Microstructural evolution and characterisation of interfacial phases in Al<inf>2</inf>O<inf>3</inf>/Ag-Cu-Ti/Al<inf>2</inf>O<inf>3</inf> braze joints

Alumina ceramics with different levels of purity have been joined to themselves using an active braze alloy (ABA) Ag–35.3Cu–1.8Ti wt.% and brazing cycles that peak at temperatures between 815 °C and 875 °C for 2 to 300 min. The microstructures of the joints have been studied using scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy. A limited number of joints prepared with the ABA Ag–26.7Cu–4.5Ti wt.% have also been studied. In terms of characterising the interfacial phases, efforts were made to understand the interfacial reactions, and to determine the influence of various brazing parameters, such as the peak temperature (Tp) and time at Tp (τ), on the microstructure. In addition, the extent to which impurities in the alumina affect the interfacial microstructure has been determined. Ti3Cu3O has been identified as the main product of the reactions at the ABA/alumina interfaces. At the shortest joining time used, this phase was observed in the form of a micron-size continuous layer in contact with the ABA, alongside a nanometre-size layer on the alumina that was mostly composed of γ-TiO grains. Occasionally, single grains of Ti3O2 were observed in the thin layer on alumina. In the joints prepared with Ag–35.3Cu–1.8Ti wt.%, the interfacial structure evolved considerably with joining time, eventually leading to a high degree of inhomogeneity across the length of the joint at the highest Tp. The level of purity of alumina was not found to affect the overall interfacial microstructure, which is attributed to the formation of various solid solutions. It is suggested that Ti3Cu3O forms initially on the alumina. Diffusion of Ti occurs subsequently to form titanium oxide at the Ti3Cu3O/alumina interface.The authors acknowledge the financial support for this study provided by AWE.This is the author accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S1359645415003791

Interfacial reactions between sapphire and Ag-Cu-Ti-based active braze alloys

The interfacial reactions between two commercially available Ag–Cu–Ti-based active braze alloys and sapphire have been studied. In separate experiments, Ag– 35.3Cu–1.8Ti wt.% and Ag–26.7Cu–4.5Ti wt.% alloys have been sandwiched between pieces of R-plane orientated sapphire and heated in argon to temperatures between 750 and 900 °C for 1 min. The phases at the Ag–Cu– Ti/sapphire interfaces have been studied using selected area electron diffraction, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy. Gradual and subtle changes at the Ag–Cu–Ti/sapphire interfaces were observed as a function of temperature, along with the formation of a transient phase that permitted wetting of the sapphire. Unequivocal evidence is shown that when the active braze alloys melt, titanium first migrates to the sapphire and reacts to dissolve up to ~33 at.% oxygen, forming a nanometre-size polycrystalline layer with a chemical composition of Ti₂O₁₋ₓ (x<<1). Ti₃Cu₃O particles subsequently nucleate behind the Ti₂O₁₋ₓ layer and grow to become a continuous micrometre-size layer, replacing the Ti₂O₁₋ₓ layer. Finally at 845 °C, a nanometre-size γ-TiO layer forms on the sapphire to leave a typical interfacial structure of Ag–Cu/Ti₃Cu₃O/γ-TiO/sapphire consistent with that seen in samples of polycrystalline alumina joined to itself with these active braze alloys. These experimental observations have been used to establish a definitive bonding mechanism for the joining of sapphire with Ag–Cu alloys activated by small amounts of titaniumWe are grateful for the financial support for this study provided by AWE.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.actamat.2015.11.01

Evolution of the interfacial phases in Al2_{2}O3_{3}–Kovar joints®^{®} brazed using a Ag–Cu–Ti-based alloy

A systematic investigation of the brazing of Al$_{2}$O$_{3}$ to Kovar$^{®}$ (Fe–29Ni–17Co wt.%) using the active braze alloy (ABA) Ag–35.25Cu–1.75Ti wt.% has been undertaken to study the chemical reactions at the interfaces of the joints. The extent to which silica-based secondary phases in the Al$_{2}$O$_{3}$ participate in the reactions at the ABA/Al$_{2}$O$_{3}$ interface has been clarified. Another aspect of this work has been to determine the influence of various brazing parameters, such as the peak temperature, $\textit{T}$$_{p}$, and time at $\textit{T}$$_{p}$, $\tau$, on the resultant microstructure. As a consequence, the microstructural evolution of the joints as a function of $\textit{T}$$_{p}$ and $\tau$ is discussed in some detail. The formation of a Fe$_{2}$Ti layer on the Kovar$^{®}$ and its growth, along with adjacent Ni$_{3}$Ti particles in the ABA, dominate the microstructural developments at the ABA/Kovar$^{®}$ interface. The presence of Kovar$^{®}$ next to the ABA does not change the intrinsic chemical reactions occurring at the ABA/Al$_{2}$O$_{3}$ interface. However, the extent of these reactions is limited if the purity of the Al$_{2}$O$_{3}$ is high, and so it is necessary to have some silica-rich secondary phase in the Al$_{2}$O$_{3}$ to facilitate the formation of a Ti$_{3}$Cu$_{3}$O layer on the Al$_{2}$O$_{3}$. Breakdown of the Ti$_{3}$Cu$_{3}$O layer, together with fracture of the Fe$_{2}$Ti layer and separation of this layer from the Kovar$^{®}$, has been avoided by brazing at temperatures close to the liquidus temperature of the ABA for short periods of time, e.g. for $\textit{T}$$_{p}$ between 820 and 830 °C and $\tau$ between 2 and 8 min.We are grateful for the contribution and support for this study by AWE plc

Active metal brazing of Al2_{2}O3_{3} to Kovar® (Fe–29Ni–17Co wt.%) using Copper ABA® (Cu–3.0Si–2.3Ti–2.0Al wt.%)

The application of an active braze alloy (ABA) known as Copper ABA® (Cu–3.0Si–2.3Ti–2.0Al wt.%) to join Al$_{2}$O$_{3}$ to Kovar® (Fe–29Ni–17Co wt.%) has been investigated. This ABA was selected to increase the operating temperature of the joint beyond the capabilities of typically used ABAs such as Ag–Cu–Ti-based alloys. Silica present as a secondary phase in the Al$_{2}$O$_{3}$ at a level of ~5 wt.% enabled the ceramic component to bond to the ABA chemically by forming a layer of Si$_{3}$Ti$_{5}$ at the ABA/Al$_{2}$O$_{3}$ interface. Appropriate brazing conditions to preserve a near-continuous Si$_{3}$Ti$_{5}$ layer on the Al$_{2}$O$_{3}$ and a continuous Fe$_{3}$Si layer on the Kovar® were found to be a brazing time of ≤15 min at 1025 °C or ≤2 min at 1050 °C. These conditions produced joints that did not break on handling and could be prepared easily for microscopy. Brazing for longer periods of time, up to 45 min, at these temperatures broke down the Si$_{3}$Ti$_{5}$ layer on the Al$_{2}$O$_{3}$, while brazing at ≥1075 °C for 2–45 min broke down the Fe$_{3}$Si layer on the Kovar® significantly. Further complications of brazing at ≥1075 °C included leakage of the ABA out of the joint and the formation of a new brittle silicide, Ni$_{16}$Si$_{7}$Ti$_{6}$, at the ABA/Al$_{2}$O$_{3}$ interface. This investigation demonstrates that it is not straightforward to join Al$_{2}$O$_{3}$ to Kovar® using Copper ABA®, partly because the ranges of suitable values for the brazing temperature and time are quite limited. Other approaches to increase the operating temperature of the joint are discussed.We are grateful for the financial support for this study provided by AWE

Evolution of the interfacial phases in Al2_{2}O3_{3}–Kovar joints®^{®} brazed using a Ag–Cu–Ti-based alloy

A systematic investigation of the brazing of Al$_{2}$O$_{3}$ to Kovar$^{®}$ (Fe–29Ni–17Co wt.%) using the active braze alloy (ABA) Ag–35.25Cu–1.75Ti wt.% has been undertaken to study the chemical reactions at the interfaces of the joints. The extent to which silica-based secondary phases in the Al$_{2}$O$_{3}$ participate in the reactions at the ABA/Al$_{2}$O$_{3}$ interface has been clarified. Another aspect of this work has been to determine the influence of various brazing parameters, such as the peak temperature, $\textit{T}$$_{p}$, and time at $\textit{T}$$_{p}$, $\tau$, on the resultant microstructure. As a consequence, the microstructural evolution of the joints as a function of $\textit{T}$$_{p}$ and $\tau$ is discussed in some detail. The formation of a Fe$_{2}$Ti layer on the Kovar$^{®}$ and its growth, along with adjacent Ni$_{3}$Ti particles in the ABA, dominate the microstructural developments at the ABA/Kovar$^{®}$ interface. The presence of Kovar$^{®}$ next to the ABA does not change the intrinsic chemical reactions occurring at the ABA/Al$_{2}$O$_{3}$ interface. However, the extent of these reactions is limited if the purity of the Al$_{2}$O$_{3}$ is high, and so it is necessary to have some silica-rich secondary phase in the Al$_{2}$O$_{3}$ to facilitate the formation of a Ti$_{3}$Cu$_{3}$O layer on the Al$_{2}$O$_{3}$. Breakdown of the Ti$_{3}$Cu$_{3}$O layer, together with fracture of the Fe$_{2}$Ti layer and separation of this layer from the Kovar$^{®}$, has been avoided by brazing at temperatures close to the liquidus temperature of the ABA for short periods of time, e.g. for $\textit{T}$$_{p}$ between 820 and 830 °C and $\tau$ between 2 and 8 min.We are grateful for the contribution and support for this study by AWE plc

Change of initial oral antidiabetic therapy in type 2 diabetic patients

Objective To explore the 'real-life' therapy of type 2 diabetes mellitus with oral antidiabetic drugs (OADs). Methods From the PHARMO Record Linkage System comprising linked drug dispensing and clinical laboratory data from approximately 2.5 million individuals in the Netherlands, among others, new users of OADs were identified in the period 1999-2004. New users, aged 30 years and older, without insulin use before cohort entry date and with at least one year follow-up were included. We determined per initial therapy patient characteristics and first therapy change. Results Overall 35,514 patients were included. Metformin and sulfonylureas (SU) were the most frequent initial therapy. Patients on thiazolidinedione (TZD) monotherapy had lower percentages baseline HbA1c ≥ 7% compared to patients on metformin and SU. The proportion of patients still on initial therapy after one year ranged from 46% (TZDs) to around 60% (SU). Among patients starting on monotherapy, add-on (15-20%) and discontinuation (16-25%) of therapy occurred most frequently. In patients starting on combination therapy, a switch occurred in 30% of the patients. Conclusion In more than 40% of the patients a change in initial OAD-therapy is already observed in the first year of therapy. Maintaining patients on initial therapy remains a challenge

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Dupuytren's contracture: a retrospective database analysis to determine hospitalizations in the Netherlands

Background: Dupuytren's contracture is a condition of the palmar fascia involving contractures of the fascia and skin in the hand. Current treatment for Dupuytren's contracture is mainly limited to surgery. In the Netherlands, little is known about the prevalence of Dupuytren's contracture. In this study we determined the prevalence of patients with a hospitalization for Dupuytren's contracture in the Netherlands and characterized their (re)hospitalizations. Methods. From the PHARMO database, which consists of multiple observational databases linked on a patient level, all patients hospitalized for Dupuytren's contracture between 2004 and 2007 were included in the source population (ICD-9-CM code 728.6). Numbers from this source population were used to provide estimates of hospitalizations for Dupuytren's contracture in the Netherlands. Patients with a medical history in the PHARMO database of at least 12 months before their hospitalization were included in the study cohort and followed until end of data collection, death, or end of study period, whichever occurred first. Type of admission, length of stay, recorded procedures, treating specialty, number of rehospitalizations for Dupuytren's contracture, and time to first rehospitalization were assessed. Results: Of 3, 126 patients included in the source population, 3, 040 were included in the study population. The overall prevalence of patients with a hospitalization for Dupuytren'

Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations

To investigate the regulation of seed metabolism and to estimate the degree of metabolic natural variability, metabolite profiling and network analysis were applied to a collection of 76 different homozygous tomato introgression lines (ILs) grown in the field in two consecutive harvest seasons. Factorial ANOVA confirmed the presence of 30 metabolite quantitative trait loci (mQTL). Amino acid contents displayed a high degree of variability across the population, with similar patterns across the two seasons, while sugars exhibited significant seasonal fluctuations. Upon integration of data for tomato pericarp metabolite profiling, factorial ANOVA identified the main factor for metabolic polymorphism to be the genotypic background rather than the environment or the tissue. Analysis of the coefficient of variance indicated greater phenotypic plasticity in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability suggested that the mode of inheritance of metabolite traits in the seed differed from that in the fruit. Correlation-based metabolic network analysis comparing metabolite data for the seed with that for the pericarp showed that the seed network displayed tighter interdependence of metabolic processes than the fruit. Amino acids in the seed metabolic network were shown to play a central hub-like role in the topology of the network, maintaining high interactions with other metabolite categories, i.e., sugars and organic acids. Network analysis identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile, Val, and Pro. The strong interdependence of this group was confirmed by the mQTL mapping. Taken together these results (i) reflect the extensive redundancy of the regulation underlying seed metabolism, (ii) demonstrate the tight co-ordination of seed metabolism with respect to fruit metabolism, and (iii) emphasize the centrality of the amino acid module in the seed metabolic network. Finally, the study highlights the added value of integrating metabolic network analysis with mQTL mapping

Downregulation of pyrophosphate: d-fructose-6-phosphate 1-phosphotransferase activity in sugarcane culms enhances sucrose accumulation due to elevated hexose-phosphate levels

Analyses of transgenic sugarcane clones with 45–95% reduced cytosolic pyrophosphate: d-fructose-6-phosphate 1-phosphotransferase (PFP, EC 2.7.1.90) activity displayed no visual phenotypical change, but significant changes were evident in in vivo metabolite levels and fluxes during internode development. In three independent transgenic lines, sucrose concentrations increased between three- and sixfold in immature internodes, compared to the levels in the wildtype control. There was an eightfold increase in the hexose-phosphate:triose-phosphate ratio in immature internodes, a significant restriction in the triose phosphate to hexose phosphate cycle and significant increase in sucrose cycling as monitored by 13C nuclear magnetic resonance. This suggests that an increase in the hexose-phosphate concentrations resulting from a restriction in the conversion of hexose phosphates to triose phosphates drive sucrose synthesis in the young internodes. These effects became less pronounced as the tissue matured. Decreased expression of PFP also resulted in an increase of the ATP/ADP and UTP/UDP ratios, and an increase of the total uridine nucleotide and, at a later stage, the total adenine nucleotide pool, revealing strong interactions between PPi metabolism and general energy metabolism. Finally, decreased PFP leads to a reduction of PPi levels in older internodes indicating that in these developmental stages PFP acts in the gluconeogenic direction. The lowered PPi levels might also contribute to the absence of increases in sucrose contents in the more mature tissues of transgenic sugarcane with reduced PFP activity