Evaluation of the need for simultaneous orthogonal gated setup imaging

Image‐guided patient setup for respiratory‐gated radiotherapy often relies on a pair of respiratory‐gated orthogonal radiographs, acquired one after the other. This study quantifies the error due to changes in the internal/external correlation which may affect asynchronous (non‐simultaneous) imaging. The dataset from eight patients includes internal and external coordinates acquired at 30Hz during multi‐fraction SBRT treatments using the Mitsubishi RTRT system coupled with an external surrogate gating device. We performed a computational simulation of the position of an implanted fiducial marker in an asynchronous orthogonal image set. A comparison is made to the reference position, the actual 3D fiducial location at the initial time point, as would be obtainable by simultaneous orthogonal setup imaging at that time point. The time interval between the two simulated radiographic acquisitions was set to a minimum of 30, 60 or 90 seconds, based on our clinical experience. The setup position is derived from a combination of both the initial (AP) and the final (LR) simulated 2D images in the following way: LRsetup=LRinitial,SIsetup=SIinitial+(SIfinal−SIinitial)/2,APsetup=APfinal. The 3D error is then the magnitude of the vector from the initial (reference) position to the setup position. The calculation was done for every exhale phase in the data for which there was another one at least 30, 60 or 90 seconds later, at an amplitude within 0.5 mm from the first. A correlation between the time interval and the 3D error was also sought. The mean 3D error is found to be roughly equivalent for time intervals (tinterval) of 30, 60 and 90 seconds between the orthogonal simulated images (0.8 mm, 0.8 mm, 0.6 mm, respectively). The 3D error is less than 1, 2 and 3 mm for 77%, 89% and 98% of the data points, respectively. The actual time between simulated images turned out to be very close to tinterval, with 90% of the second simulated image acquisitions being completed within 38, 68 and 95 seconds of the first simulated image for tinterval of 30, 60 and 90 seconds, respectively. No correlation was found between the length of the time interval and the 3D error. When acquiring respiratory‐gated radiographs for patient setup, only small errors should be expected if those images are not taken simultaneously. PACS number: 87.55.n

Application of a spring-dashpot system to clinical lung tumor motion data

A spring-dashpot system based on the Voigt model was developed to model the correlation between abdominal respiratory motion and tumor motion during lung radiotherapy. The model was applied to clinical data comprising 52 treatment beams from 10 patients, treated on the Mitsubishi Real-Time Radiation Therapy system, Sapporo, Japan. In Stage 1, model parameters were optimized for individual patients and beams to determine reference values and to investigate how well the model can describe the data. In Stage 2, for each patient the optimal parameters determined for a single beam were applied to data from other beams to investigate whether a beam-specific set of model parameters is sufficient to model tumor motion over a course of treatment. In Stage 1 the baseline root mean square (RMS) residual error for all individually-optimized beam data was 0.90 plus or minus 0.40 mm. In Stage 2, patient-specific model parameters based on a single beam were found to model the tumor position closely, even for irregular beam data, with a mean increase with respect to Stage 1 values in RMS error of 0.37 mm. On average the obtained model output for the tumor position was 95% of the time within an absolute bound of 2.0 mm and 2.6 mm in Stage 1 and 2, respectively. The model was capable of dealing with baseline, amplitude and frequency variations of the input data, as well as phase shifts between the input tumor and output abdominal signals. These results indicate that it may be feasible to collect patient-specific model parameters during or prior to the first treatment, and then retain these for the rest of the treatment period. The model has potential for clinical application during radiotherapy treatment of lung tumors

Epigenetic control of the ubiquitin carboxyl terminal hydrolase 1 in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>The ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) gene involved in the regulation of cellular ubiquitin levels plays an important role in different cellular processes including cell growth and differentiation. Aberrant expression of UCHL1 has been found in a number of human solid tumors including renal cell carcinoma (RCC). In RCC, UCHL1 overexpression is associated with tumor progression and an altered von Hippel Lindau gene expression.</p> <p>Methods</p> <p>To determine the underlying mechanisms for the heterogeneous UCHL1 expression pattern in RCC the UCHL1 promoter DNA methylation status was determined in 17 RCC cell lines as well as in 32 RCC lesions and corresponding tumor adjacent kidney epithelium using combined bisulfite restriction analysis as well as bisulfite DNA sequencing.</p> <p>Results</p> <p>UCHL1 expression was found in all 32 tumor adjacent kidney epithelium samples. However, the lack of or reduced UCHL1 mRNA and/or protein expression was detected in 13/32 RCC biopsies and 7/17 RCC cell lines and due to either a total or partial methylation of the UCHL1 promoter DNA. Upon 2'-deoxy-5-azacytidine treatment an induction of UCHL1 mRNA and protein expression was found in 9/17 RCC cell lines, which was linked to the demethylation degree of the UCHL1 promoter DNA.</p> <p>Conclusion</p> <p>Promoter hypermethylation represents a mechanism for the silencing of the UCHL1 gene expression in RCC and supports the concept of an epigenetic control for the expression of UCHL1 during disease progression.</p

Biochemical aspects of nitric oxide synthase feedback regulation by nitric oxide

Nitric oxide (NO) is a small gas molecule derived from at least three isoforms of the enzyme termed nitric oxide synthase (NOS). More than 15 years ago, the question of feedback regulation of NOS activity and expression by its own product was raised. Since then, a number of trials have verified the existence of negative feedback loop both in vitro and in vivo. NO, whether released from exogenous donors or applied in authentic NO solution, is able to inhibit NOS activity and also intervenes in NOS expression processes by its effect on transcriptional nuclear factor NF-κB. The existence of negative feedback regulation of NOS may provide a powerful tool for experimental and clinical use, especially in inflammation, when massive NOS expression may be detrimental

Liquid marbles: topical context within soft matter and recent progress

The study of particle stabilized interfaces has a long history in terms of emulsions, foams and related dry powders. The same underlying interfacial energy principles also allow hydrophobic particles to encapsulate individual droplets into a stable form as individual macroscopic objects, which have recently been called "Liquid Marbles". Here we discuss conceptual similarities to superhydrophobic surfaces, capillary origami, slippery liquids-infused porous surfaces (SLIPS) and Leidenfrost droplets. We provide a review of recent progress on liquid marbles, since our earlier Emerging Area article (Soft Matter, 2011, 7, 5473–5481), and speculate on possible future directions from new liquid-infused liquid marbles to microarray applications. We highlight a range of properties of liquid marbles and describe applications including detecting changes in physical properties (e.g. pH, UV, NIR, temperature), use for gas sensing, synthesis of compounds/composites, blood typing and cell culture

Expression of the blood-group-related glycosyltransferase B4galnt2 influences the intestinal microbiota in mice

Glycans on mucosal surfaces have an important role in host–microbe interactions. The locus encoding the blood-group-related glycosyltransferase β-1,4-N-acetylgalactosaminyltransferase 2 (B4galnt2) is subject to strong selective forces in natural house-mouse populations that contain a common allelic variant that confers loss of B4galnt2 gene expression in the gastrointestinal (GI) tract. We reasoned that altered glycan-dependent intestinal host–microbe interactions may underlie these signatures of selection. To determine whether B4galnt2 influences the intestinal microbial ecology, we profiled the microbiota of wild-type and B4galnt2-deficient siblings throughout the GI tract using 16S rRNA gene pyrosequencing. This revealed both distinct communities at different anatomic sites and significant changes in composition with respect to genotype, indicating a previously unappreciated role of B4galnt2 in host–microbial homeostasis. Among the numerous B4galnt2-dependent differences identified in the abundance of specific bacterial taxa, we unexpectedly detected a difference in the pathogenic genus, Helicobacter, suggesting Helicobacter spp. also interact with B4galnt2 glycans. In contrast to other glycosyltransferases, we found that the host intestinal B4galnt2 expression is not dependent on presence of the microbiota. Given the long-term maintenance of alleles influencing B4galnt2 expression by natural selection and the GI phenotypes presented here, we suggest that variation in B4galnt2 GI expression may alter susceptibility to GI diseases such as infectious gastroenteritis

The elements of human cyclin D1 promoter and regulation involved

Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the promoter at different time to get the correct cell cycle switch. Disorder regulation or special extracellular stimuli can result in cell cycle out of control through the promoter activity regulation. Epigenetic modifications such as DNA methylation and histone acetylation may involved in cyclin D1 transcriptional regulation