A Method for Neuronal Source Identification

Multi-sensor microelectrodes for extracellular action potential recording have significantly improved the quality of in vivo recorded neuronal signals. These microelectrodes have also been instrumental in the localization of neuronal signal sources. However, existing neuron localization methods have been mostly utilized in vivo, where the true neuron location remains unknown. Therefore, these methods could not be experimentally validated. This article presents experimental validation of a method capable of estimating both the location and intensity of an electrical signal source. A four-sensor microelectrode (tetrode) immersed in a saline solution was used to record stimulus patterns at multiple intensity levels generated by a stimulating electrode. The location of the tetrode was varied with respect to the stimulator. The location and intensity of the stimulator were estimated using the Multiple Signal Classification (MUSIC) algorithm, and the results were quantified by comparison to the true values. The localization results, with an accuracy and precision of ~ 10 microns, and ~ 11 microns respectively, imply that MUSIC can resolve individual neuronal sources. Similarly, source intensity estimations indicate that this approach can track changes in signal amplitude over time. Together, these results suggest that MUSIC can be used to characterize neuronal signal sources in vivo.Comment: 14 pages, 5 figure

The Spitzer c2d Survey of Nearby Dense Cores. V. Discovery of a VeLLO in the "Starless" Dense Core L328

This paper reports the discovery of a Very Low Luminosity Object (VeLLO) in the "starless" dense core L328, using the Spitzer Space Telescope and ground based observations from near-infrared to millimeter wavelengths. The Spitzer 8 micron image indicates that L328 consists of three subcores of which the smallest one may harbor a source, L328-IRS while two other subcores remain starless. L328-IRS is a Class 0 protostar according to its bolometric temperature (44 K) and the high fraction ~72 % of its luminosity emitted at sub-millimeter wavelengths. Its inferred "internal luminosity" (0.04 - 0.06 Lsun) using a radiative transfer model under the most plausible assumption of its distance as 200 pc is much fainter than for a typical protostar, and even fainter than other VeLLOs studied previously. Note, however, that its inferred luminosity may be uncertain by a factor of 2-3 if we consider two extreme values of the distance of L328-IRS (125 or 310 pc). Low angular resolution observations of CO do not show any clear evidence of a molecular outflow activity. But broad line widths toward L328, and Spitzer and near-infrared images showing nebulosity possibly tracing an outflow cavity, strongly suggest the existence of outflow activity. Provided that an envelope of at most ~0.1 Msunis the only mass accretion reservoir for L328-IRS, and the star formation efficiency is close to the canonical value ~30%, L328-IRS has not yet accreted more than 0.05 Msun. At the assumed distance of 200 pc, L328-IRS is destined to be a brown dwarf.Comment: 29 pages, 8 figures, 1 table, to be published in Astrophysical Journa

Periampullary Diverticulum Perforation Following Endoscopic Retrograde Cholangiopancreatography (ERCP); a Case Report

Endoscopic Retrograde Cholangiopancreatography (ERCP) is widely used for the diagnosis and treatment of biliary and pancreatic tract disease. Perforation is a rare complication of it, but it is associated with high rate of mortality, an overall mortality rate of 1.0-1.5%. Here, a case of massive subcutaneous emphysema following ERCP was reported without an obvious retroperitoneal or peritoneal perforation

Troubleshooting Arterial-Phase MR Images of Gadoxetate Disodium-Enhanced Liver.

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking

Schr\"{o}dinger Fields on the Plane with non-Abelian Chern-Simons Interactions

Physical content of the nonrelativistic quantum field theory with non-Abelian Chern-Simons interactions is clarified with the help of the equivalent first- quantized description which we derive in any physical gauge.Comment: 12 pages, LaTex, SNUTP 94-1

Allogeneic mesenchymal stromal cells overexpressing mutant human Hypoxia-inducible factor 1-α (HIF1-α) in an ovine model of acute myocardial infarction

Background-Bone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-α (HIF1-α), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-α would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. Methods and Results-Allogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-α (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7±1.3% (P < 0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P < 0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-α-transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF. Conclusions-Intramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic.Fil: Hnatiuk, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Ong, Sang-Ging. Stanford University School of Medicine; Estados UnidosFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Riegler, Johannes. Stanford University School of Medicine; Estados UnidosFil: Lee, Won Hee. Stanford University School of Medicine; Estados UnidosFil: Jen, Cheng Hao. University of London; Reino UnidoFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Laguens, Rubén. Universidad Favaloro; ArgentinaFil: Wu, Joseph C.. Stanford University School of Medicine; Estados UnidosFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate.

Recent genome analysis of human prostate cancers demonstrated that both AR gene amplification and TP53 mutation are among the most frequently observed alterations in advanced prostate cancer. However, the biological role of these dual genetic alterations in prostate tumorigenesis is largely unknown. In addition, there are no biologically relevant models that can be used to assess the molecular mechanisms for these genetic abnormalities. Here, we report a novel mouse model, in which elevated transgenic AR expression and Trp53 deletion occur simultaneously in mouse prostatic epithelium to mimic human prostate cancer cells. These compound mice developed an earlier onset of high-grade prostatic intraepithelial neoplasia and accelerated prostate tumors in comparison with mice harboring only the AR transgene. Histological analysis showed prostatic sarcomatoid and basaloid carcinomas with massive squamous differentiation in the above compound mice. RNA-sequencing analyses identified a robust enrichment of the signature genes for human prostatic basal cell carcinomas in the above prostate tumors. Master regulator analysis revealed SOX2 as a transcriptional regulator in prostatic basal cell tumors. Elevated expression of SOX2 and its downstream target genes were detected in prostatic tumors of the compound mice. Chromatin immunoprecipitation analyses implicate a coregulatory role of AR and SOX2 in the expression of prostatic basal cell signature genes. Our data demonstrate a critical role of SOX2 in prostate tumorigenesis and provide mechanistic insight into prostate tumor aggressiveness and progression mediated by aberrant AR and p53 signaling pathways

Source-Frequency Phase-Referencing Observation of AGNs with KaVA Using Simultaneous Dual-Frequency Receiving

The KVN(Korean VLBI Network)-style simultaneous multi-frequency receiving mode is demonstrated to be promising for mm-VLBI observations. Recently, other Very long baseline interferometry (VLBI) facilities all over the globe start to implement compatible optics systems. Simultaneous dual/multi-frequency VLBI observations at mm wavelengths with international baselines are thus possible. In this paper, we present the results from the first successful simultaneous 22/43 GHz dual-frequency observation with KaVA(KVN and VERA array), including images and astrometric results. Our analysis shows that the newly implemented simultaneous receiving system has brought a significant extension of the coherence time of the 43 GHz visibility phases along the international baselines. The astrometric results obtained with KaVA are consistent with those obtained with the independent analysis of the KVN data. Our results thus confirm the good performance of the simultaneous receiving systems for the non-KVN stations. Future simultaneous observations with more global stations bring even higher sensitivity and micro-arcsecond level astrometric measurements of the targets.Comment: 8 pages, 6 figures, Published in JKA