D-brane Instantons on the T^6/Z_3 orientifold

We give a detailed microscopic derivation of gauge and stringy instanton generated superpotentials for gauge theories living on D3-branes at Z_3-orientifold singularities. Gauge instantons are generated by D(-1)-branes and lead to Affleck, Dine and Seiberg (ADS) like superpotentials in the effective N=1 gauge theories with three generations of bifundamental and anti/symmetric matter. Stringy instanton effects are generated by Euclidean ED3-branes wrapping four-cycles on T^6/\Z_3. They give rise to Majorana masses in one case and non-renormalizable superpotentials for the other cases. Finally we determine the conditions under which ADS like superpotentials are generated in N=1 gauge theories with adjoints, fundamentals, symmetric and antisymmetric chiral matter.Comment: 31 pages, no figure

Effects of vincristine and monosodium glutamate on gastrointestinal motility and visceral sensitivity

Background Chemotherapy‐induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy‐treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats. Methods Young male Wistar rats were exposed or not to MSG (4 g L−1) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg−1) or vincristine (0.1 mg kg−1). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections. Key Results Vincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine‐treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine. Conclusions and Inferences MSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients

Flavour in Intersecting Brane Models and Bounds on the String Scale

We study flavour issues in nonsupersymmetric intersecting brane models. Specifically, the purpose of the present paper is twofold: (i) to determine whether realistic flavour structures can be obtained in these models, and (ii) to establish whether the non-supersymmetric models address the gauge hierarchy problem. To this end, we find that realistic flavour structures, although absent at tree level, can arise even in the simplest models after effects of 4 fermion instanton--induced operators and radiative corrections have been taken into account. On the other hand, our analysis of flavour changing neutral currents (FCNC), electric dipole moments (EDM), supernova SN1987A and other constraints shows that the string scale has to be rather high, 10^4 TeV. This implies that non-supersymmetric intersecting brane models face a severe finetuning problem. Finally, we comment on how non--trivial flavour structures can arise in supersymmetric models.Comment: 33 pages, 11 figures, matches the NPB versio

Potent CCR3 Receptor Antagonist, SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis

Eosinophils and their regulatory molecules have been associated with chronic intestinal inflammation and gastrointestinal dysfunctions; eosinophil accumulation in the gut is prominent in inflammatory bowel disease (IBD). The chemokine receptor CCR3 plays a pivotal role in local and systemic recruitment and activation of eosinophils. In this study, we targeted CCR3-ligand interactions with a potent CCR3 receptor antagonist, SB328437, to alleviate eosinophil-associated immunological responses in the Winnie model of spontaneous chronic colitis. Winnie and C57BL/6 mice were treated with SB328437 or vehicle. Clinical and histopathological parameters of chronic colitis were assessed. Flow cytometry was performed to discern changes in colonic, splenic, circulatory, and bone marrow-derived leukocytes. Changes to the serum levels of eosinophil-associated chemokines and cytokines were measured using BioPlex. Inhibition of CCR3 receptors with SB328437 attenuated disease activity and gross morphological damage to the inflamed intestines and reduced eosinophils and their regulatory molecules in the inflamed colon and circulation. SB328437 had no effect on eosinophils and their progenitor cells in the spleen and bone marrow. This study demonstrates that targeting eosinophils via the CCR3 axis has anti-inflammatory effects in the inflamed intestine, and also contributes to understanding the role of eosinophils as potential end-point targets for IBD treatment

New live attenuated tuberculosis vaccine MTBVAC induces trained immunity and confers protection against experimental lethal pneumonia

Among infectious diseases, tuberculosis is the leading cause of death worldwide, and represents a serious threat, especially in developing countries. The protective effects of Bacillus Calmette-Guerin (BCG), the current vaccine against tuberculosis, have been related not only to specific induction of T-cell immunity, but also with the long-term epigenetic and metabolic reprogramming of the cells from the innate immune system through a process termed trained immunity. Here we show that MTBVAC, a live attenuated strain of Mycobacterium tuberculosis, safe and immunogenic against tuberculosis antigens in adults and newborns, is also able to generate trained immunity through the induction of glycolysis and glutaminolysis and the accumulation of histone methylation marks at the promoters of proinflammatory genes, facilitating an enhanced response after secondary challenge with non-related bacterial stimuli. Importantly, these findings in human primary myeloid cells are complemented by a strong MTBVAC-induced heterologous protection against a lethal challenge with Streptococcus pneumoniae in an experimental murine model of pneumonia.M.G.N. was supported by an ERC Advanced grant (#833247) and by a Spinoza Grant of the Netherlands Organization for Scientific Research (https://erc.europa.eu/). UNIZAR Team was supported by Ministry of Science and Universities Grant RTI2018-097625-B-100 (http://www.ciencia.gob.es/portal/site/MICINN/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Detecting the presence-absence of bluefin tuna by automated analysis of medium-range sonars on fishing vessels

This study presents a methodology for the automated analysis of commercial medium range sonar signals for detecting presence/absence of bluefin tuna (Tunnus thynnus) in the Bay of Biscay. The approach uses image processing techniques to analyze sonar screen shots. For each sonar image we extracted measurable regions and analyzed their characteristics. Scientific data was used to classify each region into a class ("tuna" or "no-tuna") and build a dataset to train and evaluate classification models by using supervised learning. The methodology performed well when validated with commercial sonar screenshots, and has the potential to automatically analyze high volumes of data at a low cost. This represents a first milestone towards the development of acoustic, fishery-independent indices of abundance for bluefin tuna in the Bay of Biscay. Future research lines and additional alternatives to inform stock assessments are also discussed.This research was supported by the Basque Government through PhD grant 0033-2011 to JU and grant GV 351NPVA00062 to HA (AZTI-Tecnalia). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Detecting the presence-absence of bluefin tuna by automated analysis of medium-range sonars on fishing vessels

<div><p>This study presents a methodology for the automated analysis of commercial medium-range sonar signals for detecting presence/absence of bluefin tuna (<i>Tunnus thynnus</i>) in the Bay of Biscay. The approach uses image processing techniques to analyze sonar screenshots. For each sonar image we extracted measurable regions and analyzed their characteristics. Scientific data was used to classify each region into a class (“tuna” or “no-tuna”) and build a dataset to train and evaluate classification models by using supervised learning. The methodology performed well when validated with commercial sonar screenshots, and has the potential to automatically analyze high volumes of data at a low cost. This represents a first milestone towards the development of acoustic, fishery-independent indices of abundance for bluefin tuna in the Bay of Biscay. Future research lines and additional alternatives to inform stock assessments are also discussed.</p></div