Analysis of crystallographic slip and grain boundary sliding in a Ti-45Al-2Nb-2Mn (at%)-0.8 vol%TiB2 alloy by high temperature in situ mechanical testing

This work aims to contribute to a further understanding of the fundamentals of crystallographic slip and grain boundary sliding in the γ-TiAl Ti–45Al–2Nb–2Mn (at%)–0.8 vol%TiB2 intermetallic alloy, by means of in situ high-temperature tensile testing combined with electron backscatter diffraction (EBSD). Several microstructures, containing different fractions and sizes of lamellar colonies and equiaxed γ-grains, were fabricated by either centrifugal casting or powder metallurgy, followed by heat treatment at 1300 °C and furnace cooling. in situ tensile and tensile-creep experiments were performed in a scanning electron microscope (SEM) at temperatures ranging from 580 °C to 700 °C. EBSD was carried out in selected regions before and after straining. Our results suggest that, during constant strain rate tests, true twin γ/γ interfaces are the weakest barriers to dislocations and, thus, that the relevant length scale might be influenced by the distance between non-true twin boundaries. Under creep conditions both grain/colony boundary sliding (G/CBS) and crystallographic slip are observed to contribute to deformation. The incidence of boundary sliding is particularly high in γ grains of duplex microstructures. The slip activity during creep deformation in different microstructures was evaluated by trace analysis. Special emphasis was placed in distinguishing the compliance of different slip events with the Schmid law with respect to the applied stress.

Analysis of pressure transients and cavitation in a distributor

During pressure testing of a large distributor the weld securing the bulkhead failed, which triggered large pressure transients and cavitation phenomena. The problem has been studied by explicit integration, using shell elements for the structural parts and acoustic elements for the water. Although the calculations had to be carried out in the absence of any information about the outcome of the accident, very good consistency was achieved between the predictions and the actual observations.

Analysis of Combined Bending and Punching Tests of Reinforced Concrete Slabs within IMPACT III Project

The paper reports on a collaborative effort between the Swiss Federal Nuclear Safety Inspectorate (ENSI) and their consultants Principia and Stangenberg. As part of the IMPACT III project, reduced scale impact tests of reinforced concrete structures were carried out. The simulation of test X3 is presented here and the numerical results are compared with those obtained in the test, carried out in August 2013. The general object is to improve the safety of nuclear facilities and, more specifically, to demonstrate the capabilities of current simulation techniques to reproduce the behaviour of a reinforced concrete structure impacted by a soft missile. The missile is a steel tube with a mass of 50 kg and travelling at 140 m/s. The target is a 250 mm thick, 2,1 m by 2,1 m reinforced concrete wall, held in a stiff supporting frame. The reinforcement includes both longitudinal and transverse rebars. Calculations were carried out before and after the test with Abaqus (Principia) and SOFiSTiK (Stangenberg). In the Abaqus simulation the concrete is modelled using solid elements and a damaged plasticity formulation, the rebars with embedded beam elements, and the missile with shell elements. In SOFiSTiK the target is modelled with non-linear, layered shell elements for the reinforcement on both sides; non-linear shear deformations of shell/plate elements are approximately included. The results generally indicate a good agreement between calculations and measurements.

Analysis of signal impairment and crosstalk penalty induced by different types of optical filters in 100 Gbps PM-DQPSK based systems

Optical filters are crucial elements in optical communication networks. Their influence toward the optical signal will affect the communication quality seriously. In this paper we will study and simulate the optical signal impairment and crosstalk penalty caused by different kinds of filters, which include Butterworth, Bessel, Fiber Bragg Grating (FBG) and Fabry-Perot (F-P). Signal impairment from filter concatenation effect and crosstalk penalty from out-band and in-band are analyzed from Q-penalty, eye opening penalty (EOP) and optical spectrum. The simulation results show that signal impairment and crosstalk penalty induced by the Butterworth filter is the minimum among these four types of filters. Signal impairment caused by filter concatenation effect shows that when center frequency of all filters is aligned perfectly with the laser's frequency, 12 50-GHz Butterworth filters can be cascaded, with 1-dB EOP. This value is reduced to 9 when the center frequency is misaligned with 5 GHz. In the 50-GHz channel spacing DWDM networks, total Q-penalty induced by a pair of Butterworth filters based demultiplexer and multiplexer is lower than 0.5 dB when the filter bandwidth is in the range of 42-46 GHz.

Functional analysis of DNA bending and unwinding by the high mobility group domain of LEF-1

LEF-1 (lymphoid enhancer-binding factor 1) is a cell type-specific member of the family of high mobility group (HMG) domain proteins that recognizes a specific nucleotide sequence in the T cell receptor (TCR) α enhancer. In this study, we extend the analysis of the DNA-binding properties of LEF-1 and examine their contributions to the regulation of gene expression. We find that LEF-1, like nonspecific HMG-domain proteins, can interact with irregular DNA structures such as four-way junctions, albeit with lower efficiency than with specific duplex DNA. We also show by a phasing analysis that the LEF-induced DNA bend is directed toward the major groove. In addition, we find that the interaction of LEF-1 with a specific binding site in circular DNA changes the linking number of DNA and unwinds the double helix. Finally, we identified two nucleotides in the LEF-1-binding site that are important for protein-induced DNA bending. Mutations of these nucleotides decrease both the extent of DNA bending and the transactivation of the TCRα enhancer by LEF-1, suggesting a contribution of protein-induced DNA bending to the function of TCRα enhancer.

PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis

Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 (PEG-3), whose expression directly correlates with cancer progression and acquisition of oncogenic potential by transformed rodent cells. We presently demonstrate that forced expression of PEG-3 in tumorigenic rodent cells, and in human cancer cells, increases their oncogenic potential in nude mice as reflected by a shorter tumor latency time and the production of larger tumors with increased vascularization. Moreover, inhibiting endogenous PEG-3 expression in progressed rodent cancer cells by stable expression of an antisense expression vector extinguishes the progressed cancer phenotype. Cancer aggressiveness of PEG-3 expressing rodent cells correlates directly with increased RNA transcription, elevated mRNA levels, and augmented secretion of vascular endothelial growth factor (VEGF). Furthermore, transient ectopic expression of PEG-3 transcriptionally activates VEGF in transformed rodent and human cancer cells. Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.

Genomic analysis of orthologous mouse and human olfactory receptor loci

Olfactory receptor (OR) genes represent ≈1% of genomic coding sequence in mammals, and these genes are clustered on multiple chromosomes in both the mouse and human genomes. We have taken a comparative genomics approach to identify features that may be involved in the dynamic evolution of this gene family and in the transcriptional control that results in a single OR gene expressed per olfactory neuron. We sequenced ≈350 kb of the murine P2 OR cluster and used synteny, gene linkage, and phylogenetic analysis to identify and sequence ≈111 kb of an orthologous cluster in the human genome. In total, 18 mouse and 8 human OR genes were identified, including 7 orthologs that appear to be functional in both species. Noncoding homology is evident between orthologs and generally is confined within the transcriptional unit. We find no evidence for common regulatory features shared among paralogs, and promoter regions generally do not contain strong promoter motifs. We discuss these observations, as well as OR clustering, in the context of evolutionary expansion and transcriptional regulation of OR repertoires.

Conditional Synergism between Cryptochrome 1 and Phytochrome B Is Shown by the Analysis of phyA, phyB, and hy4 Simple, Double, and Triple Mutants in Arabidopsis

Wild-type or phyA, phyB, or hy4 mutant Arabidopsis seedlings lacking phytochrome A (phyA), phytochrome B (phyB), or cryptochrome 1 (cry1), respectively, and the double and triple mutants were used in combination with blue-light treatments given simultaneously with red or far-red light. We investigated the interaction between phytochromes and cry1 in the control of hypocotyl growth and cotyledon unfolding. Under conditions deficient for cry1 (short exposures to blue light) or phyB (far-red background), these photoreceptors acted synergistically: Under short exposures to blue light (3 h/d) added to a red-light background, cry1 activity required phyB (e.g. the hy4 mutant was taller than the wild type but the phyBhy4 mutant was not taller than the phyB mutant). Under prolonged exposures to blue light (24 h/d) added to a far-red light background, phyB activity required cry1 (e.g. the phyAphyB mutant was taller than the phyA mutant but the phyAphyBhy4 mutant was not taller than the phyAhy4 mutant). Under more favorable light inputs, i.e. prolonged exposures to blue light added to a red-light background, the effects of cry1 and phyB were independent. Thus, the synergism between phyB and cry1 is conditional. The effect of cry1 was not reduced by the phyA mutation under any tested light condition. Under continuous blue light the triple mutant phyAphyBhy4 showed reduced hypocotyl growth inhibition and cotyledon unfolding compared with the phyAphyB mutant. The action of cry1 in the phyAphyB double mutant was higher under the red-light than the far-red-light background, indicating a synergistic interaction between cry1 and phytochromes C, D, or E; however, a residual action of cry1 independent of any phytochrome is likely to occur.

Analysis of Cell Division and Elongation Underlying the Developmental Acceleration of Root Growth in Arabidopsis thaliana1

To investigate the relation between cell division and expansion in the regulation of organ growth rate, we used Arabidopsis thaliana primary roots grown vertically at 20°C with an elongation rate that increased steadily during the first 14 d after germination. We measured spatial profiles of longitudinal velocity and cell length and calculated parameters of cell expansion and division, including rates of local cell production (cells mm−1 h−1) and cell division (cells cell−1 h−1). Data were obtained for the root cortex and also for the two types of epidermal cell, trichoblasts and atrichoblasts. Accelerating root elongation was caused by an increasingly longer growth zone, while maximal strain rates remained unchanged. The enlargement of the growth zone and, hence, the accelerating root elongation rate, were accompanied by a nearly proportionally increased cell production. This increased production was caused by increasingly numerous dividing cells, whereas their rates of division remained approximately constant. Additionally, the spatial profile of cell division rate was essentially constant. The meristem was longer than generally assumed, extending well into the region where cells elongated rapidly. In the two epidermal cell types, meristem length and cell division rate were both very similar to that of cortical cells, and differences in cell length between the two epidermal cell types originated at the apex of the meristem. These results highlight the importance of controlling the number of dividing cells, both to generate tissues with different cell lengths and to regulate the rate of organ enlargement.

Structural analysis of p185c-neu and epidermal growth factor receptor tyrosine kinases: oligomerization of kinase domains.

The epidermal growth factor receptor (EGFR) and p185c-neu proteins associate as dimers to create an efficient signaling assembly. Overexpression of these receptors together enhances their intrinsic kinase activity and concomitantly results in oncogenic cellular transformation. The ectodomain is able to stabilize the dimer, whereas the kinase domain mediates biological activity. Here we analyze potential interactions of the cytoplasmic kinase domains of the EGFR and p185c-neu tyrosine kinases by homology molecular modeling. This analysis indicates that kinase domains can associate as dimers and, based on intermolecular interaction calculations, that heterodimer formation is favored over homodimers. The study also predicts that the self-autophosphorylation sites located within the kinase domains are not likely to interfere with tyrosine kinase activity, but may regulate the selection of substrates, thereby modulating signal transduction. In addition, the models suggest that the kinase domains of EGFR and p185c-neu can undergo higher order aggregation such as the formation of tetramers. Formation of tetrameric complexes may explain some of the experimentally observed features of their ligand affinity and hetero-receptor internalization.

Lens complementation system for the genetic analysis of growth, differentiation, and apoptosis in vivo.

A genetic approach has been established that combines the advantages of blastocyst complementation with the experimental attributes of the developing lens for the functional analysis of genes governing cellular proliferation, terminal differentiation, and apoptosis. This lens complementation system (LCS) makes use of a mutant mouse strain, aphakia (ak), homozygotes of which fail to develop an ocular lens. We demonstrate that microinjection of wild-type embryonic stem (ES) cells into ak/ak blastocysts produces chimeras with normal ES-cell-derived lenses and that microinjection of Rb-/- ES cells generates an aberrant lens phenotype identical to that obtained through conventional gene targeting methodology. Our determination that a cell autonomous defect underlies the aphakia condition assures that lenses generated through LCS are necessarily ES-cell-derived. LCS provides for the rapid phenotypic analysis of loss-of-function mutations, circumvents the need for germ-line transmission of null alleles, and, most significantly, facilitates the study of essential genes whose inactivation is associated with early lethal phenotypes.

Analysis of internal astigmatism and higher order aberrations in eyes implanted with a new diffractive multifocal toric intraocular lens

Background To evaluate the intraocular lens (IOL) position by analyzing the postoperative axis of internal astigmatism as well as the higher-order aberration (HOA) profile after cataract surgery following the implantation of a diffractive multifocal toric IOL. Methods Prospective study including 51 eyes with corneal astigmatism of 1.25D or higher of 29 patients with ages ranging between 20 and 61 years old. All cases underwent uneventful cataract surgery with implantation of the AT LISA 909 M toric IOL (Zeiss). Visual, refractive and corneal topograpy changes were evaluated during a 12-month follow-up. In addition, the axis of internal astigmatism as well as ocular, corneal, and internal HOA (5-mm pupil) were evaluated postoperatively by means of an integrated aberrometer (OPD Scan II, Nidek). Results A significant improvement in uncorrected distance and near visual acuities (p < 0.01) was found, which was consistent with a significant correction of manifest astigmatism (p < 0.01). No significant changes were observed in corneal astigmatism (p = 0.32). With regard to IOL alignment, the difference between the axes of postoperative internal and preoperative corneal astigmatisms was close to perpendicularity (12 months, 87.16° ± 7.14), without significant changes during the first 6 months (p ≥ 0.46). Small but significant changes were detected afterwards (p = 0.01). Additionally, this angular difference correlated with the postoperative magnitude of manifest cylinder (r = 0.31, p = 0.03). Minimal contribution of intraocular optics to the global magnitude of HOA was observed. Conclusions The diffractive multifocal toric IOL evaluated is able to provide a predictable astigmatic correction with apparent excellent levels of optical quality during the first year after implantation.