TDP-43 inclusions are found in many Alzheimer's disease (AD) patients presenting faster disease progression and greater brain atrophy. Previously, we showed full-length TDP-43 forms spherical ...oligomers and perturbs amyloid-β (Aβ) fibrillization. To elucidate the role of TDP-43 in AD, here, we examined the effect of TDP-43 in Aβ aggregation and the attributed toxicity in mouse models. We found TDP-43 inhibited Aβ fibrillization at initial and oligomeric stages. Aβ fibrillization was delayed specifically in the presence of N-terminal domain containing TDP-43 variants, while C-terminal TDP-43 was not essential for Aβ interaction. TDP-43 significantly enhanced Aβ's ability to impair long-term potentiation and, upon intrahippocampal injection, caused spatial memory deficit. Following injection to AD transgenic mice, TDP-43 induced inflammation, interacted with Aβ, and exacerbated AD-like pathology. TDP-43 oligomers mostly colocalized with intracellular Aβ in the brain of AD patients. We conclude that TDP-43 inhibits Aβ fibrillization through its interaction with Aβ and exacerbates AD pathology.
As the VLSI technology continues to scale down, combined with increasing demands for large bandwidth and low-power consumption, the optical interconnections with wavelength-division multiplexing ...(WDM) become an attractive alternative for on-chip signal transmission. Previous WDM-aware optical routing works consist of three main drawbacks: they are based mainly on heuristics or restricted integer linear programming to handle optical routing, the addressed types of insertion loss, and WDM overheads are incomplete, and the crosstalk noise during concurrent signal transmission is neglected. As a result, no performance guarantees can be achieved on their WDM clustering results, the reliability of the optical network is impaired, and/or their computations are too time consuming. To remedy these disadvantages, we present a new WDM-aware optical routing flow to minimize the insertion loss, the WDM overheads, and the crosstalk noise with a significant speedup. In the proposed flow, the WDM-aware path clustering algorithm guarantees to find an optimal solution for 1-, 2-, and 3-path clustering and has the constant performance bound for most cases of 4-path clustering; the crosstalk-aware path assignment guarantees to minimize the number of crosstalk signal pairs within the given displacement bound. Experimental results based on the ISPD 2007 and 2019 contest benchmarks and a real optical design show that our optical router significantly outperforms published works in wirelength, insertion loss, wavelength power, crosstalk noise, and runtimes.
Understanding the electronic structures of high‐valent metal complexes aids the advancement of metal‐catalyzed cross coupling methodologies. A prototypical complex with formally high valency is ...Cu(CF3)4− (1), which has a formal Cu(III) oxidation state but whose physical analysis has led some to a Cu(I) assignment in an inverted ligand field model. Recent examinations of 1 by X‐ray spectroscopies have led previous authors to contradictory conclusions, motivating the re‐examination of its X‐ray absorption profile here by a complementary method, resonant diffraction anomalous fine structure (DAFS). From analysis of DAFS measurements for a series of seven mononuclear Cu complexes including 1, here it is shown that there is a systematic trifluoromethyl effect on X‐ray absorption that blue shifts the resonant Cu K‐edge energy by 2–3 eV per CF3, completely accounting for observed changes in DAFS profiles between formally Cu(III) complexes like 1 and formally Cu(I) complexes like (Ph3P)3CuCF3 (3). Thus, in agreement with the inverted ligand field model, the data presented herein imply that 1 is best described as containing a Cu(I) ion with dn count approaching 10.
The electronic structures of Cu(CF3)4− and other Cu−CF3 complexes are (re−)evaluated using resonant X‐ray diffraction methods. A systematic trend was identified by which each additional CF3 ligand shifts the resonant Cu K‐edge energy by 2–3 eV, completely accounting for observed differences between complexes with different formal oxidation states. The recently debated assignment of Cu(CF3)4− as containing a Cu(I) ion is, thus, verified.
The wavelength-routed optical network on chip (WRONoC) is a promising solution for signal transmission in modern System-on-Chip (SoC) designs. Previous works do not simultaneously handle all the ...following four main issues for WRONoCs: 1) correlations between the topological structure and physical layout; 2) tradeoffs between the maximum insertion loss and the number of wavelengths; 3) runtime scalability of wavelength assignment scheme; and 4) a fully automated flow to generate predictable designs. As a result, their insertion loss estimation is inaccurate, their wavelength assignment is inefficient, and thus, only suboptimal results are obtained. To remedy these disadvantages, we present a fully automated topological structure and a physical layout co-design flow with improved wavelength assignment schemes to minimize the maximum insertion loss and the laser power simultaneously with a significant speedup. The experimental results show that our co-design flow significantly outperforms state-of-the-art works in the maximum insertion loss, laser power, and runtimes.
CELLO2GO (http://cello.life.nctu.edu.tw/cello2go/) is a publicly available, web-based system for screening various properties of a targeted protein and its subcellular localization. Herein, we ...describe how this platform is used to obtain a brief or detailed gene ontology (GO)-type categories, including subcellular localization(s), for the queried proteins by combining the CELLO localization-predicting and BLAST homology-searching approaches. Given a query protein sequence, CELLO2GO uses BLAST to search for homologous sequences that are GO annotated in an in-house database derived from the UniProt KnowledgeBase database. At the same time, CELLO attempts predict at least one subcellular localization on the basis of the species in which the protein is found. When homologs for the query sequence have been identified, the number of terms found for each of their GO categories, i.e., cellular compartment, molecular function, and biological process, are summed and presented as pie charts representing possible functional annotations for the queried protein. Although the experimental subcellular localization of a protein may not be known, and thus not annotated, CELLO can confidentially suggest a subcellular localization. CELLO2GO should be a useful tool for research involving complex subcellular systems because it combines CELLO and BLAST into one platform and its output is easily manipulated such that the user-specific questions may be readily addressed.
Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and ...resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted.
High‐performance non‐fullerene OSCs with PCEs of up to ca. 6.0% are demonstrated based on PBDTT‐F‐TT polymer and a molecular di‐PBI acceptor through comprehensive molecular, interfacial, and device ...engineering. Impressive PCEs can also be retained in devices with relatively thick BHJ layer and processed through non‐halogenated solvents, indicating these high‐performance non‐fullerene OSCs are promising for large‐area printing applications.
We give exact and asymptotic counting results for the number of galled networks and reticulation-visible networks with few reticulation vertices. Our results are obtained with the component graph ...method, which was introduced by L. Zhang and his coauthors, and generating function techniques. For galled networks, we in addition use analytic combinatorics. Moreover, in an appendix, we consider maximally reticulated reticulation-visible networks and derive their number, too.
A ratiometric fluorescence sensor for sensitive and selective dopamine detection based on carbon dots-gold nanoclusters hybrid
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•A ratiometric fluorescence sensor based on CDots-AuNCs ...hybrid was designed for dopamine detection.•The sensor provided remarkable ratiometric fluorescence intensity change.•The sensor exhibited excellent sensitivity and selectivity.•Human serum samples were analyzed.
In this work, a novel fluorescence resonance energy transfer (FRET)-based ratiometric fluorescent probe, carbon dots-gold nanoclusters hybrid (CDots-AuNCs), was fabricated for selective, sensitive and reliable sensing of dopamine (DA). This FRET probe is comprised of a two-fluorophore, where carbon dots (CDots) serve as the energy donor and gold nanoclusters (AuNCs) as the acceptor, with dual emission peaks at 420 nm and 610 nm under a single excitation wavelength of 380 nm. The addition of DA to this probe solution resulted in the fluorescence at 610 nm quenching, while the blue fluorescence at 420 nm recovering. By monitoring the change of ratiometric fluorescent intensity at 420 and 610 nm, the DA could be detected with the range from 5 to 180 nM and a limit of detection around 2.9 nM. Finally, the developed sensing method was successfully applied to DA determination in serum samples with satisfactory recoveries in the range of 95%–105%.
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