Magnetically Guidable Proteinaceous Adhesive Microbots for Targeted Locoregional Therapeutics Delivery in the Highly Dynamic Environment of the Esophagus

The esophagus is a tubular-shaped muscular organ where swallowed fluids and muscular contractions constitute a highly dynamic environment. The turbulent, coordinated processes that occur through the oropharyngeal conduit can often compromise targeted administration of therapeutic drugs to a lesion, significantly reducing therapeutic efficacy. Here, magnetically guidable drug vehicles capable of strongly adhering to target sites using a bioengineered mussel adhesive protein (MAP) to achieve localized delivery of therapeutic drugs against the hydrodynamic physiological conditions are proposed. A suite of highly uniform microparticles embedded with iron oxide (IO) nanoparticles (MAP@IO MPs) is microfluidically fabricated using the genipin-mediated covalent cross-linking of bioengineered MAP. The MAP@IO MPs are successfully targeted to a specific region and prolongedly retained in the tubular-structured passageway. In particular, orally administered MAP@IO MPs are effectively captured in the esophagus in vivo in a magnetically guidable manner. Moreover, doxorubicin (DOX)-loaded MAP@IO MPs exhibit a sustainable DOX release profile, effective anticancer therapeutic activity, and excellent biocompatibility. Thus, the magnetically guidable locomotion and robust underwater adhesive properties of the proteinaceous soft microbots can provide an intelligent modular approach for targeted locoregional therapeutics delivery to a specific lesion site in dynamic fluid-associated tubular organs such as the esophagus.     

Unsupervised Segmentation of Stereoscopic Video Objects: Constrained Segmentation Fusion Versus Greedy Active Contours

In this paper, we present a novel memory access reduction scheme (MARS) for two-dimension fast cosine transform (2-D FCT). It targets programmable DSPs with high memory-access latency. It reduces the number of memory accesses by: 1) reducing the number of weighting factors and 2) combining butterflies in vector-radix 2-D FCT pruning diagram from two stages to one stage with an efficient structure. Hardware platform based on general purpose processor is used to verify the effectiveness of the proposed method for vector-radix 2-D FCT pruning implementation. Experimental results validate the benefits of the proposed method with reduced memory access, less clock cycle and fewer memory space compared with the conventional implementation.     

Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Estimates of pollutant temporal and spatial variability in commercial buildings from the joint urban 2003 field experiments

In this paper, we report on the indoor concentrations from a suite of full-scale outdoor tracer-gas point releases conducted in the downtown area of Oklahoma City in 2003. A point release experiment consisted of releases of sulfur hexafluoride (SF₆) in multiple buildings and from different outdoor locations. From the measurements, we are able to estimate the concentration variations indoors for a building operating under “typical” operating conditions. The mean indoor spatial coefficients of variation are 30% to 45% from a daytime outdoor release are around 80% during an outdoor evening release. Having estimates of the spatial coefficient of variation provides stakeholders, including first responders, with the likely range of concentrations in the building when little is known about the building characteristics and operating behavior, such as developing urban-scale hazard and consequence analyses. We show differences in indoor measurements at different distances to the release points, floors of the building, and heating, ventilation, and air conditioning system (HVAC) operation. We also show estimates at different time resolutions. The statistics show that in the studied medium to large commercial buildings, spatial differences would result in peak indoor concentrations in certain parts of the buildings that may be substantially higher than the building average. To our knowledge, very few tracer gas measurements have been conducted in buildings of this scope, particularly with measurements on multiple floors and within a floor. The resulting estimates of spatial variability provide a unique opportunity for hazard assessment, and comparison to multi-zone models.     

Isolation of antimicrobial agent from the marine algae Cystoseira hakodatensis

Cystoseira hakodatensis is an unutilised brown algae belonging to family Sargassaceae. A crude methanol extract from the algae showed inhibitory effects on the growths of Bacillus cereus and Bacillus licheniformis. To isolate the major antimicrobial agent, a sequential active‐guided isolation procedure was applied: liquid–liquid extraction, column chromatography and bio‐autography. A marked antimicrobial agent (active α) was isolated in hydrophobic fraction and was determined to phenolics without carbohydrates and proteins by phytochemical test. Regarding the antimicrobial potential, the isolated active α showed better inhibitory effects against B. cereus and B. licheniformis at 2 and 4 times of lower concentrations (62.5 and 31.3 μg mL^?1) in comparison with epigallocatechin gallate. These results showed that C. hakodatensis is a potential source of antimicrobial agent capable of preventing the growth of the two bacteria.     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.