions, provided that the Mueller matrix representation of the interaction is available

Non-invasive diagnosis in a case of bronchopulmonary sequestration and proposal of diagnostic algorhythm

The case of a 43-year-old woman with intralobar pulmonary sequestration, Pryce type one, is presented. The medical history was characterised by recurrent bronchopneumonia, productive cough with purulent sputum and hemoptysis in the last three years. Diagnosis was made by CT angiography: multiplanar, maximum intensity projection and volume rendering reconstructions were visualised. A volume reduction of middle and lower lobe with multiple cyst-like bronchiectasis was detected and no evident relationship with tracheobronchial tree was pointed out. Reconstructions aimed at evaluating bronchial structures demonstrated no patency of middle and lower lobar bronchi. The study carried out after contrast medium infusion in arterial phase showed a vascular disorder characterised by an accessory arterial branch arising from the upper portion of thoracic aorta which, after moving caudally to pulmonary hilus with a tortuous course, supplied the atelectatic parenchyma. No anomalous venous drainage was detected. The patient underwent surgery with resection of two pulmonary lobes. CT compares favourably with other alternative imaging technique for pulmonary sequestration as multiplanar reconstructions allow not only the detection of supplying vessel, but also the accurate description of heterogeneous characteristics of the mass and adjacent structures. Finally an imaging-based diagnostic algorhythm is proposed

A Self-Consistent Model for Positronium Formation from Helium Atoms

The differential and total cross sections for electron capture by positrons from helium atoms are calculated using a first-order distorted wave theory satisfying the Coulomb boundary conditions. In this formalism a parametric potential is used to describe the electron screening in a consistent and realistic manner. The present procedure is self consistent because (i) it satisfies the correct boundary conditions and post-prior symmetry, and (ii) the potential and the electron binding energies appearing in the transition amplitude are consistent with the wave functions describing the collision system. The results are compared with the other theories and with the available experimental measurements. At the considered range of collision energies, the results agree reasonably well with recent experiments and theories. [Note: This paper will be published on volume 42 of the Brazilian Journal of Physics

Spectroscopy Apparatus for the Measurement of The Hyperfine Structure of Antihydrogen

The ASACUSA CUSP collaboration at the Antiproton Decelerator (AD) of CERN is planning to measure the ground-state hyperfine splitting of antihydrogen using an atomic spectroscopy beamline. We describe here the latest developments on the spectroscopy apparatus developed to be coupled to the antihydrogen production setup (CUSP).Comment: Proceedings of the 11th International Conference on Low Energy Antiproton Physics (LEAP 2013) held in Uppsala, Sweden, 10 to 15 June, 201

Non-Hematopoietic Essential Functions of Bone Marrow Cells: A Review of Scientific and Clinical Literature and Rationale for Treating Bone Defects.

Hematopoiesis as the only essential function of bone marrow cells has been challenged for several decades through basic science (in vitro and in vivo) and clinical data. Such work has shed light on two other essential functions of bone marrow cells: osteopoiesis and angio-genesis/vasculogenesis. Clinical utility of autologous concentrated bone marrow aspirate (CBMA) has demonstrated both safety and efficacy in treating bone defects. Moreover, CBMA has been shown to be comparable to the gold standard of iliac crest bone graft (ICBG), or autograft, with regard to being osteogenic and osteoinductive. ICBG is not considered an advanced therapy medicinal product (ATMP), but CBMA may become regulated as an ATMP. The European Medicines Agency Committee for Advanced Therapies (EMA:CAT) has issued a reflection paper (20 June 2014) in which reversal of the 2013 ruling that CBMA is a non-ATMP has been proposed. We review bone marrow cell involvement in osteopoiesis and angiogenesis/vasculogenesis to examine EMA:CAT 2013 decision to use CBMA for treatment of osteonecrosis (e.g, of the femoral head) should be considered a non-ATMP. This paper is intended to provide discussion on the 20 June 2014 reflection paper by reviewing two non-hematopoietic essential functions of bone marrow cells. Additionally, we provide clinical and scientific rationale for treating osteonecrosis with CBMA

siRNA screen identifies QPCT as a druggable target for Huntington's disease.

Huntington's disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified new modifiers of mutant HTT toxicity by performing a large-scale 'druggable genome' siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone αB-crystallin and reduced the aggregation of diverse proteins. We generated new QPCT inhibitors using in silico methods followed by in vitro screening, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a new HD druggable target affecting mutant HTT aggregation and provide proof of principle for a discovery pipeline from druggable genome screen to drug development

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection

Serological Markers for Inflammatory Bowel Disease in AIDS Patients with Evidence of Microbial Translocation

Background: Breakdown of the gut mucosal barrier during chronic HIV infection allows translocation of bacterial products such as lipopolysaccharides (LPS) from the gut into the circulation. Microbial translocation also occurs in inflammatory bowel disease (IBD). IBD serological markers are useful in the diagnosis of IBD and to differentiate between Crohn's disease (CD) and ulcerative colitis (UC). Here, we evaluate detection of IBD serological markers in HIV-infected patients with advanced disease and their relationship to HIV disease markers.Methods IBD serological markers (ASCA, pANCA, anti-OmpC, and anti-CBir1) were measured by ELISA in plasma from AIDS patients (n = 26) with low CD4 counts (<300 cells/$\mu$l) and high plasma LPS levels, and results correlated with clinical data. For meta-analysis, relevant data were abstracted from 20 articles. Results: IBD serological markers were detected in approximately 65% of AIDS patients with evidence of microbial translocation. An antibody pattern consistent with IBD was detected in 46%; of these, 75% had a CD-like pattern. Meta-analysis of data from 20 published studies on IBD serological markers in CD, UC, and non-IBD control subjects indicated that IBD serological markers are detected more frequently in AIDS patients than in non-IBD disease controls and healthy controls, but less frequently than in CD patients. There was no association between IBD serological markers and HIV disease markers (plasma viral load and CD4 counts) in the study cohort. Conclusions: IBD serological markers may provide a non-invasive approach to monitor HIV-related inflammatory gut disease. Further studies to investigate their clinical significance in HIV-infected individuals are warranted