Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration

PURPOSE. Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. METHODS. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. RESULTS. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. CONCLUSIONS. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways

Influence of powder-bed temperature on the microstructure and mechanical properties of Ti-6Al-4V produced by selective laser melting

Advanced characterisation techniques were used on LPBF Ti-6Al-4V samples produced on a heated base plate. When the substrate temperature is 100{\deg}C the elongation is 6\%, which increases and peaks at 10\% at 570{\deg}C, then sharply decreases to zero ductility at 770{\deg}C. At 100{\deg}C, a heavily strained and twinned microstructure, primarily composed of {\alpha}+{\alpha}', was observed and it was comparable to asbuilt microstructures obtained by conventional LPBF methods. At higher temperatures, twins are no longer present and instead nano-scale {\beta} precipitates are observed within {\alpha}' and {\alpha}, as well as dislocation networks (570{\deg}C) and tangles (770{\deg}C). Solute segregation at crystal defects was observed in all pre-heating conditions. Al and V segregation at microtwins was observed in the 100{\deg}C sample, reporting for the first time `selective' and mutually exclusive Al- and V-rich regions forming in adjacent twins. V segregation at dislocations was observed in the 570{\deg}C and 770{\deg}C samples, consistent with the higher preheating temperatures. High O contents were measured in all samples but with apparent opposing effects. At 100{\deg}C and 570{\deg}C was estimated to be below the critical threshold for O embrittlement and locally aids in maintaining a strength high by solid solution strengthening, whereas at 770{\deg}C it was above the threshold, therefore failing in a brittle fashion. Based on these observations, the initial increase in ductility from 100{\deg}C to 570{\deg}C is attributed to a reduction in microtwins and the dislocation networks acting as `soft barriers' for slip within a coarser microstructure. The lack of ductility at 770{\deg}C was attributed to local solute redistribution causing dislocation pinning and an increase of O content in this sample

Effect of Substrate Bed Temperature on Solute Segregation and Mechanical Properties in Ti–6Al–4V Produced by Laser Powder Bed Fusion

Titanium alloys are particularly sensitive to temperature during additive manufacturing processes, due to their dual phase microstructure and sensitivity to oxygen uptake. In this paper, laser powder bed fusion (LPBF) was used in conjunction with a heated substrate bed at 100 °C, 570 °C and 770 °C to produce specimens of Ti–6Al–4V, to investigate the change in mechanical properties and segregation of alloying elements. An initial increase in ductility was observed when increasing the temperature from 100 °C to 570 °C, followed by a significant loss in ductility when samples were produced at 770 °C. A suite of multi-scale characterisation techniques revealed that the as-printed microstructure was drastically different across the range of temperatures. At 100 °C, α + α′ phases were identified. Deformation twinning was extensively observed in the a phase, with Al and V segregating at the twin interfaces. At 570 °C (the most ductile sample), α′, α and nano-particles of β were observed, with networks of entangled dislocations showing V segregation. At 770 °C, no martensitic α′ was identified. The microstructure was an α + β microstructure and an increased volume fraction of tangled dislocations with localised V segregation. Thermodynamic modelling based on the Gibbs-free energy of formation showed that the increased V concentration at dislocations was insufficient to locally nucleate β phase. However, b-phase nucleation at grain boundaries (not dislocations) caused pinning of grain boundaries, impeding slip and leading to a reduction in ductility. It is likely that the increased O-content within specimens printed at increased temperatures also played a key role in high-temperature embrittlement. Building operations are therefore best performed below sub-transus temperatures, to encourage the growth of strengthening phases via solute segregation, and the build atmosphere must be tightly controlled to reduce oxygen uptake within the samples

Influence of powder-bed temperature on the microstructure and mechanical properties of Ti-6Al-4V produced by selective laser melting

Advanced characterisation techniques were used on LPBF Ti-6Al-4V samples produced on a heated base plate. When the substrate temperature is 100°C the elongation is 6\%, which increases and peaks at 10\% at 570°C, then sharply decreases to zero ductility at 770°C. At 100°C, a heavily strained and twinned microstructure, primarily composed of {\alpha}+{\alpha}', was observed and it was comparable to asbuilt microstructures obtained by conventional LPBF methods. At higher temperatures, twins are no longer present and instead nano-scale {\beta} precipitates are observed within {\alpha}' and {\alpha}, as well as dislocation networks (570°C) and tangles (770°C). Solute segregation at crystal defects was observed in all pre-heating conditions. Al and V segregation at microtwins was observed in the 100°C sample, reporting for the first time `selective' and mutually exclusive Al- and V-rich regions forming in adjacent twins. V segregation at dislocations was observed in the 570°C and 770°C samples, consistent with the higher preheating temperatures. High O contents were measured in all samples but with apparent opposing effects. At 100°C and 570°C was estimated to be below the critical threshold for O embrittlement and locally aids in maintaining a strength high by solid solution strengthening, whereas at 770°C it was above the threshold, therefore failing in a brittle fashion. Based on these observations, the initial increase in ductility from 100°C to 570°C is attributed to a reduction in microtwins and the dislocation networks acting as `soft barriers' for slip within a coarser microstructure. The lack of ductility at 770°C was attributed to local solute redistribution causing dislocation pinning and an increase of O content in this sample

Current Challenges and Opportunities in Microstructure-Related Properties of Advanced High-Strength Steels

This is a viewpoint paper on recent progress in the understanding of the microstructure–property relations of advanced high-strength steels (AHSS). These alloys constitute a class of high-strength, formable steels that are designed mainly as sheet products for the transportation sector. AHSS have often very complex and hierarchical microstructures consisting of ferrite, austenite, bainite, or martensite matrix or of duplex or even multiphase mixtures of these constituents, sometimes enriched with precipitates. This complexity makes it challenging to establish reliable and mechanism-based microstructure–property relationships. A number of excellent studies already exist about the different types of AHSS (such as dual-phase steels, complex phase steels, transformation-induced plasticity steels, twinning-induced plasticity steels, bainitic steels, quenching and partitioning steels, press hardening steels, etc.) and several overviews appeared in which their engineering features related to mechanical properties and forming were discussed. This article reviews recent progress in the understanding of microstructures and alloy design in this field, placing particular attention on the deformation and strain hardening mechanisms of Mn-containing steels that utilize complex dislocation substructures, nanoscale precipitation patterns, deformation-driven transformation, and twinning effects. Recent developments on microalloyed nanoprecipitation hardened and press hardening steels are also reviewed. Besides providing a critical discussion of their microstructures and properties, vital features such as their resistance to hydrogen embrittlement and damage formation are also evaluated. We also present latest progress in advanced characterization and modeling techniques applied to AHSS. Finally, emerging topics such as machine learning, through-process simulation, and additive manufacturing of AHSS are discussed. The aim of this viewpoint is to identify similarities in the deformation and damage mechanisms among these various types of advanced steels and to use these observations for their further development and maturation.</p

Effect of substrate bed temperature on solute segregation and mechanical properties in Ti–6Al–4V produced by laser powder bed fusion

Titanium alloys are particularly sensitive to temperature during additive manufacturing processes, due to their dual phase microstructure and sensitivity to oxygen uptake. In this paper, laser powder bed fusion (LPBF) was used in conjunction with a heated substrate bed at 100 °C, 570 °C and 770 °C to produce specimens of Ti–6Al–4V, to investigate the change in mechanical properties and segregation of alloying elements. An initial increase in ductility was observed when increasing the temperature from 100 °C to 570 °C, followed by a significant loss in ductility when samples were produced at 770 °C. A suite of multi-scale characterisation techniques revealed that the as-printed microstructure was drastically different across the range of temperatures. At 100 °C, α + α′ phases were identified. Deformation twinning was extensively observed in the a phase, with Al and V segregating at the twin interfaces. At 570 °C (the most ductile sample), α′, α and nano-particles of β were observed, with networks of entangled dislocations showing V segregation. At 770 °C, no martensitic α′ was identified. The microstructure was an α + β microstructure and an increased volume fraction of tangled dislocations with localised V segregation. Thermodynamic modelling based on the Gibbs-free energy of formation showed that the increased V concentration at dislocations was insufficient to locally nucleate β phase. However, b-phase nucleation at grain boundaries (not dislocations) caused pinning of grain boundaries, impeding slip and leading to a reduction in ductility. It is likely that the increased O-content within specimens printed at increased temperatures also played a key role in high-temperature embrittlement. Building operations are therefore best performed below sub-transus temperatures, to encourage the growth of strengthening phases via solute segregation, and the build atmosphere must be tightly controlled to reduce oxygen uptake within the samples

A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS.

The identification and characterization of rare immune cell populations in humans can be facilitated by their growth advantage in the context of specific genetic diseases. Here, we use autoimmune lymphoproliferative syndrome to identify a population of FAS-controlled TCRαβ+ T cells. They include CD4+, CD8+, and double-negative T cells and can be defined by a CD38+CD45RA+T-BET- expression pattern. These unconventional T cells are present in healthy individuals, are generated before birth, are enriched in lymphoid tissue, and do not expand during acute viral infection. They are characterized by a unique molecular signature that is unambiguously different from other known T cell differentiation subsets and independent of CD4 or CD8 expression. Functionally, FAS-controlled T cells represent highly proliferative, noncytotoxic T cells with an IL-10 cytokine bias. Mechanistically, regulation of this physiological population is mediated by FAS and CTLA4 signaling, and its survival is enhanced by mTOR and STAT3 signals. Genetic alterations in these pathways result in expansion of FAS-controlled T cells, which can cause significant lymphoproliferative disease

Full field electroretinogram in autism spectrum disorder

Purpose To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. Methods Dark adapted (DA) ERGs were acquired to a range of flash strengths, (-4.0 to 2.3 log phot cd.s.m-2), including and extending the ISCEV standard, from two subject groups: (ASD) N=11 and (Control) N=15 for DA and N=14 for light adapted (LA) ERGs who were matched for mean age and range. Naka-Rushton curves were fitted to DA b-wave amplitude growth over the first limb (-4.0 to -1.0 log phot cd.s.m-2). The derived parameters (Vmax, Km and n) were compared between groups. Scotopic 15 Hz flicker ERGs (14.93Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td.s to assess the slow and fast rod pathways respectively. LA ERGs were acquired to a range of flash strengths, (-0.5 to 1.0 log phot cd.s.m-2). Photopic 30 Hz, flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120 ms ON- OFF stimuli were also recorded. Results For some individuals the DA b-wave amplitudes fell below the control 5th centile of the controls with up to four ASD participants (36%) at the 1.5 log phot cd.s.m-2 flash strength and two (18%) ASD participants at the lower -2 log phot cd.s.m-2 flash strength. However, across the thirteen flash strengths there were no significant group differences for b-wave amplitude’s growth (repeated measures ANOVA p=0.83). Nor were there any significant differences between the groups for the Naka-Rushton parameters (p>0.09). No group differences were observed in the 15Hz scotopic flicker phase or amplitude (p>0.1), DA ERG a- wave amplitude or time to peak (p>26). The DA b-wave time to peak at 0.5 log phot cd.s.m-2 were longer in the ASD group (corrected p=0.04). The single ISCEV LA 0.5 log phot cd.s.m-2 (p0.08) to the single flash stimuli although there was a significant interaction between group and flash strength for the b-wave amplitude (corrected p=0.006). The prolonged 120 ms ON-responses were smaller in the ASD group (corrected p=0.003), but the OFF response amplitude (p>0.6) and ON and OFF times to peaks (p>0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants, however no other differences were apparent in the OPs or 30Hz flicker waveforms. Conclusion Some ASD individuals show subnormal DA ERG b-wave amplitudes. Under LA conditions the b-wave is reduced across the ASD group along with the ON response of the ERG. These exploratory findings, suggest there is altered cone-ON bipolar signalling in ASD