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Precision health and deafness–optimizing genetic diagnosisSloan-Heggen, Christina Marie 01 May 2018 (has links)
Deafness is the most common sensory deficit in humans. In the United States 1-2 in a thousand babies is born with significant deafness, well over half of which is hereditary. Providing a patient and their family with a genetic diagnosis is the ultimate form of precision health and medicine; it can provide education, impact medical testing and treatment, provide peace of mind, and someday will be the key to providing gene specific therapies. Historically, providing this diagnosis was difficult, expensive, and time consuming due to the extreme clinical and genetic heterogeneity of non-syndromic hearing loss (NSHL).
Targeted genomic enrichment and massively parallel sequencing (TGE+MPS) have revolutionized the field of precision health and medicine, allowing for comprehensive genetic diagnosis of many complicated conditions, including NSHL. To take advantage of this advance in technology, the OtoSCOPE® platform was created, targeting all known deafness-causing genes and creating the first comprehensive genetic test for this condition.
With the implementation of OtoSCOPE® we aspire to accomplish two aims: providing comprehensive genetic diagnosis for patients all over the world and characterizing the full spectrum of hereditary hearing loss. The goal of my thesis work has been to use OtoSCOPE® to better understand the landscape of NSHL in multiple populations and to use this knowledge to further optimize it to be the most effective and tailored diagnostic tool possible for individuals with deafness.
In order to achieve these goals, we investigated a few unique populations. We first evaluated the effectiveness of diagnosis of OtoSCOPE® on two preselected cohorts of 302 Iranian and 9 Cameroonian probands with autosomal recessive NSHL (ARNSHL). We can now better define the frequent causes of NSHL in Iranians with a high degree of inbreeding, and begin to understand the spectrum of deafness in Sub-Saharan Africa that has previously been underutilized.
Next we sought to determine the spectrum of hearing loss within a clinical cohort in the United States by evaluating 1119 sequentially accrued probands for whom the OtoSCOPE® panel was ordered as a diagnostic test. This analysis allowed us to determine the overall diagnostic success of OtoSCOPE® (39%), the most common genes responsible for NSHL, the overall breadth of genes that can be identified within a cohort like this (49 genes), and patient characteristics which impact the likelihood of providing a positive diagnosis. This study permitted us to recommend use of OtoSCOPE® or other TGE+MPS diagnostic tools early in the diagnostic process of a patient with NSHL.
Finally, we interrogated the contribution of syndromic forms of deafness which may actually manifest as NSHL (NSHL mimics) within two deafness cohorts. We performed a retrospective chart review of 14 families with syndromic deafness seen by the Genetic-Eye-Ear Clinics to determine which methods are the most efficient and effective at providing an accurate diagnosis through the combination of collaborative clinical and molecular genetic diagnostic tools. We also performed a secondary analysis of 2384 sequentially accrued probands clinically evaluated with OtoSCOPE®, specifically evaluating the impact of panel versioning and inclusion of additional NSHL mimics. We recommend use of OtoSCOPE® as a diagnostic tool to most patients with apparent NSHL, and utilize an automatic positive feedback loop to ensure the most comprehensive and accurate diagnosis possible.
All of these studies have lead to the better understanding of the genes and variants that cause NSHL and its mimics, providing a more accurate genetic diagnosis, which is prerequisite to a future of targeted genetic therapies.
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XM982 Excalibur : användbar i krig och konflikter?Boqvist, Robin January 2009 (has links)
<p>Denna uppsats behandlar precisionsgranaten XM982 Excalibur. Syftet med arbetet var att öka kunskapen inom Försvarsmakten avseende Excalibur inför ett nyttjande av granaten i krig och konflikter.</p><p>Syftet var också att definiera faktorer som är viktiga att tänka på vid nyttjandet av Excalibur i krig och konflikter.</p><p>Frågeställning jag ställde upp för detta arbete är: Hur kan XM982 Excalibur användas i krig och konflikter?</p><p>För att kunna svara på frågeställningen så besvarades tre olika delfrågor.</p><p>De tre delfrågorna är:</p><ul><li>Vilka tekniska och taktiska faktorer framkommer genom information från industrin?</li><li>Vilka tekniska och taktiska faktorer framkommer genom information från Försvarsmakten?<em></em></li><li>Vilka faktorer framkommer genom information från nyttjandet av Excalibur av USA i Irak? <em> </em></li><li>Metoden som användes var litteraturstudier samt intervjuer av personer som arbetat med utveckling av granaten. Varje frågeställning avslutas med en diskussion där de olika faktorerna som framkommit diskuteras. Efter att ha diskuterat de tre olika frågorna avslutas arbetet med en sammanfattande diskussion.</li></ul><p>I resultaten från avhandlingen framkom att Excalibur är en väldigt teknisk artillerigranat med mycket bra egenskaper för att kunna underlätta för markförbanden, främst i strid i urban terräng.</p>
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Design and Metrology of a Precision XY Planar StageGorniak, Jeffrey Michael January 2010 (has links)
In recent years, the manufacturing industry has seen an increase in demand for micro-components in biomedical, opto-mechatronics, and automotive applications. Traditional machine tools are no longer a viable solution to meet the tolerances required by the customers. Hence, new ultra-precision machine tools have emerged with nanometer level accuracy in response to these demands. This thesis presents a novel ultra-precision machine tool with the intent to bridge the gap between traditional machine tools with larger work volumes and lower accuracy, and ultra-precision machine tools with high accuracy and small work volumes. The machine was designed using a T-type gantry and worktable configuration with a precision ground granite base, to achieve a work area of 300x300 mm2, with a maximum velocity of 1 m/s and a maximum acceleration of 10 m/s2. Actuation is provided by direct drive linear motors with high resolution feedback supplied by 4 µm grating linear encoders with 4096x interpolation. Aerostatic porous bearings are employed to reduce the effect of friction while maintain high stiffness of the guideways and structure. A Vacuum Pre-Loaded (VPL) air bearing supports the worktable on the granite, decoupling vertical load from the gantry. Thermal error reduction is achieved using environmental temperature control (20 ± 0.2°C) to help reduce thermal errors. As well, internally cooled couplings were designed to remove heat generated by the motors, thus further reducing the effects that contribute to thermal error.
The target static stiffness of the machine was 50 N/µm and was measured to be 22.2 N/µm and 23.9 N/µm in the x and y axes respectively. Frequency response experiments were used to identify the open-loop transfer functions for each axis. A multivariable framework was implemented for the y-axis due to the cross coupling between the primary and secondary motors of the gantry. Two prominent vibration modes were identified at 68 Hz and 344 Hz. The first mode is attributed to the rigid body yaw mode of the gantry while the higher frequency is related to the bending mode of the beam. The first mode of the x-axis is seen at 220 Hz. A state space, active mode compensation control law was developed for the y-axis, in collaboration with Mr. Daniel Gordon, which eliminates the effects of the 68 Hz mode, allowing for high performance from the motors. The following error during a high speed (200 mm/s) test was measured at 2.74 µm and 2.41 µm in the x and y axes respectively.
Metrology tests using laser interferometry were performed in accordance with international and American metrology standards for linear positioning, vertical and horizontal straightness, and yaw and pitch errors. The results will be used for geometric error compensation in future work. Finally, an overall error budget is presented with focus on the geometric, dynamic, servo, and thermal errors, where the maximum static resultant error of the machine was estimated to be 1.44 µm, and the maximum dynamic resultant error of 3.69 µm.
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XM982 Excalibur : användbar i krig och konflikter?Boqvist, Robin January 2009 (has links)
Denna uppsats behandlar precisionsgranaten XM982 Excalibur. Syftet med arbetet var att öka kunskapen inom Försvarsmakten avseende Excalibur inför ett nyttjande av granaten i krig och konflikter. Syftet var också att definiera faktorer som är viktiga att tänka på vid nyttjandet av Excalibur i krig och konflikter. Frågeställning jag ställde upp för detta arbete är: Hur kan XM982 Excalibur användas i krig och konflikter? För att kunna svara på frågeställningen så besvarades tre olika delfrågor. De tre delfrågorna är: Vilka tekniska och taktiska faktorer framkommer genom information från industrin? Vilka tekniska och taktiska faktorer framkommer genom information från Försvarsmakten? Vilka faktorer framkommer genom information från nyttjandet av Excalibur av USA i Irak? Metoden som användes var litteraturstudier samt intervjuer av personer som arbetat med utveckling av granaten. Varje frågeställning avslutas med en diskussion där de olika faktorerna som framkommit diskuteras. Efter att ha diskuterat de tre olika frågorna avslutas arbetet med en sammanfattande diskussion. I resultaten från avhandlingen framkom att Excalibur är en väldigt teknisk artillerigranat med mycket bra egenskaper för att kunna underlätta för markförbanden, främst i strid i urban terräng.
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Precisionsmarknadsföring : Framtiden ger inte utrymme för gissningarArvidsson, Karolina, Palmér, Anna January 2011 (has links)
SAMMANFATTNING Titel: Precisionsmarknadsföring - Framtiden ger inte utrymme för gissningar Författare: Karolina Arvidsson och Anna Palmér Handledare: Navid Ghannad Nivå: Kandidatuppsats, Marknadsföring 15 Hp. VT 2011 Nyckelord: Precisionsmarknadsföring, beslutstöd, dataanalys Problemformulering: 1. Vad innebär precisionsmarknadsföring? 2. Hur används precisionsmarknadsföring i telebranschen i Sverige? Syfte: Syftet med uppsatsen var primärt att få ökad förståelse kring vad precisionsmarknadsföring innebär för att sekundärt få ökad förståelse för hur det används inom de två företag i telebranschen som i störst utsträckning använder dataanalys för riktad kommunikation. Metod: En kvalitativ metodansats med ett deduktivt tillvägagångssätt har använts för att besvara problemformuleringen. Intervjuer har gjorts med telebolagen. Teoretiskt perspektiv: Tidigare forskning inom precisionsmarknadsföring presenterades och begreppet bröts ner i val av konsument, budskap, kommunikationskanal och tid. Beslutstöd för marknadsföringsåtgärder var en viktig del för precisionsmarknadsföring varför beslutstöd framhävdes i uppsatsen. Empiriskt perspektiv: Primärdata presenterades: två respondenter från vardera telebolag: Tre och TeliaSonera samt en respondet från SAS Institute. Slutsats: Precisionsmarknadsföring innebär att kommunikation riktas till specifika kundgrupper med ett relevant budskap, kommunikationskanal och tid sammanlänkat vilket identifieras utifrån affärsproblem och aktuellt beslutsunderlag. Utifrån framtagen definition används inte precisionsmarknadsföringens fulla potential i telebranschen i dagsläget.
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Design and Metrology of a Precision XY Planar StageGorniak, Jeffrey Michael January 2010 (has links)
In recent years, the manufacturing industry has seen an increase in demand for micro-components in biomedical, opto-mechatronics, and automotive applications. Traditional machine tools are no longer a viable solution to meet the tolerances required by the customers. Hence, new ultra-precision machine tools have emerged with nanometer level accuracy in response to these demands. This thesis presents a novel ultra-precision machine tool with the intent to bridge the gap between traditional machine tools with larger work volumes and lower accuracy, and ultra-precision machine tools with high accuracy and small work volumes. The machine was designed using a T-type gantry and worktable configuration with a precision ground granite base, to achieve a work area of 300x300 mm2, with a maximum velocity of 1 m/s and a maximum acceleration of 10 m/s2. Actuation is provided by direct drive linear motors with high resolution feedback supplied by 4 µm grating linear encoders with 4096x interpolation. Aerostatic porous bearings are employed to reduce the effect of friction while maintain high stiffness of the guideways and structure. A Vacuum Pre-Loaded (VPL) air bearing supports the worktable on the granite, decoupling vertical load from the gantry. Thermal error reduction is achieved using environmental temperature control (20 ± 0.2°C) to help reduce thermal errors. As well, internally cooled couplings were designed to remove heat generated by the motors, thus further reducing the effects that contribute to thermal error.
The target static stiffness of the machine was 50 N/µm and was measured to be 22.2 N/µm and 23.9 N/µm in the x and y axes respectively. Frequency response experiments were used to identify the open-loop transfer functions for each axis. A multivariable framework was implemented for the y-axis due to the cross coupling between the primary and secondary motors of the gantry. Two prominent vibration modes were identified at 68 Hz and 344 Hz. The first mode is attributed to the rigid body yaw mode of the gantry while the higher frequency is related to the bending mode of the beam. The first mode of the x-axis is seen at 220 Hz. A state space, active mode compensation control law was developed for the y-axis, in collaboration with Mr. Daniel Gordon, which eliminates the effects of the 68 Hz mode, allowing for high performance from the motors. The following error during a high speed (200 mm/s) test was measured at 2.74 µm and 2.41 µm in the x and y axes respectively.
Metrology tests using laser interferometry were performed in accordance with international and American metrology standards for linear positioning, vertical and horizontal straightness, and yaw and pitch errors. The results will be used for geometric error compensation in future work. Finally, an overall error budget is presented with focus on the geometric, dynamic, servo, and thermal errors, where the maximum static resultant error of the machine was estimated to be 1.44 µm, and the maximum dynamic resultant error of 3.69 µm.
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Analysis and research of an ultra-precision XY positioning stageHuang, Bo-Tse 05 August 2004 (has links)
Abstract
This paper reports about a precision positioning XY stage utilizing flexure hinges and piezoelectric actuators. XY stage was designed with the aim of reducing the stress-concentration of flexure hinges and the low interference between two actuating axes. Utilized the expression of matrix to figure out the properties of the bellow-type flexure hinges, and proved these by mathematical software. Experiments demonstrated that the stage actuated by a stairstep driving signal with maximum displacement 1.3£gm and interference 50nm along X axis; along Y axis with maximum displacement 0.8£gm and interference 11nm. The stage actuated by a ramp signal with maximum displacement 1.2£gm and interference 45nm along X axis; along Y axis with maximum displacement 0.9£gm and interference 35nm. The finite element method (FEM) was used to analyse the stress-concentration of the stage. and the simulated results were compared with the experiments. Referred to the testing results, the target object could be moved in the aimed position accurately.
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Multiple Precision Iterative Floating-Point Multiplier for Low-Power ApplicationsGuo, Cang-yuan 03 February 2010 (has links)
In many multimedia applications, a little error in the output results is allowable. Therefore, this thesis presents an iterative floating-point multiplier with multiple precision to reduce the energy consumption of floating-point multiplication operations. The multiplier can provide the users with three kinds of modes. The distinction among the three modes is the accepted output error and the achievable energy saving through reducing the length of mantissa in the multiplication operation.
In addition, to reduce the area of multiple precision floating-point multiplier we use the iterative structure to implement the mantissa multiplier in a floating point multiplier. Moreover the C++ language is adopted to evaluate the product error between each mode and the IEEE754 single precision multiplier. When the multimedia applications request high precision, the multiple precision floating-point multiplier will iteratively execute the 4-2 compression tree three times and the product error is around 10e-5%. The second-mode with the middle accuracy will iteratively execute the 4-2 compression tree two times and the product error is around 10e-3%. The third mode with the lowest accuracy will execute the 4-2 compression tree once and the product error is around 1%, it requires less execution cycle number. When compared with the tree-stage IEEE754 single-precision multiplier, the proposed iterative floating-point multiplier can save 42.54% area. For IDCT application, it can save 37.78% energy under 1% error constraint, For YUV to RGB application, it can save 31.36% energy under 1.1% error constraint. The experimental results demonstrate that the proposed multiple precision iterative floating-point multiplier can
significantly reduce the energy consumption of multimedia applications that allow a little output distortion
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United States Air Force precision engagement against mobile targets is man in or out? /Kosan, Keith J. January 1900 (has links)
Thesis--School of Advanced Airpower Studies, Maxwell Air Force Base, Ala., 1999-2000. / Title from title screen (viewed Oct. 28, 2003). "November 2001." Includes bibliographical references.
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Segregation of Visual Information in the Bee BrainPaulk, Angelique January 2008 (has links)
Photoreceptors in the eye basically provide information about light intensities from which brains extract different kinds of visual cues (e.g. color, movement, pattern). How do the properties and response characteristic of visual interneurons differ from the periphery to the central brain? I intracellularly recorded from neurons in the second and third optic ganglia (medulla and lobula) and the central brain (protocerebrum) of bees (mainly bumblebees; Bombus impatiens) while presenting color and motion stimuli. Bees rely on such stimuli during flight and foraging and show sophisticated visual learning abilities. We found that neurons in the distal medulla are color specific while ones in the proximal medulla show complex, often antagonistic color responses. Neurons in the distal lobula (layers 1-4) mainly process motion information while the proximal lobula (layers 5 and 6) seems to combine color and motion responses. Anterior parts of the central brain receive complex input representing combinations of motion and color information characterized by specific temporal properties (e.g. temporal precision, 'novelty' information or entrainment). This kind of often sparsely coded information is also represented in the mushroom bodies, learning and memory centers in the insect brain. In contrast, posterior parts of the central brain receive mainly motion information and show more reliable responses yet less precise spike timing. While the former kind of information (temporally precise or novelty in anterior pathways) is suited to form stimulus associations relevant during foraging, the latter, more reliable information is thought to support fast optomotor flight control maneuvers and other less plastic behaviors.
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