An integrated particle sampler and lung radiation dosimeter

A lung dosimeter that can record the nonradiological hazard of aerosol particles to the lung as well as the radiological hazard of air borne radionuclides that are attached to aerosol particles has been developed. The dosimeter is capable of recording aerosol particles of diameters from 10-2 μm to 102 μ by electrostatic collection in a specially designed dosimeter body. The aerosol size distribution is recorded on a mylar strip and the activity size distribution of α, β, and γ radiation emitting aerosols recorded on another strip coated with α-Al2O3:C. Both strips can be read by a specially built reader, the output of which can be used to calculate the nonradiological hazard and radiological hazard, respectively, and to give an overall picture of the exposure.published_or_final_versio

Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3

Background: The rearranged during transfection (RET) gene encodes a single-pass receptor whose proper expression and function are essential for the development of enteric nervous system. Mutations in RET regulatory regions are also associated with Hirschsprung disease (HSCR) (aganglionosis of the colon). We previously showed that 2 polymorphisms in RET promoter are associated with the increased risk of HSCR. These single nucleotide polymorphisms overlap with the NK2 homeobox 1 (Nkx2-1) binding motif interrupting the physical interaction of NKX2-1 with the RET promoter and result in reduced RET transcription. In this study, we further delineated Nkx2-1-mediated RET Transcription. Methods and results: First, we demonstrated that PHOX2B, like SOX10 and NKX2-1, is expressed in the mature enteric ganglions of human gut by immunohistochemistry. Second, subsequent dual-luciferase-reporter studies indicated that Nkx2-1 indeed works coordinately with Phox2b and Sox10, but not Pax3, to mediate RET transcription. In addition, identification of Phox2b responsive region in RET promoter further provides solid evidence of the potential functional interaction between Phox2b and RET. Conclusion: In sum, Phox2b and Sox10 act together with Nkx2.1 to modify RET signaling and this interaction may also contribute to HSCR susceptibility. © 2009 Elsevier Inc. All rights reserved.postprin

An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus

published_or_final_versio

Pandemic A/H1N1 2009 Influenza Virus-like Particles Elicited Higher and Broader Immune Responses than the Commercial Panenza Vaccine

Objectives: The aim was to construct 2009 pandemic A/H1N1 influenza VLPs (virus-like particles) and compare the immunogenicity and protection efficacy with the commercial Panenza vaccine in BALB/c mouse model. Methods: VLPs derived from influenza A/Hong Kong/01/2009 (H1N1) virus were constructed by Bac-to-Bac baculovirus expression system. VLPs were purified by sucrose density gradient ultracentrifugation and then characterized by Western blotting analysis and transmission electron microscopy. After single dose vaccination with 3 µg of VLPs and equal amount of Panenza vaccine, the immune responses and efficacy of protection induced by VLPs were compared with those elicited by the Panenza vaccine in 6-8 week female BALB/c mice. Key findings: VLPs could induce higher antibody titer as determined by hemagglutinin inhibition and microneutralization assay. Furthermore, we demonstrated that VLPs induced better antibody response to neuraminidase. In addition, VLP vaccinated mice had stronger cell-mediated immune response. As a result, our VLPs conferred 100% protection while the Panenza vaccine only conferred 67% protection. Conclusion: From the results, we concluded that influenza VLPs are highly immunogenic and they are promising to be developed as an alternative strategy to vaccine production in order to control the spread of influenza viruses.published_or_final_versio

Circulating microRNAs as Specific Biomarkers for Breast Cancer Detection

Background: We previously showed microRNAs (miRNAs) in plasma are potential biomarkers for colorectal cancer detection. Here, we aimed to develop specific blood-based miRNA assay for breast cancer detection. Methodology/Principal Findings: TaqMan-based miRNA profiling was performed in tumor, adjacent non-tumor, corresponding plasma from breast cancer patients, and plasma from matched healthy controls. All putative markers identified were verified in a training set of breast cancer patients. Selected markers were validated in a case-control cohort of 170 breast cancer patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set of 70 breast cancer patients and 50 healthy controls. Profiling results showed 8 miRNAs were concordantly up-regulated and 1 miRNA was concordantly down-regulated in both plasma and tumor tissue of breast cancer patients. Of the 8 up-regulated miRNAs, only 3 were significantly elevated (p<0.0001) before surgery and reduced after surgery in the training set. Results from the validation cohort showed that a combination of miR-145 and miR-451 was the best biomarker (p<0.0001) in discriminating breast cancer from healthy controls and all other types of cancers. In the blind validation, these plasma markers yielded Receiver Operating Characteristic (ROC) curve area of 0.931. The positive predictive value was 88% and the negative predictive value was 92%. Altered levels of these miRNAs in plasma have been detected not only in advanced stages but also early stages of tumors. The positive predictive value for ductal carcinoma in situ (DCIS) cases was 96%. Conclusions: These results suggested that these circulating miRNAs could be a potential specific biomarker for breast cancer screening. © 2013 Ng et al.published_or_final_versio

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

published_or_final_versio

Hedgehog/notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans

Hirschsprung (HSCR) disease is a complex genetic disorder attributed to a failure of the enteric neural crest cells (ENCCs) to form ganglia in the hindgut. Hedgehog and Notch are implicated in mediating proliferation and differentiation of ENCCs. Nevertheless, how these signaling molecules may interact to mediate gut colonization by ENCCs and contribute to a primary etiology for HSCR are not known. Here, we report our pathway- based epistasis analysis of data generated by a genome-wide association study on HSCR disease, which indicates that specific genotype constellations of Patched (PTCH1) (which encodes a receptor for Hedgehog) and delta-like 3 (DLL3) (which encodes a receptor for Notch) SNPs confer higher risk to HSCR. Importantly, deletion of Ptch1 in mouse ENCCs induced robust Dll1 expression and activation of the Notch pathway, leading to premature gliogenesis and reduction of ENCC progenitors in mutant bowels. Dll1 integrated Hedgehog and Notch pathways to coordinate neuronal and glial cell differentiation during enteric nervous system development. In addition, Hedgehog-mediated gliogenesis was found to be highly conserved, such that Hedgehog was consistently able to promote gliogenesis of human neural crest-related precursors. Collectively, we defined PTCH1 and DLL3 as HSCR susceptibility genes and suggest that Hedgehog/Notch-induced premature gliogenesis may represent a new disease mechanism for HSCR.published_or_final_versio

Interactive Multi-Stage Robotic Positioner for Intra-Operative MRI-Guided Stereotactic Neurosurgery

Magnetic resonance imaging (MRI) demonstrates clear advantages over other imaging modalities in neurosurgery with its ability to delineate critical neurovascular structures and cancerous tissue in high-resolution 3D anatomical roadmaps. However, its application has been limited to interventions performed based on static pre/post-operative imaging, where errors accrue from stereotactic frame setup, image registration, and brain shift. To leverage the powerful intra-operative functions of MRI, e.g., instrument tracking, monitoring of physiological changes and tissue temperature in MRI-guided bilateral stereotactic neurosurgery, a multi-stage robotic positioner is proposed. The system positions cannula/needle instruments using a lightweight (203 g) and compact (Ø97 × 81 mm) skull-mounted structure that fits within most standard imaging head coils. With optimized design in soft robotics, the system operates in two stages: i) manual coarse adjustment performed interactively by the surgeon (workspace of ±30°), ii) automatic fine adjustment with precise (<0.2° orientation error), responsive (1.4 Hz bandwidth), and high-resolution (0.058°) soft robotic positioning. Orientation locking provides sufficient transmission stiffness (4.07 N/mm) for instrument advancement. The system's clinical workflow and accuracy is validated with lab-based (<0.8 mm) and MRI-based testing on skull phantoms (<1.7 mm) and a cadaver subject (<2.2 mm). Custom-made wireless omni-directional tracking markers facilitated robot registration under MRI

An optical coherence tomography and endothelial shear stress study of a novel bioresorbable bypass graft

Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal "flap" identified during OCT acquisition. The "flap" compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the "flap". In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p < 0.0001; maximum OSI 0.4612 versus 0.4837). Conversely, OSI increased as the catheter was withdrawn which can potentially cause back-and-forth motions of the "flap", triggering tissue fatigue failure. CFD analysis in this report provided sophisticated physiological information that complements the anatomic assessment from imaging enabling a complete understanding of biorestorative graft pathophysiology

Sunscreens - Which and what for?

It is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel