13 research outputs found
Fundamentals of laser powder bed fusion of metals, 1st Edition, Elsevier (2021), p. 676, Igor Yadroitsev, Ina Yadroitsava, Anton Du Plessis, Eric MacDonald, ISBN: 9780128240908 [book review]
No full text© 2001 The Author. Published by Elsevier This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website:https://doi.org/10.1016/j.aime.2022.100070Accepted versio
Growth And Characterization of Si-Ge-Sn Semiconductor Thin Films using a Simplified PECVD Reactor
No full textabstract: The realization of Silicon based photonic devices will enable much faster data transmission than is possible today using the current electronics based devices. Group IV alloys germanium tin (GeSn) and silicon germanium tin (SiGeSn) have the potential to form an direct bandgap material and thus, they are promising candidates to develop a Si compatible light source and advance the field of silicon photonics. However, the growth of the alloys is challenging as it requires low temperature growth and proper strain management in the films during growth to prevent tin segregation. In order to satisfy these criteria, various research groups have developed novel chemical vapor deposition (CVD) reactors to deposit the films. While these reactors have been highly successful in depositing high crystal quality high Sn concentration films, they are generally expensive set-ups which utilize several turbomolecular/cryogenic pumps and/or load-lock systems. An more economical process than the state-of-the art to grow group IV materials will be highly valuable. Thus, the work presented in this dissertation was focused on deposition of group IV semiconductor thin films using simplified plasma enhanced CVD (PECVD) reactors.
Two different in-house assembled PECVD reactor systems, namely Reactor No. 1 and 2, were utilized to deposit Ge, GeSn and SiGeSn thin films. PECVD technique was used as plasma assistance allows for potentially depositing the films at growth temperatures lower than those of conventional CVD. Germane (GeH4) and Digermane (Ge2H6) were used as the Ge precursor while Disilane (Si2H6) and tin chloride (SnCl4) were used as the precursors for Si and Sn respectively. The growth conditions such as growth temperature, precursor flow rates, precursor partial pressures, and chamber pressure were varied in a wide range to optimize the growth conditions for the films. Polycrystalline Ge films and SiGeSn films with an Sn content upto 8% were deposited using Reactor No. 1 and 2. Development of epitaxial Ge buffers and GeSn films was accomplished using a modified Reactor No. 2 at temperatures <400oC without the aid of ultra-high vacuum conditions or a high temperature substrate pre-deposition bake thereby leading to a low economic and thermal budget for the deposition process.Dissertation/ThesisDoctoral Dissertation Materials Science and Engineering 202
Independent glial subtypes delay development and extend healthy lifespan upon reduced insulin-PI3K signalling
No full textBackground: The increasing age of global populations highlights the urgent need to understand the biological
underpinnings of ageing. To this end, inhibition of the insulin/insulin-like signalling (IIS) pathway can extend
healthy lifespan in diverse animal species, but with trade-offs including delayed development. It is possible that
distinct cell types underlie effects on development and ageing; cell-type-specific strategies could therefore
potentially avoid negative trade-offs when targeting diseases of ageing, including prevalent neurodegenerative
diseases. The highly conserved diversity of neuronal and non-neuronal (glial) cell types in the Drosophila nervous
system makes it an attractive system to address this possibility. We have thus investigated whether IIS in distinct
glial cell populations differentially modulates development and lifespan in Drosophila.
Results: We report here that glia-specific IIS inhibition, using several genetic means, delays development while
extending healthy lifespan. The effects on lifespan can be recapitulated by adult-onset IIS inhibition, whereas
developmental IIS inhibition is dispensable for modulation of lifespan. Notably, the effects we observe on both
lifespan and development act through the PI3K branch of the IIS pathway and are dependent on the transcription
factor FOXO. Finally, IIS inhibition in several glial subtypes can delay development without extending lifespan,
whereas the same manipulations in astrocyte-like glia alone are sufficient to extend lifespan without altering
developmental timing.
Conclusions: These findings reveal a role for distinct glial subpopulations in the organism-wide modulation of
development and lifespan, with IIS in astrocyte-like glia contributing to lifespan modulation but not to
developmental timing. Our results enable a more complete picture of the cell-type-specific effects of the IIS
network, a pathway whose evolutionary conservation in humans make it tractable for therapeutic interventions. Our
findings therefore underscore the necessity for cell-type-specific strategies to optimise interventions for the diseases
of agein
A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation
No full textMany important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium Escherichia coli, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the in vivo MinDE localization dynamics by accounting for the previously reported properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally. © 2009 The Author(s)
The neuronal receptor tyrosine kinase Alk is a target for longevity
No full textInhibition of signalling through several receptor tyrosine kinases (RTKs), including the insulin-like growth factor receptor and its orthologues, extends healthy lifespan in organisms from diverse evolutionary taxa. This raises the possibility that other RTKs, including those already well studied for their roles in cancer and developmental biology, could be promising targets for extending healthy lifespan. Here, we focus on anaplastic lymphoma kinase (Alk), an RTK with established roles in nervous system development and in multiple cancers, but whose effects on aging remain unclear. We find that several means of reducing Alk signalling, including mutation of its ligand jelly belly (jeb), RNAi knock-down of Alk, or expression of dominant-negative Alk in adult neurons, can extend healthy lifespan in female, but not male, Drosophila. Moreover, reduced Alk signalling preserves neuromuscular function with age, promotes resistance to starvation and xenobiotic stress, and improves night sleep consolidation. We find further that inhibition of Alk signalling in adult neurons modulates the expression of several insulin-like peptides, providing a potential mechanistic link between neuronal Alk signalling and organism-wide insulin-like signalling. Finally, we show that TAE-684, a small molecule inhibitor of Alk, can extend healthy lifespan in Drosophila, suggesting that the repurposing of Alk inhibitors may be a promising direction for strategies to promote healthy aging.sponsorship: Biotechnology and Biological Sciences Research Council, Grant/Award Number: BB/M029093/1 (Alic); Alzheimer's Society, Grant/Award Number: Junior Fellowship (Woodling); Wellcome Trust, Grant/Award Number: Strategic Award (Partridge); Alzheimer's Research Trust, Grant/Award Number: ARUK UCL Network Pump-Priming Award (Woodling) (Biotechnology and Biological Sciences Research Council|BB/M029093/1, Alzheimer's Society, Wellcome Trust, Alzheimer's Research Trust)status: Publishe
Short-Term, Intermittent Fasting Induces Long-Lasting Gut Health and TOR-Independent Lifespan Extension
No full textIntermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF. Early-life IF also led to higher lipid content in 60-day-old flies, a potential explanation for increased longevity. Guts of flies 40 days post-IF showed a significant reduction in age-related pathologies and improved gut barrier function. Improved gut health was also associated with reduced relative bacterial abundance. Early IF thus induced profound long-term changes. Pharmacological and genetic epistasis analysis showed that IF acted independently of the TOR pathway because rapamycin and IF acted additively to extend lifespan, and global expression of a constitutively active S6K did not attenuate the IF-induced lifespan extension. We conclude that short-term IF during early life can induce long-lasting beneficial effects, with robust increase in lifespan in a TOR-independent manner, probably at least in part by preserving gut health.sponsorship: We thank Dr. Elizabeth Skinner for helpful comments and Dr. Nathan Woodling for help with statistics. We are grateful to members of the Partridge and Gems laboratories for helpful discussions. This work was funded by a Wellcome Trust Strategic Award (098565). (Wellcome Trust|098565, Wellcome Trust|098565/Z/12/Z)status: Publishe
Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system
No full textReduced activity of insulin/insulin-like growth factor signaling (IIS) increases healthy lifespan among diverse animal species. Downstream of IIS, multiple evolutionarily conserved transcription factors (TFs) are required; however, distinct TFs are likely responsible for these effects in different tissues. Here we have asked which TFs can extend healthy lifespan within distinct cell types of the adult nervous system in Drosophila. Starting from published single-cell transcriptomic data, we report that forkhead (FKH) is endogenously expressed in neurons, whereas forkhead-box-O (FOXO) is expressed in glial cells. Accordingly, we find that neuronal FKH and glial FOXO exert independent prolongevity effects. We have further explored the role of neuronal FKH in a model of Alzheimer’s disease-associated neuronal dysfunction, where we find that increased neuronal FKH preserves behavioral function and reduces ubiquitinated protein aggregation. Finally, using transcriptomic profiling, we identify Atg17, a member of the Atg1 autophagy initiation family, as one FKH-dependent target whose neuronal overexpression is sufficient to extend healthy lifespan. Taken together, our results underscore the importance of cell type-specific mapping of TF activity to preserve healthy function with age
Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila
No full textAmyloid β (Aβ) accumulation is a hallmark of Alzheimer's disease. In adult Drosophila brains, human Aβ overexpression harms climbing and lifespan. It's uncertain whether Aβ is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aβ toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aβ, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aβ resistance mechanism. Other laminin subunits and collagen IV also alleviate Aβ toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aβ secretion. LanB1's rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aβ toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aβ toxicity, offering a new therapeutic avenue for Alzheimer's disease
Protein retention in the endoplasmic reticulum rescues Aβ toxicity in Drosophila
No full textAmyloid β (Aβ) accumulation is a hallmark of Alzheimer’s disease. In adult Drosophila brains, human Aβ overexpression harms climbing and lifespan. It’s uncertain whether Aβ is intrinsically toxic or activates downstream neurodegeneration pathways. Our study uncovers a novel protective role against Aβ toxicity: intra-endoplasmic reticulum (ER) protein accumulation with a focus on laminin and collagen subunits. Despite high Aβ, laminin B1 (LanB1) overexpression robustly counters toxicity, suggesting a potential Aβ resistance mechanism. Other laminin subunits and collagen IV also alleviate Aβ toxicity; combining them with LanB1 augments the effect. Imaging reveals ER retention of LanB1 without altering Aβ secretion. LanB1’s rescue function operates independently of the IRE1α/XBP1 ER stress response. ER-targeted GFP overexpression also mitigates Aβ toxicity, highlighting broader ER protein retention advantages. Proof-of-principle tests in murine hippocampal slices using mouse Lamb1 demonstrate ER retention in transduced cells, indicating a conserved mechanism. Though ER protein retention generally harms, it could paradoxically counter neuronal Aβ toxicity, offering a new therapeutic avenue for Alzheimer’s disease
Advances in additive manufacturing of fuel cells: A review of technologies, materials, and challenges
No full text© 2025 The Author. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link: https://doi.org/10.1016/j.susmat.2025.e01317Fuel cells offer high-efficiency power production compared to internal combustion (IC) engines and gas/steam turbines. They are also very clean and come in several types, including PEM fuel cells, solid oxide fuel cells, direct methanol fuel cells, alkaline fuel cells, molten carbonate fuel cells, and phosphoric acid fuel cells. This diversity enables a broad market for decentralized power supply—both stationary and vehicular. In recent years, significant progress has been made in using additive manufacturing (AM) to fabricate fuel cell components such as electrolytes, electrodes, and casings. AM has revolutionised fuel cell fabrication by providing a sustainable process for producing parts with complex geometries, high material flexibility, and enhanced efficiency. This review aims to summarize the importance and current status of AM in fuel cell production. Various AM techniques (such as vat photopolymerization, material jetting, and powder bed fusion (PBF)) used in manufacturing different fuel cell components are discussed, along with recent advancements in materials and their corresponding properties. The review critically analyses the state of the art, highlighting the advantages and limitations of different techniques. Furthermore, this analysis extends to identifying suitable solutions to address challenges in fuel cell fabrication, providing valuable insights for researchers and engineers focused on clean energy production. This review article will benefit researchers interested in exploring the scope of AM in fuel cells.Published versio
