► Local stress–strain curves are plotted using strain data from tensile testing of transverse specimens. ► The constitutive behaviour of welds is accessed from the local tensile stress–strain curves. ...► Local ultimate tensile strength of the welds is estimated using Considère criterion. ► Mis-matching in yield stress and plastic properties, across different weld sub-zones, is accessed.
In this paper a simple procedure for the characterization of the constitutive behaviour of welds is presented. Digital Image Correlation (DIC) is used for accessing local strain fields in transverse weld tensile samples and the stress distribution is calculated taking into account local strain data and thickness variation across the samples. The constitutive behaviour of the welds is assessed from local tensile stress–strain curves, plotted up to moderate values of plastic deformation, by fitting an appropriate work-hardening model to the experimental results and the ultimate tensile strength of the welds is estimated using the Considère criterion. Based on this information it is possible to assess the constitutive behaviour of different weld sub-zones, which cannot be derived from the hardness measurements, as well as evaluating the mis-match in yield stress and plastic properties across the welds. The proposed methodology is validated by comparing local stress–strain curves obtained by testing transverse weld samples of friction stir welds in very thin plates with those obtained by testing longitudinal samples of the same welds.
•Evolution of the contact conditions with welding parameters.•Analysis of strain rate sensitivity to process parameters.•Prediction of grain size evolution with process parameters.•Influence of ...contact conditions on heat generation.•Analysis of the mechanisms governing material flow.
In friction stir welding (FSW), the real contact conditions between the tool and the workpiece and the range of strain rates experienced remain quite unclear. In this work, a coupled 3D thermo-mechanical numerical model was used to simulate the FSW process. A Parametric finite element analysis of the evolution of the contact conditions, strain rates and temperatures with the processing parameters, tool dimensions and base material plastic properties was conducted. The numerical model was able to capture the evolution of the mixed slipping/sticking contact conditions with the welding time and welding parameters. The temperature and strain rate gradients obtained in the numerical simulations were validated with experimental data, by calculating the grain size distribution, in the stirred volume, using the Zener-Hollomon parameter. Full sticking, full slipping and mixed slipping-sticking contact domains were identified in a process parameters chart. It was found that, meanwhile the temperature and the sticking fraction evolve in the same way with the processing parameters, the strain rate is mainly determined by the tool rotation speed, varying from an average of 68 to 324 s−1, when the tool rotation speed is increased from 300 to 1200 rpm. The contact conditions and the base material plastic properties were also found to mutually influence the material flow. In full sticking contact, high strength materials, with high strain rate sensitivity, may display a similar flow pattern to that of low strength materials. However, coarser and more uniform grain structures may result from the welding of high strength materials, as a result of the narrower range of strain rates experienced during welding combined with high heat input.
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•Tool dimensions and the tool rotational are the main factors governing heat generation and torque evolution.•The tool traverse speed and the plate thickness have a strong influence on heat ...dissipation and on torque, but mainly in thick plates welding.•Torque and temperature evolution with process parameters is similar for the different aluminium alloys series.•Analytical coefficients were determined for calculating the welding temperature (CT) and the torque (CM) under different welding conditions.•A threshold in heat generation was determined for CT > 20,000.
An analysis of the evolution of the torque and of the temperature with welding conditions, in Friction Stir Welding (FSW) of aluminium alloys, was conducted. More precisely, torque and temperature results from a large number of publications, on FSW of AA2xxx, AA5xxx, AA6xxx and AA7xxx aluminium alloys series, were collected. The literature data was complemented with results from a fully coupled thermomechanical analysis of the FSW welding process. Coupling the experimental data, from the literature, with numerical simulation results, the individual influence of the main process parameters, tools and plates characteristics, on the torque and on the temperatures in FSW was assessed. It was found that the tool rotational speed govern the heat generation, while the tool dimensions have a very important influence, not only on the heat generation but also on the volume of material being stirred during welding, which is another important factor determining the welding torque. The traverse speed and the base material thickness were also found to be important factors governing the torque during welding. However, the influence of the traverse speed on torque evolution is conditioned by the tool dimensions. A parametric analysis enabling to understand the relation between process parameters, heat generation, heat dissipation and base material stirring, was conducted. Analytical relations, which enable calculating the torque and the temperature, in FSW of aluminium alloys, were developed based on numerical results and tested using the data from the literature review.
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Dissimilar friction stir welding (FSW) of heat (AA 6082-T6) and non-heat (AA 5754-H22) treatable aluminium alloys, in lap joint configuration, was performed in this work. The base material plates ...were 1mm thick. Welds were performed combining different plates positioning, relative to the tool shoulder, in order to assess the influence of base materials properties on welds strength. Three different tools were tested, one cylindrical and two conical, with different taper angles. Welds strength was characterized by performing transverse and tensile–shear tests. Strain data acquisition by Digital Image Correlation (DIC) was used to determine local weld properties. The results obtained enabled to conclude that the dissimilar welds strength is strongly dependent on the presence of the well-known hooking defect and that the hooking characteristics are strongly conditioned by base materials properties/positioning. By placing the AA 6082-T6 alloy, as top plate, in contact with the tool shoulder, superior weld properties are achieved independently of the tool geometry. It is also concluded that the use of unthreaded conical pin tools, with a low shoulder/pin diameter relation, is the most suitable solution for the production of welds with similar strengths for advancing and retreating sides.
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•The hooking defect determines the weld strength.•The hook formation depends on tool geometry and base material positioning.•Dissimilar base material combination influences the material flow during welding.•Strongest welds are produced by placing the AA 6xxx alloy in the top.•Conical tools with low shoulder/pin diameters ratio hinder hooking formation.
Ordered arrays of Co sub(x) Ni sub(1-x) nanowires (0 < x <1) were fabricated by a template-assisted method using electrodeposition into anodic aluminum oxide membranes. Tuning of the Co-alloy ...composition by changing the Ni content enables control of the effective anisotropy axis, which is determined by the balance between the hcp and fcc magnetocrystalline and shape anisotropies. We report on the nanowires' structural and magnetic properties (e.g., hysteresis curves and their parameters as well as first-order reversal curve analysis), paying particular attention to their angular dependence. It is confirmed that the crystal phase of nanowires with length 2.5 mu m and diameter 35 nm shifts from hcp to fcc as the Ni content increases. That results in a significant modification of the magnetization process and, accordingly, of the magnetic properties of the array. Analytical calculations of the angular dependence of the coercivity allow us to confirm that the magnetization reversal is mostly ascribed to the propagation of a transverse domain wall. Fitting of the experiment to these calculations indicates the presence of a transverse crystalline anisotropy (ascribed to the hcp phase) in Co wires, while this changes to an axial anisotropy (fcc phase) as the Ni content increases.
This paper intends to provide a perspective on the current development of the friction stir welding (FSW) technology. The industrialisation of the technology and related research were assessed by ...analysing patent and scientific publications databases. The literature reviews on FSW and related technologies were also collected and analysed. The work performed enabled to understand the main areas of industry/research where the FSW technology is being applied/explored and the geographical distribution of the main players in its implementation/research. The main FSW process variants, the materials already welded/processed using it, as well as the applications envisaged, were also analysed. The data collected shows that the FSW technology, originally developed for the joining of light alloys, became a research tool with interest in several fields of engineering and material science.
The N-end rule links the identity of the N-terminal amino acid of a protein to its in vivo half-life, as some N-terminal residues confer metabolic instability to a protein via their recognition by ...the cellular machinery that targets them for degradation. Since its discovery, the N-end rule has generally been defined as set of rules of whether an N-terminal residue is stabilizing or not. However, recent studies are revealing that the N-terminal code of amino acids conferring protein instability is more complex than previously appreciated, as recent investigations are revealing that the identity of adjoining downstream residues can also influence the metabolic stability of N-end rule substrate. This is exemplified by the recent discovery of a new branch of N-end rule pathways that target proteins bearing N-terminal proline. In addition, recent investigations are demonstrating that the molecular machinery in N-termini dependent protein degradation may also target proteins for lysosomal degradation, in addition to proteasome-dependent degradation. Herein, we describe some of the recent advances in N-end rule pathways and discuss some of the implications regarding the emerging additional sequence requirements.
A new device architecture using giant magnetoresistive sensors demonstrates the capability to detect very low magnetic fields on the pT range. A combination of vertically packed spin-valve sensors ...with two-dimensional in-plane arrays, connected in series and in parallel, delivers a final detection level of 360 pT/Formula: see text at 10 Hz at room temperature. The device design is supported by an analytical model developed for a vertically packed spin-valve system, which takes into account all magnetic couplings present. Optimization concerning the spacer thickness and sensor physical dimensions depending on the number of pilled up spin-valves is necessary. To push the limits of detection, arrays of a large number of sensing elements (up to 440,000) are patterned with a geometry that improves sensitivity and in a configuration that reduces the resistance, leading to a lower noise level. The final device performance with pT detectivity is demonstrated in an un-shielded environment suitable for detection of bio-signals.
Ultrasensitive magnetic field sensors envisaged for applications on biomedical imaging require the detection of low-intensity and low-frequency signals. Therefore linear magnetic sensors with ...enhanced sensitivity low noise levels and improved field detection at low operating frequencies are necessary. Suitable devices can be designed using magnetoresistive sensors, with room temperature operation, adjustable detected field range, CMOS compatibility and cost-effective production. The advent of spintronics set the path to the technological revolution boosted by the storage industry, in particular by the development of read heads using magnetoresistive devices. New multilayered structures were engineered to yield devices with linear output. We present a detailed study of the key factors influencing MR sensor performance (materials, geometries and layout strategies) with focus on different linearization strategies available. Furthermore strategies to improve sensor detection levels are also addressed with best reported values of ∼40 pT/√Hz at 30 Hz, representing a step forward the low field detection at room temperature.
Background
The molecular chaperone, Hsp90, is a key player in the protein quality control system that maintains homeostasis under cellular stress conditions. It is a homodimer with ATP-dependent ...activity, and is a prominent member of the chaperone machinery that stabilizes, matures and (re)folds an extensive list of client proteins. Hsp90 occurs as four isoforms, cytosolic Hsp90α and Hsp90β, mitochondrial TRAP1 and Grp94 present in the endoplasmic reticulum. An aberrant role of Hsp90 has been attributed to several cancers and neurodegenerative disorders. Consequently, Hsp90 has emerged as an attractive therapeutic target. However, pan-Hsp90 inhibition often leads to detrimental dose-limiting toxicities. Novel strategies for Hsp90-targeted therapy intend to avoid this by using isoform-specific Hsp90 inhibition. In this respect, the radiosynthesis of carbon-11 labeled SNX-ab was developed and
11
CSNX-ab was evaluated as a Hsp90α,β isoform-selective PET probe, which could potentially allow to quantify in vivo Hsp90α,β expression.
Results
11
CSNX-ab was synthesized with excellent radiochemical yields of 45% and high radiochemical purity (> 98%). In vitro autoradiography studies on tissue slices of healthy mouse brain, mouse B16.F10 melanoma and U87 glioblastoma using homologous (SNX-ab, SNX-0723) and heterologous (Onalespib and PU-H71) Hsp90 inhibitors demonstrated only limited reduction of tracer binding, indicating that the binding of
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CSNX-ab was not fully Hsp90-specific. Similarly,
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CSNX-ab binding to U87 cells was not efficiently inhibited by Hsp90 inhibitors.
Ex vivo
biodistribution studies in healthy mice revealed limited brain exposure of
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CSNX-ab and predominantly hepatobiliary clearance, which was confirmed by in vivo full-body dynamic µPET studies.
Conclusion
Our results suggest that
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CSNX-ab is not an ideal probe for in vivo visualization and quantification of Hsp90α/β expression levels in tumour and brain. Future research in the development of next-generation Hsp90 isoform-selective PET tracers is warranted to dissect the role played by each isoform towards disease pathology and support the development of subtype-specific Hsp90 therapeutics.
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