Application of protein structure alignments to iterated hidden Markov model protocols for structure prediction.

BackgroundOne of the most powerful methods for the prediction of protein structure from sequence information alone is the iterative construction of profile-type models. Because profiles are built from sequence alignments, the sequences included in the alignment and the method used to align them will be important to the sensitivity of the resulting profile. The inclusion of highly diverse sequences will presumably produce a more powerful profile, but distantly related sequences can be difficult to align accurately using only sequence information. Therefore, it would be expected that the use of protein structure alignments to improve the selection and alignment of diverse sequence homologs might yield improved profiles. However, the actual utility of such an approach has remained unclear.ResultsWe explored several iterative protocols for the generation of profile hidden Markov models. These protocols were tailored to allow the inclusion of protein structure alignments in the process, and were used for large-scale creation and benchmarking of structure alignment-enhanced models. We found that models using structure alignments did not provide an overall improvement over sequence-only models for superfamily-level structure predictions. However, the results also revealed that the structure alignment-enhanced models were complimentary to the sequence-only models, particularly at the edge of the "twilight zone". When the two sets of models were combined, they provided improved results over sequence-only models alone. In addition, we found that the beneficial effects of the structure alignment-enhanced models could not be realized if the structure-based alignments were replaced with sequence-based alignments. Our experiments with different iterative protocols for sequence-only models also suggested that simple protocol modifications were unable to yield equivalent improvements to those provided by the structure alignment-enhanced models. Finally, we found that models using structure alignments provided fold-level structure assignments that were superior to those produced by sequence-only models.ConclusionWhen attempting to predict the structure of remote homologs, we advocate a combined approach in which both traditional models and models incorporating structure alignments are used

Transient and steady-state velocity of domain walls for a complete range of drive fields

Approximate analytic solutions for transient and steady-state 180 deg domain wall motion in bulk magnetic material are obtained from the dynamic torque equations with a Gilbert damping term. The results for the Walker region in which the transient solution approaches the familiar Walker steady-state solution are presented in a slightly new form for completeness. An analytic solution corresponding to larger drive fields predicts an oscillatory motion with an average value which decreases with drive field for reasonable values of the damping parameter. These results agree with those obtained by a computer solution of the torque equation and those obtained with the assumption of a very large anisotropy field

Wall contraction in Bloch wall films

The phenomenon of wall contraction characterized by a peak in the velocity field relationship and a region of negative differential mobility is observed. Uniaxial magnetic thin films of various compositions and magnetic properties are studied in careful interrupted pulse experiments. The observed results agree quite well with the theory for bulk samples

Intra-cavitary uterine pathology in women with abnormal uterine bleeding: a prospective study of 1220 women.

OBJECTIVES: Our primary aim was to assess how patients characteristics, bleeding pattern, sonographic endometrial thickness (ET) and additional features at unenhanced ultrasound examination (UTVS) and at fluid instillation sonography (FIS) contribute to the diagnosis of intracavitary uterine pathology in women presenting with abnormal uterine bleeding (AUB). We further aimed to report the prevalence of pathology in women presenting with AUB. METHODS: 1220 consecutive women presenting with AUB underwent UTVS, colour Doppler imaging (CDI) and FIS. Most women (n = 1042) had histological diagnosis. RESULTS: Mean age was 50 years and 37% were postmenopausal. Of 1220 women 54% were normal, polyps were diagnosed in 26%, intracavitary fibroids in 11%, hyperplasia without atypia in 4% and cancer in 3%. All cancers were diagnosed in postmenopausal (7%) or perimenopausal (1%) women. ET had a low predictive value in premenopausal women (LR+ and LR- of 1.34 and 0.74, respectively), while FIS had a LR+ and LR- of 6.20 and 0.24, respectively. After menopause, ET outperformed all patient characteristics for the prediction of endometrial pathology (LR+ and LR- of 3.13 and 0.24). The corresponding LR+ and LR- were 10.85 and 0.71 for CDI and 8.23 and 0.26 for FIS. CONCLUSION: About half of the women presenting to a bleeding clinic will have pathology. In premenopausal women, benign lesions are often the cause of AUB. For the prediction of intracavitary pathology ET is of little value in premenopausal women. CDI and FIS substantially improve the diagnostic accuracy

How Will the Use of Technology in Translation and Testing Affect Language Learning?

Technology has an ever increasing impact on how we work and live. Article adressed the issue of the impact of technology in two key areas of language learning. On the one side learners increasingly used technology to translate. Given this trend, was there any real need to learn a language. On the other side, educational institutions increasingly used technology to rate language proficiency. Given this trend, would the work of the teacher become less and less important. The survey was conducted by using quantitative method. The respondents' age range was 18-25. There were 53 respondents, 35% were male and 65% were female. The instrument was a questionaire having 9 questions describing the students' reliance on computer in translation. It can be concluded that learners of English indicate that they accept and welcome the role of technology in language learning, but there is a doubt that the role and participation of humans in the learning process will be completely replaced. The human element remains an important ingredient. (EE

Low frequency creep in CoNiFe films

The results of an investigation of domain wall motion excited by slow rise-time, bipolar, hard-axis pulses in vacuum deposited CoNiFe films 1500A to 2000A thick are presented. The results are consistent with those of comparable NiFe films in spite of large differences in film properties. The present low frequency creep data together with previously published results in this and other laboratories can be accounted for by a model which requires that the wall structure change usually associated with low frequency creep be predominately a gyromagnetic process. The correctness of this model is reinforced by the observation that the wall coercive force, the planar wall mobility, and the occurrence of an abrupt wall structure change are the only properties closely correlated to the creep displacement characteristics of a planar wall in low dispersion films

T-PHOT version 2.0: improved algorithms for background subtraction, local convolution, kernel registration, and new options

We present the new release v2.0 of T-PHOT, a publicly available software package developed to perform PSF-matched, prior-based, multiwavelength deconfusion photometry of extragalactic fields. New features included in the code are presented and discussed: background estimation, fitting using position dependent kernels, flux prioring, diagnostical statistics on the residual image, exclusion of selected sources from the model and residual images, individual registration of fitted objects. These new options improve on the performance of the code, allowing for more accurate results and providing useful aids for diagnostics.Comment: 7 pages, 8 figure

Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio

Practical guidance for applying the ADNEX model from the IOTA group to discriminate between different subtypes of adnexal tumors.

All gynecologists are faced with ovarian tumors on a regular basis, and the accurate preoperative diagnosis of these masses is important because appropriate management depends on the type of tumor. Recently, the International Ovarian Tumor Analysis (IOTA) consortium published the Assessment of Different NEoplasias in the adneXa (ADNEX) model, the first risk model that differentiates between benign and four types of malignant ovarian tumors: borderline, stage I cancer, stage II-IV cancer, and secondary metastatic cancer. This approach is novel compared to existing tools that only differentiate between benign and malignant tumors, and therefore questions may arise on how ADNEX can be used in clinical practice. In the present paper, we first provide an in-depth discussion about the predictors used in ADNEX and the ability for risk prediction with different tumor histologies. Furthermore, we formulate suggestions about the selection and interpretation of risk cut-offs for patient stratification and choice of appropriate clinical management. This is illustrated with a few example patients. We cannot propose a generally applicable algorithm with fixed cut-offs, because (as with any risk model) this depends on the specific clinical setting in which the model will be used. Nevertheless, this paper provides a guidance on how the ADNEX model may be adopted into clinical practice

Analysis of model sheet pile walls with plastic hinges

As part of a wider project investigating the implications of Eurocode 3, Design of steel structures – Part 5: Piling, centrifuge testing of model sheet pile walls and numerical back-analysis were undertaken. The aims of the study were to examine the effect of plastic hinging on embedded retaining wall response, and to verify calculation methods for use in wider generic calculations. Physical modelling of an anchored wall embedded in dry sand was undertaken. In some of the tests a hinge zone was introduced into the wall in order to reproduce a kinematic mechanism similar to that associated with plastic hinge formation. Finite-element calculations were undertaken using Lade's double-hardening cap model to represent the behaviour of the sand. The analyses generally yielded good accord with the test results in many aspects of the wall behaviour. In terms of the aims of the testing, the study of the effect of plastic hinging was not realistically captured, because the hinge zone was present from the outset of the test, allowing greater than expected earth pressure redistribution, and because the moment–curvature characteristic of the notched wall did not reproduce the buckling effects seen in the plastic bending response of steel sheet piles. On the other hand, the satisfactory agreement between the test observations and the numerical predictions gave confidence in the use of the calculation model for further generic calculations using realistic steel sheet pile moment–plastic curvature characteristics. </jats:p