Elliptic logarithms, diophantine approximation and the Birch and Swinnerton-Dyer conjecture

Most, if not all, unconditional results towards the abc-conjecture rely ultimately on classical Baker's method. In this article, we turn our attention to its elliptic analogue. Using the elliptic Baker's method, we have recently obtained a new upper bound for the height of the S-integral points on an elliptic curve. This bound depends on some parameters related to the Mordell-Weil group of the curve. We deduce here a bound relying on the conjecture of Birch and Swinnerton-Dyer, involving classical, more manageable quantities. We then study which abc-type inequality over number fields could be derived from this elliptic approach.Comment: 20 pages. Some changes, the most important being on Conjecture 3.2, three references added ([Mas75], [MB90] and [Yu94]) and one reference updated [BS12]. Accepted in Bull. Brazil. Mat. So

Decitabine impact on the endocytosis regulator RhoA, the folate carriers RFC1 and FOLR1, and the glucose transporter GLUT4 in human tumors.

BackgroundIn 31 solid tumor patients treated with the demethylating agent decitabine, we performed tumor biopsies before and after the first cycle of decitabine and used immunohistochemistry (IHC) to assess whether decitabine increased expression of various membrane transporters. Resistance to chemotherapy may arise due to promoter methylation/downregulation of expression of transporters required for drug uptake, and decitabine can reverse resistance in vitro. The endocytosis regulator RhoA, the folate carriers FOLR1 and RFC1, and the glucose transporter GLUT4 were assessed.ResultsPre-decitabine RhoA was higher in patients who had received their last therapy >3 months previously than in patients with more recent prior therapy (P = 0.02), and varied inversely with global DNA methylation as assessed by LINE1 methylation (r = -0.58, P = 0.006). Tumor RhoA scores increased with decitabine (P = 0.03), and RFC1 also increased in patients with pre-decitabine scores ≤150 (P = 0.004). Change in LINE1 methylation with decitabine did not correlate significantly with change in IHC scores for any transporter assessed. We also assessed methylation of the RFC1 gene (alias SLC19A1). SLC19A1 methylation correlated with tumor LINE1 methylation (r = 0.45, P = 0.02). There was a small (statistically insignificant) decrease in SLC19A1 methylation with decitabine, and there was a trend towards change in SLC19A1 methylation with decitabine correlating with change in LINE1 methylation (r = 0.47, P <0.15). While SLC19A1 methylation did not correlate with RFC1 scores, there was a trend towards an inverse correlation between change in SLC19A1 methylation and change in RFC1 expression (r = -0.45, P = 0.19).ConclusionsIn conclusion, after decitabine administration, there was increased expression of some (but not other) transporters that may play a role in chemotherapy uptake. Larger patient numbers will be needed to define the extent to which this increased expression is associated with changes in DNA methylation

Social Entrepreneurship—Building Sustainability Through Business Models and Measurement of Social Impact

Social entrepreneurshipSocial entrepreneurship is gaining unprecedented momentum in the recent years and it is overwhelming to learn how social entrepreneurs are able to create both social and economic value overcoming all odds and sustain and grow their ventures. Social enterprise can be a for-profit or a not-for- profit venture in their constitution. This research study presents a comparative case analysis of four social ventures two of them are not-for-profit organisations and depend mainly on philanthropic partners for funding. The other two are for-profit social venturesNot-for-profit Social venture and create products and services which are commercially viable. Three of the founders are Ashoka fellows and one is a national award winning social entrepreneur, all based in India. Irrespective of the nature of enterprise, developing a viable business modelBusiness model is crucial for the sustainabilitySustainability of the venture. Analysis of these organisations’ business models reveals different patterns. The findings suggest that successful social entrepreneurial organisations proactively create their own ways to partner with multiple stakeholders who share their social visionVision ; deploy resources effectively as an integral part of the business model; and integrate the target group into the social value network

The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

We extend the effective fragment molecular orbital method (EFMO) into treating fragments connected by covalent bonds. The accuracy of EFMO is compared to FMO and conventional ab initio electronic structure methods for polypeptides including proteins. Errors in energy for RHF and MP2 are within 2 kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides similar to FMO but obtained two to five times faster. For proteins, the errors are also within a few kcal/mol of the FMO results. We developed both the RHF and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip

Internal and external cooling methods and their effect on body temperature, thermal perception and dexterity

© 2018 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0191416© 2018 Maley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective The present study aimed to compare a range of cooling methods possibly utilised by occupational workers, focusing on their effect on body temperature, perception and manual dexterity. Methods Ten male participants completed eight trials involving 30 min of seated rest followed by 30 min of cooling or control of no cooling (CON) (34C, 58% relative humidity). The cooling methods utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14C (CV14), evaporative cooling vest (CVEV), arm immersion in 10C water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice slushy ingestion (SL). Immediately before and after cooling, participants were assessed for fine (Purdue pegboard task) and gross (grip and pinch strength) manual dexterity. Rectal and skin temperature, as well as thermal sensation and comfort, were monitored throughout. Results Compared with CON, SL was the only method to reduce rectal temperature (P = 0.012). All externally applied cooling methods reduced skin temperature (P0.05). Conclusion The present study observed that ice ingestion or ice applied to the skin produced the greatest effect on rectal and skin temperature, respectively. AI should not be utilised if workers require subsequent fine manual dexterity. These results will help inform future studies investigating appropriate pre-cooling methods for the occupational worker.This project is financially supported by the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Canine Ependymoma: Diagnostic Criteria and Common Pitfalls

Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms

Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions

Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error

Changes in visual function after intraocular pressure reduction using antiglaucoma medications

Purpose To evaluate the change in visual function after starting glaucoma treatment and correlate this to a decrease in intraocular pressure (IOP) in primary open-angle glaucoma patients.Methods A prospective, randomized clinical trial was carried out involving 54 glaucoma patients (54 eyes). After inclusion, patients randomly received timolol maleate 0.5%, brimonidine tartrate 0.2%, or travoprost 0.004% in one randomly selected eye. Patients underwent Goldmann applanation tonometry, visual acuity test, standard automated perimetry (SAP), visual quality perception test (visual analogue scale), and contrast sensitivity (CS) test, in a random order before and after the 4-week glaucoma treatment.Results There were statistically significant changes in IOP (mean change [standard deviation], 7.8 [3.6] mmHg, P 0.001), SAP mean deviation index (0.84 [2.45] dB, P = 0.02), visual quality perception (0.56 [1.93], P = 0.045), and CS at frequencies of 12 cycles/degree (0.10 [0.37], P = 0.03) and 18 cycles/degree (0.18 [0.42], P = 0.02) after the 4-week treatment when compared with baseline. No statistically significant differences were found between the treatment groups in visual function changes after treatment (P > 0.40). No significant correlations between IOP reduction and changes in visual function were found (P > 0.30).Conclusions Visual quality perception, visual field mean deviation index, and CS at higher frequencies improve after starting glaucoma therapy. However, no correlation was found between IOP reduction and changes in visual function, and no differences were found in visual function when the three medications studied were compared. Eye (2009) 23, 1081-1085; doi:10.1038/eye.2008.226; published online 1 August 2008Universidade Federal de São Paulo, Glaucoma Serv, Dept Ophthalmol, BR-01404001 São Paulo, BrazilUniversidade Federal de São Paulo, Glaucoma Serv, Dept Ophthalmol, BR-01404001 São Paulo, BrazilWeb of Scienc