Non-Invasive Assessment of Disease Progression in Transgenic Murine Models of Duchenne Muscular Dystrophy

Introduction: Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease which arises from the mutation of the cytoskeletal structural protein, dystrophin. Currently, no established non-invasive method exists to assess disease progression. In the present study we have used dynamic contrast-enhanced computed tomography (DCE-CT), positron emission tomography (PET) and high frequency ultrasound (HFU) imaging to non-invasively measure changes in muscle perfusion, metabolism and architecture starting at 6 weeks of age for 16 weeks in two dystrophie murine models, mdx (mutated dystrophin) and udx (mdx:utrophin-null). Methods: Mice were divided into 4 groups by genotype and exercise treatment to induce muscle damage: (1) wild-type (wt)-run, (2) mutated dystrophin (mdx)-run, (3) mdx-walk, and (4) mdx/utrophin-null (udx)-walk. All mice in the ‘run’ groups were exercised on a motorized treadmill at a speed of 15 meters per minute (mpm) and a 7- degree incline for 30 minutes, 3 times weekly from 6 to 22 weeks of age. All ‘walk’ mice followed the same exercise regime but walked for 10 minutes at 5-7 mpm with no incline. Mice were imaged at baseline, imaging was then bi-weekly after exercise sessions with DCE-CT, FDG-PET and HFU to measure gastrocnemius muscle blood flow (BF) and volume (BV), F-FDG uptake (metabolism) as standardized uptake value (SUV) and to grade skeletal musculature changes using HFU. Results: Mean gastrocnemius blood flow in udx and mdx mice peaked at 8 weeks of age and was 40% and 35% higher (p\u3c0.05), respectively, than baseline or those for wt mice. Udx and mdx mice at early post exercise had 55% and 20% higher SUV iii (p\u3c0.05), respectively, than wt mice. Initial increases in BF, BV and SUV were followed by a slow decline with increased duration post exercise. HFU discriminated the severity of muscle damage between wt and dystrophie models, as well as between the mdx and udx dystrophie models. Udx mice displayed continual increase in muscle damage throughout the study. Mdx mice (Ex, N.E) displayed an initial increase in muscle damage followed by reduced degeneration till 22 weeks of age. Conclusion: The patterns of changes in imaging parameters are consistent with initial muscle de/regeneration, inflammation and subsequent muscle necrosis seen in histology. Imaging was capable of differentiating between wild type and affected animals as an non-invasive assessment of disease progression

Distribution Systems Prevalant in Pakistan and the US: An Analysis and Comparison

http://deepblue.lib.umich.edu/bitstream/2027.42/106640/1/BBA Nabeel-Ahmad-Batlay Ana-Muriel Winter 1999.PD

Online advertisement morphing : empirical and strategic implications

Thesis (S.M.)--Massachusetts Institute of Technology, Sloan School of Management, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 100-103).Today's age of information centric globalization over the Internet requires customer awareness by not only good content communication, but also trust and empathy. Trust and Empathy can be generated only when the sellers understand customers. This is only possible when sellers are aware about how the customers conceive the advertisement presented to them over the web. Fortunately, this knowledge is facilitated by analyzing customer buying behaviour and understanding the cognitive behaviour of the customer using cognitive engines, stochastic measures and analytics. My research will focus towards empirical substantiation of the affects and implications of Morphing. The study includes methodologies that corporate world can formulate to develop strategic measures to target potential customers based on individual cognitive styles. The study also includes an analysis of the online advertising industry trends, interviews & perspectives of industry thought leaders, and business models of the future.by Nabeel A. Siddiqui.S.M

Performance Measures of Direct Metal Laser Sintering Hybrid Milling: Mechanical Properties and Environmental Performance Indicators

University of Minnesota M.S.M.E. thesis.July 2019. Major: Mechanical Engineering. Advisor: Emmanuel Enemuoh. 1 computer file (PDF); ix, 64 pages + 1 supplementary tableApplications of metal additive manufacturing (AM) has increased substantially because it allows cost and resources efficient small-scale production required in industries such as aerospace and mold and die manufacturing. Geometric and dimensional accuracy of parts produced by AM is still subpar compared to conventional subtractive approaches. Recently, hybrid additive-subtractive called direct metal laser sintering hybrid milling (DMLS-HM) technology has been introduced which combines strengths and robustness of both additive and subtractive units. This thesis explores the adoption consequences and impacts of DMLS-HM through relative performance measures of mechanical and metallurgical properties as well as environmental impact assessment. This was achieved by first characterizing mechanical properties of Maraging steel powder and comparing it with conventional DMLS to understand the degree of variability. It was found out that DMLS-HM has superior mechanical properties for impact toughness and surface finish; however, tensile strength and hardness values were similar with DMLS. Environmental performance assessment was achieved by first identifying and finding the energy requirements in subsystems (additive and subtractive) of DMLS-HM and then converting into equivalent carbon emission. Carbon emission results for DMLS-HM printed geometry were compared with two other manufacturing approaches namely electron beam melting and conventional milling which fabricated the same geometry. The DMLS-HM process showed higher energy consumption during the part production stage with an average 84% more than EBM and CM processes. However, the CM was dominant in energy consumption during the procurement stage with an around 70% more energy than DMLS-HM and EBM processes. The outcome of this research project will contribute to the understanding of basic physics of energy consumption in AM and can be used in suitable process selection and setting sustainable manufacturing goals

Genetic variability and regression analysis for yield and quality traits in Brassica napus

An experiment was conducted to estimate the genetic variability and regression analysis for yield and quality traits in a set of eight brassica genotypes in a randomized complete block design with three replications at The University of Agriculture Peshawar, during 2011-12 cropping season. Significant genetic variability was recorded among genotypes for plant height, pods main receme-1, pod length, seed yield plant-1, 1000-seed weight, seeds pod-1, oil content, protein content, glucosinolate content, erucic acid content, oleic acid content and linolenic acid content except for primary branch plant-1 and pods plant-1 which showed non-significant differences. Genotypes, AUP-401, AUP-402, AUP-404 and AUP-407 showed potential performance for glucosinolate content (55.1 µmol g-1), seed yield plant-1 (23.93 g), pods plant-1 (268.83), protein contents (21.1 %), erucic acid contents (42.7 %) and oil contents (53.3 %). Seed yield plant-1 was taken as a dependent variable to study the effects of many morphological yield traits on it. Branches plant-1, pods main raceme-1, pods plant-1, and seed pod-1 showed a positive effect on seed yield plant-1, while 1000-seed weight, pod length, and plant height showed a negative effect on seed yield plant-1. Seed yield plant-1 as an independent variable showed a negative effect on oil content. Protein content as an independent variable showed a positive effect on erucic acid content, while oil contents as independent variables show a negative effect on protein contents, respectively. The developed germplasm could be used in the upcoming brassica breeding programs to release high yielding, disease resistance, stress tolerance, and insect resistance varieties, which will eventually upsurge the productivity and decrease the gap between demand and domestic production of the brassica crop

Osteocalcin levels in gingival crevicular fluid periodontitis patient with and without type 2 Diabetes Mellitus

Background: Diabetes Mellitus (DM) is a systemic disease with a high prevalence in Indonesia. Periodontitis is a complication of DM with frequent occurrences. Periodontitis with DM causes greater bone damage than non-DM periodontitis because its conditions can affect osteoblast and osteoclast activity. Osteocalcin (OC), mostly synthesized by osteoblasts, regulates the activity of bone formation and turnover so that it can be a marker of bone formation and turnover to see the severity of the disease. OC can be found in gingival crevicular fluid (GCF). This study aimed to determine osteocalcin levels in gingival crevicular fluid periodontitis patients with uncontrolled type 2 Diabetes Mellitus and non-Diabetes Mellitus.Method: Samples used in this study were gingival crevicular fluid taken from 20 samples of periodontitis patients with DM type 2 (DMT2P) and 20 samples of periodontitis non-DM patients. The OC levels were analyzed using ELISA Kit Osteocalcin then statistical tests were carried out.Result: The results showed that the OC level of the DMT2P group was 0.369 ± 0.140 while the periodontitis non-DM group was 0.664 ± 0.141.Conclusion: The OC levels of periodontitis patients with DM are lower than periodontitis patients non-DM

Developing highly symmetric Microelectromechanical systems (MEMS) based butterfly gyroscopes

Microelectromechanical systems (MEMS) is the technology combining electrical components with mechanical systems at a micro scale. The combination of these two technologies allowed devices to interact with each other and build complex structures. System on the chips are built with components such as masses, electrodes, anchors, actuators and detectors. Reducing the size, weight, energy usage and cost is key while maintaining the sensors integrity. Sensitivity is an important factor when evaluating a gyroscope’s performance. This research presents beam modeling techniques for maximizing mechanical sensitivity of the butterfly resonator for gyroscopic applications. It investigates the geometric aspects of synchronizing beam that connects the wings of a butterfly resonator. The results show that geometric variation in the synchronizing beam can have a large effect on the frequency split and sensitivity of the device. The model simulation demonstrates a sensitivity of 10e-12 (m/°/sec) for a frequency split of 10 Hz, resulting from the optimized synchronous beam. Out of plane actuation was developed to drive and sense the resonators displacement. A butterfly sensor chip was fabricated to capture the dynamic responses of the resonator and to observe the theoretical and experimental results. Two butterfly resonators were tested, and the experimental results show a frequency split of 305 Hz and 400 Hz, while the model illustrated a split of 195 Hz and 220 Hz, respectively. The design and analysis presented in this thesis can further aid the development of MEMS butterfly resonators for inertial sensing applications

Spasmolytic effect of grewia asiatica fruit extract on isolated smooth muscles is mediated via multiple pathways

Background: Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract.Methods: A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract.Results: Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). When tested on low K+-(25 mM) sustained contractions, Ga.Cr cumulatively suppressed these contractions (0.1-10 mg/ml), indicating an opening of K+ channels (KCO) as the mechanism. Cromakalim, a standard KCO, was also more specific in blocking low K+-induced contractions. For the effect in aorta tissues, Ga.Cr suppressed the agonist-induced contractions from 0.3 mg/ml to 10 mg/ml. Upon challenge with L-NAME, a nitric oxide (NO) blocker, the extract response curve shifted right, indicating vasodilation was mediated via endothelial NO.Conclusion: This study shows that GI antispasmodic and vasodilator activities of Ga.Cr may be mediated via a KCO mechanism in the GI tract and through the release of NO from vascular endothelium

11 Years Old Female with Synergistic Presentation of Cranial and Spinal Pathologies: Myxopapillary Ependymoma with Hydrocephalus - A Rare Entity

The correlation between hydrocephalus and spinal cord tumor was first described by Kyrieleis et. al. 1% concomitant presence was documented by Mirroni et.al. Moreover, the understanding of the pathophysiological association between these two conditions is still lacking. 11 years old girl presented in the outpatient department of Jinnah hospital Lahore with complaints of difficulty in walking for the last 2 years, numbness of right leg for the last one year, and severe bilateral sciatica for 2 months. On further inquiry, she told that she is also suffering from headaches and blurred vision for the last 6 months. Her neuroimaging revealed hydrocephalus and mixed density heterogeneously enhancing intradural lesion at the conus. She underwent ventriculoperitoneal shunting for hydrocephalus and laminoplasty followed by excision of spinal tumor reported being myxopapillary ependymoma grade II. The presence of headache along with signs & symptoms of raised intracranial pressure in these patients warrant cranial imaging. CSF diversion for hydrocephalus and gross total excision of the spinal lesion is the standard acceptable treatment