'Special K' and a loss of cell-to-cell adhesion in proximal tubule-derived epithelial cells: modulation of the adherens junction complex by ketamine

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention

ALMA Temporal Phase Stability and the Effectiveness of Water Vapor Radiometer

Atacama Large Millimeter/submillimeter Array (ALMA) will be the world largest mm/submm interferometer, and currently the Early Science is ongoing, together with the commissioning and science verification (CSV). Here we present a study of the temporal phase stability of the entire ALMA system from antennas to the correlator. We verified the temporal phase stability of ALMA using data, taken during the last two years of CSV activities. The data consist of integrations on strong point sources (i.e., bright quasars) at various frequency bands, and at various baseline lengths (up to 600 m). From the observations of strong quasars for a long time (from a few tens of minutes, up to an hour), we derived the 2-point Allan Standard Deviation after the atmospheric phase correction using the 183 GHz Water Vapor Radiometer (WVR) installed in each 12 m antenna, and confirmed that the phase stability of all the baselines reached the ALMA specification. Since we applied the WVR phase correction to all the data mentioned above, we also studied the effectiveness of the WVR phase correction at various frequencies, baseline lengths, and weather conditions. The phase stability often improves a factor of 2 - 3 after the correction, and sometimes a factor of 7 improvement can be obtained. However, the corrected data still displays an increasing phase fluctuation as a function of baseline length, suggesting that the dry component (e.g., N2 and O2) in the atmosphere also contributes the phase fluctuation in the data, although the imperfection of the WVR phase correction cannot be ruled out at this moment.Comment: Proc. SPIE 8444-125, in press (7 pages, 4 figures, 1 table

No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials

Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myelold leukemia (AML) but the most efficacious therapy for FLT3/ ITD+ patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .001). It remained prognostic for increased relapse in patients who received a transplant (odds ratio [OR] = 1.91; 95% confidence intervals [CIs] 1.13-3.21; P = .02), with no evidence of a difference in effect between patients who received an autograft (OR = 2.39; CIs = 1.24-4.62) and patients who received an allograft (OR = 1.31; CIs = 0.56-3.06) (test for interaction, P = .3) or between patients who did or did not receive a transplant (P = .4). These results were confirmed in an analysis of 186 patients randomized to receive or not receive an autograft in first CR and in a donor-versus-no donor analysis of 683 patients to assess the role of allograft (for latter, FLT3/ITD- OR = 0.70, CIs = 0.53-0.92; FLT3/ITD+ OR = 0.59, CIs = 0.40-0.87; test for interaction, P = .5). These results suggest that at present there is no strong evidence that FLT3 status should influence the decision to proceed to transplantation

Lunar Surface Potential Changes Possible Associated with Traversals of the Bow Shock

We report an analysis of seven Apollo 14 Apollo Lunar Surface Experiments Package (ALSEP) Suprathermal Ion Detector Experiment (SIDE) "resonance" events from January 1972 through January 1973. The events appear to be associated with traversals of the Moon through the terrestrial bow shock

Superfluid turbulence and pulsar glitch statistics

Experimental evidence is reviewed for the existence of superfluid turbulence in a differentially rotating, spherical shell at high Reynolds numbers (\Rey\gsim 10^3), such as the outer core of a neutron star. It is shown that torque variability increases with \Rey, suggesting that glitch activity in radio pulsars may be a function of \Rey as well. The \Rey distribution of the 67 glitching radio pulsars with characteristic ages $\tau_c \leq 10^6$ {\rm yr} is constructed from radio timing data and cooling curves and compared with the \Rey distribution of all 348 known pulsars with $\tau_c \leq 10^6$ {\rm yr}. The two distributions are different, with a Kolmogorov-Smirnov probability $\geq 1 - 3.9 \times 10^{-3}$. The conclusion holds for (modified) Urca and nonstandard cooling, and for Newtonian and superfluid viscosities

Magnetoroton scattering by phonons in the fractional quantum Hall regime

Motivated by recent phonon spectroscopy experiments in the fractional quantum Hall regime we consider processes in which thermally excited magnetoroton excitations are scattered by low energy phonons. We show that such scattering processes can never give rise to dissociation of magnetorotons into unbound charged quasiparticles as had been proposed previously. In addition we show that scattering of magnetorotons to longer wavelengths by phonon absorption is possible because of the shape of the magnetoroton dispersion curve and it is shown that there is a characteristic cross-over temperature above which the rate of energy transfer to the electron gas changes from an exponential (activated) to a power law dependence on the effective phonon temperature.Comment: LaTex document, 3 eps figures. submitted to Phys Rev

A Primer on Eulerian Computational Fluid Dynamics for Astrophysics

We present a pedagogical review of some of the methods employed in Eulerian computational fluid dynamics (CFD). Fluid mechanics is governed by the Euler equations, which are conservation laws for mass, momentum, and energy. The standard approach to Eulerian CFD is to divide space into finite volumes or cells and store the cell-averaged values of conserved hydro quantities. The integral Euler equations are then solved by computing the flux of the mass, momentum, and energy across cell boundaries. We review both first-order and second-order flux assignment schemes. All linear schemes are either dispersive or diffusive. The nonlinear, second-order accurate total variation diminishing (TVD) approach provides high resolution capturing of shocks and prevents unphysical oscillations. We review the relaxing TVD scheme, a simple and robust method to solve systems of conservation laws like the Euler equations. A 3-D relaxing TVD code is applied to the Sedov-Taylor blast wave test. The propagation of the blast wave is accurately captured and the shock front is sharply resolved. We apply a 3-D self-gravitating hydro code to simulating the formation of blue straggler stars through stellar mergers and present some numerical results. A sample 3-D relaxing TVD code is provided in the appendix.Comment: 23 pages, 12 figures; includes sample 3-D hydro code and new section on stellar mergers; accepted by PAS

Update on Apollo Data Restoration by the NSSDC and the PDS Lunar Data Node

The Lunar Data Node (LDN) , under the auspices of the Geosciences Node of the Planetary Data System (PDS) and the National Space Science Data Center (NSSDC), is continuing its efforts to recover and restore Apollo science data. The data being restored are in large part archived with NSSDC on older media, but unarchived data are also being recovered from other sources. They are typically on 7- or 9-track magnetic tapes, often in obsolete formats, or held on microfilm, microfiche, or paper documents. The goal of the LDN is to restore these data from their current form, which is difficult for most researchers to access, into common digital formats with all necessary supporting data (metadata) and archive the data sets with PDS. Restoration involves reading the data from the original media, deciphering the data formats to produce readable digital data and converting the data into usable tabular formats. Each set of values in the table must then be understood in terms of the quantity measured and the units used. Information on instrument properties, operational history, and calibrations is gathered and added to the data set, along with pertinent references, contacts, and other ancillary documentation. The data set then undergoes a peer review and the final validated product is archived with PDS. Although much of this effort has concentrated on data archived at NSSDC in the 1970's, we have also recovered data and information that were never sent to NSSDC. These data, retrieved from various outside sources, include raw and reduced Gamma-Ray Spectrometer data from Apollos 15 and 16, information on the Apollo 17 Lunar Ejecta And Meteorites experiment, Dust Detector data from Apollos 11, 12, 14, and I5, raw telemetry tapes from the Apollo ALSEPs, and Weekly Status Reports for all the Apollo missions. These data are currently being read or organized, and supporting data is being gathered. We are still looking for the calibrated heat flow data from Apollos 15 and 17 for the period 1975-1977, any assistance or information on these data would be welcome. NSSDC has recently been tasked to release its hard-copy archive, comprising photography, microfilm, and microfiche. The details are still being discussed, but we are concentrating on recovering the valuable lunar data from these materials while they are still readily accessible. We have identified the most critical of these data and written a LASER proposal to fund their restoration. Included in this effort are data from the Apollo 15 and 16 Mass Spectrometers and the Apollo 17 Par-UV Spectrometer and ancillary information on the Apollo 17 Surface Electrical Properties Experiment

Population-based study of ischemic stroke risk after trauma in children and young adults.

OBJECTIVE:To quantify the incidence, timing, and risk of ischemic stroke after trauma in a population-based young cohort. METHODS:We electronically identified trauma patients (&lt;50 years old) from a population enrolled in a Northern Californian integrated health care delivery system (1997-2011). Within this cohort, we identified cases of arterial ischemic stroke within 4 weeks of trauma and 3 controls per case. A physician panel reviewed medical records, confirmed cases, and adjudicated whether the stroke was related to trauma. We calculated the 4-week stroke incidence and estimated stroke odds ratios (OR) by injury location using logistic regression. RESULTS:From 1,308,009 trauma encounters, we confirmed 52 trauma-related ischemic strokes. The 4-week stroke incidence was 4.0 per 100,000 encounters (95% confidence interval [CI] 3.0-5.2). Trauma was multisystem in 26 (50%). In 19 (37%), the stroke occurred on the day of trauma, and all occurred within 15 days. In 7/28 cases with cerebrovascular angiography at the time of trauma, no abnormalities were detected. In unadjusted analyses, head, neck, chest, back, and abdominal injuries increased stroke risk. Only head (OR 4.1, CI 1.1-14.9) and neck (OR 5.6, CI 1.03-30.9) injuries remained associated with stroke after adjusting for demographics and trauma severity markers (multisystem trauma, motor vehicle collision, arrival by ambulance, intubation). CONCLUSIONS:Stroke risk is elevated for 2 weeks after trauma. Onset is frequently delayed, providing an opportunity for stroke prevention during this period. However, in one-quarter of stroke cases with cerebrovascular angiography at the time of trauma, no vascular abnormality was detected

Circinus X-1: survivor of a highly asymmetric supernova

We have analyzed the kinematical parameters of Cir X-1 to constrain the nature of its companion star, the eccentricity of the binary and the pre-supernova parameter space. We argue that the companion is most likely to be a low-mass (< 2.0 M_sun) unevolved star and that the eccentricity of the orbit is 0.94 +/- 0.04. We have evaluated the dynamical effects of the supernova explosion and we find it must have been asymmetric. On average, we find that a kick of 740 km/s is needed to account for the recently measured radial velocity of +430 km/s (Johnston, Fender & Wu) for this extreme system. The corresponding minimum kick velocity is 500 km/s. This is the largest kick needed to explain the motion of any observed binary system. If Cir X-1 is associated with the supernova remnant G321.9-0.3 then we find a limiting minimum age of this remnant of 60000 yr. Furthermore, we predict that the companion star has lost 10% of its mass as a result of stripping and ablation from the impact of the supernova shell shortly after the explosion.Comment: 6 pages, 3 figues, 2 tables, accepted for publication in MNRA