101 research outputs found
Provably Total Functions of Arithmetic with Basic Terms
A new characterization of provably recursive functions of first-order
arithmetic is described. Its main feature is using only terms consisting of 0,
the successor S and variables in the quantifier rules, namely, universal
elimination and existential introduction.Comment: In Proceedings DICE 2011, arXiv:1201.034
The 35S U5 snRNP is generated from the activated spliceosome during In vitro splicing
Primary gene transcripts of eukaryotes contain introns, which are removed during processing by splicing machinery. Biochemical studies In vitro have identified a specific pathway in which introns are recognised and spliced out. This occurs by progressive formation of spliceosomal complexes designated as E, A, B, and C. The composition and structure of these spliceosomal conformations have been characterised in many detail. In contrast, transitions between the complexes and the intermediates of these reactions are currently less clear. We have previously isolated a novel 35S U5 snRNP from HeLa nuclear extracts. The protein composition of this particle differed from the canonical 20S U5 snRNPs but was remarkably similar to the activated B* spliceosomes. Based on this observation we have proposed a hypothesis that 35S U5 snRNPs represent a dissociation product of the spliceosome after both transesterification reactions are completed. Here we provide experimental evidence that 35S U5 snRNPs are generated from the activated B* spliceosomes during In vitro splicing
Agile gesture recognition for capacitive sensing devices: adapting on-the-job
Automated hand gesture recognition has been a focus of the AI community for decades. Traditionally, work in this domain revolved largely around scenarios assuming the availability of the flow of images of the user hands. This has partly been due to the prevalence of camera-based devices and the wide availability of image data. However, there is growing demand for gesture recognition technology that can be implemented on low-power devices using limited sensor data instead of high-dimensional inputs like hand images. In this work, we demonstrate a hand gesture recognition system and method that uses signals from capacitive sensors embedded into the etee hand controller. The controller generates real-time signals from each of the wearer five fingers. We use a machine learning technique to analyse the time series signals and identify three features that can represent 5 fingers within 500 ms. The analysis is composed of a two stage training strategy, including dimension reduction through principal component analysis and classification with K nearest neighbour. Remarkably, we found that this combination showed a level of performance which was comparable to more advanced methods such as supervised variational autoencoder. The base system can also be equipped with the capability to learn from occasional errors by providing it with an additional adaptive error correction mechanism. The results showed that the error corrector improve the classification performance in the base system without compromising its performance. The system requires no more than 1 ms of computing time per input sample, and is smaller than deep neural networks, demonstrating the feasibility of agile gesture recognition systems based on this technology.Depto. de Análisis Matemático y Matemática AplicadaFac. de Ciencias MatemáticasFALSEunpu
Comparative study of reactions between µ-nitrido- or µ-oxo-bridged iron tetrasulfophthalocyanines and sulfur-containing reductants
A comparative study of reactivity of μ-nitrido- and μ-oxo-dimers of iron
tetrasulfophthalocyanine has been performed in aqueous solutions of various
acidity. The substantially higher stability of nitrido-bridged structure
under both strongly acidic and strongly alkaline environments was
demonstrated. Reactions of the complexes with sulfur-containing reductants
(sodium dithionite, thiourea dioxide, sodium hydroxymethanesulfinate,
L-cysteine) has been studied. Differences in reduction processes were
explained
Preparing a commercial quantum key distribution system for certification against implementation loopholes
A commercial quantum key distribution (QKD) system needs to be formally
certified to enable its wide deployment. The certification should include the
system's robustness against known implementation loopholes and attacks that
exploit them. Here we ready a fiber-optic QKD system for this procedure. The
system has a prepare-and-measure scheme with decoy-state BB84 protocol,
polarisation encoding, qubit source rate of 312.5 MHz, and is manufactured by
QRate in Russia. We detail its hardware and post-processing. We analyse the
hardware for any possible implementation loopholes and discuss countermeasures.
We then amend the system design to address the highest-risk loopholes
identified. We also work out technical requirements on the certification lab
and outline its possible structure.Comment: 33 pages, 11 figures, 2 table
Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs
Copyright @ 2011 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Spliceosomes remove introns from primary gene transcripts. They assemble de novo on each intron through a series of steps that involve the incorporation of five snRNP particles and multiple non-snRNP proteins. In mammals, all the intermediate complexes have been characterized on one transcript (MINX), with the exception of the very first, complex E. We have purified this complex by two independent procedures using antibodies to either U1-A or PRPF40A proteins, which are known to associate at an early stage of assembly. We demonstrate that the purified complexes are functional in splicing using commitment assays. These complexes contain components expected to be in the E complex and a number of previously unrecognized factors, including survival of motor neurons (SMN) and proteins of the SMN-associated complex. Depletion of the SMN complex proteins from nuclear extracts inhibits formation of the E complex and causes non-productive complexes to accumulate. This suggests that the SMN complex stabilizes the association of U1 and U2 snRNPs with pre-mRNA. In addition, the antibody to PRPF40A precipitated U2 snRNPs from nuclear extracts, indicating that PRPF40A associates with U2 snRNPs
Na,K-ATPase Acts as a Beta-Amyloid Receptor Triggering Src Kinase Activation
Beta-amyloid (Aβ) has a dual role, both as an important factor in the pathology of Alzheimer’s disease and as a regulator in brain physiology. The inhibitory effect of Aβ42 oligomers on Na,K-ATPase contributes to neuronal dysfunction in Alzheimer’s disease. Still, the physiological role of the monomeric form of Aβ42 interaction with Na,K-ATPase remains unclear. We report that Na,K-ATPase serves as a receptor for Aβ42 monomer, triggering Src kinase activation. The co-localization of Aβ42 with α1- and β1-subunits of Na,K-ATPase, and Na,K-ATPase with Src kinase in SH-SY5Y neuroblastoma cells, was observed. Treatment of cells with 100 nM Aβ42 causes Src kinase activation, but does not alter Na,K-ATPase transport activity. The interaction of Aβ42 with α1β1 Na,K-ATPase isozyme leads to activation of Src kinase associated with the enzyme. Notably, prevention of Na,K-ATPase:Src kinase interaction by a specific inhibitor pNaKtide disrupts the Aβ-induced Src kinase activation. Stimulatory effect of Aβ42 on Src kinase was lost under hypoxic conditions, which was similar to the effect of specific Na,K-ATPase ligands, the cardiotonic steroids. Our findings identify Na,K-ATPase as a Aβ42 receptor, thus opening a prospect on exploring the physiological and pathological Src kinase activation caused by Aβ42 in the nervous system
Intravenously Injected Amyloid-β Peptide With Isomerized Asp7 and Phosphorylated Ser8 Residues Inhibits Cerebral β-Amyloidosis in AβPP/PS1 Transgenic Mice Model of Alzheimer’s Disease
Cerebral β-amyloidosis, an accumulation in the patient’s brain of aggregated amyloid-β (Aβ) peptides abnormally saturated by divalent biometal ions, is one of the hallmarks of Alzheimer’s disease (AD). Earlier, we found that exogenously administrated synthetic Aβ with isomerized Asp7 (isoD7-Aβ) induces Aβ fibrillar aggregation in the transgenic mice model of AD. IsoD7-Aβ molecules have been implied to act as seeds enforcing endogenous Aβ to undergo pathological aggregation through zinc-mediated interactions. On the basis of our findings on zinc-induced oligomerization of the metal-binding domain of various Aβ species, we hypothesize that upon phosphorylation of Ser8, isoD7-Aβ loses its ability to form zinc-bound oligomeric seeds. In this work, we found that (i) in vitro isoD7-Aβ with phosphorylated Ser8 (isoD7-pS8-Aβ) is less prone to spontaneous and zinc-induced aggregation in comparison with isoD7-Aβ and intact Aβ as shown by thioflavin T fluorimetry and dynamic light scattering data, and (ii) intravenous injections of isoD7-pS8-Aβ significantly slow down the progression of institutional β-amyloidosis in AβPP/PS1 transgenic mice as shown by the reduction of the congophilic amyloid plaques’ number in the hippocampus. The results support the role of the zinc-mediated oligomerization of Aβ species in the modulation of cerebral β-amyloidosis and demonstrate that isoD7-pS8-Aβ can serve as a potential molecular tool to block the aggregation of endogenous Aβ in AD
Phosphorylation of the Amyloid-Beta Peptide Inhibits Zinc-Dependent Aggregation, Prevents Na,K-ATPase Inhibition, and Reduces Cerebral Plaque Deposition
The triggers of late-onset sporadic Alzheimer’s disease (AD) are still poorly understood. Impairment of protein phosphorylation with age is well-known; however, the role of the phosphorylation in β-amyloid peptide (Aβ) is not studied sufficiently. Zinc-induced oligomerization of Aβ represents a potential seeding mechanism for the formation of neurotoxic Aβ oligomers and aggregates. Phosphorylation of Aβ by Ser8 (pS8-Aβ), localized inside the zinc-binding domain of the peptide, may significantly alter its zinc-induced oligomerization. Indeed, using dynamic light scattering, we have shown that phosphorylation by Ser8 dramatically reduces zinc-induced aggregation of Aβ, and moreover pS8-Aβ suppresses zinc-driven aggregation of non-modified Aβ in an equimolar mixture. We have further analyzed the effect of pS8-Aβ on the progression of cerebral amyloidosis with serial retro-orbital injections of the peptide in APPSwe/PSEN1dE9 murine model of AD, followed by histological analysis of amyloid burden in hippocampus. Unlike the non-modified Aβ that has no influence on the amyloidosis progression in murine models of AD, pS8-Aβ injections reduced the number of amyloid plaques in the hippocampus of mice by one-third. Recently shown inhibition of Na+,K+-ATPase activity by Aβ, which is thought to be a major contributor to neuronal dysfunction in AD, is completely reversed by phosphorylation of the peptide. Thus, several AD-associated pathogenic properties of Aβ are neutralized by its phosphorylation
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