bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender‐specific expression of GIBBERELLIC ACID INSENSITIVE is critical for unisexual organ initiation in dioecious Spinacia oleracea
Authors: West Nicholas W. , Golenberg Edward M. 
Published: December 2017

Summary

While unisexual flowers have evolved repeatedly throughout angiosperm families, the actual identification of sex‐determining genes has been elusive, and their regulation within populations remains largely undefined. Here, we tested the mechanism of the feminization pathway in cultivated spinach (Spinacia oleracea), and investigated how this pathway may regulate alternative sexual development.

We tested the effect of gibberellic acid (GA) on sex determination through exogenous applications of GA and inhibitors of GA synthesis and proteasome activity. GA concentrations in multiple tissues were estimated by enzyme‐linked immunosorbent assay analysis. Gene function was investigated and pathway analysis was performed through virus‐induced gene silencing. Relative gene expression levels were estimated by quantitative reverse transcription−polymerase chain reaction.

Inhibition of GA production and proteasome activity feminized male flowers. However, there was no difference in GA content in tissues between males and females. We characterized a single DELLA family transcription factor gene (GIBBERELLIC ACID INSENSITIVE (SpGAI)) and observed inflorescence expression in females two‐fold higher than in males. Reduction of SpGAI expression in females to male levels phenocopied exogenous GA application with respect to flower development.

These results implicate SpGAI as the feminizing factor in spinach, and suggest that the feminizing pathway is epistatic to the masculinizing pathway. We present a unified model for alternative sexual development and discuss the implications for established theory.
The Asymmetric Impact of Customer Information Portability on Service Competition: Evidence from the Global Wireless Industry
Authors: Wei Xiahua , Zhu Kevin Xiaoguo 
Published: December 2017

We study the impact of customer information portability on market competition in customer‐centric, technology‐intensive service industries. By allowing customer information to be transferrable among service providers, portability in theory may help reduce switching costs and promote competition. Yet the actual consequences are unclear. To investigate this issue, we focus on the global wireless industry, and examine the impact of mobile number portability (MNP) policy. We construct a duopoly model with heterogeneous switching costs, which predicts that the market share of the large firm will shrink after MNP, while the average price may depend on firms’ customer base composition. We test these hypotheses empirically on a panel dataset of 218 wireless operators in 52 countries over 6 years. We find relative market share gains for small firms and reductions for large firms under MNP. However, large firms can maintain higher prices than small firms. Probing deeper into customer segmentation, we find that on average, the share of contract customers increases for large firms after MNP, while it decreases for small firms. Large firms are able to retain higher‐value contract customers while small firms tend to attract lower‐value “pay‐as‐you‐go” customers. Contrary to the policy intention, large firms tend to remain dominant, and MNP is incapable of changing this. In fact, contracts become even more important after MNP, highlighting the sticky “lock‐in” effect of contracts. Our findings have broad applicability to other service industries (e.g., healthcare, financial services, and digital media), where policymakers are considering making customer information more portable in hopes of increasing competition.
Determining radius of convergence of Newton’s method using radius of curvature
Authors: Pandiya Ridwan , Mohd Ismail 
Published: December 2017

In this paper, we propose a method on how to manage the convergence of Newton’s method if its iteration process encounters a local extremum. This idea establishes the osculating circle at a local extremum. It then uses the radius of the osculating circle also known as the radius of the curvature as an additional number of the local extremum. It then takes that additional number and combines it with the local extremum. This is then used as an initial guess in finding a root near to that local extremum. This paper will provide several examples which demonstrate that our idea is successful and they perform to fulfill the aim of this paper.
Cartografías de la sorpresa: prácticas artísticas y paisajes sonoros urbanos en Colombia
Authors: Jaramillo Arango Julian 
Published: December 2017

<p>Este texto se propone reseñar de manera crítica tres esfuerzos investigativos que proponen cartografías sonoras de espacios urbanos en Bogotá, Cali y Medellín. Estos trabajos manifiestan una evolución conceptual de las prácticas artísticas asociadas a la valoración del paisaje sonoro y discuten, desde el arte, la arquitectura y la cinematografía interactiva asuntos como la escucha, la identidad cultural y el patrimonio inmaterial. A lo largo del texto serán examinados algunos de los principales conceptos que rodean el paisaje sonoro identificando sus gestores y su adopción en las prácticas sonoras en Colombia. Además, serán discutidos aspectos subjetivos e individuales de la escucha y su relación con el paisaje sonoro, lo cual permitirá reconocer el alcance de los proyectos y sus conexiones con algunas contingencias de las ciudades contemporáneas. El criterio de utilización de los medios fonográficos es también tomado como un asunto de interés artístico que evidencia la diversidad de intenciones y procedimientos en las prácticas de mapeo sonoro en el país.</p><p class="normal"> </p>
Whole-Cell Screen of Fragment Library Identifies Gut Microbiota Metabolite Indole Propionic Acid as Antitubercular
Authors: Negatu Dereje A. , Liu Joe J. J. , Zimmerman Matthew , Kaya Firat , Dartois Véronique , Aldrich Courtney C. , Gengenbacher Martin , Dick Thomas 
Published: December 2017

ABSTRACT

Several key antituberculosis drugs, including pyrazinamide, with a molecular mass of 123.1 g/mol, are smaller than the usual drug-like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular masses centered around 400 to 500 g/mol. Fragment (molecular mass < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1,000 fragments, present in the Maybridge Ro3 library, for whole-cell activity against
Mycobacterium tuberculosis
. Twenty-nine primary hits showed dose-dependent growth inhibition equal to or better than that of pyrazinamide. The most potent hit, indole propionic acid [IPA; 3-(1
H
-indol-3-yl)propanoic acid], a metabolite produced by the gut microbiota, was profiled
in vivo
. The molecule was well tolerated in mice and showed adequate pharmacokinetic properties. In a mouse model of acute
M. tuberculosis
infection, IPA reduced the bacterial load in the spleen 7-fold. Our results suggest that IPA should be evaluated as an add-on to current regimens and that fragment libraries should be further explored to identify antimycobacterial lead candidates.
Adverse Effects of Intravenous Vancomycin-Based Prophylaxis during Therapy for Pediatric Acute Myeloid Leukemia
Authors: Sun Yilun , Huskey Rachael L. , Tang Li , Inaba Hiroto , Gaur Aditya H. , Ribeiro Raul , Rubnitz Jeffrey E. , Wolf Joshua 
Published: December 2017

ABSTRACT

Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infections, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk but might increase the risks of renal or liver toxicity or
Clostridium difficile
infection (CDI). A retrospective review of data for patients treated for newly diagnosed AML at St. Jude Children's Research Hospital between 2002 and 2008 was conducted. Nephrotoxicity was classified according to pediatric risk, injury, failure, loss, and end-stage renal disease (pRIFLE) criteria and hepatotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. The risks of nephrotoxicity, hepatotoxicity, and CDI were compared between patients receiving vancomycin-based prophylaxis, no intravenous prophylaxis, or other prophylaxis. Generalized linear mixed models were used to address potential confounding. A total of 392 chemotherapy courses (108 with no intravenous prophylaxis, 218 with vancomycin-based prophylaxis, and 66 with other prophylaxis) for 111 patients were included. Development of pRIFLE risk, injury, and failure occurred in 190, 44, and 2 courses, respectively. Increases of at least one, two, and three grades for hepatotoxicity occurred in 189, 52, and 19 courses, respectively. After adjustment for confounders, vancomycin-based prophylaxis was not associated with nephrotoxicity or hepatotoxicity and reduced the risk of CDI, compared to no intravenous prophylaxis (0.9% versus 6.5%;
P
= 0.007) or other prophylactic regimens (0.9% versus 3.0%;
P
= 0.23). Despite concerns about vancomycin toxicity, vancomycin-based prophylaxis in pediatric patients with AML did not increase the risk of nephrotoxicity or hepatotoxicity and reduced the risk of CDI. Caution is advised to avoid contributing to antibiotic resistance.
Plasmodium falciparum Recrudescence Two Years after Treatment of an Uncomplicated Infection without Return to an Area Where Malaria Is Endemic
Authors: Malvy Denis , Torrentino-Madamet Marylin , L'Ollivier Coralie , Receveur Marie-Catherine , Jeddi Fakhri , Delhaes Laurence , Piarroux Renaud , Millet Pascal , Pradines Bruno 
Published: December 2017

ABSTRACT

We report evidence, confirmed by the lack of travel activity outside of France and genetic diversity analysis using polymorphic microsatellite markers, that
Plasmodium falciparum
malaria infection effectively treated with an artemisinin-based combination can remain dormant and relapse during pregnancy at least 2 years after treatment.
Cystatins 9 and C as a Novel Immunotherapy Treatment That Protects against Multidrug-Resistant New Delhi Metallo-Beta-Lactamase-1-Producing Klebsiella pneumoniae
Authors: Holloway Alex J. , Yu JiehJuen , Arulanandam Bernard P. , Hoskinson Sarah M. , Eaves-Pyles Tonyia 
Published: December 2017

ABSTRACT

Multidrug-resistant (MDR) bacterial pneumonia can induce dysregulated pulmonary and systemic inflammation leading to morbidity and mortality. Antibiotics to treat MDR pathogens do not function to modulate the extent and intensity of inflammation and can have serious side effects. Here we evaluate the efficacy of two human cysteine proteinase inhibitors, cystatin 9 (CST9) and cystatin C (CSTC), as a novel immunotherapeutic treatment to combat MDR New Delhi metallo-beta-lactamase-1 (NDM-1)-producing
Klebsiella pneumoniae
. Our results showed that mice infected intranasally (i.n.) with a 90% lethal dose (LD
90
) challenge of NDM-1
K. pneumoniae
and then treated with the combination of human recombinant CST9 (rCST9) and rCSTC (rCSTs; 50 pg of each i.n. at 1 h postinfection [p.i.] and/or 500 pg of each intraperitoneally [i.p.] at 3 days p.i.) had significantly improved survival compared to that of infected mice alone or infected mice treated with individual rCSTs (
P
< 0.05). Results showed that both of our optimal rCST treatment regimens modulated pulmonary and systemic proinflammatory cytokine secretion in the serum, lungs, liver, and spleen in infected mice (
P
< 0.05). Treatment also significantly decreased the bacterial burden (
P
< 0.05) while preserving lung integrity, with reduced inflammatory cell accumulation compared to that in infected mice. Further, rCST treatment regimens reduced lipid peroxidation and cell apoptosis in the lungs of infected mice. Additionally,
in vitro
studies showed that rCSTs (50 or 500 pg of each) directly decreased the viability of NDM-1
K. pneumoniae
. In conclusion, the data showed that rCST9/rCSTC worked synergistically to modulate host inflammation against MDR NDM-1
K. pneumoniae
pneumonia, which significantly improved survival. Therefore, rCST9/rCSTC is a promising therapeutic candidate for the treatment of bacterial pneumonia.
Protocol for the specialist supervised individualised multifactorial treatment of new clinically diagnosed type 2 diabetes in general practice (IDA): a prospective controlled multicentre open-label intervention study
Authors: Stidsen Jacob Volmer , Nielsen Jens Steen , Henriksen Jan Erik , Friborg Søren Gunnar , Thomsen Reimar Wernich , Olesen Thomas Bastholm , Olsen Michael Hecht , Beck-Nielsen Henning 
Published: December 2017

IntroductionWe present the protocol for a multifactorial intervention study designed to test whether individualised treatment, based on pathophysiological phenotyping and individualised treatment goals, improves type 2 diabetes (T2D) outcomes.Methods and analysisWe will conduct a prospective controlled multicentre open-label intervention study, drawing on the longitudinal cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2). New clinically diagnosed patients with T2D in the intervention group will be assigned to receive individualised treatment by their general practitioner. Intervention patients will be compared with a matched control cohort of DD2 patients receiving routine clinical care. Among intervention patients, we will first do pathophysiological phenotyping to classify patients into WHO-defined T2D or other specific types of diabetes (monogenic diabetes, secondary diabetes etc). Patients with WHO-defined T2D will then be further subcharacterised by their beta-cell function (BCF) and insulin sensitivity (IS), using the revised homeostatic assessment model, as having either insulinopaenic T2D (high IS and low BCF), classical T2D (low IS and low BCF) or hyperinsulinaemic T2D (low IS and high BCF). For each subtype, a specific treatment algorithm will target the primary pathophysiological defect. Similarly, antihypertensive treatment will be targeted at the specific underlying pathophysiology, characterised by impedance cardiography (relative importance of vascular resistance, intravascular volume and cardiac inotropy). All treatment goals will be based on individual patient assessment of expected positive versus adverse effects. Web-based and face-to-face individualised lifestyle intervention will also be implemented to empower patients to make a sustainable improvement in daily physical activity and to change to a low-carbohydrate diet.Ethics and disseminationThe study will use well-known pharmacological agents according to their labels; patient safety is therefore considered high. Study results will be published in international peer-reviewed journals.Trial registration numberNCT02015130; Pre-results.
Investigation of time to first presentation and extrahospital factors in the treatment of neovascular age-related macular degeneration: a retrospective cross-sectional study
Authors: Sim Peng Yong , Gajree Sonul , Dhillon Baljean , Borooah Shyamanga 
Published: December 2017

ObjectivesTo assess the time from symptom onset to treatment for neovascular age-related macular degeneration (nvAMD) and to measure the awareness of AMD in Southeast Scotland.DesignRetrospective cross-sectional study.SettingSecondary care, Southeast of Scotland.MethodsPatients treated with intravitreal therapy (IVT) for nvAMD in Southeast Scotland between 2013 and 2015 were identified using a treatment register. Notes were retrospectively reviewed. We measured time from: (A) symptom onset to first presentation at primary care, (B) referral to ophthalmic clinic appointment and (C) ophthalmic clinic appointment to first IVT treatment. To investigate AMD awareness, we performed a cluster random sample survey of patients visiting non-AMD ophthalmic clinics using a previously validated 12-item questionnaire.Results195 patients (mean age 78 years) were included in the study. The mean delays between the different stages—A, B and C—were 54.2 (95% CI ±13), 28.2 (95% CI ±4.0) and 31.5 (95% CI ±3.6) days, respectively. There was an additional mean delay of 7.5 (95% CI ±1.6) days when patients were indirectly referred by optometrists via general practitioners (P<0.05). 140 patients (mean age 78) participated in the awareness survey; 62.1% reported being ‘aware’ of AMD but only 37.3% described AMD symptoms correctly.ConclusionsThere was a significant delay at every step of the nvAMD care pathway. The causes for this were multifactorial and included delays in first presentation to a healthcare provider, referral from primary care and initiation of secondary care treatment. Our data are likely to underestimate prehospital delays as a large number of cases are likely to have undefined symptoms and onset. We also identified suboptimal awareness of AMD which could account for a substantial delay in presentation from symptom onset. These findings highlight the need to address AMD awareness and the need for urgent treatment to prevent avoidable vision loss resulting from nvAMD.
Adapting the emergency first aid responder course for Zambia through curriculum mapping and blueprinting
Authors: Pigoga Jennifer L , Cunningham Charmaine , Kafwamfwa Muhumpu , Wallis Lee A 
Published: December 2017

ObjectivesCommunity members are often the first to witness and respond to medical and traumatic emergencies, making them an essential first link to emergency care systems. The Emergency First Aid Responder (EFAR) programme is short course originally developed to help South Africans manage emergencies at the community level, pending arrival of formal care providers. EFAR was implemented in two rural regions of Zambia in 2015, but no changes were originally made to tailor the course to the new setting. We undertook this study to identify potential refinements in the original EFAR curriculum, and to adapt it to the local context in Zambia.DesignThe EFAR curriculum was mapped against available chief complaint data. An expert group used information from the map, in tandem with personal knowledge, to rank each course topic for potential impact on patient outcomes and frequency of use in practice. Individual blueprints were compiled to generate a refined EFAR curriculum, the time breakdown of which reflects the relative weight of each topic.SettingThis study was conducted based on data collected in Kasama, a rural region of Zambia’s Northern Province.ParticipantsAn expert group of five physicians practising emergency medicine was selected; all reviewers have expertise in the Zambian context, EFAR programme and/or curriculum development.ResultsThe range of emergencies that Zambian EFARs encounter indicates that the course must be broad in scope. The refined curriculum covers 54 topics (seven new) and 25 practical skills (five new). Practical and didactic time devoted to general patient care and scene management increased significantly, while time devoted to most other clinical, presentation-based categories (eg, trauma care) decreased.ConclusionsDiscrepancies between original and refined curricula highlight a mismatch between the external curriculum and local context. Even with limited data and resources, curriculum mapping and blueprinting are possible means of resolving these contextual issues.
SPPC/CEPC lattice design and beam dynamics study
Authors: Su Feng , Gao Jie , Chen Yukai , Tang Jingyu , Wang Yiwei , Wang Dou , Bai Sha , Bian Tianjian , Zhang Yuan , Geng Huiping 
Published: December 2017

In this paper, we introduced the parameter choice and the first version lattice design for a 61 km and 100-km Super Proton–Proton Collider (SPPC). We started the lattice design and the beam dynamics study from last year and showed the preliminary dynamic aperture result of these two SPPC lattice versions. We also showed the layout, the lattice design and the dynamic aperture study of a CEPC partial double ring, an advanced partial double ring and a fully partial double ring schemes.
100 km CEPC parameters and lattice design
Authors: Wang Dou , Gao Jie , Yu Chenghui , Zhang Yuan , Wang Yiwei , Su Feng , Zhai Jiyuan , Bai Sha , Geng Huiping , Bian Tianjian , Wang Na , Cui Xiaohao , Zhang Chuang 
Published: December 2017

In this paper, a consistent calculation method for the CEPC parameter choice with a crab waist scheme is reported. A crosscheck of luminosity with beam–beam simulations has been done. With this new scheme, a higher Higgs luminosity (+[Formula: see text]170%) can be reached while keeping Pre-CDR beam power or the beam power (19 MW) can be reduced while keeping the same Pre-CDR luminosity. CEPC is compatible with W and Z experiment. The luminosity for Z is at the level of [Formula: see text]. Requirement for energy acceptance of Higgs has been reduced to 1.5% by enlarging the ring to 100 km. The arc optics and the Final Focus System (FFS) with crab sextupoles have been designed, and also some primary Dynamic Aperture (DA) results were introduced.
Impact of additional bosons on the exploration of the Higgs boson at the LHC
Authors: Fang Yaquan , Kumar Mukesh , Mellado Bruce , Zhang Yu , Zhu Maosen 
Published: December 2017

The LHC is making strides in the exploration of the properties of the newly discovered Higgs boson, [Formula: see text]. In Refs. 7–9 the compatibility of the proton–proton data reported in the Run I period with the presence of a heavy scalar, [Formula: see text], with a mass around 270 GeV and its implications were explored. This boson would decay predominantly to [Formula: see text], where [Formula: see text], is a lighter scalar boson. The production cross-section of [Formula: see text] is considerable and it would significantly affect the inclusive rate of [Formula: see text]. The contamination from this new production mechanism would depend strongly on the final state used to measure the rate of [Formula: see text]. The contamination in the rate measurement of [Formula: see text], [Formula: see text], [Formula: see text] is estimated to be small. This statement does not depend strongly on assumptions made on the decay of [Formula: see text]. The impact on other channels related to the search of Vector Boson Fusion and [Formula: see text] production with the diphoton decay is evaluated, where the dependence on assumption on the decay of [Formula: see text] is expected to be significant.
NMSSM light decoupled Higgs singlet at CEPC
Authors: Potter C. T. 
Published: December 2017

We describe the phenomenology of light singlet Higgs bosons in the Next-to-Minimal Supersymmetry Model (NMSSM) which are mostly decoupled from the rest of Supersymmetry. Noting that the Large Hadron Collider has not excluded this scenario, we describe previous searches for light Higgs bosons at the Large Electron Positron collider and evaluate the sensitivity to neutralino production and decay to light singlet Higgs bosons at the proposed [Formula: see text] GeV Circular Electron Positron Collider.