Dynamic phase-mapping of domain nucleation on MgO : LiNbO3 crystal by digital holographic interferometry

The quantitative phase-mapping of the domain nucleation in MgO:LiNbO3 crystals is presented by using the digital holographic interferometry. An unexpected peak phase at the beginning of the domain nucleation is observed and it is lowered as the spreading of the domain nucleus. The existence of the nucleus changes the moving speed of the domain wall by pinning it for 3s. Such in-situ quantitative analysis of the domain nucleation process is a key to optimizing domain structure fabrication.

Is there a subgroup of long-term evolution among patients with advanced lung cancer?: Hints from the analysis of survival curves from cancer registry data

Background: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. Methods: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short-and long-term survivors. Bayesian information criterion was used for model selection. Results: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. Conclusions: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short-and long-term survival subpopulations should be considered in clinical research.

Rigorous transmittance analysis of a sub-wavelength Sb thin film lens

We quantitatively analysed the factors contributing to the optical transmission enhancement of a sub-wavelength Sb thin film lens, using the finite-difference time-domain (FDTD) method. The results show that the transmission enhancement of the dielectric with a Gaussian distributed refractive index loaded in a sub-wavelength circular hole is not only due to the high refractive index dielectric, but also due to the specific distributions of refractive index. It is the first study about the effects of the refractive index distribution on the transmission of a sub-wavelength aperture. This kind of lens has practical applications in the very small aperture lasers and for near-field optical storage and lithography.

Viral metagenomic analysis of feces of wild small carnivores

Background: Recent studies have clearly demonstrated the enormous virus diversity that exists among wild animals. This exemplifies the required expansion of our knowledge of the virus diversity present in wildlife, as well as the potential transmission of these viruses to domestic animals or humans. Methods: In the present study we evaluated the viral diversity of fecal samples (n = 42) collected from 10 different species of wild small carnivores inhabiting the northern part of Spain using random PCR in combination with next-generation sequencing. Samples were collected from American mink (Neovison vison), European mink (Mustela lutreola), European polecat (Mustela putorius), European pine marten (Martes martes), stone marten (Martes foina), Eurasian otter (Lutra lutra) and Eurasian badger (Meles meles) of the family of Mustelidae; common genet (Genetta genetta) of the family of Viverridae; red fox (Vulpes vulpes) of the family of Canidae and European wild cat (Felis silvestris) of the family of Felidae. Results: A number of sequences of possible novel viruses or virus variants were detected, including a theilovirus, phleboviruses, an amdovirus, a kobuvirus and picobirnaviruses. Conclusions: Using random PCR in combination with next generation sequencing, sequences of various novel viruses or virus variants were detected in fecal samples collected from Spanish carnivores. Detected novel viruses highlight the viral diversity that is present in fecal material of wild carnivores.

Structure-function analysis of USP1: insights into the role of Ser313 phosphorylation site and the effect of cancer-associated mutations on autocleavage

Background: In complex with its cofactor UAF1, the USP1 deubiquitinase plays an important role in cellular processes related to cancer, including the response to DNA damage. The USP1/UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified. These include the role of the serine 313 phosphorylation site, the relative contribution of different USP1 sequence motifs to UAF1 binding, and the potential effect of cancer-associated mutations on USP1 regulation by autocleavage. Methods: We have generated a large set of USP1 structural variants, including a catalytically inactive form (C90S), non-phosphorylatable (S313A) and phosphomimetic (S313D) mutants, deletion mutants lacking potential UAF1 binding sites, a mutant (GG/AA) unable to undergo autocleavage at the well-characterized G670/G671 diglycine motif, and four USP1 mutants identified in tumor samples that cluster around this cleavage site (G667A, L669P, K673T and A676T). Using cell-based assays, we have determined the ability of these mutants to bind UAF1, to reverse DNA damage-induced monoubiquitination of PCNA, and to undergo autocleavage. Results: A non-phosphorylatable S313A mutant of USP1 retained the ability to bind UAF1 and to reverse PCNA ubiquitination in cell-based assays. Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay. The UAF1 binding site in a second UAF1-interacting DUB, USP46, was mapped to a region homologous to USP1(420-520). Regarding USP1 autocleavage, co-expression of the C90S and GG/AA mutants did not result in cleavage, while the cancer-associated mutation L669P was found to reduce cleavage efficiency. Conclusions: USP1 phosphorylation at S313 is not critical for PCNA deubiquitination, neither for binding to UAF1 in a cellular environment. In this context, USP1 amino acid motif 420-520 is necessary and sufficient for UAF1 binding. This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs. On the other hand, our results support the view that USP1 autocleavage may occur in cis, and can be altered by a cancer-associated mutation.

CLADP - THE CAMBRIDGE LINEAR ANALYSIS AND DESIGN PROGRAMS USER REFERENCE MANUAL (4TH ISSUE: APRIL 1983).

CLADP is an engineering software program developed at Cambridge University for the interactive computer aided design of feedback control systems. CLADP contains a wide range of tools for the analysis of complex systems, and the assessment of their performance when feedback control is applied, thus enabling control systems to be designed to meet difficult performance objectives. The range of tools within CLADP include the latest techniques in the field whose central theme is the extension of classical frequency domain concepts (well known and well proven for single loop systems) to multivariable or multiloop systems, and by making extensive use of graphical presentation information is provided in a readily understood form.

Structure analysis of CCR5 from human and primates

It is well known that the chemokine receptor CCR5 plays very important roles in HIV-1 virus infection. A three-dimensional molecular model of human CCR5 was generated by SYBYL, a distance geometry-based homologous modeling package, using the corresponding transmembrane domain of bacteriorhodopsin as the template. On the basis of human CCR5 model, we also built 18 3D molecular models of CCR5 in primates from Pongo pygmaeus, Pygathrix nemaeus, Macaca assameniss, Trachy-pithecus phayrei, T. francoisi, M. arotoides, Rhinopithecus roxellance, R, bieti, R. avunculus, Hylobates leucogenys, Pan troglodytes, Gorilla gorilla, Cercopithecus aethiops 1, C. aethiops 2, Papio hamadryas M. mulatta, M. fascicularis and M. nemestrina. Structural analyses and statistics results suggested that the main-chains of the primate CCR5 were similar to that of the human CCR5 and that the fit-RMS deviation values of these primate CCR5 were less than 0.1 Angstrom. Moreover, the structures of these CCR5 proteins, except those of the African green monkey 1 (C.aet1), do not have a remarkable difference. It is proved that the 14th residue is possibly very important in the inhibition infections by M-tropic HIV-1, and it is also demonstrated that the 13th residue of human CCR5 was changed from asparagine into aspartic acid in all these primates. It means that the primate CCR5 no longer depend on CD4 for efficient entry, but human CCR5 may have evolved subsequently due to the use of CD4 as a receptor, allowing the high-affinity chemokine receptor-binding site of HIV to be sequestered from host immune surveillance. (C) 2000 Elsevier Science B.V. All rights reserved.

Evolutionary implications of avian infectious Bronchitis Virus (AIBV) analysis

For developing efficient vaccines, it is essential to identify which amino acid changes are most important to the survival of the virus. We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus (AIBV) antigenic domain o

Genomic organization and sequence analysis of the vomeronasal receptor V2R genes in mouse genome

Two multigene superfamilies, named V1R and V2R, encoding seven-transmembrane-domain G-protein coupled receptors (GPCRs) have been identified as pheromone receptors in mammals. Three V2R gene families have been described in mouse and rat. Here we screened

Identification, characteristic and phylogenetic analysis of type II DNA topoisomerase gene in Giardia lamblia

The genes encoding type II DNA topoisomerases were investigated in Giardia lamblia genome, and a type IIA gene, GlTop 2 was identified. It is a single copy gene with a 4476 by long ORF without intron. The deduced amino acid sequence shows strong homology to eukaryotic DNA Top 2. However, some distortions were found, such as six insertions in the ATPase domain and the central domain, a similar to 100 as longer central domain; a similar to 200 as shorter C-terminal domain containing rich charged residues. These features revealed by comparing with Top 2 of the host, human, might be helpful in exploiting drug selectivity for antigiardial therapy. Phylogenetic analysis of eukaryotic enzymes showed that kinetoplastids, plants, fungi, and animals were monophyletic groups, and the animal and fungi lineages shared a more recent common ancestor than either did with the plant lineage; microsporidia grouped with fungi. However, unlike many previous phylogenetic analyses, the "amitochondriate" G. lamblia was not the earliest branch but diverged after mitochondriate kinetoplastids in our trees. Both the finding of typical eukaryotic type IIA topoisomerase and the phylogenetic analysis suggest G. lamblia is not possibly as primitive as was regarded before and might diverge after the acquisition of mitochondria. This is consistent with the recent discovery of mitochondrial remnant organelles in G. lamblia.

Characterize dynamic conformational space of human CCR5 extracellular domain by molecular modeling and molecular dynamics simulation

The chemokine receptor CCR5 is the receptor for several chemokines and major coreceptor for R5 human immunodeficiency virus type-1 strains entry into cell. Three-dimensional models of CCR5 were built by using homology modeling approach and 1 ns molecular dynamics (MD) simulation, because studies of site-directed mutagenesis and chimeric receptors have indicated that the N-terminus (Nt) and extracellular loops (ECLs) of CCR5 are important for ligands binding and viral fusion and entry, special attention was focused on disulfide bond function, conformational flexibility, hydrogen bonding, electrostatic interactions, and solvent-accessible surface area of Nt and ECLs of this protein part. We found that the extracellular segments of CCR5 formed a well-packet globular domain with complex interactions occurred between them in a majority of time of MID simulation, but Nt region could protrude from this domain sometimes. The disulfide bond Cys20-Cys269 is essential in controlling specific orientation of Nt region and maintaining conformational integrity of extracellular domain. RMS comparison analysis between conformers revealed the ECL1 of CCR5 stays relative rigid, whereas the ECL2 and Nt are rather flexible. Solvent-accessible surface area calculations indicated that the charged residues within Nt and ECL2 are often exposed to solvent. Integrating these results with available experimental data, a two-step gp120-CCR5 binding mechanism was proposed. The dynamic interaction of CCR5 extracellular domain with gp120 was emphasized. (C) 2004 Elsevier B.V. All rights reserved.

A critical analysis of loudness calculation methods

The physical meaning and calculation procedures for determining loudness was critically analyzed. Four noise sources were used in comparing the software packages dBFA dBSonic, which were used in the investigation to a public domain code. The purpose of the comparison was to evaluate the validity of the results obtained and to gain an idea of the shortcomings of the relevant standards. A comparison of the results for loudness was computed from various methods, used in the study. Two basic sources of input data such as a sound level meter (SLM) and a 01 dB data acquisition system (DAQ), were available for the comparison. The SLM directly gave 1/3 octave band levels, while the data from the DAQ was filtered to give the results. Five processing methods, including a Visual Basic (VB) program and a VB program adapted from dBFA, were used for the study. It was found that the calculation of loudness from 1/3 octave cannot be separated from the filtering process.

Vowel normalisation: Time-domain processing of the internal dynamics of speech

Human listeners can identify vowels regardless of speaker size, although the sound waves for an adult and a child speaking the ’same’ vowel would differ enormously. The differences are mainly due to the differences in vocal tract length (VTL) and glottal pulse rate (GPR) which are both related to body size. Automatic speech recognition machines are notoriously bad at understanding children if they have been trained on the speech of an adult. In this paper, we propose that the auditory system adapts its analysis of speech sounds, dynamically and automatically to the GPR and VTL of the speaker on a syllable-to-syllable basis. We illustrate how this rapid adaptation might be performed with the aid of a computational version of the auditory image model, and we propose that an auditory preprocessor of this form would improve the robustness of speech recognisers.

Antiwindup design for induction motor control in the field weakening domain

Operation of induction machines in the high-speed and/or high-torque range requires field-weakening to comply with voltage and current physical limitations. This paper presents an anti-windup approach to this problem: rather than developing an ad-hoc field weakening strategy in the high-speed region, we equip an unconstrained vector-control design with an anti-windup module that automatically adjusts the current and flux set-points so that voltage and current constraints are satisfied at every operating point. The anti-windup module includes a feedforward modification of the set point aimed at maximizing the available torque in steady-state and a feedback modification of the controller based on an internal model-based antiwindup scheme. This paper includes a complete stability analysis of the proposed solution and presents encouraging experimental results on an industrial drive. © 2012 IEEE.

A coupled hydro-mechanical analysis for prediction of hydraulic fracture propagation in saturated porous media using EFG mesh-less method

The details of the Element Free Galerkin (EFG) method are presented with the method being applied to a study on hydraulic fracturing initiation and propagation process in a saturated porous medium using coupled hydro-mechanical numerical modelling. In this EFG method, interpolation (approximation) is based on nodes without using elements and hence an arbitrary discrete fracture path can be modelled.The numerical approach is based upon solving two governing partial differential equations of equilibrium and continuity of pore water simultaneously. Displacement increment and pore water pressure increment are discretized using the same EFG shape functions. An incremental constrained Galerkin weak form is used to create the discrete system of equations and a fully implicit scheme is used for discretization in the time domain. Implementation of essential boundary conditions is based on the penalty method. In order to model discrete fractures, the so-called diffraction method is used.Examples are presented and the results are compared to some closed-form solutions and FEM approximations in order to demonstrate the validity of the developed model and its capabilities. The model is able to take the anisotropy and inhomogeneity of the material into account. The applicability of the model is examined by simulating hydraulic fracture initiation and propagation process from a borehole by injection of fluid. The maximum tensile strength criterion and Mohr-Coulomb shear criterion are used for modelling tensile and shear fracture, respectively. The model successfully simulates the leak-off of fluid from the fracture into the surrounding material. The results indicate the importance of pore fluid pressure in the initiation and propagation pattern of fracture in saturated soils. © 2013 Elsevier Ltd.