Three-dimensional modeling of the human fallopian tube fimbriae

OBJECTIVE: Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests that the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis.

METHODS: Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5μg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment.

RESULTS: 3D fimbriae cultures maintained normal tissue architecture up to 7days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although it was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome.

CONCLUSIONS: 3D alginate cultures of human fallopian fimbriae provide an important microphysiological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube.

Microphysiological modeling of the reproductive tract: A fertile endeavor

Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as 'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology.

The Type IIP Supernova 2012aw in M95: Hydrodynamical Modeling of the Photospheric Phase from Accurate Spectrophotometric Monitoring

We present an extensive optical and near-infrared photometric and spectroscopic campaign of the Type IIP supernova SN 2012aw. The data set densely covers the evolution of SN 2012aw shortly after the explosion through the end of the photospheric phase, with two additional photometric observations collected during the nebular phase, to fit the radioactive tail and estimate the ⁵⁶Ni mass. Also included in our analysis is the previously published Swift UV data, therefore providing a complete view of the ultraviolet-optical- infrared evolution of the photospheric phase. On the basis of our data set, we estimate all the relevant physical parameters of SN 2012aw with our radiation-hydrodynamics code: envelope mass M _env ∼ 20 M _⊙, progenitor radius R ∼ 3 × 10¹³ cm (∼430 R_⊙), explosion energy E ∼ 1.5 foe, and initial ⁵⁶Ni mass ∼0.06 M_⊙. These mass and radius values are reasonably well supported by independent evolutionary models of the progenitor, and may suggest a progenitor mass higher than the observational limit of 16.5 ± 1.5 M _⊙of the Type IIP events. 

A Parametric Study Of A Turbogenerator On A Diesel-Electric Hybrid Bus

The fuel consumption of automotive vehicles has become a prime consideration to manufacturers and operators as fuel prices continue to rise steadily, and legislation governing toxic emissions becomes ever more strict. This is particularly true for bus operators as government fuel subsidies are cut or removed.

In an effort to reduce the fuel consumption of a diesel-electric hybrid bus, an exhaust recovery turbogenerator has been selected from a wide ranging literature review as the most appropriate method of recovering some of the wasted heat in the exhaust line. This paper examines the effect on fuel consumption of a turbogenerator applied to a 2.4-litre diesel engine.

A validated one-dimensional engine model created using Ricardo WAVE was used as a baseline, and was modified in subsequent models to include a turbogenerator downstream, and in series with, the turbocharger turbine. A fuel consumption map of the modified engine was produced, and an in-house simulation tool was then used to examine the fuel economy benefit delivered by the turbogenerator on a bus operating on various drive-cycles.

A parametric study is presented which examined the performance of turbogenerators of various size and power output. The operating strategy of the turbogenerator was also discussed with a view to maximising turbine efficiency at each operating point.

The performance of the existing turbocharger on the hybrid bus was also investigated; both the compressor and turbine were optimised and the subsequent benefits to the fuel consumption of the vehicle were shown.

The final configuration is then presented and the overall improvement in fuel economy of the hybrid bus was determined over various drive-cycles.

A Parametric Study of a Drive by Bridge Inspection System Based on the Morlet Wavelet

Many of the bridges currently in use worldwide are approaching the end of their design lives. However, rehabilitating and extending the lives of these structures raises important safety issues. There is also a need for increased monitoring which has considerable cost implications for bridge management systems. Existing structural health monitoring (SHM) techniques include vibration-based approaches which typically involve direct instrumentation of the bridge and are important as they can indicate the deterioration of the bridge condition. However, they can be labour intensive and expensive. In the past decade, alternative indirect vibration-based approaches which utilise the response of a vehicle passing over a bridge have been developed. This paper investigates such an approach; a low-cost approach for the monitoring of bridge structures which consists of the use of a vehicle fitted with accelerometers on its axles. The approach aims to detect damage in the bridge while obviating the need for direct instrumentation of the bridge. Here, the effectiveness of the approach in detecting damage in a bridge is investigated using a simplified vehicle-bridge interaction (VBI) model in theoretical simulations and a scaled VBI model in a laboratory experiment. In order to identify the existence and location of damage, the vehicle accelerations are recorded and processed using a continuous Morlet wavelet transform and a damage index is established. A parametric study is carried out to investigate the effect of parameters such as the bridge span length, vehicle speed, vehicle mass, damage level and road surface roughness on the accuracy of results.

Reliability and factorial validity of Adolescent Time Inventory-Time Attitude (ATI-TA) Scores in Scottish and Northern Irish adolescents

The contemporary literature investigating the construct broadly known as time perspective is replete with methodological and conceptual concerns. These concerns focus on the reliability and factorial validity of measurement tools, and the sample-specific modification of scales. These issues continue to hamper the development of this potentially useful psychological construct. An emerging body of evidence has supported the six-factor structure of scores on the Adolescent Time Inventory-Time Attitudes Scale, as well as their reliability. The present study utilized data from the first wave of a longitudinal study in the United Kingdom to examine the reliability, validity, and cross-cultural invariance of the scale. Results showed that the hypothesized six-factor model provided the best fit for the data; all alpha and omega estimates were >. .70; scores on ATI-TA factors related meaningfully to self-efficacy scores; and the factor structure was invariant across both research sites. Results are discussed in the context of the extant temporal literature.

Parametric scans of HB and LS-RPA regimes employing Petawatt laser

By contrast to the Target Normal Sheath acceleration (TNSA) mechanism [1], Radiation Pressure Acceleration (RPA) is currently attracting a substantial amount of experimental [2,3] and theoretical [4-6] attention worldwide due to its superior scaling in terms of ion energy and laser-ion conversion efficiency. Employing Vulcan Petawatt lasers of the Rutherford Appleton Laboratory, UK, both the Hole-boring (HB) and the Light-Sail (LS) regimes of the RPA have been extensively explored. When the target thickness is of the order of hole-boring velocity times the laser pulse duration, highly collimated plasma jets of near solid density are ejected from the foil, lasting up to ns after the laser interaction. By changing the linear polarisation of the laser to circular, improved homogeneity in the jet's spatial density profile is achieved which suggests more uniform and sustained radiation pressure drive on target ions. By decreasing the target areal density or increasing irradiance on the target, the LS regime of the RPA is accessed where relatively high flux (~ 1012 particles/MeV/Sr) of ions are accelerated to ~ 10 MeV/nucleon energies in a narrow energy bandwidth. The ion energy scaling obtained from the parametric scans agrees well with theoretical estimation based on RPA mechanism and the narrow bandwidth feature in the ion spectra is studied by 2D particle-in-simulations.