bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Metalloporphyrins on Heme Oxygenase-1 Transcription: Correlative Cell Culture Assays Guide in Vivo Imaging
Authors: Hajdena-Dawson Monica , Zhang Weisheng , Contag Pamela R. , Wong Ronald J. , Vreman Hendrik J. , Stevenson David K. , Contag Christopher H.
Published: March 2018

Heme oxygenase (HO) is the rate-limiting step in the heme degradation pathway and is a potential target for the control, or prevention, of pathologic jaundice in neonates. Metalloporphyrins (Mps), a diverse set of synthetic derivatives of heme, can competitively inhibit the HO enzymes. However, certain Mps are phototoxic and some increase transcription of HO-1, the inducible HO isozyme. Therefore, effective development of this class of compounds as therapeutics for treating pathologic jaundice will require rapid and integrated biological screens to identify the most efficacious and safe Mps. To study the safety of these compounds, we assessed their cytotoxic effects and measured luciferase activity by bioluminescent imaging (BLI) as an index of HO-1 transcription, first in live cell cultures and then in living transgenic reporter mice. A total of 12 Mps were first evaluated in the correlative cell culture assay. Based on results from this study, 2 Mps, zinc protoporphyrin (ZnPP) and zinc bis glycol porphyrin (ZnBG), were selected for further studies in the live animal model. In vitro BLI showed ZnPP to be a strong inducer of HO-1 transcription in comparison to ZnBG, which showed minimal induction. Cytotoxicity studies revealed that ZnPP was phototoxic, whereas ZnBG had no effect on cell viability. In vivo BLI showed that both ZnPP and ZnBG had minimal effects on the levels of HO-1 transcription in the animals. Furthermore, serum enzyme assays indicated that neither caused detectable liver toxicity. These findings, and especially those with ZnBG, support the use of selected Mps as therapies for pathologic jaundice. Coupling the high throughput advantage of cell culture with the capability of imaging for whole-body temporal analyses could accelerate and refine the preclinical phases of drug development. Thus, this study serves as a model for understanding the effects of specific compounds in relation to defined targets using an integrated approach.
A Novel Polyacrylamide Magnetic Nanoparticle Contrast Agent for Molecular Imaging using MRI
Authors: Moffat Bradford A. , Reddy G. Ramachandra , McConville Patrick , Hall Daniel E. , Chenevert Thomas L. , Kopelman Raoul R. , Philbert Martin , Weissleder Ralph , Rehemtulla Alnawaz , Ross Brian D.
Published: March 2018

A novel Polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single Polyacrylamide matrix ( Poly Acrylamide Magnetic [PAM] nanoparticles). This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec−1 mM−1. Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa) to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.
Thermostability of Firefly Luciferases Affects Efficiency of Detection by in Vivo Bioluminescence
Authors: Baggett Brenda , Roy Rupali , Momen Shafinaz , Morgan Sherif , Tisi Laurence , Morse David , Gillies Robert J.
Published: March 2018

Luciferase from the North American firefly ( Photinis pyralis) is a useful reporter gene in vivo, allowing noninvasive imaging of tumor growth, metastasis, gene transfer, drug treatment, and gene expression. Luciferase is heat labile with an in vitro half-life of approximately 3 min at 37°C. We have characterized wild type and six thermostabilized mutant luciferases. In vitro, mutants showed half-lives between 2- and 25-fold higher than wild type. Luciferase transfected mammalian cells were used to determine in vivo half-lives following cycloheximide inhibition of de novo protein synthesis. This showed increased in vivo thermostability in both wild-type and mutant luciferases. This may be due to a variety of factors, including chaperone activity, as steady-state luciferase levels were reduced by geldanamycin, an Hsp90 inhibitor. Mice inoculated with tumor cells stably transfected with mutant or wild-type luciferases were imaged. Increased light production and sensitivity were observed in the tumors bearing thermostable luciferase. Thermostable proteins increase imaging sensitivity. Presumably, as more active protein accumulates, detection is possible from a smaller number of mutant transfected cells compared to wild-type transfected cells.
Characterization of Coelenterazine Analogs for Measurements of Renilla Luciferase Activity in Live Cells and Living Animals
Authors: Zhao Hui , Doyle Timothy C. , Wong Ronald J. , Cao Yuan , Stevenson David K. , Piwnica-Worms David , Contag Christopher H.
Published: March 2018

In vivo imaging of bioluminescent reporters relies on expression of light-emitting enzymes, luciferases, and delivery of chemical substrates to expressing cells. Coelenterazine (CLZN) is the substrate for a group of bioluminescent enzymes obtained from marine organisms. At present, there are more than 10 commercially available CLZN analogs. To determine which analog is most suitable for activity measurements in live cells and living animals, we characterized 10 CLZN analogs using Renilla luciferase (Rluc) as the reporter enzyme. For each analog, we monitored enzyme activity, auto-oxidation, and efficiency of cellular uptake. All CLZN analogs tested showed higher auto-oxidation signals in serum than was observed in phosphate buffer or medium, mainly as a result of auto-oxidation by binding to albumin. CLZN- f, -h, and -e analogs showed 4- to 8-fold greater Rluc activity, relative to CLZN- native, in cells expressing the enzyme from a stable integrant. In studies using living mice expressing Rluc in hepatocytes, administration of CLZN- e and -native produced the highest signal. Furthermore, distinct temporal differences in signal for each analog were revealed following intravenous or intraperitoneal delivery. We conclude that the CLZN analogs that are presently available vary with respect to hRluc utilization in culture and in vivo, and that the effective use of CLZN-utilizing enzymes in living animals depends on the selection of an appropriate substrate.
Visualization of the Dynamics of Gene Expression in the Living Mouse
Authors: Ryan Amy , Scrable Heidi
Published: March 2018

Reporter genes can monitor the status and activity of recombinant genomes in a diverse array of organisms, from bacteria and yeast to plants and animals. We have combined luciferase reporter genes with a conditional gene expression system based on regulatory elements from the lac Operon of Escherichia coli to visualize the dynamics of gene expression in realtime in the living mouse. Using this technology, we have determined the rate of gene induction and repression, the level of target gene activity in response to different doses of inducer, and the schedule of induction during early embryogenesis of both the endogenous and the experimentally manipulated programs of mammalian gene expression associated with the HD/Hdh locus. The combination of in vivo imaging and lac regulation is a powerful tool for generating conditional transgenic mice that can be screened rapidly for optimal regulation and expression patterns, and for monitoring the induction and repression of regulated genes noninvasively in the living animal.
Imaging Reactive Oxygen Species in Arthritis
Authors: Chen Wei-Tsung , Tung Ching-Hsuan , Weissleder Ralph
Published: March 2018

Reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.
Factors Influencing Quantification of in Vivo Bioluminescence Imaging: Application to Assessment of Pancreatic Islet Transplants
Authors: Virostko John , Chen Zhongyi , Fowler Michael , Poffenberger Greg , Powers Alvin C. , Jansen E. Duco
Published: March 2018

The aim of this study is to determine and characterize factors influencing in vivo bioluminescence imaging (BLI) and apply them to the specific application of imaging transplanted pancreatic islets. Noninvasive quantitative assessment of transplanted pancreatic islets poses a formidable challenge. Murine pancreatic islets expressing firefly luciferase were transplanted under the renal capsule or into the portal vein of nonobese diabetic–severe combined immunodeficiency mice and the bioluminescence was quantified with a cooled charge coupled device camera and digital photon image analysis. The important, but often neglected, effects of wound healing, mouse positioning, and transplantation site on bioluminescence measurements were investigated by imaging a constant emission, isotropic light-emitting bead (λ = 600) implanted at the renal or hepatic site. The renal beads emitted nearly four times more light than hepatic beads with a smaller spot size, indicating that light absorption and scatter are greatly influenced by the transplant site and must be accounted for in BLI measurements. Detected luminescence decreased with increasing angle between the mouse surface normal and optical axis. By defining imaging parameters such as postsurgical effects, animal positioning, and light attenuation as a function of transplant site, this study develops BLI as a useful imaging modality for quantitative assessment of islets post-transplantation.
Quantitative Analysis of Micro-CT Imaging and Histopathological Signatures of Experimental Arthritis in Rats
Authors: Silva Matthew D. , Savinainen Anneli , Kapadia Rasesh , Ruan Jason , Siebert Elizabeth , Avitahl Nicole , Mosher Rebecca , Anderson Karen , Jaffee Bruce , Schopf Lisa , Chandra Sudeep
Published: March 2018

Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws ( n = 10) stored in formalin consisted of approximately 600 30-μm slices acquired on a 512 × 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.
Near-Infrared Optical Imaging of Integrin αvβ3 in Human Tumor Xenografts
Authors: Wang Wei , Ke Shi , Wu Qingping , Charnsangavej Chusilp , Gurfinkel Mikhail , Gelovani Juri G. , Abbruzzese James L. , Sevick-Muraca Eva M. , Li Chun
Published: March 2018

In vivo optical imaging is potentially useful for evaluating the presence of tumor markers that are targets of molecular medicine. Here we report the synthesis and characterization of integrin αvβ3-targeted peptide cyclo(Lys–Arg–Gly–Asp–Phe) [c(KRGDf)] labeled with fluorescence dyes with wavelength spanning from the visible/near infrared (Cy5.5) to the true near infrared (IRDye800) for optical imaging. In vitro, the peptide–dye conjugates bound specifically to tumor cells expressing αvβ3. When administered intravenously into mice at a dose of 6 nmol/mouse, the conjugates accumulated in tumors expressing αvβ3. The tumor-to-background ratios for human KS1767 Kaposi's sarcoma in mice injected with Cy5.5–c(KRGDf) and Cy5.5 were 5.5 and 1.5, respectively. Preinjection of c(KRGDf) blocked the uptake of Cy5.5–c(KRGDf) in tumors by 89%. In αvβ3-positive M21 and αvβ3-negative M21-L human melanoma, fluorescence intensity in the tumor of mice injected with IRDye800–c(KRGDf) was 2.3 and 1.3 times that in normal tissue, respectively. Dynamic imaging revealed that Cy5.5–c(KRGDf) was rapidly taken up by KS1767 tumor immediately after bolus injection. The rate of its uptake in the tumor was reduced by preinjection of c(KRGDf) in an interval time-dependent manner. Our data suggest that near-infrared fluorescence imaging may be applied to the detection of tumors expressing integrin αvβ3 and to the assessment of the optimal biological dose and schedule of targeted therapies.
Combined in Vivo Bioluminescence and Fluorescence Imaging for Cancer Gene Therapy
Authors: Mocanu J. D. , Moriyama E. H. , Chia M. C. , Li J.-H. , Yip K. W. , Huang D. P. , Bastianutto C. , Wilson B. C. , Liu F.-F.
Published: March 2018

Nasopharyngeal carcinoma is intimately associated with the Epstein-Barr virus (EBV), which we have exploited therapeutically by constructing an EBV-specific synthetic enhancer sequence, within an adenoviral vector, denoted as adv.oriP. The achievement of tumor targeting provides therapeutic potential when delivered systemically, which could impact on distant metastases. We demonstrate here the feasibility and potential utility of combined, minimally invasive in vivo bioluminescence and fluorescence imaging to monitor adenoviral infection of subcutaneous C666-1 nasopharyngeal xenograft tumors stably expressing the DsRed2 gene. Fluorescence imaging was used to monitor the location and size of the C666-1. DsRed2 tumors, whereas bioluminescence imaging demonstrated the distribution and specificity of a transcriptionally targeted adenoviral vector, adv.oriP. fluc, expressing the firefly luciferase gene. Fluorescence, bioluminescence, and photographic images were aligned using grids to examine co-localization of adenovirus and tumors. Bioluminescence and fluorescence co-localized in 92% (11/12) of tumors at 24 hr and 100% (12/12) at 96 hr after adv.oriP. fluc (109 ifu) was administered intravenously. Nonspecific luciferase signal was detected in the liver area. The combined imaging was therefore successful in monitoring the uptake of systemically administered adenovirus in implanted tumors. This may ultimately lead to an effective noninvasive method to monitor the response of metastases to adenoviral gene therapy.
3-D Image Analysis of Fluorescent Drug Binding
Authors: Miquel M. Raquel , Segura Venessa , Ali Z. , D'Ocon M. P. , McGrath J. C. , Daly Craig J.
Published: March 2018

Fluorescent ligands provide the means of studying receptors in whole tissues using confocal laser scanning microscopy and have advantages over antibody- or non-fluorescence-based method. Confocal microscopy provides large volumes of images to be measured. Histogram analysis of 3-D image volumes is proposed as a method of graphically displaying large amounts of volumetric image data to be quickly analyzed and compared. The fluorescent ligand BODIPY FL-prazosin (QAPB) was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor binding under different conditions and the technique is sensitive enough to detect changes in receptor availability after antagonist incubation or genetic manipulations. QAPB binding was concentration dependent, causing concentration-related rightward shifts in the histogram. In the presence of 10 μM phenoxybenzamine (blocking agent), the QAPB (50 nM) histogram overlaps the autofluorescence curve. The histogram obtained for the 1D knockout aorta lay to the left of that of control and 1B knockout aorta, indicating a reduction in 1D receptors. We have shown, for the first time, that it is possible to graphically display binding of a fluorescent drug to a biological tissue. Although our application is specific to adrenergic receptors, the general method could be applied to any volumetric, fluorescence-image-based assay.
hNIS-IRES-eGFP Dual Reporter Gene Imaging
Authors: Che Jiantu , Doubrovin Mikhail , Serganova Inna , Ageyeva Ludmila , Zanzonico Pat , Blasberg Ronald
Published: March 2018

The human and rodent sodium iodide symporters ( NIS) have recently been cloned and are being investigated as potential therapeutic and reporter genes. We have extended this effort by constructing an internal ribosomal entry site (IRES)-linked human NIS (hNIS)-enhanced green fluorescent protein ( eGFP) hybrid reporter gene for both nuclear and optical imaging. A self-inactivating retroviral vector, termed pQCNIG, containing hNIS-IRES-eGFP dual reporter gene, driven by a constitutive CMV promoter, was constructed and used to generate RG2-pQCNIG cells and RG2-pQCNIG tumors. 131I-iodide and 99mTcO4-pertechnetate accumulation studies plus fluorescence microscopy and intensity assays were performed in vitro, and gamma camera imaging studies in RG2-pQCNIG and RG2 tumor-bearing athymic rats were performed. RG2-pQCNIG cells expressed high levels of hNIS protein and showed high intensity of eGFP fluorescence compared with RG2 wild-type cells. RG2-pQCNIG cells accumulated Na131I and 99mTcO4– to a 50:1 and a 170:1 tissue/medium ratio at 10 min, compared with 0.8:1.2 tissue/medium ratio in wild-type RG2 cells. A significant correlation between radiotracer accumulation and eGFP fluorescence intensity was demonstrated. RG2-pQCNIG and RG2 tumors were readily differentiated by in vivo gamma camera imaging; radiotracer uptake increased in RG2-pQCNIG but declined in RG2 tumors over the 50-min imaging period. Stomach and thyroid were the major organs of radionuclide accumulation. The IRES-linked hNIS-eGFP dual reporter gene is functional and stable in transduced RG2-pQCNIG cells. Optical and nuclear imaging of tumors produced from these cell lines provides the opportunity to monitor tumor growth and response to therapy. These studies indicate the potential for a wider application of hNIS reporter imaging and translation into patient studies using radioisotopes that are currently available for human use for both SPECT and PET imaging.
Detection of Dysplastic Intestinal Adenomas Using a Fluorescent Folate Imaging Probe
Authors: Chen Wei-Tsung , Khazaie Khashayarsha , Zhang Guoying , Weissleder Ralph , Tung Ching-Hsuan
Published: March 2018

Macrophages have long been recognized as a prominent component of tumors. Activated macrophages overexpress folate receptors and we used this phenomenon to image inflammatory reactions in colon dysplasia using a fluorescent folate probe (FFP). APCΔ468 mice injected with FFP showed fluorescent adenomas (target-to-background ratio, adenoma vs. adjacent normal mucosa, of 2.46 ± 0.41), significantly higher ( p < .001) than adenomas in animals injected with a non-folate-containing control probe. Fluorescence-activated cell-sorting analysis revealed a 3-fold higher content of Mac1-positive cells in colonic adenomas compared with normal adjacent mucosa (6.8% vs. 2.2%), and confirmed the source of FFP-positive cells to be primarily an F4/80-positive macrophage subpopulation. Taken together, these results indicate that FFP potentially can be used to image dysplastic intestinal adenomas in vivo.
Optical Imaging of Tumor Hypoxia and Evaluation of Efficacy of a Hypoxia-Targeting Drug in Living Animals
Authors: Harada Hiroshi , Kizaka-Kondoh Shinae , Hiraoka Masahiro
Published: March 2018

Solid tumors containing more hypoxic regions show a more malignant phenotype by increasing the expression of genes encoding angiogenic and metastatic factors. Hypoxia-inducible factor-1 (HIF-1) is a master transcriptional activator of such genes, and thus, imaging and targeting hypoxic tumor cells where HIF-1 is active are important in cancer therapy. In the present study, HIF-1 activity was monitored via an optical in vivo imaging system by using a luciferase reporter gene under the regulation of an artificial HIF-1-dependent promoter, 5HRE. To monitor tumor hypoxia, we isolated a stable reporter-transfectant, HeLa/5HRE-Luc, which expressed more than 100-fold luciferase in response to hypoxic stress, and observed bioluminescence from its xenografts. Immunohistochemical analysis of the xenografts with a hypoxia marker, pimonidazole, confirmed that the luciferase-expressing cells were hypoxic. Evaluation of the efficacy of a hypoxia-targeting prodrug, TOP3, using this optical imaging system revealed that hypoxic cells were significantly diminished by TOP3 treatment. Immunohistochemical analysis of the TOP3-treated xenografts confirmed that hypoxic cells underwent apoptosis and were removed after TOP3 treatment. These results demonstrate that this model system using the 5HRE-luciferase reporter construct provides qualitative information (hypoxic status) of solid tumors and enables one to conveniently evaluate the efficacy of cancer therapy on hypoxia in malignant solid tumors.
Meeting Report: High-Throughput Technologies for In Vivo Imaging Agents
Authors: Gillies Robert J. , Hoffman John M. , Lam Kit S. , Menkens Anne E. , Piwnica-Worms David R. , Sullivan Daniel C. , Weissleder Ralph
Published: March 2018

Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo imaging agents. Important differences in the biological and pharmacological properties needed for imaging agents, compared to those for a therapeutic agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good imaging agent candidate.
Glucose Metabolism of Human Prostate Cancer Mouse Xenografts
Authors: Jadvar Hossein , Li Xiankui , Shahinian Antranik , Park Ryan , Tohme Michel , Pinski Jacek , Conti Peter S.
Published: March 2018

We hypothesized that the glucose metabolism of prostate cancer is modulated by androgen. We performed in vivo biodistribution and imaging studies of [F-18] fluorodeoxyglucose (FDG) accumulation in androgen-sensitive (CWR-22) and androgen-independent (PC-3) human prostate cancer xenografts implanted in castrated and noncastrated male athymic mice. The growth pattern of the CWR-22 tumor was best approximated by an exponential function (tumor size in mm3 = 14.913 e0.108 × days, R2 = .96, n = 5). The growth pattern of the PC-3 tumor was best approximated by a quadratic function (tumor size in mm3 = 0.3511 × days2 + 49.418 × day −753.33, R2 = .96, n = 3). The FDG accumulation in the CWR-22 tumor implanted in the castrated mice was significantly lower, by an average of 55%, in comparison to that implanted in the noncastrated host (1.27 vs. 2.83, respectively, p < .05). The 3-week maximal standardized uptake value (SUVmax) was 0.99 ± 0.43 (mean ± SD) for CWR-22 and 1.21 ± 0.32 for PC-3, respectively. The 5-week SUVmax was 1.22 ± 0.08 for CWR-22 and 1.35 ± 0.17 for PC-3, respectively. The background muscle SUVmax was 0.53 ± 0.11. Glucose metabolism was higher in the PC-3 tumor than in the CWR-22 tumor at both the 3-week (by 18%) and the 5-week (by 9.6%) micro-PET imaging sessions. Our results support the notions that FDG PET may be useful in the imaging evaluation of response to androgen ablation therapy and in the early prediction of hormone refractoriness in men with metastatic prostate cancer.
Organic Alternatives to Quantum Dots for Intraoperative Near-Infrared Fluorescent Sentinel Lymph Node Mapping
Authors: Ohnishi Shunsuke , Lomnes Stephen J. , Laurence Rita G. , Gogbashian Andrew , Mariani Giuliano , Frangioni John V.
Published: March 2018

Intraoperative near-infrared (NIR) fluorescence imaging provides the surgeon with real-time image guidance during cancer and other surgeries. We have previously reported the use of NIR fluorescent quantum dots (QDs) for sentinel lymph node (SLN) mapping. However, because of concerns over potential toxicity, organic alternatives to QDs will be required for initial clinical studies. We describe a family of 800 nm organic heptamethine indocyanine-based contrast agents for SLN mapping spanning a spectrum from 775 Da small molecules to 7 MDa nanocolloids. We provide a detailed characterization of the optical and physical properties of these contrast agents and discuss the advantages and disadvantages of each. We present robust methods for the covalent conjugation, purification, and characterization of proteins with tetra-sulfonated heptamethine indocyanines, including mass spectroscopic site mapping of highly substituted molecules. One contrast agent, NIR fluorescent human serum albumin (HSA800), emerged as the molecule with the best overall performance with respect to entry to lymphatics, flow to the SLN, retention in the SLN, fluorescence yield and reproducibility. This preclinical study, performed on large animals approaching the size of humans, should serve as a foundation for future clinical studies.
Cellular MR Imaging
Authors: Modo Michel , Hoehn Mathias , Bulte Jeff W.M.
Published: March 2018

Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall) superparamagnetic iron oxide [(U)SPIO] particles or (polymeric) paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (U)SPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune) cell trafficking and of novel guided (stem) cell-based therapies aimed to be translated to the clinic in the future.
Taxonomic review of the Sinopoda okinawana-group (Araneae: Sparassidae) in China
Authors: ZHONG YANG , JÄGER PETER , CHEN JIAN , LIU JIE
Published: March 2018

Five Sinopoda species in the okinawana-group including one new species from central and south-western China are treated in the current paper: S. cochlearia Zhang, Zhang & Zhang, 2015, S. fasciculata Jäger, Gao & Fei, 2002, S. guangyuanensis sp. nov., S. hamata (Fox, 1937) and S. wangi Song & Zhu, 1999. The female of S. fasciculata is described for the first time. New province records are provided as well as photos of copulatory organs and habitus.
Using Equatorial Pacific Sea Surface Temperature Anomalies to Forecast Seasonal Energy Demand in Four U.S. Regions: An Applied Climate Research Experience for Undergraduate Meteorology Students
Authors: Russo Mark , Changnon David , Podolak Mike , Freestrom Hugh , Davis Jon B.
Published: March 2018

The El Niño-Southern Oscillation (ENSO) phenomenon explains some of the interannual climate variability in many tropical and midlatitude regions. It is important in developing more accurate seasonal climate forecasts and thus in aiding long-range weather-sensitive decision making in various sectors.

The degree to which ENSO information could forecast one of three classes of seasonal cooling degree days (CDD) and heating degree days (HDD) was examined using 1) the magnitude of the ENSO event during a given season, 2) the preseason rate of change of sea surface temperature (SSTs) (December–May for summers and June–October for winters), and 3) the effects of strong winter ENSO events on future seasons. All three ENSO-related indices were based on monthly equatorial Pacific SST anomalies in the Niño-3.4 region. Regional probabilities of each HDD/CDD category (above, average, and below) were determined for each ENSO predictive index. The highest probability of experiencing an HDD/CDD anomaly occurs with strong preseason SST trends. When presummer SST cooling occurs, the northeast and midcontinent experience above-average CDD (80% and 75%, respectively). Other interesting relationships were found between strong winter ENSO events and ensuing HDD/CDD anomalies. These results suggest that utility-based decision makers who can utilize enhanced climate information may reap benefits during particular years by integrating the ENSO information into their models. This study was part of a special student training experiment conducted at Northern Illinois University.
Patterns of Climate Extremes in the Coastal and Highland Regions of Balochistan, Pakistan
Authors: Abbas Farhat , Sarwar Nida , Ibrahim Muhammad , Adrees Muhammad , Ali Shafaqat , Saleem Farhan , Hammad Hafiz Mohkum
Published: March 2018

Climatic extremes have direct and indirect effects on an ecosystem, whereby thermal variations bring warm and cold weather, and hydrological anomalies cause droughts and floods. Changing patterns of 13 temperature and 11 precipitation extreme indices for a 36-yr period (1980–2015) for four cities of the Balochistan province of Pakistan (Pasni, Jiwani, Khuzdar, and Dalbadin) were computed using RClimdex. A nonparametric Mann–Kendall test and Sen’s slope estimates were used to determine the statistical significance and magnitude of a trend, respectively. Most of the indices calculated for temperature extremes show statistically significant changes in their historic pattern, depicting a clear picture of warming in the regions. The indices calculated for precipitation extremes show statistically significant as well as nonsignificant results, depicting asymmetrical droughts in the region. If the patterns of humid weather with hot and wet extremes in the coastal cities of Balochistan continue for a couple of future decades, there will be challenges in implementing the multibillion-dollar Balochistan coastal development projects of the Pakistani port of Gwadar—a doorway to the Middle East for Chinese-planned business endeavors through Pakistan.
Investigating the Scale Adaptivity of a Size-Filtered Mass Flux Parameterization in the Gray Zone of Shallow Cumulus Convection
Authors: Brast Maren , Schemann Vera , Neggers Roel A. J.
Published: March 2018

In this study, the scale adaptivity of a new parameterization scheme for shallow cumulus clouds in the gray zone is investigated. The eddy diffusivity/multiple mass flux [ED(MF)n] scheme is a bin-macrophysics scheme in which subgrid transport is formulated in terms of discretized size densities. While scale adaptivity in the ED component is achieved using a pragmatic blending approach, the MF component is filtered such that only the transport by plumes smaller than the grid size is maintained. For testing, ED(MF)n is implemented into a large-eddy simulation (LES) model, replacing the original subgrid scheme for turbulent transport. LES thus plays the role of a nonhydrostatic testing ground, which can be run at different resolutions to study the behavior of the parameterization scheme in the boundary layer gray zone. In this range, convective cumulus clouds are partially resolved. The authors find that for quasi-equilibrium marine subtropical conditions at high resolutions, the clouds and the turbulent transport are predominantly resolved by the LES. This partitioning changes toward coarser resolutions, with the representation of shallow cumulus clouds gradually becoming completely carried by the ED(MF)n. The way the partitioning changes with grid spacing matches the behavior diagnosed in coarse-grained LES fields, suggesting that some scale adaptivity is captured. Sensitivity studies show that the scale adaptivity of the ED closure is important and that the location of the gray zone is found to be moderately sensitive to some model constants.
From Wall 1.0 to Wall 2.0: Graffiti, Social Media, and Ideological Acts of Resistance and Recognition Among Palestinian Refugees
Authors: Li Eric Ping Hung , Prasad Ajnesh
Published: March 2018

Writing as an ideological act of resistance and recognition among members of the socially disenfranchised has been engaged with in myriad contested political and cultural terrains. Historically, for Palestinian refugees living under conditions of Israeli occupation, expressions of resistance and recognition were visually and textually inscribed through provocative displays of graffiti on the very separatist wall erected by their occupiers. More recently, however, these acts have been (re)articulated through various forms of social media. We capture this phenomenon as being one dimension of transmedia storytelling, and specifically as a consolidation of, what we are calling here, Wall 1.0 and Wall 2.0. We argue that this consolidation has engendered significant implications for how ideological acts of resistance and recognition among disempowered subjects ought to be conceptualized. Indeed, this consolidation marks a necessary move in the contest over place from geographically constrained physical spaces to spreadable and editable digital spaces. In terms of theoretical contribution, it has illuminated how discursive political claims are transitioning from a state of temporality and attributed ownership to a state of permanence and coproduction.
Prevention of Radial Artery Occlusions Following Coronary Procedures: Forward and Backward Steps in Improving Radial Artery Patency Rates
Authors: Hahalis George , Tsigkas Grigorios , Kounis Nikos , Patsilinakos Sotirios , Kafkas Nikolaos , Ziakas Antonios , Patsourakos Nikolaos , Almpanis George , Koniari Ioanna , Xanthopoulou Ioanna , Koutsogiannis Nikolaos , Despotopoulos Stefanos , Leopoulou Marianna , Tassi Vasiliky , Miliordos Ioannis , Anastasopoulou Maria , Roumeliotis Anastasios , Dapergola Athina , Aznaouridis Konstantinos , Chatzis Dimitrios , Davlouros Periklis
Published: March 2018

Radial artery (RA) occlusion (RAO) remains the Achilles heel of transradial coronary procedures. Although of silent nature, RAO is relatively frequent, results in graft shortage for future coronary artery bypass surgery, and may occur even after short-lasting, 5F coronary angiography (CAG). The most frequent predictors of RAO are RA size, body size, female gender, and periprocedural anticoagulation intensity. Methods to detect RAO are variable, of which the Barbeau test and ultrasonography have similar diagnostic accuracy. Data indicate that late RAO recanalization may occur. Meticulous handling of RA and the use of appropriate hemostatic devices and techniques along with sufficient heparin dose appear important measures to reduce RAO rates. Recent contradictory studies indicate that the decreasing incidence of RAO overtime is not as uniform as previously thought. In 2 meta-analyses, the benefit of higher over lower anticoagulation intensity became evident. As “it may all be appropriate anticoagulation” for a simplified approach against RAO, the results of an ongoing trial comparing 100 with 50 IU/kg body weight in transradial CAG are eagerly awaited.
Self-authorship and creative industries workers’ career decision-making
Authors: Bennett Dawn , Hennekam Sophie
Published: March 2018

Career decision-making is arguably at its most complex within professions where work is precarious and career calling is strong. This article reports from a study that examined the career decision-making of creative industries workers, for whom career decisions can impact psychological well-being and identity just as much as they impact individuals’ work and career. The respondents were 693 creative industries workers who used a largely open-ended survey to create in-depth reflections on formative moments and career decision-making. Analysis involved the theoretical model of self-authorship, which provides a way of understanding how people employ their sense of self to make meaning of their experiences. The self-authorship process emerged as a complex, non-linear and consistent feature of career decision-making. Theoretical contributions include a non-linear view of self-authorship that exposes the authorship of visible and covert multiple selves prompted by both proactive and reactive identity work.
Did the Individual Consent to the Risk of Harm? A Comparative Jurisdictional Analysis of Consent in Cases of Sexual Transmission/Exposure to HIV
Authors: Hughes David
Published: March 2018

This article considers the necessary ingredients for an individual to consent to running the risk of the HIV virus being transmitted through high-risk unprotected sexual intercourse. In order to achieve this aim, an assessment of what should equate to a fully informed consent is evaluated. The article will provide a comparative jurisdictional analysis of the consent requirement in three particularised jurisdictions: England, Canada and the USA. A comparison of relational judicial precepts will follow the discussion of extant law in each country. It will be established that few jurisdictions fully consider the requirements of a fully informed consent. The final part of the article will suggest a bespoke new legislative framework that will account for the circumstances that are necessary for an individual to provide a fully informed consent to the risk of acquiring the virus.
New Breast Cancer Radiotherapy Technology Confers Higher Complications and Costs Before Effectiveness Proven: A Medicare Data Analysis
Authors: Gold Heather T. , Walter Dawn , Tousimis Eleni , Hayes Mary Katherine
Published: March 2018

A new breast cancer treatment, brachytherapy-based accelerated partial breast radiotherapy (RT), was adopted before long-term effectiveness evidence, potentially increasing morbidity and costs compared with whole breast RT. The aim of this study was to estimate complication rates and RT-specific and 1-year costs for a cohort of female Medicare beneficiaries diagnosed with breast cancer (N = 47 969). We analyzed 2005-2007 Medicare claims using multivariable logistic regression for complications and generalized linear models (log link, gamma distribution) for costs. Overall, 11% (n = 5296) underwent brachytherapy-based RT; 9.4% had complications. Odds of any complication were higher (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.49-1.76) for brachytherapy versus whole breast RT, similarly to seroma (OR: 2.85; 95% CI: 1.97-4.13), wound complication/infection (OR: 1.72; 95% CI: 1.52-1.95), cellulitis (OR: 1.48; 95% CI: 1.27-1.73), and necrosis (OR: 2.07; 95% CI: 1.55-2.75). Mean RT-specific and 1-year total costs for whole breast RT were $6375, and $19 917, $4886, and $4803 lower than brachytherapy ( P < .0001). Multivariable analyses indicated brachytherapy yielded 76% higher RT costs (risk ratio: 1.76; 95% CI: 1.74-1.78, P < .0001) compared with whole breast RT. Brachytherapy had higher complications and costs before long-term evidence proved its effectiveness. Policies should require treatment registries with reimbursement incentives to capture surveillance data for new technologies.
The Economy, the News, and the Public: A Longitudinal Study of the Impact of Economic News on Economic Evaluations and Expectations
Authors: Damstra Alyt , Boukes Mark
Published: March 2018

This article studies the tripartite relationship between the economy, economic news, and public economic perceptions. Our analysis is twofold: We investigate the impact of the real economy on economic news in Dutch newspapers (2002-2015, N = 127,120); second, we analyze the impact of economic news on public economic perceptions. Our empirical approach builds on and contributes to the literature by making nuanced distinctions between (a) economic levels and changes (positive/negative), (b) volume and tone of coverage (positive/negative), and, most importantly, (c) people’s retrospective and prospective economic judgments. Our analyses show that the public is presented a version of economic reality that is skewed to the negative, which strongly affects people’s economic expectations but not evaluations. Extending media-dependency theory, these results demonstrate the necessity to both conceptually and empirically distinguish between people’s retrospective and prospective judgments.
Information, Knowledge, and the Return of Social Physics
Authors: Adolf Marian T. , Stehr Nico
Published: March 2018

The article discusses two vital aspects of the current debate about the societal importance and future role of data, information, and knowledge in the context of social organization, administration, and government. First, it is argued that the debate concerning Big Data suffers from faulty assumptions regarding the societal significance and power of information which needs to be extended to a more comprehensive investigation about the social role of knowledge. Second, the theoretical positions brought forward are illustrated by revisiting an episode from the early history of the social sciences, arguing that misguided ideas about the possibility of “Social Physics” have failed before and are likely to fail again, due to the complexity of social behavior.
Postacquisition Boundary Spanning: A Relational Perspective on Integration
Authors: Colman Helene Loe , Rouzies Audrey
Published: March 2018

Through a longitudinal, qualitative study, we explore how preexisting embedded relationships shape boundary-spanning actions in the postacquisition integration process. We examine the role of union representatives in the integration process and find that in our case, they are significant boundary spanners. They share knowledge, promote the acquisition, and mitigate conflicts both within and between the merging organizations. Their intra- and interorganizational preacquisition relationships are the contingencies for their boundary-spanning actions. Our study makes several contributions to the literature. First, we show how a set of actors, mostly ignored by the mergers and acquisitions literature, can play a key facilitating role in the integration process. Second, we extend the understanding of the autonomy-integration dilemma in the postacquisition integration literature by conceptualizing preexisting relationships as precursors to postacquisition boundary spanning. Third, we challenge the classical conception of relational inertia as a path-dependent hindrance by showing that preexisting relationships can be leveraged to facilitate postacquisition integration. Finally, we contribute to the boundary-spanning literature by identifying the nature of embedded preacquisition relationships as an important contingency to boundary-spanning actions in interorganizational encounters.
DISC: Disambiguating homonyms using graph structural clustering
Authors: Hussain Ijaz , Asghar Sohail
Published: March 2018

Author name ambiguity degrades information retrieval, database integration, search results and, more importantly, correct attributions in bibliographic databases. Some unresolved issues include how to ascertain the actual number of authors, how to improve the performance and how to make the method more effective in terms of representative clustering metrics (average cluster purity, average author purity, K-metric, pairwise precision, pairwise recall, pairwise-F1, cluster precision, cluster recall and cluster-F1). It is a non-trivial task to disambiguate authors using only the implicit bibliographic information. An effective method ‘DISC’ is proposed that uses graph community detection algorithm, feature vectors and graph operations to disambiguate homonyms. The citation data set is pre-processed and ambiguous author blocks are formed. A co-authors graph is constructed using authors and their co-author’s relationships. A graph structural clustering ‘gSkeletonClu’ is applied to identify hubs, outliers and clusters of nodes in a co-author’s graph. Homonyms are resolved by splitting these clusters of nodes across the hub if their feature vector similarity is less than a predefined threshold. DISC utilises only co-authors and titles that are available in almost all bibliographic databases. With little modifications, DISC can also be used for entity disambiguation. To validate the DISC performance, experiments are performed on two Arnetminer data sets and compared with five previous unsupervised methods. Despite using limited bibliographic metadata, DISC achieves on average K-metric, pairwise-F1, and cluster-F1 of 92%, 84% and 74%, respectively, using Arnetminer-S and 86%, 80% and 57%, respectively, using Arnetminer-L. About 77.5% and 73.2% clusters are within the range (ground truth clusters ± 3) in Arnetminer-S and Arnetminer-L, respectively.
Comprehensive Overview of the Problem of Violence Against Athletes in Sport
Authors: Parent Sylvie , Fortier Kristine
Published: March 2018

The problem of violence against athletes is of growing concern. However, the scientific literature in this field tends to be specific to certain forms of violence and does not always provide a clear portrayal of the problem. To better understand issues concerning violence against athletes in sport and to identify needs in this area of research, we must look at violence in a more inclusive way and see violence against athlete as a global problem. This article presents a comprehensive overview of the problem of interpersonal violence against athletes in the sport context. We discuss definitions of violence in sport through the lens of athletes’ victimization. We also look at the various manifestations of interpersonal violence against athletes, the perpetrators involved, the factors associated to the risk of victimization, and the possible consequences of this violence on the mental and physical health of athletes. Finally, future directions for research on this topic are discussed.
Understanding Short-run Stock Price Movements through System Dynamics
Authors: Srinivasan S , Mohapatra P K J , Sahu K C
Published: March 2018

The Capital Assets Pricing Model (CAPM) provides insights into the equilibrium price of stocks but does not offer a structural framework for short range price movements.

In this paper, Srinivasan, Mohapatra, and Sahu use the System Dynamics methodology and demonstrate through their model how short-run price movements can be explained. This model may be useful to finance managers who are concerned about the equity issue price for pricing new issues when they go to the capital market. It is also useful to financial institutions interested in buying and selling securities.

The authors exhort researchers to develop a unified model combining CAPM and the System Dynamics model to explain long-run and short-run price movements.