The growing dependence of society on rare-earth elements poses a challenge to achieving a just low-carbon transition globally. While circular economy strategies have gained attention, their... Show moreThe growing dependence of society on rare-earth elements poses a challenge to achieving a just low-carbon transition globally. While circular economy strategies have gained attention, their specific impacts remain unmeasured. Here we present an integrated model that quantifies how circular economy strategies can reshape global supply chains of the critical rare-earth elements such as neodymium, praseodymium, dysprosium and terbium. The model considers both in-ground and in-use stocks across ten regions from 2021 to 2050. The projections include the full deployment of three widely accepted climate scenarios. We find a considerable mismatch between in-ground stocks, supply and demand at specific region and element levels, with the mismatch for heavy rare-earth elements as a key obstacle for achieving net-zero emissions targets. We suggest that, as in-ground stocks decline among mineral suppliers, the accumulation of in-use stocks in consuming regions can foster a more balanced and less polarized geopolitical landscape for rare-earth elements, and circular economy strategies can lead to an increase of 701 kt secondary supply and a decrease of 2,306 kt demand within the next three decades. Implementing these circular economy strategies will require international cooperation in the governance of rare-earth elements amid sustainable transition. Show less
To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH... Show moreTo investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl2 and Δ-[1]Cl2. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl2 amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (Kd = 0.061 μM for the binding of Λ-[1]Cl2 to αIIbβ3), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl2 were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl2 efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl2. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo. Show less
Self-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a... Show moreSelf-assembling molecular drugs combine the easy preparation typical of small-molecule chemotherapy and the tumour-targeting properties of drug-nanoparticle conjugates. However, they require a supramolecular interaction that survives the complex environment of a living animal. Here we report that the metallophilic interaction between cyclometalated palladium complexes generates supramolecular nanostructures in living mice that have a long circulation time (over 12 h) and efficient tumour accumulation rate (up to 10.2% of the injected dose per gram) in a skin melanoma tumour model. Green light activation leads to efficient tumour destruction due to the type I photodynamic effect generated by the self-assembled palladium complexes, as demonstrated in vitro by an up to 96-fold cytotoxicity increase upon irradiation. This work demonstrates that metallophilic interactions are well suited to generating stable supramolecular nanotherapeutics in vivo with exceptional tumour-targeting properties. Show less
Improving resource efficiency (RE) is an important objective of the Sustainable Development Goals. In this study we find a strong exponential relationship between economic complexity index (ECI)... Show moreImproving resource efficiency (RE) is an important objective of the Sustainable Development Goals. In this study we find a strong exponential relationship between economic complexity index (ECI) and RE of countries. ECI measures the level of accumulated knowledge of a society enabling the products it makes. The relationship between ECI and RE is stronger for primary material importers and countries with stable institutions. Assessing a country's level of ECI also allows the outlook of future RE trends. We explain how ECI influences RE at the product level by establishing the product space for each country and by defining core products that contribute to a high product complexity index, high RE (i.e., unit price) and promising expansibility (i.e., core number), which indicates the potential to produce more advanced products in the future. Policies that improve economic complexity and invest in core products seem to be a priority to achieve sustainable development. Show less
Opsin-based transmembrane voltage sensors (OTVSs) are membrane proteins increasingly used in optogenetic applications to measure voltage changes across cellular membranes. In order to better... Show moreOpsin-based transmembrane voltage sensors (OTVSs) are membrane proteins increasingly used in optogenetic applications to measure voltage changes across cellular membranes. In order to better understand the photophysical properties of OTVSs, we used a combination of UV-Vis absorption, fluorescence and FT-Raman spectroscopy to characterize QuasAr2 and NovArch, two closely related mutants derived from the proton pump archaerhodopsin-3 (AR3). We find both QuasAr2 and NovArch can be optically cycled repeatedly between O-like and M-like states using 5-min exposure to red (660 nm) and near-UV (405 nm) light. Longer red-light exposure resulted in the formation of a long-lived photoproduct similar to pink membrane, previously found to be a photoproduct of the BR O intermediate with a 9-cis retinylidene chromophore configuration. However, unlike QuasAr2 whose O-like state is stable in the dark, NovArch exhibits an O-like state which slowly partially decays in the dark to a stable M-like form with a deprotonated Schiff base and a 13-cis,15-anti retinylidene chromophore configuration. These results reveal a previously unknown complexity in the photochemistry of OTVSs including the ability to optically switch between different long-lived states. The possible molecular basis of these newly discovered properties along with potential optogenetic and biotechnological applications are discussed. Show less
In multi/many-core System-on-Chips (SoCs), the performance is almost linearly scaling with the number of processing elements. In order to achieve higher performance, the many-core SoCs have to... Show moreIn multi/many-core System-on-Chips (SoCs), the performance is almost linearly scaling with the number of processing elements. In order to achieve higher performance, the many-core SoCs have to integrate more processing elements, which results in the communication between processing elements being a bottleneck for the performance improvement. A Network-on-Chip (NoC), with low network latency, high bandwidth, good scalability, and reusability, is promising communication fabric for the many-core SoCs. However, NoCs consume too much power in real chips, which constraints the utilization of NoCs in future large-scale many-core SoC. Meanwhile, with more advanced semiconductor technologies, applied in chip manufacturing, the static power consumption takes a larger proportion of the total power consumption of a NoC. Thus, in this thesis, we have focused our attention on reducing the static power consumption of NoCs in two directions: applying efficient power gating on NoCs to reduce the static power consumption and realizing a confined-interference communication on a simplified NoC infrastructure to achieve energy-efficient packet transmission. Show less
Opsin-based transmembrane voltage sensors (OTVSs) are increasingly important tools for neuroscience enabling neural function in complex brain circuits to be explored in live, behaving animals.... Show moreOpsin-based transmembrane voltage sensors (OTVSs) are increasingly important tools for neuroscience enabling neural function in complex brain circuits to be explored in live, behaving animals. However, the visible wavelengths required for fluorescence excitation of the current generation of OTVSs limit optogenetic imaging in the brain to depths of only a few mm due to the strong absorption and scattering of visible light by biological tissues. We report that substitution of the native A1 retinal chromophore of the widely used QuasAr1/2 OTVSs with the retinal analog MMAR containing a methylamino-modified dimethylphenyl ring results in over a 100-nm redshift of the maxima of the absorption and fluorescence emission bands to near 700 and 840 nm, respectively. FT-Raman spectroscopy reveals that at pH 7 QuasAr1 with both the A1 and MMAR chromophores possess predominantly an all-trans protonated Schiff base configuration with the MMAR chromophore exhibiting increased torsion of the polyene single-/double-bond system similar to the O-intermediate of the BR photocycle. In contrast, the A1 and the MMAR chromophores of QuasAr2 exist partially in a 13-cis PSB configuration. These results demonstrate that QuasArs containing the MMAR chromophore are attractive candidates for use as NIR-OTVSs, especially for applications such as deep brain imaging. Show less
There are only a limited number of studies that have developed appropriate models which incorporate bioavailability to estimate mixture toxicity. Here, we explored the applicability of the extended... Show moreThere are only a limited number of studies that have developed appropriate models which incorporate bioavailability to estimate mixture toxicity. Here, we explored the applicability of the extended biotic ligand model (BLM) and the WHAM-F tox approach for predicting and interpreting mixture toxicity, with the assumption that interactions between metal ions obey the BLM theory. Seedlings of lettuce Lactuca sativa were exposed to metal mixtures (Cu-Ni, Cu-Cd, and Ni-Cd) contained in hydroponic solutions for 4 days. Inhibition to root elongation was the endpoint used to quantify the toxic response. Assuming that metal ions compete with each other for binding at a single biotic ligand, the extended BLM succeeded in predicting toxicity of three mixtures to lettuce, with more than 82 % of toxicity variation explained. There were no significant differences in the values of f mix50 (i.e., the overall amounts of metal ions bound to the biotic ligand inducing 50 % effect) for the three mixture combinations, showing the possibility of extrapolating these values to other binary metal combinations. The WHAM-F tox approach showed a similar level of precision in estimating mixture toxicity while requiring fewer parameters than the BLM-f mix model. External validation of the WHAM-F tox approach using literature data showed its applicability for other species and other mixtures. The WHAM-F tox model is suitable for delineating mixture effects where the extended BLM also applies. Therefore, in case of lower data availability, we recommend the lower parameterized WHAM-F tox as an effective approach to incorporate bioavailability in quantifying mixture toxicity. Show less