257 research outputs found
Failure Probabilities and Tough-Brittle Crossover of Heterogeneous Materials with Continuous Disorder
The failure probabilities or the strength distributions of heterogeneous 1D
systems with continuous local strength distribution and local load sharing have
been studied using a simple, exact, recursive method. The fracture behavior
depends on the local bond-strength distribution, the system size, and the
applied stress, and crossovers occur as system size or stress changes. In the
brittle region, systems with continuous disorders have a failure probability of
the modified-Gumbel form, similar to that for systems with percolation
disorder. The modified-Gumbel form is of special significance in weak-stress
situations. This new recursive method has also been generalized to calculate
exactly the failure probabilities under various boundary conditions, thereby
illustrating the important effect of surfaces in the fracture process.Comment: 9 pages, revtex, 7 figure
Morphological characterization of shocked porous material
Morphological measures are introduced to probe the complex procedure of shock
wave reaction on porous material. They characterize the geometry and topology
of the pixelized map of a state variable like the temperature. Relevance of
them to thermodynamical properties of material is revealed and various
experimental conditions are simulated. Numerical results indicate that, the
shock wave reaction results in a complicated sequence of compressions and
rarefactions in porous material. The increasing rate of the total fractional
white area roughly gives the velocity of a compressive-wave-series.
When a velocity is mentioned, the corresponding threshold contour-level of
the state variable, like the temperature, should also be stated. When the
threshold contour-level increases, becomes smaller. The area increases
parabolically with time during the initial period. The curve goes
back to be linear in the following three cases: (i) when the porosity
approaches 1, (ii) when the initial shock becomes stronger, (iii) when the
contour-level approaches the minimum value of the state variable. The area with
high-temperature may continue to increase even after the early
compressive-waves have arrived at the downstream free surface and some
rarefactive-waves have come back into the target body. In the case of energetic
material ... (see the full text)Comment: 3 figures in JPG forma
Generalized Interpolation Material Point Approach to High Melting Explosive with Cavities Under Shock
Criterion for contacting is critically important for the Generalized
Interpolation Material Point(GIMP) method. We present an improved criterion by
adding a switching function. With the method dynamical response of high melting
explosive(HMX) with cavities under shock is investigated. The physical model
used in the present work is an elastic-to-plastic and thermal-dynamical model
with Mie-Gr\"uneissen equation of state. We mainly concern the influence of
various parameters, including the impacting velocity , cavity size , etc,
to the dynamical and thermodynamical behaviors of the material. For the
colliding of two bodies with a cavity in each, a secondary impacting is
observed. Correspondingly, the separation distance of the two bodies has a
maximum value in between the initial and second impacts. When the
initial impacting velocity is not large enough, the cavity collapses in a
nearly symmetric fashion, the maximum separation distance increases
with . When the initial shock wave is strong enough to collapse the cavity
asymmetrically along the shock direction, the variation of with
does not show monotonic behavior. Our numerical results show clear indication
that the existence of cavities in explosive helps the creation of ``hot
spots''.Comment: Figs.2,4,7,11 in JPG format; Accepted for publication in J. Phys. D:
Applied Physic
Sideband Cooling Micromechanical Motion to the Quantum Ground State
The advent of laser cooling techniques revolutionized the study of many
atomic-scale systems. This has fueled progress towards quantum computers by
preparing trapped ions in their motional ground state, and generating new
states of matter by achieving Bose-Einstein condensation of atomic vapors.
Analogous cooling techniques provide a general and flexible method for
preparing macroscopic objects in their motional ground state, bringing the
powerful technology of micromechanics into the quantum regime. Cavity opto- or
electro-mechanical systems achieve sideband cooling through the strong
interaction between light and motion. However, entering the quantum regime,
less than a single quantum of motion, has been elusive because sideband cooling
has not sufficiently overwhelmed the coupling of mechanical systems to their
hot environments. Here, we demonstrate sideband cooling of the motion of a
micromechanical oscillator to the quantum ground state. Entering the quantum
regime requires a large electromechanical interaction, which is achieved by
embedding a micromechanical membrane into a superconducting microwave resonant
circuit. In order to verify the cooling of the membrane motion into the quantum
regime, we perform a near quantum-limited measurement of the microwave field,
resolving this motion a factor of 5.1 from the Heisenberg limit. Furthermore,
our device exhibits strong-coupling allowing coherent exchange of microwave
photons and mechanical phonons. Simultaneously achieving strong coupling,
ground state preparation and efficient measurement sets the stage for rapid
advances in the control and detection of non-classical states of motion,
possibly even testing quantum theory itself in the unexplored region of larger
size and mass.Comment: 13 pages, 7 figure
The impact of CFNS-causing EFNB1 mutations on ephrin-B1 function
BACKGROUND: Mutations of EFNB1 cause the X-linked malformation syndrome craniofrontonasal syndrome (CFNS). CFNS is characterized by an unusual phenotypic pattern of inheritance, because it affects heterozygous females more severely than hemizygous males. This sex-dependent inheritance has been explained by random X-inactivation in heterozygous females and the consequences of cellular interference of wild type and mutant EFNB1-expressing cell populations. EFNB1 encodes the transmembrane protein ephrin-B1, that forms bi-directional signalling complexes with Eph receptor tyrosine kinases expressed on complementary cells. Here, we studied the effects of patient-derived EFNB1 mutations predicted to give rise to truncated ephrin-B1 protein or to disturb Eph/ephrin-B1 reverse ephrin-B1 signalling. Five mutations are investigated in this work: nonsense mutation c.196C > T/p.R66X, frameshift mutation c.614_615delCT, splice-site mutation c.406 + 2T > C and two missense mutations p.P54L and p.T111I. Both missense mutations are located in the extracellular ephrin domain involved in Eph-ephrin-B1 recognition and higher order complex formation. METHODS: Nonsense mutation c.196C > T/p.R66X, frameshift mutation c.614_615delCT and splice-site mutation c.406+2T > C were detected in the primary patient fibroblasts by direct sequencing of the DNA and were further analysed by RT-PCR and Western blot analyses.The impact of missense mutations p.P54L and p.T111I on cell behaviour and reverse ephrin-B1 cell signalling was analysed in a cell culture model using NIH 3T3 fibroblasts. These cells were transfected with the constructs generated by in vitro site-directed mutagenesis. Investigation of missense mutations was performed using the Western blot analysis and time-lapse microscopy. RESULTS AND DISCUSSION: Nonsense mutation c.196C > T/p.R66X and frameshift mutation c.614_615delCT escape nonsense-mediated RNA decay (NMD), splice-site mutation c.406+2T > C results in either retention of intron 2 or activation of a cryptic splice site in exon 2. However, c.614_615delCT and c.406+2T > C mutations were found to be not compatible with production of a soluble ephrin-B1 protein. Protein expression of the p.R66X mutation was predicted unlikely but has not been investigated.Ectopic expression of p.P54L ephrin-B1 resists Eph-receptor mediated cell cluster formation in tissue culture and intracellular ephrin-B1 Tyr324 and Tyr329 phosphorylation. Cells expressing p.T111I protein show similar responses as wild type expressing cells, however, phosphorylation of Tyr324 and Tyr329 is reduced. CONCLUSIONS: Pathogenic mechanisms in CFNS manifestation include impaired ephrin-B1 signalling combined with cellular interference
AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11
Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway. MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro. In primary human fibroblasts, activated AKT suppresses MRN complex expression to escalate RAS-induced DNA damage and thereby reinforce oncogene-induced senescence. Taken together, our data demonstrate that deregulation of the PI3K-AKT/ mTORC1/ p70S6K pathways, an event frequently observed in cancer, exert profound effects on genome stability via MRE11 with potential implications for tumour initiation and therapy
Genome-Wide Comparative Gene Family Classification
Correct classification of genes into gene families is important for understanding gene function and evolution. Although gene families of many species have been resolved both computationally and experimentally with high accuracy, gene family classification in most newly sequenced genomes has not been done with the same high standard. This project has been designed to develop a strategy to effectively and accurately classify gene families across genomes. We first examine and compare the performance of computer programs developed for automated gene family classification. We demonstrate that some programs, including the hierarchical average-linkage clustering algorithm MC-UPGMA and the popular Markov clustering algorithm TRIBE-MCL, can reconstruct manual curation of gene families accurately. However, their performance is highly sensitive to parameter setting, i.e. different gene families require different program parameters for correct resolution. To circumvent the problem of parameterization, we have developed a comparative strategy for gene family classification. This strategy takes advantage of existing curated gene families of reference species to find suitable parameters for classifying genes in related genomes. To demonstrate the effectiveness of this novel strategy, we use TRIBE-MCL to classify chemosensory and ABC transporter gene families in C. elegans and its four sister species. We conclude that fully automated programs can establish biologically accurate gene families if parameterized accordingly. Comparative gene family classification finds optimal parameters automatically, thus allowing rapid insights into gene families of newly sequenced species
Literatures of resistance under U.S. “cultural siege”: Kazuo Ishiguro’s narratives of occupation
Through close readings of An Artist of the Floating World and The Remains of the Day, supported by references to his other works, this article argues that Japanese-British writer Kazuo Ishiguro’s novels betray an understated but distinct anti-American sentiment. Much has been made of the narcissism of Ishiguro’s narrators and their attempts to manipulate historical and personal records to serve their own purposes. However, one of those purposes that have gone undetected is a willful political resistance to the postwar Americanization of Japan and Europe. In other words, the article argues that the novels discussed are, in fact, works of propaganda and, further, that they evidence, with a high degree of subtlety and linguistic sophistication, Ishiguro’s own concerns that world literature and world culture more broadly were, as a result of World War II, subsumed into the American model, becoming homogenized
Nuclear Reprogramming: Kinetics of Cell Cycle and Metabolic Progression as Determinants of Success
Establishment of totipotency after somatic cell nuclear transfer (NT) requires not only reprogramming of gene expression, but also conversion of the cell cycle from quiescence to the precisely timed sequence of embryonic cleavage. Inadequate adaptation of the somatic nucleus to the embryonic cell cycle regime may lay the foundation for NT embryo failure and their reported lower cell counts. We combined bright field and fluorescence imaging of histone H2b-GFP expressing mouse embryos, to record cell divisions up to the blastocyst stage. This allowed us to quantitatively analyze cleavage kinetics of cloned embryos and revealed an extended and inconstant duration of the second and third cell cycles compared to fertilized controls generated by intracytoplasmic sperm injection (ICSI). Compared to fertilized embryos, slow and fast cleaving NT embryos presented similar rates of errors in M phase, but were considerably less tolerant to mitotic errors and underwent cleavage arrest. Although NT embryos vary substantially in their speed of cell cycle progression, transcriptome analysis did not detect systematic differences between fast and slow NT embryos. Profiling of amino acid turnover during pre-implantation development revealed that NT embryos consume lower amounts of amino acids, in particular arginine, than fertilized embryos until morula stage. An increased arginine supplementation enhanced development to blastocyst and increased embryo cell numbers. We conclude that a cell cycle delay, which is independent of pluripotency marker reactivation, and metabolic restraints reduce cell counts of NT embryos and impede their development
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