A fish-specific transposable element shapes the repertoire of p53 target genes in zebrafish.

Transposable elements, as major components of most eukaryotic organisms' genomes, define their structural organization and plasticity. They supply host genomes with functional elements, for example, binding sites of the pleiotropic master transcription factor p53 were identified in LINE1, Alu and LTR repeats in the human genome. Similarly, in this report we reveal the role of zebrafish (Danio rerio) EnSpmN6_DR non-autonomous DNA transposon in shaping the repertoire of the p53 target genes. The multiple copies of EnSpmN6_DR and their embedded p53 responsive elements drive in several instances p53-dependent transcriptional modulation of the adjacent gene, whose human orthologs were frequently previously annotated as p53 targets. These transposons define predominantly a set of target genes whose human orthologs contribute to neuronal morphogenesis, axonogenesis, synaptic transmission and the regulation of programmed cell death. Consistent with these biological functions the orthologs of the EnSpmN6_DR-colonized loci are enriched for genes expressed in the amygdala, the hippocampus and the brain cortex. Our data pinpoint a remarkable example of convergent evolution: the exaptation of lineage-specific transposons to shape p53-regulated neuronal morphogenesis-related pathways in both a hominid and a teleost fish.

Three-dimensional patient-specific dosimetry in radioimmunotherapy with 90Y-ibritumomab-tiuxetan.

Aim of the present article was to perform three-dimensional (3D) single photon emission tomography-based dosimetry in radioimmunotherapy (RIT) with (90)Y-ibritumomab-tiuxetan. A custom MATLAB-based code was used to elaborate 3D images and to compare average 3D doses to lesions and to organs at risk (OARs) with those obtained with planar (2D) dosimetry. Our 3D dosimetry procedure was validated through preliminary phantom studies using a body phantom consisting of a lung insert and six spheres with various sizes. In phantom study, the accuracy of dose determination of our imaging protocol decreased when the object volume decreased below 5 mL, approximately. The poorest results were obtained for the 2.58 mL and 1.30 mL spheres where the dose error evaluated on corrected images with regard to the theoretical dose value was -12.97% and -18.69%, respectively. Our 3D dosimetry protocol was subsequently applied on four patients before RIT with (90)Y-ibritumomab-tiuxetan for a total of 5 lesions and 4 OARs (2 livers, 2 spleens). In patient study, without the implementation of volume recovery technique, tumor absorbed doses calculated with the voxel-based approach were systematically lower than those calculated with the planar protocol, with average underestimation of -39% (range from -13.1% to -62.7%). After volume recovery, dose differences reduce significantly, with average deviation of -14.2% (range from -38.7.4% to +3.4%, 1 overestimation, 4 underestimations). Organ dosimetry in one case overestimated, in the other underestimated the dose delivered to liver and spleen. However, both for 2D and 3D approach, absorbed doses to organs per unit administered activity are comparable with most recent literature findings.

A study compared nine patient-specific indices for musculoskeletal disorders.

BACKGROUND AND OBJECTIVE: Patient-specific quality of life indices show great potential, but certain conceptual and methodological concerns have yet to be fully addressed. The present study reviewed nine patient-specific instruments used in musculoskeletal disorders: the Canadian Occupational Performance Measure (COPM), Juvenile Arthritis Quality of life Questionnaire (JAQQ), McMaster-Toronto Arthritis questionnaire (MACTAR), Measure Yourself Medical Outcome Profile (MYMOP), Patient-Specific Index (PASI) for total hip arthroplasty, Problem Elicitation Technique (PET), Patient Generated Index (PGI) of quality of life, Patient-Specific Functional Scale (PSFS), and Schedule for the Evaluation of Individual Quality of Life (SEIQoL). STUDY DESIGN AND SETTING: Each tool was evaluated for purpose, content validity, face validity, feasibility, psychometric properties, and responsiveness. RESULTS: This critical appraisal revealed important differences in terms of the concept underlying these indices, the domains covered, the item-generation techniques and the scoring (response scale, methods) in each scale. The nine indices would generate different responses and likely scores for the same patient, despite the fact that they all include patient-generated items. CONCLUSION: Although the value of these indices in treatment planning and monitoring at an individual level is strong, more studies are needed to improve our understanding of how to interpret the numeric scores of patient-specific indices at both an individual and a group level.

Strengthening of Existing Single Span Steel Beam and Concrete Deck Bridges, HR-238, Part II, 1985

The unifying objective of Phases I and II of this study was to determine the feasibility of the post-tensioning strengthening method and to implement the technique on two composite bridges in Iowa. Following completion of these two phases, Phase III was undertaken and is documented in this report. The basic objectives of Phase III were further monitoring bridge behavior (both during and after post-tensioning) and developing a practical design methodology for designing the strengthening system under investigation. Specific objectives were: to develop strain and force transducers to facilitate the collection of field data; to investigate further the existence and effects of the end restraint on the post-tensioning process; to determine the amount of post-tensioning force loss that occurred during the time between the initial testing and the retesting of the existing bridges; to determine the significance of any temporary temperature-induced post-tensioning force change; and to develop a simplified design methodology that would incorporate various variables such as span length, angle-of-skew, beam spacing, and concrete strength. Experimental field results obtained during Phases II and III were compared to the theoretical results and to each other. Conclusions from this research are as follows: (1) Strengthening single-span composite bridges by post-tensioning is a viable, economical strengthening technique. (2) Behavior of both bridges was similar to the behavior observed from the bridges during field tests conducted under Phase II. (3) The strain transducers were very accurate at measuring mid-span strain. (4) The force transducers gave excellent results under laboratory conditions, but were found to be less effective when used in actual bridge tests. (5) Loss of post-tensioning force due to temperature effects in any particular steel beam post-tensioning tendon system were found to be small. (6) Loss of post-tensioning force over a two-year period was minimal. (7) Significant end restraint was measured in both bridges, caused primarily by reinforcing steel being continuous from the deck into the abutments. This end restraint reduced the effectiveness of the post-tensioning but also reduced midspan strains due to truck loadings. (8) The SAP IV finite element model is capable of accurately modeling the behavior of a post-tensioned bridge, if guardrails and end restraints are included in the model. (9) Post-tensioning distribution should be separated into distributions for the axial force and moment components of an eccentric post-tensioning force. (10) Skews of 45 deg or less have a minor influence on post-tensioning distribution. (11) For typical Iowa three-beam and four-beam composite bridges, simple regression-derived formulas for force and moment fractions can be used to estimate post-tensioning distribution at midspan. At other locations, a simple linear interpolation gives approximately correct results. (12) A simple analytical model can accurately estimate the flexural strength of an isolated post-tensioned composite beam.

Field Monitoring of Curved Girder Bridges with Integral Abutments, TPF-5(169), 2014

Nationally, there are questions regarding the design, fabrication, and erection of horizontally curved steel girder bridges due to unpredicted girder displacements, fit-up, and locked-in stresses. One reason for the concerns is that up to one-quarter of steel girder bridges are being designed with horizontal curvature. There is also an urgent need to reduce bridge maintenance costs by eliminating or reducing deck joints, which can be achieved by expanding the use of integral abutments to include curved girder bridges. However, the behavior of horizontally curved bridges with integral abutments during thermal loading is not well known nor understood. The purpose of this study was to investigate the behavior of horizontal curved bridges with integral abutment (IAB) and semi-integral abutment bridges (SIAB) with a specific interest in the response to changing temperatures. The long-term objective of this effort is to establish guidelines for the use of integral abutments with curved girder bridges. The primary objective of this work was to monitor and evaluate the behavior of six in-service, horizontally curved, steel-girder bridges with integral and semi-integral abutments. In addition, the influence of bridge curvature, skew and pier bearing (expansion and fixed) were also part of the study. Two monitoring systems were designed and applied to a set of four horizontally curved bridges and two straight bridges at the northeast corner of Des Moines, Iowa—one system for measuring strains and movement under long term thermal changes and one system for measuring the behavior under short term, controlled live loading. A finite element model was developed and validated against the measured strains. The model was then used to investigate the sensitivity of design calculations to curvature, skew and pier joint conditions. The general conclusions were as follows: (1) There were no measurable differences in the behavior of the horizontally curved bridges and straight bridges studied in this work under thermal effects. For preliminary member sizing of curved bridges, thermal stresses and movements in a straight bridge of the same length are a reasonable first approximation. (2) Thermal strains in integral abutment and semi-integral abutment bridges were not noticeably different. The choice between IAB and SIAB should be based on life – cycle costs (e.g., construction and maintenance). (3) An expansion bearing pier reduces the thermal stresses in the girders of the straight bridge but does not appear to reduce the stresses in the girders of the curved bridge. (4) An analysis of the bridges predicted a substantial total stress (sum of the vertical bending stress, the lateral bending stress, and the axial stress) up to 3 ksi due to temperature effects. (5) For the one curved integral abutment bridge studied at length, the stresses in the girders significantly vary with changes in skew and curvature. With a 10⁰ skew and 0.06 radians arc span length to radius ratio, the curved and skew integral abutment bridges can be designed as a straight bridge if an error in estimation of the stresses of 10% is acceptable.

Nonlinear Finite Element Study of Piles in Integral Abutment Bridges, HR-227, Part 2, 1982

The highway departments of the states which use integral abutments in bridge design were contacted in order to study the extent of integral abutment use in skewed bridges and to survey the different guidelines used for analysis and design of integral abutments in skewed bridges. The variation in design assumptions and pile orientations among the various states in their approach to the use of integral abutments on skewed bridges is discussed. The problems associated with the treatment of the approach slab, backfill, and pile cap, and the reason for using different pile orientations are summarized in the report. An algorithm based on a state-of-the-art nonlinear finite element procedure previously developed by the authors was modified and used to study the influence of different factors on behavior of piles in integral abutment bridges. An idealized integral abutment was introduced by assuming that the pile is rigidly cast into the pile cap and that the approach slab offers no resistance to lateral thermal expansion. Passive soil and shear resistance of the cap are neglected in design. A 40-foot H pile (HP 10 X 42) in six typical Iowa soils was analyzed for fully restrained pile head and pinned pile head. According to numerical results, the maximum safe length for fully restrained pile head is one-half the maximum safe length for pinned pile head. If the pile head is partially restrained, the maximum safe length will lie between the two limits. The numerical results from an investigation of the effect of predrilled oversized holes indicate that if the length of the predrilled oversized hole is at least 4 feet below the ground, the vertical load-carrying capacity of the H pile is only reduced by 10 percent for 4 inches of lateral displacement in very stiff clay. With no predrilled oversized hole, the pile failed before the 4-inch lateral displacement was reached. Thus, the maximum safe lengths for integral abutment bridges may be increased by predrilling. Four different typical Iowa layered soils were selected and used in this investigation. In certain situations, compacted soil (> 50 blow count in standard penetration tests) is used as fill on top of natural soil. The numerical results showed that the critical conditions will depend on the length of the compacted soil. If the length of the compacted soil exceeds 4 feet, the failure mechanism for the pile is similar to one in a layer of very stiff clay. That is, the vertical load-carrying capacity of the H pile will be greatly reduced as the specified lateral displacement increases.

Statistical properties of population differentiation estimators under stepwise mutation in a finite island model.

Microsatellite loci mutate at an extremely high rate and are generally thought to evolve through a stepwise mutation model. Several differentiation statistics taking into account the particular mutation scheme of the microsatellite have been proposed. The most commonly used is R(ST) which is independent of the mutation rate under a generalized stepwise mutation model. F(ST) and R(ST) are commonly reported in the literature, but often differ widely. Here we compare their statistical performances using individual-based simulations of a finite island model. The simulations were run under different levels of gene flow, mutation rates, population number and sizes. In addition to the per locus statistical properties, we compare two ways of combining R(ST) over loci. Our simulations show that even under a strict stepwise mutation model, no statistic is best overall. All estimators suffer to different extents from large bias and variance. While R(ST) better reflects population differentiation in populations characterized by very low gene-exchange, F(ST) gives better estimates in cases of high levels of gene flow. The number of loci sampled (12, 24, or 96) has only a minor effect on the relative performance of the estimators under study. For all estimators there is a striking effect of the number of samples, with the differentiation estimates showing very odd distributions for two samples.

Siltanosturin teräsrakenteen suunnittelun avuksi luodun ohjelman jatkokehitys

Diplomityössä tehdään jatkokehitystä KCI Konecranes yrityksen siltanosturin laskentaohjelmaan. Ohjelman tärkeimmät jatkokehityskohteet kartoitettiin käyttäjäkyselyn avulla ja niistä valittiin toivotuimmat, sekä diplomityön lujuusopilliseen aihepiiriin parhaiten soveltuvat. Työhön valitut kaksi aihetta ovat koteloprofiilin kaksiosaisen uuman lujuuslaskennan selvittäminen ja siltanosturin kahdeksanpyöräisenpäätykannattajan elementtimallin suunnittelu. Diplomityössä selvitetään jatkokehityskohteisiin liittyvä teoria, mutta varsinainen ohjelmointi jätetään työn ulkopuolelle. Kaksiosaisella uumalla varustetussa koteloprofiilissa nostovaunun kulkukiskon alla olevan uuman yläosa tehdään paksummaksi, jotta uuma kestäisi nostovaunun pyöräkuormasta aiheutuvan paikallisen jännityksen, eliniin sanotun rusennusjännityksen. Rusennusjännityksen määrittäminen uumalevyissä on kaksiosaisen uuman lujuuslaskennan tärkein tehtävä. Rusennuksen aiheuttamankalvojännityksen ja jännityskeskittymien määrittämiseen erilaisissa konstruktioissa etsittiin sopivimmat menetelmät kirjallisuudesta ja standardeista. Kalvojännitys voidaan määrittää luotettavasti käyttäen joko 45 asteen sääntöä tai standardin mukaista menetelmää ja jännityskonsentraatioiden suuruus saadaan kertomallakalvojännitys jännityskonsentraatiokertoimilla. Menetelmien toimivuus verifioitiin tekemällä kymmeniä uuman elementtimalleja erilaisin dimensioin ja reunaehdoin ja vertaamalla elementtimallien tuloksia käsin laskettuihin. Käsin lasketut jännitykset saatiin vastaamaan tarkasti elementtimallien tuloksia. Kaksiosaisen uuman lommahdus- ja väsymislaskentaa tutkittiin alustavasti. Kahdeksanpyöräisiä päätykannattajia käytetään suurissa siltanostureissa pienentämään pyöräkuormia ja radan rusennusjännityksiä. Kahdeksanpyöräiselle siltanosturin päätykannattajalle suunniteltiin elementtimallit molempiin rakenteesta käytettyihin konstruktioihin: nivelöityyn ja jäykkäkehäiseen malliin. Elementtimallien rakentamisessa hyödynnettiin jo olemassa olevia malleja, jolloin niiden lisääminen ohjelmakoodiin nopeutuu ja ne ovat varmasti yhteensopivia muiden laskentamoduuleiden kanssa. Elementtimallien värähtelyanalyysin reunaehtoja tarkasteltiin. Värähtelyanalyysin reunaehtoihin ei tutkimuksen perusteella tarvitse tehdä muutoksia, mutta staattisen analyysin reunaehdot kaipaavat vielä lisätutkimusta.

Impact of the Femoral Head Position on Moment Arms in Total Hip Arthroplasty: A Parametric Finite Element Study.

BACKGROUND: Although the importance of accurate femoral reconstruction to achieve a good functional outcome is well documented, quantitative data on the effects of a displacement of the femoral center of rotation on moment arms are scarce. The purpose of this study was to calculate moment arms after nonanatomical femoral reconstruction. METHODS: Finite element models of 15 patients including the pelvis, the femur, and the gluteal muscles were developed. Moment arms were calculated within the native anatomy and compared to distinct displacement of the femoral center of rotation (leg lengthening of 10 mm, loss of femoral offset of 20%, anteversion ±10°, and fixed anteversion at 15°). Calculations were performed within the range of motion observed during a normal gait cycle. RESULTS: Although with all evaluated displacements of the femoral center of rotation, the abductor moment arm remained positive, some fibers initially contributing to extension became antagonists (flexors) and vice versa. A loss of 20% of femoral offset led to an average decrease of 15% of abductor moment. Femoral lengthening and changes in femoral anteversion (±10°, fixed at 15°) led to minimal changes in abductor moment arms (maximum change of 5%). Native femoral anteversion correlated with the changes in moment arms induced by the 5 variations of reconstruction. CONCLUSION: Accurate reconstruction of offset is important to maintaining abductor moment arms, while changes of femoral rotation had minimal effects. Patients with larger native femoral anteversion appear to be more susceptible to femoral head displacements.

Modelling syntectonic sedimentation: combining a discrete element model of tectonic. Deformation and process-based sedimentary Model in 3D.

This paper presents a new numerical program able to model syntectonic sedimentation. The new model combines a discrete element model of the tectonic deformation of a sedimentary cover and a process-based model of sedimentation in a single framework. The integration of these two methods allows us to include the simulation of both sedimentation and deformation processes in a single and more effective model. The paper describes briefly the antecedents of the program, Simsafadim-Clastic and a discrete element model, in order to introduce the methodology used to merge both programs to create the new code. To illustrate the operation and application of the program, analysis of the evolution of syntectonic geometries in an extensional environment and also associated with thrust fault propagation is undertaken. Using the new code, much more complex and realistic depositional structures can be simulated together with a more complex analysis of the evolution of the deformation within the sedimentary cover, which is seen to be affected by the presence of the new syntectonic sediments.