Influence of the type of imaging on the delineation process during the treatment planning

AimThe aim of this study was to compare the intra- and interobserver contouring variability for structures with density of organ at risk in two types of tomography: kilovoltage computed tomography (KVCT) versus megavoltage computed tomography (MVCT). The intra- and interobserver differences were examined on both types of tomography for structures which simulate human tissue or organs.Materials and methodsSix structures with density of the liver, bone, trachea, lung, soft tissue and muscle were created and used. For the measurements, the special water phantom with all structures was designed. To evaluate interobserver variability, five observers delineated the structures in both types of computed tomography (CT).ResultsIntraobserver variability was in the range of 1–14% and was the largest for the liver. The observers segmented larger volumes on MVCT compared with KVCT for the trachea (79.56 ccm vs.74.91 ccm), lung (87.61 vs. 82.50), soft tissue (154.24 vs. 145.47) and muscle (164.01 vs. 157.89). For the liver (98.13 vs. 99.38) and bone (51.86 vs. 67.97), the volume on MVCT was smaller than KVCT. The statistically significant differences between observers were observed for structures with density of the liver, bone and soft tissue on KVCT and for the liver, lung and soft tissue on MVCT. For the structures with density of the trachea and muscles, there were no significant differences for both types of tomography.ConclusionsDuring the contouring process the interobserver and intraobserver contouring uncertainty was larger on MVCT, especially for structures with HU near 80, compared with KVCT.     

Influence of thiol capping on the photoluminescence properties of L‐cysteine‐, mercaptoethanol‐ and mercaptopropionic acid‐capped ZnS nanoparticles

Mercaptoethanol (ME), mercaptopropionic acid (MPA) and L‐cysteine (L‐Cys) having ‐SH functional groups were used as surface passivating agents for the wet chemical synthesis of ZnS nanoparticles. The effect of the thiol group on the optical and photoluminescence (PL) properties of ZnS nanoparticles was studied. L‐Cysteine‐capped ZnS nanoparticles showed the highest PL intensity among the studied capping agents, with a PL emission peak at 455 nm. The PL intensity was found to be dependent on the concentration of Zn²⁺ and S^2– precursors. The effect of buffer on the PL intensity of L‐Cys‐capped ZnS nanoparticles was also studied. UV/Vis spectra showed blue shifting of the absorption edge. Copyright © 2015 John Wiley & Sons, Ltd.     

Real‐time calcium measurements of live optically trapped microorganisms

A system has been developed that allows for the real‐time measurement of calcium dynamics in swimming sperm. Specifically, the ratiometric dye Indo‐I is used as a fluorescent indicator of intracellular calcium dynamics. The dual emissions are collected by a high‐sensitivity back‐illuminated CCD camera coupled to a Dual‐View imaging system. From the CCD, the images are sent to a custom developed algorithm which processes the images and outputs the calcium measurements in real‐time. Additionally, sperm velocity and position data are processed and outputted in real‐time. The velocity and position data are obtained using a separate coupled red light (>670 nm) phase contrast imaging setup that does not optically interfere with the fluorescent imaging. Using this system the effects of optical trapping on calcium dynamics was determined. Optical trapping of sperm with a decaying focused laser power of 510 mW to 3 mW over 8 seconds causes a statistically insignificant change in calcium dynamics between in‐trap and out‐of‐trap conditions. Progesterone, a calcium activator, was added and sperm were trapped under the 8 second power decay conditions. Progesterone treated sperm has a statistically higher average calcium level than untreated sperm, but shows no statistical difference between progesterone treated in‐trap and out‐of‐trap conditions. Trapping at 16 seconds at 510 mW without decay, which have been shown to decrease sperm motility, shows a statistical difference between baseline pre‐trap and in‐trap intracellular calcium levels. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature

Background

Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders.

Materials and methods

Two adult patients with CBFs are described and a PubMed search was performed using the keywords “coronary bronchial artery fistulas” in the period from 2008 to 2013.

Results

Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %).

Conclusions

CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.     

Two steps forward,one step back: Determining XPD helicase mechanism by single-molecule fluorescence and high-resolution optical tweezers

XPD-like helicases constitute a prominent DNA helicase family critical for many aspects of genome maintenance. These enzymes share a unique structural feature, an auxiliary domain stabilized by an iron-sulphur (FeS) cluster, and a 5′–3′ polarity of DNA translocation and duplex unwinding. Biochemical analyses alongside two single-molecule approaches, total internal reflection fluorescence microscopy and high-resolution optical tweezers, have shown how the unique structural features of XPD helicase and its specific patterns of substrate interactions tune the helicase for its specific cellular function and shape its molecular mechanism. The FeS domain forms a duplex separation wedge and contributes to an extended DNA binding site. Interactions within this site position the helicase in an orientation to unwind the duplex, control the helicase rate, and verify the integrity of the translocating strand. Consistent with its cellular role, processivity of XPD is limited and is defined by an idiosyncratic stepping kinetics. DNA duplex separation occurs in single base pair steps punctuated by frequent backward steps and conformational rearrangements of the protein–DNA complex. As such, the helicase in isolation mainly stabilizes spontaneous base pair opening and exhibits a limited ability to unwind stable DNA duplexes. The presence of a cognate ssDNA binding protein converts XPD into a vigorous helicase by destabilizing the upstream dsDNA as well as by trapping the unwound strands. Remarkably, the two proteins can co-exist on the same DNA strand without competing for binding. The current model of the XPD unwinding mechanism will be discussed along with possible modifications to this mechanism by the helicase interacting partners and unique features of such bio-medically important XPD-like helicases as FANCJ (BACH1), RTEL1 and CHLR1 (DDX11).     

Urine as a source for clinical proteome analysis: From discovery to clinical application

The success of clinical proteome analysis should be assessed based on the clinical impact following implementation of findings. Although there have been several technological advancements in mass spectrometry in the last years, these have not resulted in similar advancements in clinical proteomics. In addition, application of proteomic biomarkers in clinical diagnostics and practical improvement in the disease management is extremely rare. In this review, we discuss the relevant issues associated with identification of robust biomarkers of clinical value. Urine appears to be an ideal source of biomarkers, for theoretical, methodological, and practical reasons. Therefore, this review is focused on the search for biomarkers in urine within the last decade. Urine can be used for non-invasive assessment of a variety of diseases including those affecting the urogenital tract and also other pathologies such as cardiovascular disease or appendicitis. We also discuss the importance of data validation, an essential step in translating biomarkers into the clinical practice. Furthermore, we examine several examples of apparently successful proteomic biomarker discovery studies and their implications for disease diagnosis, prognosis, and therapy evaluation. We also discuss some current challenges in this field and reflect on future research prospects. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.     

Evaluation of Built‐In Potential and Loss Mechanisms at Contacts in Organic Solar Cells: Device Model Parameterization,Validation, and Prediction

Maximizing the power conversion efficiency of organic solar cells requires the simultaneous optimization of its short‐circuit current density, fill factor, and open‐circuit voltage V_oc. Several key parameters of the device model needed to understand these quantities have not been reliably determined, even for the prototypical poly(3‐hexylthiophene):phenyl‐C₆₁‐methylbutyric ester (P3HT:PCBM) photoactive layer (PAL). Detailed analysis of the loss mechanisms at contacts and their rational optimization have not been possible. Here, using crosslinked P3HT network:PCBM cells with predefined ultrafine donor–acceptor morphology and very high internal quantum efficiencies, the built‐in potential V_bi is measured to decouple and reliably extract other key parameters of the cells. Using the refined device parameters, the general optimization of organic solar cells is evaluated and the following is established: i) The PAL composition of the first optical absorption optimum is displaced towards the more strongly absorbing component due to thin film effects. ii) The optimal cell configuration is the one in which the slower carrier travels on average the shorter distance to the collection contact, a consequence of the asymmetric photogeneration profile. iii) The absorption thickness optima follows a simple λ_p/n_PAL scaling law, where λ_p is its absorption center wavelength and n_PAL is the corresponding refractive index.     

Interfacial Engineering of P3HT/ZnO Hybrid Solar Cells Using Phthalocyanines: A Joint Theoretical and Experimental Investigation

Atomistic simulations and experimental investigations are combined to study heterojunction interfaces of hybrid polymer solar cells, with the aim to better understand and precisely predict their photovoltaic properties. The focus is on a hybrid ternary model system based on a poly(3‐hexylthiophene) (P3HT)/zinc phthalocyanine (ZnPc)/ZnO interface, in which a ZnPc interlayer is applied to improve the performance of the hybrid interface. Theoretical predictions of the ternary system are validated against the properties of a concrete P3HT/ZnPc/ZnO planar heterojunction device. The theoretical predictions closely agree with the photovoltaic properties obtained in P3HT/ZnPc/ZnO solar cells, indicating the strength of the method for modeling hybrid heterojunction interfaces. The theoretical and experimental results reveal that: i) ZnPc molecules in direct contact with a ZnO surface insert new energy levels due to a strong ZnPc/ZnO coupling, ii) electron injection from these new energy levels of ZnPc into ZnO is highly efficient, iii) the ZnPc/ZnO coupling strongly influences the energy levels of the ZnO and P3HT leading to a reduction of the open circuit voltage, and iv) charge carrier recombination at the P3HT/ZnO interface is reduced by the ZnPc interlayer. The intercalation of ZnPc leads to an increase in photocurrent as well as to an overall increase in power conversion.