Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis

BACKGROUND: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials

Geometric and Radiometric Calibration of Video Infrared Imagers for Photogrammetric Applications

This thesis is concerned with the geometric and radiometric calibration of infrared imagers with a view to their use in close-range and airborne photogrammetric applications. From the geometric point of view, three quite different types of infrared imager can be distinguished - these comprise (i) the pyroelectric vidicon camera; (ii) the CCD camera based on the use of an areal array of solid-state detectors; and (iii) the thermal video frame scanner (TVFS). The special optics and the detector technologies that are used in these imagers to generate images in the middle and thermal bands of the infrared spectrum, together with the underlying video technology, are first reviewed and discussed in some detail with an emphasis on their fundamental geometric and radiometric characteristics and properties. On this basis, the design and construction of a special target plate has been undertaken that allows all these different types of imager to be calibrated both geometrically and radiometrically. After describing this target plate, the actual experiment set-up and procedures and the subsequent data processing and analysis are outlined, including the method devised and used for the automatic measurement of the positions of all the target crosses on the calibration plate employing image matching techniques. The results obtained from the successful calibration of a representative sample of CCD cameras and thermal video frame scanners are presented and discussed in detail. They provide much new and accurate information on the geometric characteristics of these types of infrared imager that will be invaluable to those undertaking photogrammetric measurements on the infrared images that are being acquired and used in military, medical, industrial and environmental applications. For the radiometric calibration of each imager, measurements of the grey level values were made over the whole of the image covering the target radiation source for a range of temperatures. Thus much original and valuable information on the radiometric characteristics of the imagers has been obtained from the work undertaken during this research project, more especially at lower operational temperatures. However the techniques used gave less good results at higher temperatures and these need to be modified if more useful results are to be obtained. Suggestions are made for the further development of the calibration technique, in particular for its use with low-resolution imagers such as the pyroelectric vidicon camera which have not been calibrated in this research project due to time and financial limitations

A study on Blunt injury abdomen solid organ injuries

INTRODUCTION: Blunt Abdominal trauma is most commonly caused by road traffic accidents. The rapid increase in number of motor vehicles and its aftermath has caused rapid increase in number of victims to blunt abdominal trauma. Motor vehicle accidents account for 75 to 80 % of blunt abdominal trauma. 2 Blunt injury of abdomen is also a result of fall from height, assault with blunt objects, industrial mishaps, sport injuries, bomb blast and fall from riding bicycle. Blunt abdominal trauma is usually not obvious. Hence, often missed, unless, repeatedly looked for. Due to the delay in diagnosis and inadequate treatment of the abdominal injuries, most of the cases are fatal. Investigative modality can only supplement the clinical evaluation and cannot replace it in the diagnosis of blunt abdominal trauma. In spite of the best techniques and advances in diagnostic and supportive care, the morbidity and mortality remains at large. The reason for this could be due to the interval between trauma and hospitalization, inadequate and lack of appropriate surgical treatment, delay in diagnosis, post operative complications and associated trauma especially to head, thorax. In view of increasing number of vehicles and consequently road traffic accidents, this dissertation has been chosen to study the cases of blunt abdominal trauma. AIM OF THE STUDY: The objectives of the study are: 1. To evaluate the incidence of blunt abdominal trauma on solid viscera. 2. To evaluate etiology and various modes of presentation. 3. To evaluate various available investigations for the detection of solid organ injuries. 4. To evaluate various modalities of treatment available with aim to reduce the mortality and morbidity. 5. To evaluate common complications of solid organ injury in blunt trauma abdomen. MATERIALS AND METHOD : Patients admitted in Governtment Rajaji hospital, Madurai from April 2011 to May 2012 and study includes 40 cases. This is a prospective study conducted over 1 year. Methods of collection of data: After admission data for my study was collected by: 1. Direct interview with the patient or patient relatives accompanying the patient and obtaining a detailed history. 2. Thorough clinical examination. 3. Clinical findings and relevant diagnostic investigations performed over the patient. After initial resuscitation of the patients, thorough assessments for injuries were carried out in all the patients. Documentation of patients, which included, identification, history, clinical findings, diagnostic test, operative findings, operative procedures, complications during the stay in the hospital and during subsequent follow-up period, were all recorded on a Proforma specially prepared. Demographic data collected included the age, sex, occupation and nature and time of accident leading to the injury. CONCLUSION: Following conclusions can be drawn from our study: Blunt injury abdomen with solid organ injury forms considerable load of patients in our society. Most common age group involved is 21-30 years. Predominantly males are affected in large proportions. Road traffic accident forms the most common mode of injury. So efforts should be made to bring road traffic regulations into strict action and traffic norms regulated. Well established trauma care centres should be established at every Taluk hospital. Measures for early transport of the patients from the accident site to the trauma centres should be undertaken. Significant number of cases will have associated injuries with blunt injury abdomen like head injury, thoracic injury, extremity fractures. Clinical presentation is varied, sometimes confusing. Blunt injury abdomen is usually less obvious. Hence, repeated examination by multispecialty personnel in a specialized trauma centre is required. Erect abdomen X ray is a useful investigation to identify associated hollow viscus injury. Falling tires in serial hematocrit value indicates ongoing bleeding. With the advent of high resolution ultrasonography (FAST), DPL and FQA investigations are becoming less opted. CECT forms the core investigation of choice in dealing with blunt injury abdomen patients, and becomes more important in deciding operative versus conservative management. Early diagnosis and repeated clinical examination and use of appropriate investigations forms the key in managing BIA injuries. Associated extra abdominal injuries like head, thoracic and orthopedic injuries influenced the morbidity and mortality of the patients

Revision topics in otology

This e book covers all important topics in otology. Frequently asked exam questions are discussed in detail in this e book. This book will help students of otolaryngology during their exam preparations. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

MOLECULAR CHARACTERIZATION OF FREE TROPOSPHERIC ORGANIC AEROSOL AND THE DEVELOPMENT OF COMPUTATIONAL TOOLS FOR MOLECULAR FORMULA ASSIGNMENT

Organic aerosol affects human health and climate. These effects are largely determined by the composition of the organic aerosol, which is a complex mixture of species. Understanding the complexity of organic aerosol is critical to determining its effect on human health and climate. In this study, long range transported organic aerosol collected at the Pico Mountain Observatory was analyzed using ultrahigh resolution mass spectrometry. Organic aerosol transported in the free troposphere had an overall lower extent of oxidation than aerosol transported in the boundary layer. It was hypothesized that the lower oxidation was related to a more viscous phase state of the aerosol during transport. The results suggest that biomass burning organic aerosol injected into the free troposphere are more persistent than organic aerosol in the boundary layer. A sample was also analyzed using tandem FT-ICR MS/MS fragmentation, providing information about the functional group composition in the aerosol sample. This was done using a segmented scan approach, which revealed an unprecedented molecular complexity of unfragmented precursor ions. In addition to the expected CO2 and H2O neutral losses, neutral losses corresponding to carbonyl functional groups (C2H4O, CO) were observed. The abundance of carbonyl functional groups suggests a slower rate of aging in the atmosphere. Analysis of nitrogen and sulfur containing neutral losses highlighted a surprising abundance of reduced nitrogen and sulfur loss (NH3 and SH2). This further supports the hypothesis of slower aging in the free troposphere. Additional research was done to develop an R software package (MFAssignR) to perform molecular formula assignment with improved decision-making transparency, noise estimation, isotope identification, and mass recalibration. MFAssignR was found to assign the same molecular formula as other molecular formula assignment methods for the majority (97-99%) of mass peaks that were assigned a molecular formula by the compared methods. Additionally, MFAssignR was more effective at assigning molecular formulas to low intensity peaks relative to the other methods tested, leading to more overall molecular formula assignments. MFAssignR is available via GitHub and is the first open source package to contain a full pipeline of functions for data preparation and analysis for ultrahigh resolution mass spectrometry

A Near-Solar Metallicity, Nitrogen-Deficient Lyman Limit Absorber Associated with two S0 Galaxies

From UV spectra of the bright quasar PHL 1811 recorded by FUSE and the E140M configuration on STIS, we have determined the abundances of various atomic species in a Lyman limit system at z = 0.0809 with log N(H I) = 17.98. Considerably more hydrogen may be in ionized form, since the abundances of C II, Si II, S II and Fe II are very large compared to that of O I, when compared to their respective solar abundance ratios. Our determination [O/H] = -0.19 in the H I-bearing gas indicates that the chemical enrichment of the gas is unusually high for an extragalactic QSO absorption system. However, this same material has an unusually low abundance of nitrogen, [N/O] < -0.59, indicating that there may not have been enough time during this enrichment for secondary nitrogen to arise from low and intermediate mass stars. In an earlier investigation we found two galaxies at nearly the same redshift as this absorption system and displaced by 34 and 87 kpc from the line of sight. An r-band image recorded by the ACS on HST indicates these are S0 galaxies. One or both of these galaxies may be the source of the gas, which might have been expelled in a fast wind, by tidal stripping, or by ram-pressure stripping. Subtraction of the ACS point-spread function from the image of the QSO reveals the presence of a face-on spiral galaxy under the glare of the quasar; although it is possible that this galaxy may be responsible for the Lyman limit absorption, the exact alignment of the QSO with the center of the galaxy suggests that the spiral is the quasar host.Comment: 74 pages, 14 figures; to be published in the Astrophysical Journal (Part 1) May 1, 2005 issue. A version of the paper with figures of better quality may be found at http://www.astro.princeton.edu/~ebj/PHL1811_paper.ps (postscript) or http://www.astro.princeton.edu/~ebj/PHL1811_paper.pdf (pdf

Strategic plan for Textile S.A.

The purpose of this thesis is to present the Strategic Plan 2019 to 2024 of the company Textile S.A., including an exhaustive review of its mission, vision, values, and code of ethics. This Strategic Plan will become the guiding light for Textile S.A. to be recognized as a relevant regional player in the textile and confection sector. This Strategic Plan was formulated using D`Alessio´s Sequential Model of the Strategic Process (2015), which included an exhaustive analysis of internal and external factors, and competitive analysis of Peru and of the company. The internal and external analysis resulted in the identification of opportunities, threats, and weaknesses associated with the company. The competitive analysis resulted in the identification of competitive advantages of Peru, and the company and the critical success factors to compete in the textile and confection sector. Textile S.A. can take advantage of the opportunities in the market, the new trends (ecofriendly and e-commerce), and favorable access to raw material in Peru. At the end of the analysis, sixteen strategies were established and ten retained strategies to make the long-term objectives included the developing of new relationships with potential clients in countries where free trade agreements apply, increasing loyalty of current customers to differentiate from competitors, positioning the company´s brand in the local market aiming a mid-high income segment with the clothing design, among others. The success in the implementation and execution of those strategies will depend on the attitude and position taken by the shareholders of the company.El propósito de esta tesis es presentar el Plan Estratégico 2019 a 2024 de la empresa Textile S.A., que incluye una revisión exhaustiva de su misión, visión, valores y código de ética. Este Plan Estratégico se formuló utilizando el Modelo Secuencial del Proceso Estratégico (2015) de D`Alessio, que incluyó un análisis completo de los factores internos y externos, y un análisis competitivo de Perú y de la empresa. Los análisis internos y externos resultaron en la identificación de oportunidades, amenazas y debilidades asociadas con la empresa. El análisis competitivo dio como resultado la identificación de las ventajas competitivas de Perú y la empresa Textile S.A., y los factores críticos de éxito para competir en el sector textil y confecciones. Al final del análisis, se establecieron dieciséis estrategias. Según lo evaluado, el éxito en la implementación y ejecución de esas estrategias dependerá de la actitud y la posición adoptada por los accionistas de la empresa, teniendo en cuenta la penetración en los mercados internacionales y nacionales.Tesi