Investigation of in-situ alloying grade 23 Titanium with Copper by Selective Laser Melting Process for biomedical applications

Thesis (Master of Engineering: Mechanical Engineering) -- Central University of Technology, Free State, 2018The medical industry has successfully utilised additive manufacturing (AM) technologies, such as laser and electron beam powder bed fusion (LPBF and E-PBF), to manufacture complex shapes from biocompatible materials in order to produce implants using computer aided design (CAD) geometry based on medical Computer Tomography (CT) scan data. AM transforms the original design of the customised digital model directly to the physical device. Modern medicine utilises the benefits of LPBF to manufacture complex customised implants with biocompatible materials. Ti6Al4V alloy is the most used Titanium alloy that has the appropriate mechanical, corrosion and biocompatible properties. Infection is the most common postoperative complication resulting in device failure after implantation. Copper is a proven antibacterial agent and in small amounts, is not toxic to the human body. Functionalisation of Ti6Al4V implants structure with Cu additions at the bone–implant interface, reduces the risk of bacterial infection. LPBF combines the advantages of powder metallurgy with complete melting of powder mixtures and provides a unique opportunity for the design of new alloys utilising compositions impossible for conventional methods. Manufacturing of titanium alloys and copper materials from a mixture of elemental powders and in-situ mixing and alloying during manufacturing, is an example of such an approach. The formation of in-situ Ti6Al4V-x at.% Cu (1%, 3% and 5% Cu) alloy structures by LPBF for application in medical implants was investigated. Ti6Al4V Extra low interstitials (ELI) powder was mixed with pure copper powder of similar particle size distribution. Process parameters such as laser power, scanning speed, hatch distance and layer thickness directly affect the surface quality and part density. Optimal process parameters were established for in-situ alloying Ti6Al4V-x% Cu to form dense parts with suitable microstructural and surface quality. Firstly, single track formation was studied at different scanning speeds for 170 W and 340 Wlaser powers. The effect of laser power and scanning speed on the track width and shape was described. Secondly, the surface roughness and single layer morphology was considered. Dense non-porous in-situ alloyed 3D samples were produced and analysed. Future research on mechanical properties, antimicrobial activity and cytotoxicity is required to substantiate the functional properties of in-situ Ti6Al4V-x at.% Cu (1%, 3% and 5% Cu) alloys

General solution methods for mixed integer quadratic programming and derivative free mixed integer non-linear programming problems

A dissertation submitted to the Faculty of Science School of Computational and Applied Mathematics, University of the Witwatersrand, Johannesburg. April 27, 2013.In a number of situations the derivative of the objective function of an optimization problem is not available. This thesis presents a novel algorithm for solving mixed integer programs when this is the case. The algorithm is the first developed for problems of this type which uses a trust region methodology. Three implementations of the algorithm are developed and deterministic proofs of convergence to local minima are provided for two of the implementations. In the development of the algorithm several other contributions are made. The derivative free algorithm requires the solution of several mixed integer quadratic programming subproblems and novel methods for solving nonconvex instances of these problems are developed in this thesis. Additionally, it is shown that the current definitions of local minima for mixed integer programs are deficient and a rigorous approach to developing possible definitions is proposed. Using this approach we propose a new definition which improves on those currently used in the literature. Other components of this thesis are an overview of derivative based mixed integer non-linear programming, extensive reviews of mixed integer quadratic programming and deterministic derivative free optimization and extensive computational results illustrating the effectiveness of the contributions mentioned in the previous paragraphs

Large-Scale Automatic Audiobook Creation

An audiobook can dramatically improve a work of literature's accessibility and improve reader engagement. However, audiobooks can take hundreds of hours of human effort to create, edit, and publish. In this work, we present a system that can automatically generate high-quality audiobooks from online e-books. In particular, we leverage recent advances in neural text-to-speech to create and release thousands of human-quality, open-license audiobooks from the Project Gutenberg e-book collection. Our method can identify the proper subset of e-book content to read for a wide collection of diversely structured books and can operate on hundreds of books in parallel. Our system allows users to customize an audiobook's speaking speed and style, emotional intonation, and can even match a desired voice using a small amount of sample audio. This work contributed over five thousand open-license audiobooks and an interactive demo that allows users to quickly create their own customized audiobooks. To listen to the audiobook collection visit \url{https://aka.ms/audiobook}

Loss of the Nutrient Sensor Tas1R3 Leads to Reduced Bone Resorption

Background: The Taste receptor, type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient needs. TAS1R member 3 (TAS1R3) either recognizes amino acids such as glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. Loss of TAS1R3 expression can cause impaired mTORC1 signaling and increased autophagy, indicating that signaling through this receptor is critical for assessing nutrient needs. Recently, it was reported that global deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass and trabecular remodeling but the underlying cellular mechanism leading to this phenotype remains unclear. Results: To address this open question, we quantified bone turnover markers in serum from 20-week-old wild type and Tas1R3 mutant mice and found that levels of the resorption marker Collagen Type I C-telopeptide (CTx) were reduced on average by \u3e60% in the absence of TAS1R3 expression. Levels of the bone formation marker Procollagen Type I N-terminal Propeptide (P1NP) tend to be higher in Tas1R3 mutant mice but this finding did not reach statistical significance (

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients

OBJECTIVES Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST ↓) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST ↓ provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST ↓ (n = 387), 1 mm ST ↓ (n = 433), and ST ↓ ≥2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of ≥0.1 ng/ml. RESULTS Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST ↓ and 26.18% among cTnT-positive patients with ST ↓ ≥2 mm. On ECGs done after 6 h of symptom onset, ST ↓ ≥2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS Quantitative ST ↓ and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making

International variation in invasive care of the elderly with acute coronary syndromes

Aims To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. Methods and results Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (≥75 years; n=1794) vs. younger patients (<75 years; n=14 043) after multivariable adjustment and by region of enrolment. The use of cardiac catheterization and revascularization were not protocol-specified. Elderly patients (median age 78 years) were more often female and more frequently had hypertension, diabetes, prior myocardial infarction, and prior coronary bypass surgery. Overall, they underwent less cardiac catheterization than younger patients [53 vs. 63%; adjusted OR 0.53 (0.46, 0.60)]. The absolute rate of cardiac catheterization in the elderly varied from 77% (vs. 91% in younger patients) in the US cohort to 27% (vs. 41% in younger patients) in the non-US cohort. Revascularization of elderly who underwent cardiac catheterization was also higher in US than non-US cohorts (71.3 vs. 53.6%). There was a significant interaction between the patient age and the use of catheterization across US and non-US regions of enrolment, as well as differences in the predictors of catheterization in the elderly. Despite these findings, after adjustment, 90-day rates of death and death or myocardial infarction (MI) were not significantly different in elderly who underwent catheterization compared with those who did not. Conclusion Although older age is universally predictive of lower use of cardiac catheterization, marked variation in catheterization of the elderly exists across international practice. Demonstrated differences in patterns of use suggest a lack of consensus regarding optimal use of an invasive strategy in the elderl

Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis: A Multicenter Cardiac Magnetic Resonance Study

Background: Aortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR).  Methods: Asymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified.  RESULTS: In 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8–4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%–158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%–25%) reduction in left ventricular mass index (P<0.0001) and an 11% (4%–16%) reduction in indexed extracellular volume (P=0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6–8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1–8.0 g]; P=0.23), with no evidence of regression even out to 2 years.  Conclusions: In patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes

Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling