Adaptive statistical iterative reconstruction for computed tomography of the spine

IntroductionThe utility of evaluating a sagittal view of CT of the spine is well-known. In many clinical cases, the sagittal view includes noise generated from surrounding objects and may degrade the image quality. Iterative reconstruction (IR) techniques are useful for noise reduction; however, they can reduce spatial resolution. The aim of this study was to evaluate the effectiveness of the adaptive statistical iterative reconstruction (ASiR) for generating sagittal CT images of the spine when compared to filtered back projection (FBP). MethodsThe image quality of clinical images from 25 patients were subjectively assessed. Three radiologists rated spatial resolution, image noise, and overall image quality using a five-point scale. For objective assessment, z-direction modulation transfer function (z-MTF) was measured using a custom-made phantom. Additionally, z-axis noise power spectrum (z-NPS) was measured using a water phantom. An improved adaptive statistical iterative reconstruction algorithm called ASiR-V was used in this study. Blending levels were 50%, and 100% (ASiR-V50, ASiR-V100, respectively). ResultsFor subjective assessments, images using ASiR-V100 were determined to have the best overall image quality, despite having received the worst score in the assessment of spatial resolution. For objective assessments, the image using ASiR-V50 and ASiR-V100 curves were slightly degraded in terms of low contrast z-MTF when compared to FBP. ConclusionASiR-V was effective to improve the image quality when compared with FBP when reviewing sagittal reformats of the spine. Implications for practiceThis study suggests that high resolution is not the only thing that is key when reviewing sagittal CT spinal reformats. Such images should be provided as part of routine CT spine protocols, where available

Chiral Zeromodes on Vortex-type Intersecting Heterotic Five-branes

We solve the gaugino Dirac equation on a smeared intersecting five-brane solution in E_8\times E_8 heterotic string theory to search for localized chiral zeromodes on the intersection. The background is chosen to depend on the full two-dimensional overall transverse coordinates to the branes. Under some appropriate boundary conditions, we compute the complete spectrum of zeromodes to find that, among infinite towers of Fourier modes, there exist only three localized normalizable zeromodes, one of which has opposite chirality to the other two. This agrees with the result previously obtained in the domain-wall type solution, supporting the claim that there exists one net chiral zeromode localized on the heterotic five-brane system.Comment: 10 pages, 2 figure

Thermoresponsive bacteriophage nanocarrier as a gene delivery vector targeted to the gastrointestinal tract.

The use of the gastrointestinal tract as a site for the local delivery of DNA is an exciting prospect. In order to obtain an effective vector capable of delivering a gene of interest to target cells to achieve sufficient and sustained transgene expression, with minimal toxicity, we developed a new generation of filamentous bacteriophage. This particular bacteriophage was genetically engineered to display an arginine-glycine-aspartic acid (RGD) motif (an integrin-binding peptide) on the major coat protein pVIII and carry a mammalian DNA cassette. One unanticipated observation is the thermoresponsive behavior of engineered bacteriophage. This finding has led us to simplify the isolation method to purify bacteriophage particles from cell culture supernatant by low-temperature precipitation. Our results showed that, in contrast to non-surface modified, the RGD-modified bacteriophage was successfully used to deliver a transgene to mammalian cells. Our in vitro model of the human intestinal follicle-associated epithelium also demonstrated that bacteriophage particles were stable in simulated gastrointestinal fluids and able to cross the human intestinal barrier. In addition, we confirmed an adjuvant property of the engineered bacteriophage to induce nitric oxide production by macrophages. In conclusion, our study demonstrated the possibility of using bacteriophage for gene transfer in the gastrointestinal tract

Integrated silicon photonic crystals toward terahertz communications

Published online: June 25, 2018The terahertz frequency range locates between 0.1 and 10 THz. This range accommodates atmospheric windows with staggering absolute bandwidth. It holds a potential for point-to-point wireless communications with an aggregate capacity reaching terabit per second in a range up to a kilometer. This unique capability is envisaged for backhauls between base stations and for local area networks. To this end, efficiency and compactness of the transceivers are crucial for successful large-scale adoption. However, stateof- the-art terahertz front ends are based on radio-frequency or photomixing technologies that are inefficient, bulky, or complicated. In principle, as a neighbor of the microwave and optics domains, the terahertz band can leverage technologies from both sides to overcome those challenges. Recently, low-loss integrated circuits based on photonic crystal waveguides are developed for routing terahertz waves. Here, a progress report on core components, including waveguides and diplexers, is presented. Additionally, the interfacing of the platform with electronic sources and detectors on one end, and with antennas for free-space coupling on the other end, is discussed. Currently, the platform can support terahertz communications at a data rate over 10 Gbit s⁻¹. Challenges and opportunities are discussed in the light of future development in this area.Withawat Withayachumnankul, Masayuki Fujita, and Tadao Nagatsum

Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer

Bacteriophage (phage) have attractive advantages as delivery sys-tems compared to mammalian viruses, but have been consideredpoor vectors because they lack evolved strategies to confrontand overcome mammalian cell barriers to infective agents. Wereasoned that improved efficacy of delivery might be achievedthrough structural modification of the viral capsid to avoid pre-and post-internalization barriers to mammalian cell transduction.We generated multifunctional hybrid AAV/phage (AAVP) particlesto enable simultaneous display of targeting ligands on the phage’sminor pIII proteins and also degradation-resistance motifs on thevery numerous pVIII coat proteins. This genetic strategy of directedevolution, bestows a next-generation of AAVP particles that fea-ture resistance to fibrinogen adsorption or neutralizing antibodies,and ability to escape endolysosomal degradation. This results insuperior gene transfer efficacyin vitroand also in preclinicalmouse models of rodent and human solid tumors. Thus, the uniquefunctions of our next-generation AAVP particles enable improvedtargeted gene delivery to tumor cells

Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles

Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through transmorphic encapsidation of human recombinant adeno-associated virus DNA using coat proteins from a tumour-targeted bacteriophage (phage). We show that Transmorphic Phage/AAV (TPA) particles provide superior delivery of transgenes over current phage-derived vectors through greater diffusion across the extracellular space and improved intracellular trafficking. We used TPA to target the delivery of cytokine-encoding transgenes for interleukin-12 (IL12), and novel isoforms of IL15 and tumour necrosis factor alpha (TNFα) for tumour immunotherapy. Our results demonstrate selective and efficient gene delivery and immunotherapy against solid tumours in vivo, without harming healthy organs. Our transmorphic particle system provides a promising modality for safe and effective gene delivery, and cancer immunotherapies through cross-species complementation of two commonly used viruses

Platelet factor-4 and its p17-70 peptide inhibit myeloma proliferation and angiogenesis in vivo

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in the development of multiple myeloma (MM). The interaction between MM cells and the bone marrow microenvironment stimulates the proliferation and migration of endothelial progenitor cells (EPCs). Vascular endothelial growth factor (VEGF) contributes to the formation of new blood vessels by actively recruiting circulating EPCs. The production of proangiogenic and antiangiogenic factors is also dysregulated in MM. Platelet factor 4 (PF4) is a potent angiostatic cytokine that inhibits angiogenesis and tumor growth in several animal models.</p> <p>Methods</p> <p>In this study, we stably transfected human myeloma cell lines with the PF4 gene or the sequence encoding its more potent p17-70 peptide and investigated the effects of PF4 and p17-70 on angiogenesis and tumor growth <it>in vitro </it>and in a SCID-rab myeloma model.</p> <p>Results</p> <p>PF4 and p17-70 significantly attenuated VEGF production, both <it>in vitro </it>and <it>in vivo</it>. In a migration study using a Transwell system, PF4 or p17-70 markedly suppressed the migration of co-cultured human endothelial progenitor cells. PF4 or p17-70 also caused a significant reduction in microvessel densities in myeloma xenografts and markedly reduced the tumor volume in the SCID mice. Kaplan-Meier analysis demonstrated that PF4 and p17-70 significantly extended the overall survival of SCID mice bearing human myeloma xenografts.</p> <p>Conclusions</p> <p>Our findings indicate that PF4 or p17-70 could be valuable in combating multiple myeloma by disrupting tumor angiogenesis.</p

Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology