3,007 research outputs found
Identification of Boundary Conditions Using Natural Frequencies
The present investigation concerns a disc of varying thickness of whose
flexural stiffness varies with the radius according to the law , where and are constants. The problem of finding boundary
conditions for fastening this disc, which are inaccessible to direct
observation, from the natural frequencies of its axisymmetric flexural
oscillations is considered. The problem in question belongs to the class of
inverse problems and is a completely natural problem of identification of
boundary conditions. The search for the unknown conditions for fastening the
disc is equivalent to finding the span of the vectors of unknown conditions
coefficients. It is shown that this inverse problem is well posed. Two theorems
on the uniqueness and a theorem on stability of the solution of this problem
are proved, and a method for establishing the unknown conditions for fastening
the disc to the walls is indicated. An approximate formula for determining the
unknown conditions is obtained using first three natural frequencies. The
method of approximate calculation of unknown boundary conditions is explained
with the help of three examples of different cases for the fastening the disc
(rigid clamping, free support, elastic fixing).
Keywords: Boundary conditions, a disc of varying thickness,inverse problem,
Plucker condition.Comment: 19 page
The PINK1-Parkin mitophagy signalling pathway is not functional in peripheral blood mononuclear cells
Mutations in the PINK1 and PRKN genes are the most common cause of early-onset familial Parkinson disease. These genes code for the PINK1 and Parkin proteins, respectively, which are involved in the degradation of dysfunctional mitochondria through mitophagy. An early step in PINK1 -Parkin mediated mitophagy is the ubiquitination of the mitofusin proteins MFN1 and -2. The ubiquitination of MFN1 and -2 in patient samples may therefore serve as a biomarker to determine the functional effects of PINK1 and PRKN mutations, and to screen idiopathic patients for potential mitophagy defects. We aimed to characterise the expression of the PINK1 -Parkin mitophagy machinery in peripheral blood mononuclear cells (PBMCs) and assess if these cells could serve as a platform to evaluate mitophagy via analysis of MFN1 and -2 ubiquitination. Mitophagy was induced through mitochondrial depolarisation by treatment with the protonophore CCCP and ubiquitinated MFN proteins were analysed by western blotting. In addition, PINK1 and PRKN mRNA and protein expression levels were characterised with reverse transcriptase quantitative PCR and western blotting, respectively. Whilst CCCP treatment led to MFN ubiquitination in primary fibroblasts, SH-SY5Y neuroblastoma cells and Jurkat leukaemic cells, treatment of PBMCs did not induce ubiquitination of MFN. PRKN mRNA and protein was readily detectable in PBMCs at comparable levels to those observed in Jurkat and fibroblast cells. In contrast, PINK1 protein was undetectable and PINK1 mRNA levels were remarkably low in control PBMCs. Our findings suggest that the PINK1 -Parkin mitophagy signalling pathway is not functional in PBMCs. Therefore, PBMCs are not a suitable biosample for analysis of mitophagy function in Parkinson disease patients
Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia
Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%). CRLF2-r co-occurred with primary chromosomal rearrangements but the majority (111/161, 69%) had B-other ALL. Copy number alteration (CNA) profiles were similar to B-other ALL, although CRLF2-r patients harbored higher frequencies of IKZF1 (60/138, 43% vs. 77/1351, 24%) and BTG1 deletions (20/138, 15% vs. 3/1351, 1%). There were significant differences in CNA profiles between IGH-CRLF2 and P2RY8-CRLF2 patients: IKZF1 (25/35, 71% vs. 36/108, 33%, P < .001), BTG1 (11/35, 31% vs. 10/108, 9%, P =.004), and ADD3 deletions (9/19, 47% vs. 5/38, 13%, P =.008). A novel gene fusion, USP9X-DDX3X, was discovered in 10/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets
Experiential aspects of tourism gift consumption
This article addresses how consumers make use of fantasy, feelings, and fun when deciding, giving, and consuming gifts of tourism and leisure. Despite little industry awareness, consumers are engaging with such behaviour because tourism gifts offer considerable scope for the creative expression of donor–recipient relationships. This UK-based interpretive qualitative study captured data from donors, recipients, and tourism and leisure providers. The feelings (emotions), fantasies (imagination and dreaming), and fun (playfulness) were interrogated through the behavioural phases of gift decision making, gift exchange, post-exchange, and gift consumption. A range of emotions were displayed by donors and recipients at different stages in the gift-giving process; donor decision making in groups for created gifts was particularly charged. Fantasies were evident both for donors planning gifts and for recipients. As an intangible gift, means of exchange allowed for creative mechanisms beyond the classic wrapping strategies associated with physical gifts. The ‘decoy’ strategy stimulated the recipient’s imagination to conjure fantastical scenarios. Fun or playfulness was built into many of the gifts and often related to an element of ‘surprise’, an attribute of the perfect gift (e.g. Belk, 1996) in Western societies
Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells
Glycosylation is a highly complex process to produce a diverse repertoire of
cellular glycans that are attached to proteins and lipids. Glycans are involved
in fundamental biological processes, including protein folding and clearance,
cell proliferation and apoptosis, development, immune responses, and
pathogenesis. One of the major types of glycans, N-linked glycans, is formed by
sequential attachments of monosaccharides to proteins by a limited number of
enzymes. Many of these enzymes can accept multiple N-linked glycans as
substrates, thereby generating a large number of glycan intermediates and their
intermingled pathways. Motivated by the quantitative methods developed in
complex network research, we investigated the large-scale organization of such
N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation
pathways are extremely modular, and are composed of cohesive topological
modules that directly branch from a common upstream pathway of glycan
synthesis. This unique structural property allows the glycan production between
modules to be controlled by the upstream region. Although the enzymes act on
multiple glycan substrates, indicating cross-talk between modules, the impact
of the cross-talk on the module-specific enhancement of glycan synthesis may be
confined within a moderate range by transcription-level control. The findings
of the present study provide experimentally-testable predictions for
glycosylation processes, and may be applicable to therapeutic glycoprotein
engineering
Electron excitation and energy transfer rates for H2O in the upper atmosphere
Recent measurements of the cross sections for electronic state excitations in
H2O have made it possible to calculate rates applicable to these excitation
processes. We thus present here calculations of electron energy transfer rates
for electronic and vibrational state excitations in H2O, as well as rates for
excitation of some of these states by atmospheric thermal and auroral secondary
electrons. The calculation of these latter rates is an important first step
towards our aim of including water into a statistical equilibrium model of the
atmosphere under auroral conditions.Comment: 15 pages, 8 figure
At the crossroads of biomacromolecular research: highlighting the interdisciplinary nature of the field
Due to their complexity and wide-ranging utility, biomacromolecular research is an especially interdisciplinary branch of chemistry. It is my goal that the Biomacromolecules subject area of Chemistry Central Journal will parallel this richness and diversity. In this inaugural commentary, I attempt to set the stage for achieving this by highlighting several areas where biomacromolecular research overlaps more traditional chemistry sub-disciplines. Specifically, it is discussed how Materials Science and Biotechnology, Analytical Chemistry, Cell Biology and Chemical Theory are each integral to modern biomacromolecular research. Investigators with reports in any of these areas, or any other dealing with biomacromolecules, are encouraged to submit their research papers to Chemistry Central Journal
Two-loop helicity amplitudes for the production of two off-shell electroweak bosons in gluon fusion
Two-orbital SU(N) magnetism with ultracold alkaline-earth atoms
Fermionic alkaline-earth atoms have unique properties that make them
attractive candidates for the realization of novel atomic clocks and degenerate
quantum gases. At the same time, they are attracting considerable theoretical
attention in the context of quantum information processing. Here we demonstrate
that when such atoms are loaded in optical lattices, they can be used as
quantum simulators of unique many-body phenomena. In particular, we show that
the decoupling of the nuclear spin from the electronic angular momentum can be
used to implement many-body systems with an unprecedented degree of symmetry,
characterized by the SU(N) group with N as large as 10. Moreover, the interplay
of the nuclear spin with the electronic degree of freedom provided by a stable
optically excited state allows for the study of spin-orbital physics. Such
systems may provide valuable insights into strongly correlated physics of
transition metal oxides, heavy fermion materials, and spin liquid phases.Comment: 15 pages, 10 figures. V2: extended experimental accessibility and
Kondo sections in the main text (including new Fig. 5b) and in the Methods;
reorganized other parts; added reference
DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2
The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes
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