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High-intensity laser–plasma interactions produce a wide array of energetic particles and beams with promising applications. Unfortunately, the high repetition rate and high average power requirements for many applications are not satisfied by the lasers, optics, targets, and diagnostics currently employed. Here, we aim to address the need for high-repetition-rate targets and optics through the use of liquids. A novel nozzle assembly is used to generate high-velocity, laminar-flowing liquid microjets which are compatible with a low-vacuum environment, generate little to no debris, and exhibit precise positional and dimensional tolerances. Jets, droplets, submicron-thick sheets, and other exotic configurations are characterized with pump–probe shadowgraphy to evaluate their use as targets. To demonstrate a high-repetition-rate, consumable, liquid optical element, we present a plasma mirror created by a submicron-thick liquid sheet. This plasma mirror provides etalon-like anti-reflection properties in the low field of 0.1% and high reflectivity as a plasma, 69%, at a repetition rate of 1 kHz. Practical considerations of fluid compatibility, in-vacuum operation, and estimates of maximum repetition rate are addressed. The targets and optics presented here demonstrate a potential technique for enabling the operation of laser–plasma interactions at high repetition rates.
OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common
primary tumor type in the central nervous system across all age groups; affected
adults have a life expectancy of just 14 months. As glioma cells invade the
surrounding normal parenchyma they remodel the composition and ultrastructure of
the surrounding extracellular matrix (ECM), suggesting that the native (i.e.,
“normal”) microenvironment is not ideal for their survival
and proliferation. Recent reports describe suppressive and/or lethal
effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources
upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic
tissue resection in humans have never been reported to facilitate cancer
recurrence. The objective of the present research is to evaluate mammalian ECM
as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM
hydrogels from porcine dermis, small intestine, and urinary bladder were
produced as described previously. Primary glioma cells were graciously supplied
by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through
ATCC. Cells were plated onto tissue culture plastic at
~60% confluence and allowed to attach for 24 hours before
treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing
lyophilized, comminuted ECM with 0.9% saline for 24 hours then
filtering the resulting mixture through a 10 kDa molecular weight cutoff column.
All assays and kits were followed according to the manufacturer’s
instructions. Cell viability was measured via MTT assay
(Vybrant® MTT Cell Proliferation Assay, Invitrogen)
and by live/dead staining
(LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time
lapse videos were created by taking images every 20 minutes for 18 hours
(phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent
was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo
work was conducted according to protocols approved by the University of
Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS:
ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder
all decreased the viability of primary glioma cells in vitro, with urinary
bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of
UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was
sufficient to recapitulate this detrimental effect upon neoplastic cells in
vitro and was used for the remainder of the experiments described herein. In a
cell viability assay normalized to the media treatment, non-neoplastic CHME5 and
N1E-115 cells scored 103% and 114% after 48 hours when
treated with UBM-SSF and 2 primary high-grade glioma cell types scored
17% and 30.5% with UBM-SSF (n=2).
Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of
UBM-SSF for 18 hours while most primary glioma cells shriveled and died within
this time. Darkfield time-lapse video of wells containing Nucview dye,
fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours
most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In
culture with primary astrocytes, high grade primary glioma cells, and U-87 MG
glioma cells for 24 hours, UBM-SSF was found to significantly increase the
population of primary astrocytes compared with media
(p<0.05) while decreasing the 2 glioma cell types to
approximately one-third as many cells as the media control
(p<0.0001). A dose-response of temozolomide from 0
to 10,000 μM showed that when treating 2 non-neoplastic cell types
(CHME5 and HFF) and 2 types of primary glioma cell there was no difference in
survivability at any concentration. Contrasted to this, a dose-response of
UBM-SSF from 350 to 7000 μg/mL showed that the
non-neoplastic cells survived significantly better than the glioma cells at
concentrations of 875 μg/mL and upward
(p<0.05). In preliminary animal experiments, large
primary glioma tumors in the flanks of athymic nude mice were resected and
replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell
origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth
if any compared with the dramatic recurrence seen in the Matrigel injection
sites (n=2). In a separate survival study comparing PBS to UBM-SSF
injections in the flank-resection model, all animals given PBS had to be
sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF
were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate
increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF
IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ
in 2005, the standard of care for patients with glioblastoma multiforme has not
improved. These findings indicate that non-neoplastic ECM contains potent
bioactive regulators capable of abrogating malignancy. Our in vitro data suggest
these molecules appear to have no deleterious effect on non-neoplastic cells
while specifically inducing apoptosis in glioma cells. Our in vivo data suggest
that these molecules may be useful in delaying glioma recurrence, thus resulting
in extended lifespan. Delivering soluble fractions of ECM to a tumor site may
represent a novel approach to glioma therapy, sidestepping traditional cytotoxic
therapies in favor of utilizing putative endogenous anti-tumor pathways.
During 2016 February, CSIRO Astronomy and Space Science and the Max-Planck-Institute for Radio Astronomy installed, commissioned, and carried out science observations with a phased array feed receiver system on the 64-m diameter Parkes radio telescope. Here, we demonstrate that the phased array feed can be used for pulsar observations and we highlight some unique capabilities. We demonstrate that the pulse profiles obtained using the phased array feed can be calibrated and that multiple pulsars can be simultaneously observed. Significantly, we find that an intrinsic polarisation leakage of −31 dB can be achieved with a phased array feed beam offset from the centre of the field of view. We discuss the possibilities for using a phased array feed for future pulsar observations and for searching for fast radio bursts with the Parkes and Effelsberg telescopes.
The purpose of this study was to dosimetrically compare TomoDirect, TomoHelical and linear accelerator-based 3D-conformal radiotherapy (Linac-3DCRT) for craniospinal irradiation (CSI) in the treatment of medulloblastoma.
Five CSI patients were replanned with Linac-3DCRT, TomoHelical, TomoDirect-3DCRT and TomoDirect-intensity-modulated radiotherapy (IMRT). Dose of 36 Gy in 20 fractions was prescribed to the planning target volume (PTV). Homogeneity index (HI), non-target integral dose (NTID), dose–volume histograms, organs-at-risk (OARs) Dmax, Dmean and treatment times were compared.
TomoHelical achieved the best PTV homogeneity compared with Linac-3DCRT, TomoDirect-3DCRT and TomoDirect-IMRT (HI of 3·6 versus 20·9, 8·7 and 9·4%, respectively). TomoDirect-IMRT achieved the lowest NTID compared with TomoDirect-3DCRT, TomoHelical and Linac-3DCRT (141 J versus 151 J, 181 J and 250 J), indicating least biological damage to normal tissues. TomoHelical plans achieved the lowest Dmax in all organs except the breasts, and lowest Dmean for most OARs, except in laterally situated OARs, where TomoDirect triumphed. Beam-on time was longest for TomoHelical, followed by TomoDirect and Linac-3DCRT.
TomoDirect has the potential to lower NTID and shorten treatment times compared with TomoHelical. It reduces PTV inhomogeneity and better spares OARs compared with Linac-3DCRT. Therefore, TomoDirect may be a CSI treatment alternative to TomoHelical and in place of Linac-3DCRT.
Shone’s syndrome is a complex consisting of mitral valve stenosis in addition to left ventricle outflow obstruction. There are a few studies evaluating the long-term outcomes in this population. We sought to determine the long-term outcomes in our paediatric population with Shone’s syndrome and the factors associated with left heart growth.
All patients diagnosed with Shone’s syndrome with biventricular circulation treated between 1978 and 2010 were reviewed. Baseline echocardiograms and data from catheterisations were also reviewed. Number of interventions (surgical+transcatheter), incidence of mitral valve replacement, and incidence of heart transplantation were tracked. Survival of the population and left heart structural growth were also reviewed.
A total of 121 patients with Shone’s syndrome presented at a median age of 28 days (0–17.3 years) and were followed-up for 7.2 years (0.01–35.5 years). These patients underwent 258 interventions during the study period, and the presence of coarctation was associated with repeat left heart interventions. The 10-year, transplant-free survival was 86%. Presence of pulmonary hypertension was associated with mortality. Left heart structural growth was seen for mitral and aortic valve annuli and left ventricular end-diastolic dimension over time.
Shone’s syndrome patients undergo a number of left heart interventions. Coarctation of the aorta is associated with an increased likelihood for repeat interventions. Survival appears to be more favourable than expected. Significant left heart growth will occur in the population. Pulmonary hypertension is associated with an increased risk of mortality.
The production of radioisotopes at the Earth's surface by cosmic-ray effects has been discussed for many years. Only in the past few years, with the higher sensitivity provided by accelerator mass spectrometry (AMS) in detecting 10Be, 26A1 and 36Cl, have the radioisotopes produced in this way been measured. We report here our measurements of cosmogenic 14C in terrestrial rocks at high altitude, and comparisons to other exposure-dating methods.
The reliability of radiocarbon ages based on soil organic matter (SOM) from Holocene buried soils in Middle Park, Colorado, is assessed by comparison with ages of charcoal. On average, 14C ages of SOM from buried surface horizons are 880 ± 230 14C yr younger than charcoal ages from the same horizon. Humic acid (HA) and low-temperature (400 °) combustion residue (LT) fractions are 390 ± 230 and 1290 ± 230 14C yr younger than charcoal ages, respectively, and HA ages are on average 860 ± 140 14C yr older than LT fractions. We interpret the offsets between 14C ages of charcoal and SOM fractions and the consistent offsets between the HA and LT fractions to reflect the duration of pedogenesis and different residence times of the SOM fractions examined here. The stratigraphic coherence of charcoal 14C ages suggests short residence time on the landscape, with little subsequent reworking. 14C ages of HA and LT fractions are complimentary to charcoal, and HA ages are interpreted to represent minimum ages for the onset of pedogenesis and LT ages are considered maximum ages for burial. The 14C chronology from buried soils indicates an episode of hillslope erosion in Middle Park during the early Holocene, followed by a long period of land surface stability and soil formation between 9000–4500 BP. Two episodes of late Holocene hillslope erosion between 3500–2500 and 1000–500 BP correspond with warming recognized in the Colorado Front Range, while surface stability and soil formation between 2500–1000 BP is contemporaneous with evidence for cooling at higher elevations.
The Harwell system for measuring milligram size samples using Brookhaven miniature gas counters is fully operative. It comprises 12 counters of different sizes which operate simultaneously within a single NaI crystal (300mm diameter × 300mm long) acting as an anti-coincidence guard counter. Brief details are given of the construction and commissioning of the system, including counter assembly, shield design, electronics, data capture, data analysis, and chemical processing and filling procedures. The performance of the system and an overall view of the fields of application for which the counters have important applications are discussed.
We study the evolution of G2 in a Compact Source Scenario, where G2 is the outflow from a low-mass central star moving on the observed orbit. This is done through 3D AMR simulations of the hydrodynamic interaction of G2 with the surrounding hot accretion flow. A comparison with observations is done by means of mock position-velocity (PV) diagrams. We found that a massive (Ṁw = 5× 10−7M⊙ yr−1) and slow (vw = 50 km s−1) outflow can reproduce G2’s properties. A faster outflow (vw = 400 km s−1) might also be able to explain the material that seems to follow G2 on the same orbit.
With the help of 3D AMR hydrodynamical simulations we aim at understanding G2’s nature, recent evolution and fate in the coming years. By exploring the possible parameter space of the diffuse cloud scenario, we find that a starting point within the disc of young stars is favoured by the observations, which may hint at G2 being the result of stellar wind interactions.
In 1988, a Joint Commission (9 and 25) meeting on the causes of the well-known limitations on the precision of infrared astronomy led to several suggestions to improve matters (see Milone 1989). These included better reporting of the photometric systems in use by practitioners, redesign of the infrared passbands to be more optimally placed inside the atmospheric windows, and development of a method to ascertain the water vapor content of the atmosphere when the astronomical infrared measurements were being made. An Infrared Astronomy Working Group was formed to look into the matter. Advice and suggestions were solicited from the community at large. All who volunteered information became, de facto, members of the Working Group. A small subgroup composed of Andrew Young, Chris Stagg, and Milone set to work on the central of the recommendations: improvement of the passbands. Young, Milone, k Stagg (1994) (hereafter YMS) summarized the work: existing JHKLMN and Q infrared passbands were found to be both far from standardized, and all too frequently defined, to various degrees, by the water vapor and other components of the terrestrial atmosphere. Following extensive numerical simulations with a MODTRAN 3 terrestrial-atmospheres model package, and Kurucz stellar atmospheres, we suggested a set of improved infrared passbands designed explicitly to fit within, and not be defined by, the terrestrial atmospheric windows; however, we sought to optimize them so as to get the maximum throughput consistent with plausible limitations on precision of manufacture of the filters. In 1995 and again in 1997, a number of improvements were made in the code with which the improved passbands were designed. While they do not much affect the optimization trials and thus the passband recommendations, they have been used to extend the modeling.
Our knowledge about the impact of coping behavior styles in people exposed to stressful disaster events is limited. Effective coping behavior has been shown to be a psychosocial stress modifier in both occupational and nonoccupational settings.
Data were collected by using a web-based survey that administered the Post-Traumatic Stress Disorder (PTSD) Checklist–Civilian, General Coping Questionnaire-30, and a supplementary questionnaire assessing various risk factors. Logistic regression models were used to test for the association of the 3 coping styles with probable PTSD following disaster exposure among federal disaster responders.
In this sample of 549 study subjects, avoidant coping behavior was most associated with probable PTSD. In tested regression models, the odds ratios ranged from 1.19 to 1.26 and 95% confidence intervals ranged from 1.08 to 1.35. With control for various predictors, emotion-based coping behavior was also found to be associated with probable PTSD (odds ratio=1.11; 95% confidence interval: 1.01-1.22).
This study found that in disaster responders exposed to traumatic disaster events, the likelihood of probable PTSD can be influenced by individual coping behavior style and other covariates. The continued probability of disasters underscores the critical importance of these findings both in terms of guiding mental health practitioners in treating exposed disaster responders and in stimulating future research. (Disaster Med Public Health Preparedness. 2016;10:108–117)
To cope with phosphorus (P) deficiency, plants adapt root morphology to enhance inorganic P (Pi) acquisition from soil by allocating more biomass to roots, but whether the responses can be modified across gradients of P supply is not fully understood. The present study examined changes in root-length density (RLD), root-hair density (RHD) and root-hair length (RHL) of wheat (Triticum aestivum L.) in two contrasting soils, the Rough and Barnfield soils. Wheat plants were grown for 3 weeks in thin-plate rhizotrons in two soils with additions of 0, 10, 25, 50, 100 and 200 mg P/kg soil. Contrary to published literature, as P additions increased it was observed that a concomitant increase in RHL (250 to 1054 µm in the Rough soil and 303–1075 µm in the Barnfield soil) and RHD (57 to 122/mm in the Rough soil and 56–120/mm in the Barnfield soil), while RLD generally decreased (2480–1130 cm/cm3 in the Rough soil and 1716–865 cm/cm3 in the Barnfield soil). The levels of added P that resulted in critical P concentrations in the soils enabling maximum shoot biomass production were 50 mg/kg P in the Rough soil and 100 mg/kg P in the Barnfield soil, and these additions influenced root morphological changes. Under severe P deficiency, P supply increased RHL and RHD, but RLD was decreased. Improvement in lateral root and root-hair responses in wheat at extreme P deficiency may be a worthy target for breeding more sustainable genotypes for future agroecosystems.
Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status – the Omega-3 Index – and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.