Assessing deployment strategies for ethanol and flex fuel vehicles in the U.S. light-duty vehicle fleet

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program, 2009.Includes bibliographical references (p. 91-92).Within the next 3-7 years the US light duty fleet and fuel supply will encounter what is commonly referred to as the "blend wall". This phenomenon describes the situation when more ethanol production has been mandated than can be blended legally in the existing gasoline fuel supply. While there are currently measures under review to extend fuel certification to from 10% to 15% ethanol blends, this will not be enough to reach the existing Renewable Fuel Standard targets that grow over the next decade to 36 billion gallons of biofuel. This research focuses on a quantitative assessment of how to effectively use policies to match the deployment of ethanol with capable vehicles to use ethanol, and the infrastructure to the fuel. A model of the light duty vehicle fleet has been used find the number of vehicles required to meet ethanol fuel usage targets. The key variables explored in this work are (i) the volumetric target for total biofuels (ii) the legal blend limit of ethanol in gasoline, (iii) fleet vehicle sales penetration and (iv) a metric for the relative utilization of ethanol and gasoline for flex fuel vehicles. Each of these factors can be varied independently to understand the existing relationship between each in the context of the US light-duty vehicle fleet. Ultimately, coordinated polices focusing on each of these key factors can ease the transformation of the automotive fuel industry away from petroleum dominated supplies.by Jeffrey L. McAulay.S.M.in Technology and Polic

Phenotypic description of cardiac findings in a population of Dogue de Bordeaux with an emphasis on atrial fibrillation

The aim of this study was to describe the clinical phenotype of Dogue de Bordeaux (DdB) referred for cardiac investigation, with particular reference to the prevalence of atrial fibrillation and associated features. Review of canine medical records of two United Kingdom veterinary referral hospitals identified 64 DdB with available echocardiographic and electrocardiographic (ECG)/Holter data. Atrial fibrillation was documented in 25 (39%) dogs and supraventricular tachycardia was recorded in five (7.8%) dogs. In a subset of 34 dogs, excluding congenital heart disease (n = 17), presence of a cardiac mass (n = 7) and non-cardiac neoplasia (n = 6), 19 (56%) dogs had atrial fibrillation, with a median heart rate of 200 beats per min (bpm) on presentation. Atrial fibrillation was inconsistently associated with cardiac chamber remodelling, but was frequently associated with systolic dysfunction (13/19, 68.4%) and right sided atrial or ventricular dilatation (14/19, 73.7%) in dogs with atrial fibrillation in this subset. No dogs in this subset had right sided atrial or ventricular dilatation in the absence of supraventricular arrhythmia or systolic dysfunction. The absence of structural heart disease in some dogs with supraventricular arrhythmias suggests that an underlying primary arrhythmic process might be responsible for initiating remodelling, although a primary cardiomyopathy cannot be ruled out

Early Virological and Immunological Events in Asymptomatic Epstein-Barr Virus Infection in African Children

Epstein-Barr virus (EBV) infection often occurs in early childhood and is asymptomatic. However, if delayed until adolescence, primary infection may manifest as acute infectious mononucleosis (AIM), a febrile illness characterised by global CD8+ T-cell lymphocytosis, much of it reflecting a huge expansion of activated EBV-specific CD8+ T-cells. While the events of AIM have been intensely studied, little is known about how these relate to asymptomatic primary infection. Here Gambian children (14–18 months old, an age at which many acquire the virus) were followed for the ensuing six months, monitoring circulating EBV loads, antibody status against virus capsid antigen (VCA) and both total and virus-specific CD8+ T-cell numbers. Many children were IgG anti-VCA-positive and, though no longer IgM-positive, still retained high virus loads comparable to AIM patients and had detectable EBV-specific T-cells, some still expressing activation markers. Virus loads and the frequency/activation status of specific T-cells decreased over time, consistent with resolution of a relatively recent primary infection. Six children with similarly high EBV loads were IgM anti-VCA-positive, indicating very recent infection. In three of these donors with HLA types allowing MHC-tetramer analysis, highly activated EBV-specific T-cells were detectable in the blood with one individual epitope response reaching 15% of all CD8+ T-cells. That response was culled and the cells lost activation markers over time, just as seen in AIM. However, unlike AIM, these events occurred without marked expansion of total CD8+ numbers. Thus asymptomatic EBV infection in children elicits a virus-specific CD8+ T-cell response that can control the infection without over-expansion; conversely, in AIM it appears the CD8 over-expansion, rather than virus load per se, is the cause of disease symptoms

Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

<p>Abstract</p> <p>Background</p> <p>The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β₂-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, <b><it>flutiform</it></b>^®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.</p> <p>Methods</p> <p>Patients aged ≥ 18 years (N = 202) with mild-to-moderate–severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4–10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV₁), at week 12.</p> <p>Results</p> <p>Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV₁at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV₁, change from pre-dose FEV₁at baseline to 2-hour post-dose FEV₁at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.</p> <p>Conclusions</p> <p>The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00476073">NCT00476073</a></p

Real Time QRS Detection Based on M-ary Likelihood Ratio Test on the DFT Coefficients

This paper shows an adaptive statistical test for QRS detection of electrocardiography (ECG) signals. The method is based on a M-ary generalized likelihood ratio test (LRT) defined over a multiple observation window in the Fourier domain. The motivations for proposing another detection algorithm based on maximum a posteriori (MAP) estimation are found in the high complexity of the signal model proposed in previous approaches which i) makes them computationally unfeasible or not intended for real time applications such as intensive care monitoring and (ii) in which the parameter selection conditions the overall performance. In this sense, we propose an alternative model based on the independent Gaussian properties of the Discrete Fourier Transform (DFT) coefficients, which allows to define a simplified MAP probability function. In addition, the proposed approach defines an adaptive MAP statistical test in which a global hypothesis is defined on particular hypotheses of the multiple observation window. In this sense, the observation interval is modeled as a discontinuous transmission discrete-time stochastic process avoiding the inclusion of parameters that constraint the morphology of the QRS complexes.This work has received research funding from the Spanish government (www.micinn.es) under project TEC2012 34306 (DiagnoSIS, Diagnosis by means of Statistical Intelligent Systems, 70K€) and projects P09-TIC-4530 (300K€) and P11-TIC-7103 (156K€) from the Andalusian government (http://www.juntadeandalucia.es/organismo​s/economiainnovacioncienciayempleo.html)

Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition

Mycobacterium tuberculosis (Mtb) is the leading infectious cause of death in humans. Synthesis of lipids critical for Mtb’s cell wall and virulence depends on phosphopantetheinyl transferase (PptT), an enzyme that transfers 4′-phosphopantetheine (Ppt) from coenzyme A (CoA) to diverse acyl carrier proteins. We identified a compound that kills Mtb by binding and partially inhibiting PptT. Killing of Mtb by the compound is potentiated by another enzyme encoded in the same operon, Ppt hydrolase (PptH), that undoes the PptT reaction. Thus, loss-of-function mutants of PptH displayed antimicrobial resistance. Our PptT-inhibitor cocrystal structure may aid further development of antimycobacterial agents against this long-sought target. The opposing reactions of PptT and PptH uncover a regulatory pathway in CoA physiology