The expression and function of midkine in the vertebrate retina

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102704/1/bph12495.pd

Atomic Carbon and CO Isotope Emission in the Vicinity of DR15

We present observations of the 3P1-3P0 fine structure transition of atomic carbon [CI], the J=3-2 transition of CO, as well as of the J=1-0 transitions of 13CO and C18O toward DR15, an HII region associated with two mid-infrared dark clouds (IRDCs). The 13CO and C18O J=1-0 emissions closely follow the dark patches seen in optical wavelength, showing two self-gravitating molecular cores with masses of 2000 Msun and 900 Msun, respectively, at the positions of the catalogued IRDCs. Our data show a rough spatial correlation between [CI] and 13CO J=1-0. Bright [CI] emission occurs in relatively cold gas behind the molecular cores, neither in highly excited gas traced by CO J=3-2 emission nor in HII region/molecular cloud interface. These results are inconsistent with those predicted by standard photodissociation region (PDR) models, suggesting an origin for interstellar atomic carbon unrelated to photodissociation processes.Comment: 11 pages Latex, 6 figures, Accepted for publication in The Astrophysical Journa

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Background TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. Trial registration EU-CTR 2009-012097-12 2009-09-0

Large-scale mapping observations of the CI(3P1-3P0) and CO(J=3-2) lines toward the Orion A molecular cloud

Large scale mapping observations of the 3P1-3P0 fine structure transition of atomic carbon (CI, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mt. Fuji submillimeter-wave telescope. The observations cover 9 square degrees, and include the Orion nebula M42 and the L1641 dark cloud complex. The CI emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO(J=1-0).The CO(J=3-2) emission shows a more featureless and extended distribution than CI.The CI/CO(J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the CI/13CO(J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the CI and 13CO(J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.Comment: Text file is 13 pages long, and 3 figure files (pdf format). NRO Report No. 508 (1999). University of Tokyo, Resceu 41/9

Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Equation of DNB Heat Flux for Upward Forced Flow of Cryogenic Liquids

Superconductivity Centennial Conference, SCC 2011 ; 18 September 2011 through 23 September 2011Knowledge of departure from nucleate boiling (DNB) heat flux is important for design of superconducting systems cooled by cryogenic liquids. We have already presented the equation of DNB heat flux that can describe the experimental data of liquid hydrogen. To see the applicability of the equation to other cryogenic liquids, similar heat transfer tests in forced flow of liquid nitrogen are performed for wide ranges of conditions in this work. It was confirmed that the DNB heat flux equation derived by the authors can express not only the data for liquid hydrogen but also those for liquid nitrogen

Regulation of Pathologic Retinal Angiogenesis in Mice and Inhibition of VEGF-VEGFR2 Binding by Soluble Heparan Sulfate

Development of the retinal vascular network is strictly confined within the neuronal retina, allowing the intraocular media to be optically transparent. However, in retinal ischemia, pro-angiogenic factors (including vascular endothelial growth factor-A, VEGF-A) induce aberrant guidance of retinal vessels into the vitreous. Here, we show that the soluble heparan sulfate level in murine intraocular fluid is high particularly during ocular development. When the eyes of young mice with retinal ischemia were treated with heparan sulfate-degrading enzyme, the subsequent aberrant angiogenesis was greatly enhanced compared to PBS-injected contralateral eyes; however, increased angiogenesis was completely antagonized by simultaneous injection of heparin. Intraocular injection of heparan sulfate or heparin alone in these eyes resulted in reduced neovascularization. In cell cultures, the porcine ocular fluid suppressed the dose-dependent proliferation of human umbilical vein endothelial cells (HUVECs) mediated by VEGF-A. Ocular fluid and heparin also inhibited the migration and tube formation by these cells. The binding of VEGF-A and HUVECs was reduced under a high concentration of heparin or ocular fluid compared to lower concentrations of heparin. In vitro assays demonstrated that the ocular fluid or soluble heparan sulfate or heparin inhibited the binding of VEGF-A and immobilized heparin or VEGF receptor 2 but not VEGF receptor 1. The recognition that the high concentration of soluble heparan sulfate in the ocular fluid allows it to serve as an endogenous inhibitor of aberrant retinal vascular growth provides a platform for modulating heparan sulfate/heparin levels to regulate angiogenesis

Liquid Hydrogen Recirculation System for Forced Flow Cooling Test of Superconducting Conductors

Advances in Cryogenic Engineering: Proceedings of the Cryogenic Engineering Conference (CEC) 2017 (previous edition: CEC-2015). 9–13 July 2017, Madison, Wisconsin, USA.The knowledge of forced flow heat transfer characteristics of liquid hydrogen (LH₂) is important and necessary for design and cooling analysis of high critical temperature superconducting devices. However, there are few test facilities available for LH₂forced flow cooling for superconductors. A test system to provide a LH₂forced flow (∼10 m/s) of a short period (less than 100 s) has been developed. The test system was composed of two LH₂tanks connected by a transfer line with a controllable valve, in which the forced flow rate and its period were limited by the storage capacity of tanks. In this paper, a liquid hydrogen recirculation system, which was designed and fabricated in order to study characteristics of superconducting cables in a stable forced flow of liquid hydrogen for longer period, was described. This LH₂loop system consists of a centrifugal pump with dynamic gas bearings, a heat exchanger which is immersed in a liquid hydrogen tank, and a buffer tank where a test section (superconducting wires or cables) is set. The buffer tank has LHe cooled superconducting magnet which can produce an external magnetic field (up to 7T) at the test section. A performance test was conducted. The maximum flow rate was 43.7 g/s. The lowest temperature was 22.5 K. It was confirmed that the liquid hydrogen can stably circulate for 7 hours