Conicoid Mirrors

The first order equation relating object and image location for a mirror of arbitrary conic-sectional shape is derived. It is also shown that the parabolic reflecting surface is the only one free of aberration and only in the limiting case of distant sources.Comment: 9 page

SYZ mirror symmetry for hypertoric varieties

We construct a Lagrangian torus fibration on a smooth hypertoric variety and a corresponding SYZ mirror variety using $T$-duality and generating functions of open Gromov-Witten invariants. The variety is singular in general. We construct a resolution using the wall and chamber structure of the SYZ base.Comment: v_2: 31 pages, 5 figures, minor revision. To appear in Communications in Mathematical Physic

Postpartum sterilization choices made by HIV-infected women.

OBJECTIVE: To assess if HIV-infected women made different choices for postpartum sterilization after implementation of the Pediatric AIDS Clinical Trials Group protocol 076 (November 1, 1994) compared to before implementation. STUDY DESIGN: A retrospective cohort study in which medical records were reviewed to obtain demographic, obstetric and HIV-related data from January 1993 through December 2002. HIV-infected women who completed a pregnancy by birth or abortion were divided into two comparison groups: "Pre-076" and "Post-076". The primary outcome was sterilization by postpartum tubal ligation.Results. Forty-two women (74%) in the Pre-076 group chose sterilization compared to 139 of 310 women (45%) in the Post-076 group (unadjusted OR 3.44, 95% CI 1.83, 6.47). Seventy-one percent of women younger than 21 years of age in the Pre-076 Group chose sterilization compared with only 35% of women younger than 21 years in the Post-076 group (p = 0.0136). Similarly, 78% of primiparous women chose sterilization after their first pregnancy in the Pre-076 group, compared to 14% in the Post-076 group (p < 0.001). CONCLUSIONS: Since the implementation of PACTG 076 protocol in November 1994, fewer HIV-infected women chose postpartum sterilization. The typical woman who now chooses postpartum sterilization is less likely to be young or primiparous than those who chose sterilization before PACTG Protocol 076 implementation

Theory of conductance and noise additivity in parallel mesoscopic conductors

We present a theory of conductance and noise in generic mesoscopic conductors connected in parallel, and we demonstrate that the additivity of conductance and of shot noise arises as a sole property of the junctions connecting the two (or more) conductors in parallel. Consequences on the functionality of devices based on the Aharonov-Bohm effect are also drawn.Comment: 4 pages, 2 figure

A randomized placebo-controlled N-of-1 trial: the effect of proton pump inhibitor in the management of gastroesophageal reflux disease

Control de acidez; Esomeprazol; Reflujo gastroesofágicoControl d'acidesa; Esomeprazol; Reflux gastroesofàgicAcid control; Esomeprazole; Gastroesophageal refluxBackground. Gastroesophageal reflux disease (GERD) is the most frequent chronic gastrointestinal disorder. It is defined as a condition developed when the reflux of gastric contents causes troublesome symptoms (heartburn and regurgitation). This requires adequate treatment since it can lead to long-term complications including esophagus adenocarcinoma. Proton pump inhibitors (PPI) are generally used to treat GERD due to their high-security profile and efficiency on most patients. However, recurrent reflux despite initial treatment is frequent. N-of-1 trial is a study that allows the identification of the best treatment for each patient. The objective of this study is to compare the efficacy of standard dose with double dosage of esomeprazole, to improve the GERD symptoms in a single patient. Methods. A single-patient trial, placebo-controlled, randomized, double-blind, was carried out from September 25th, 2012, to April 26th, 2013. It included one outpatient at the gastroenterology service in a fourth-level hospital, diagnosed with nonerosive reflux disease (NERD). Yet, his symptoms were heartburn and reflux, and his endoscopic results were normal esophageal mucosa, without hiatal hernia, though pathological pH values. A no-obese male without any tobacco or alcohol usage received esomeprazole 40 mg/day and 40 mg/bid for 24 weeks. A standardized gastroesophageal reflux disease questionnaire (GerdQ) was used weekly to evaluate symptom frequency and severity. The consumption of 90% of the capsules was considered as an adequate treatment adherence. D’agostino–Pearson and Wilcoxon test were used to determine normal or nonnormal distribution and compare both treatments, respectively, both with a significant statistical difference of p0.05). Conclusion. There was no significant improvement in the patient GERD symptoms increasing the dose of oral esomeprazole during the 6 months of study. N-of-1 trials in chronic pathologies including GERD are recommended due to their potential value as systematic methods that evaluate therapies without strong scientific evidence

Applying Goldratt’s Framework to the Banking System

This paper describes the major elements of the Goldratt’s framework – the Theory of Constraints (TOC) – in the banking sector, and examines the factors involved in the decision to adopt the TOC by companies in this sector. Through a deep literature review, analyzing similar cases that apply the Goldratt’s framework in services and in manufacturing and the severalviews of its components, we aim at formulating a framework specifically for the banking system.The study uses a qualitative methodology supported by the information extracted from reality as it is framed in a multicase study model. As part of the quantitative approach, we test several research hypotheses raised from the review of existing studies in the area.The main factors that influence the decision to adopt the TOC are the nature and the characteristics of the banking service, the attitude towards change, the leadership and the commitment of the entire institution.By using the Goldratt’s approach outlined in this article, through the location of the constraints and develop practical measurement to facilitate the banking process improvements, banks can improve resource utilization, revenues and employee satisfaction

In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines

OXFORD UNIVERSITY: This is a pre-copyedited, author-produced version of an article accepted for publication in Carcinogenesis following peer review. The version of record David Rincón-Fernández, Michael D Culler, Natia Tsomaia, Gema Moreno-Bueno, Raúl M Luque, Manuel D Gahete, Justo P Castaño; In1-ghrelin splicing variant is associated with reduced disease-free survival of breast cancer patients and increases malignancy of breast cancer cells lines, Carcinogenesis, Volume 39, Issue 3, 8 March 2018, Pages 447–457, https://doi.org/10.1093/carcin/bgx146Ghrelin gene generates several variants that regulate multiple pathophysiological functions, including tumor-related processes. In1-ghrelin is a splicing variant that was previously shown to be overexpressed in breast cancer (BCa), where it correlated with proliferation markers; however, its possible association with clinical outcome of BCa patients and underlying mechanisms are still unknown. To address this issue, expression levels and clinical associations of In1-ghrelin were analyzed in a cohort of 117 BCa samples. Additionally, a battery of cellular and molecular assays was implemented using two BCa cell lines (MCF-7 and MDA-MB-231), wherein the role of In1-ghrelin on proliferation, migration, dedifferentiation and signaling pathways was explored. The results generated revealed that high expression of In1-ghrelin in BCa samples was associated with lymph node metastasis and reduced disease-free survival. Indeed, In1-ghrelin overexpression stimulated proliferation and migration in MCF-7 and MDA-MB-231 cells. Similar results were found by treating MDA-MB-231 and MCF-7 with In1- ghrelin-derived peptides. Conversely, In1-ghrelin silencing decreased proliferation and migration capacities of MDA-MB-231. Furthermore, In1-ghrelin (but not ghrelin) overexpression increased the capacity to form mammospheres in both cell lines. These effects could be associated with activation of MAPK-ERK, Jag1/Notch, Wnt/β-catenin and/or TGF-β1 pathways. Altogether, our data indicate that In1-ghrelin could play relevant functional roles in the regulation of BCa development and progression and may provide insights to identify novel biomarkers and new therapeutic approaches for this pathology.BIO-0139, CTS-1406, PI-639-2012, PI-0541-2013 (Junta de Andalucia), BFU2013-43282-R, BFU2016-80360-R (MINECO), PI13-00651, PI16/00264 (Proyectos de Investigación en Salud FIS, funded by Instituto de Salud Carlos III), GETNE Grant 2014, Merck Serono Grant 2013 and CIBERobn (to RML and JPC); PI13/00132, RETICC RD12/0036/0007, CIBERonc and S2010/BMD-2303 (to GMB

Detergent resistant membrane-associated IDE in brain tissue and cultured cells: Relevance to Aβ and insulin degradation

<p>Abstract</p> <p>Background</p> <p>Insulin degrading enzyme (IDE) is implicated in the regulation of amyloid β (Aβ) steady-state levels in the brain, and its deficient expression and/or activity may be a risk factor in sporadic Alzheimer's disease (AD). Although IDE sub-cellular localization has been well studied, the compartments relevant to Aβ degradation remain to be determined.</p> <p>Results</p> <p>Our results of live immunofluorescence, immuno gold electron-microscopy and gradient fractionation concurred to the demonstration that endogenous IDE from brain tissues and cell cultures is, in addition to its other localizations, a detergent-resistant membrane (DRM)-associated metallopeptidase. Our pulse chase experiments were in accordance with the existence of two pools of IDE: the cytosolic one with a longer half-life and the membrane-IDE with a faster turn-over. DRMs-associated IDE co-localized with Aβ and its distribution (DRMs vs. non-DRMs) and activity was sensitive to manipulation of lipid composition in vitro and in vivo. When IDE was mis-located from DRMs by treating cells with methyl-β-cyclodextrin (MβCD), endogenous Aβ accumulated in the extracellular space and exogenous Aβ proteolysis was impaired. We detected a reduced amount of IDE in DRMs of membranes isolated from mice brain with endogenous reduced levels of cholesterol (Chol) due to targeted deletion of one seladin-1 allele. We confirmed that a moderate shift of IDE from DRMs induced a substantial decrement on IDE-mediated insulin and Aβ degradation in vitro.</p> <p>Conclusion</p> <p>Our results support the notion that optimal substrate degradation by IDE may require its association with organized-DRMs. Alternatively, DRMs but not other plasma membrane regions, may act as platforms where Aβ accumulates, due to its hydrophobic properties, reaching local concentration close to its Km for IDE facilitating its clearance. Structural integrity of DRMs may also be required to tightly retain insulin receptor and IDE for insulin proteolysis. The concept that mis-location of Aβ degrading proteases away from DRMs may impair the physiological turn-over of Aβ in vivo deserves further investigation in light of therapeutic strategies based on enhancing Aβ proteolysis in which DRM protease-targeting may need to be taken into account.</p