A new silicon detector for microdosimetry applications in proton therapy

A silicon-on-insulator diode array with a sensitive depth of 10 microns has been developed for microdosimetry in proton therapy. The detector was coupled to a radiation-hard charge sensitive amplifier with the probe assembly capable of measuring an LET down to 1.2 keV/μm. The device has been successfully tested at two proton therapy centers. The 230 MeV Northeastern Proton Therapy Center, Boston and the 250 MeV Proton Medical Research Center at Tsukuba, Japan. The device offers much improved spatial resolution compared with a proportional gas counter particularly in the critical high dose region around the proton Bragg peak. Due to its small cross-sectional area (0.04 cm2) measurements may also be made in facilities with short high intensity beams

Seasonal effects on reconciliation in Macaca Fuscata Yakui

Dietary composition may have profound effects on the activity budgets, levelof food competition, and social behavior of a species. Similarly, in seasonally breeding species, the mating season is a period in which competition for mating partners increases, affecting amicable social interactions among group members. We analyzed the importance of the mating season and of seasonal variations in dietary composition and food competition on econciliation in wild female Japanese macaques (Macaca fuscata yakui) on Yakushima Island, Japan. Yakushima macaques are appropriate subjects because they are seasonal breeders and their dietary composition significantly changes among the seasons. Though large differences occurred between the summer months and the winter and early spring months in activity budgets and the consumption of the main food sources, i.e., fruits, seeds, and leaves, the level of food competition and conciliatory tendency remained unaffected. Conversely,conciliatory tendency is significantly lower during the mating season than in the nonmating season. Moreover, conciliatory tendency is lower when 1 or both female opponents is in estrous than when they are not. Thus the mating season has profound effects on reconciliation, whereas seasonal changes in activity budgets and dietary composition do not. The detrimental effects of the mating season on female social relationships and reconciliation may be due to the importance of female competition for access to male partners in multimale, multifemale societies

Acute hypoxemia and vascular function in healthy humans.

Endothelium-dependent flow mediated dilation (FMD) and endothelium-independent dilation (GTN) are impaired at high altitude (5050 m), and FMD is impaired following acute exposure (<60-minutes) to normobaric hypoxia equivalent to ∼5050 m (∼FI O2  = 0.11). Whether glyceryl trinitrate (GTN)-induced dilation is impaired acutely, and whether FMD is impaired during milder hypoxia is unknown. Therefore, we assessed brachial FMD at baseline and following 30-minutes of mild (74 ± 2 mmHg PET O₂) and moderate (50 ± 3 mmHg PET O₂) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-dilaiton following the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared to normoxic baseline, reduction during mild and moderate hypoxic exposure were evident in FMD (mild vs moderate: -1.2 ± 1.1% vs. -3.1 ± 1.7%; P = 0.01) and GTN-dilation (-2.1 ± 1.0 vs. -4.2 ± 2.0; P = 0.01); the decline in FMD and GTN-dilation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve (SRAUC ), relative FMD was attenuated in both conditions (mild vs moderate: 0.6 ± 0.9% vs. 0.8 ± 0.7%; P ≤ 0.01). Following 30-minutes of normoxic time-control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental declines in smooth muscle vasodilator capacity (impaired GTN-dilation). Our findings from the normoxic controls study, suggest the decline in FMD in acute hypoxia also appears to be influenced by 30-minutes of supine rest/inactivity. This article is protected by copyright. All rights reserved

Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell

More than 10 years have passed since the naming of periostin derived from its expression sites in the periosteum and periodontal ligament. Following this finding, we have accumulated more data on the expression patterns of periostin, and, finally, with the generation of periostin-deficient mice, have revealed functions of periostin in the regeneration of tissues in bone, tooth, heart, and skin, and its action in cancer invasion. Since periostin is a matricellular protein, the first investigation of periostin function showed its enhancement of cell migration by acting outside the cell. On the other hand, recent observations have demonstrated that periostin functions in fibrillogenesis in association with extracellular matrix molecules inside the cell

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged ( 2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders(Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation(FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO2 –) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2 vs. 6.6 ± 0.3 m s−1; P = 0.001). These changes persisted at days 12–14, and after allometricallyscaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio ( 19%, P 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO2 – increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r=−0.53) and chronic (n = 7, r=−0.69; P 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n=11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspiredO2 fraction (FIO2 )=0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7±1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α1-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling

From Dynamic Expression Patterns to Boundary Formation in the Presomitic Mesoderm

The segmentation of the vertebrate body is laid down during early embryogenesis. The formation of signaling gradients, the periodic expression of genes of the Notch-, Fgf- and Wnt-pathways and their interplay in the unsegmented presomitic mesoderm (PSM) precedes the rhythmic budding of nascent somites at its anterior end, which later develops into epithelialized structures, the somites. Although many in silico models describing partial aspects of somitogenesis already exist, simulations of a complete causal chain from gene expression in the growth zone via the interaction of multiple cells to segmentation are rare. Here, we present an enhanced gene regulatory network (GRN) for mice in a simulation program that models the growing PSM by many virtual cells and integrates WNT3A and FGF8 gradient formation, periodic gene expression and Delta/Notch signaling. Assuming Hes7 as core of the somitogenesis clock and LFNG as modulator, we postulate a negative feedback of HES7 on Dll1 leading to an oscillating Dll1 expression as seen in vivo. Furthermore, we are able to simulate the experimentally observed wave of activated NOTCH (NICD) as a result of the interactions in the GRN. We esteem our model as robust for a wide range of parameter values with the Hes7 mRNA and protein decays exerting a strong influence on the core oscillator. Moreover, our model predicts interference between Hes1 and HES7 oscillators when their intrinsic frequencies differ. In conclusion, we have built a comprehensive model of somitogenesis with HES7 as core oscillator that is able to reproduce many experimentally observed data in mice

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

Quantitative image analysis for the characterization of microbial aggregates in biological wastewater treatment : a review

Quantitative image analysis techniques have gained an undeniable role in several fields of research during the last decade. In the field of biological wastewater treatment (WWT) processes, several computer applications have been developed for monitoring microbial entities, either as individual cells or in different types of aggregates. New descriptors have been defined that are more reliable, objective, and useful than the subjective and time-consuming parameters classically used to monitor biological WWT processes. Examples of this application include the objective prediction of filamentous bulking, known to be one of the most problematic phenomena occurring in activated sludge technology. It also demonstrated its usefulness in classifying protozoa and metazoa populations. In high-rate anaerobic processes, based on granular sludge, aggregation times and fragmentation phenomena could be detected during critical events, e.g., toxic and organic overloads. Currently, the major efforts and needs are in the development of quantitative image analysis techniques focusing on its application coupled with stained samples, either by classical or fluorescent-based techniques. The use of quantitative morphological parameters in process control and online applications is also being investigated. This work reviews the major advances of quantitative image analysis applied to biological WWT processes.The authors acknowledge the financial support to the project PTDC/EBB-EBI/103147/2008 and the grant SFRH/BPD/48962/2008 provided by Fundacao para a Ciencia e Tecnologia (Portugal)