The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected ...phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow. Although most studies suggest that transdifferentiation is extremely rare under physiological conditions, extensive regeneration of myocardial infarcts was reported recently after direct stem cell injection, prompting several clinical trials. Here, we used both cardiomyocyte-restricted and ubiquitously expressed reporter transgenes to track the fate of haematopoietic stem cells after 145 transplants into normal and injured adult mouse hearts. No transdifferentiation into cardiomyocytes was detectable when using these genetic techniques to follow cell fate, and stem-cell-engrafted hearts showed no overt increase in cardiomyocytes compared to sham-engrafted hearts. These results indicate that haematopoietic stem cells do not readily acquire a cardiac phenotype, and raise a cautionary note for clinical studies of infarct repair.
Traditional methods of assessing personality traits in medical school selection have been heavily criticised. To address this at the point of selection, “non-cognitive” tests were included in the UK ...Clinical Aptitude Test, the most widely-used aptitude test in UK medical education (UKCAT:
http://www.ukcat.ac.uk/
). We examined the predictive validity of these non-cognitive traits with performance during and on exit from medical school. We sampled all students graduating in 2013 from the 30 UKCAT consortium medical schools. Analysis included: candidate demographics, UKCAT non-cognitive scores, medical school performance data—the Educational Performance Measure (EPM) and national exit situational judgement test (SJT) outcomes. We examined the relationships between these variables and SJT and EPM scores. Multilevel modelling was used to assess the relationships adjusting for confounders. The 3343 students who had taken the UKCAT non-cognitive tests and had both EPM and SJT data were entered into the analysis. There were four types of non-cognitive test: (1) libertariancommunitarian, (2) NACE—narcissism, aloofness, confidence and empathy, (3) MEARS—self-esteem, optimism, control, self-discipline, emotional-nondefensiveness (END) and faking, (4) an abridged version of 1 and 2 combined. Multilevel regression showed that, after correcting for demographic factors, END predicted SJT and EPM decile. Aloofness and empathy in NACE were predictive of SJT score. This is the first large-scale study examining the relationship between performance on non-cognitive selection tests and medical school exit assessments. The predictive validity of these tests was limited, and the relationships revealed do not fit neatly with theoretical expectations. This study does not support their use in selection.
Utilizing the all‐sky imaging capabilities of the first station of the Long Wavelength Array along with a host of all‐sky optical cameras, we have now observed 44 optical meteor counterparts to radio ...afterglows. Combining these observations, we have determined the geographic positions of all 44 afterglows. Comparing the number of radio detections as a function of altitude above sea level to the number of expected bright meteors, we find a strong altitudinal dependence characterized by a cutoff below ∼90 km, below which no radio emission occurs, despite the fact that many of the observed optical meteors penetrated well below this altitude. This cutoff suggests that wave damping from electron collisions is an important factor for the evolution of radio afterglows. This finding agrees with the hypothesis that the emission is the result of electron plasma wave emission.
Key Points
We have measured the positions of 44 meteor radio afterglows
Meteor trails above 90 km are strongly preferred to produce radio emission
This dependence agrees with the plasma emission hypothesis
Agarose gel electrophoresis, circular dichroism and differential scanning calorimetry showed that single-stranded RNA from satellite tobacco mosaic virus transforms from a conformationally 'closed ...state' at 4°C to a more conformationally 'open state' at 65°C. The transition is reversible and shows no hysteresis. Atomic force microscopy (AFM) allowed visualization of the two states and indicated that the conformationally 'closed state' probably corresponds to the native encapsidated conformation, and that the 'open state' represents a conformation, characterized as short, thick chains of domains, as a consequence of the loss of tertiary interactions. Heating from 75°C to 85°C in the presence of EDTA was necessary to further unravel the 'open' conformation RNA into extended chains of lengths >280 nm. Virus exposed to low concentrations of phenol at 65°C, extruded RNA as distinctive 'pigtails' in a synchronous fashion, and these 'pigtails' then elongated, as the RNA was further discharged by the particles. Moderate concentrations of phenol at 65°C produced complete disruption of virions and only remains of decomposed particles and disordered RNA were evident. AFM images of RNA emerging from disrupted virions appear most consistent with linear arrangements of structural domains.
The Deployable Low‐Band Ionosphere and Transient Experiment (DLITE) is a four‐element interferometric radio telescope made from mostly commercial off‐the‐shelf parts to minimize costs and maximize ...ease of deployment. It operates in the high frequency and very high frequency (VHF) regimes, nominally in a 30–40 MHz band, but with good sensitivity (sky‐noise dominated) in the 20–80 MHz range. Its configuration is optimized to probe ionospheric structure using the so‐called “A‐Team,” exceptionally bright sources of cosmic radio emission. Methods have been developed to track the apparent positions and intensities of A‐Team sources without the need for beam forming to enable measurements of VHF scintillations as well as total electron content gradients. Time difference of arrival and frequency difference of arrival methods have been adapted for all‐sky imaging to facilitate both statistical measurements of scintillation levels and time domain astronomy. This study provides a detailed description of the system design, the analysis algorithms, and the science that can be conducted using results from two prototype DLITE systems in Maryland and New Mexico.
Key Points
A new, low‐cost radio telescope has been designed and tested to be optimized for ionospheric remote sensing
Multiple bright cosmic radio sources are tracked without beam forming to measure ionospheric gradients and scintillations
Time domain astronomy of bright sources is possible, for example, monitoring variations in low‐frequency solar emission
In three experiments participants haptically discriminated object shape using unimanual (single hand explored two objects) and bimanual exploration (both hands were used, but each hand, left or ...right, explored a separate object). Such haptic exploration (one versus two hands) requires somatosensory processing in either only one or both cerebral hemispheres; previous studies related to the perception of shape/curvature found superior performance for unimanual exploration, indicating that shape comparison is more effective when only one hemisphere is utilized. The current results, obtained for naturally shaped solid objects (bell peppers, Capsicum annuum) and simple cylindrical surfaces demonstrate otherwise: bimanual haptic exploration can be as effective as unimanual exploration, showing that there is no necessary reduction in ability when haptic shape comparison requires interhemispheric communication. We found that while successive bimanual exploration produced high shape discriminability, the participants' bimanual performance deteriorated for simultaneous shape comparisons. This outcome suggests that either interhemispheric interference or the need to attend to multiple objects simultaneously reduces shape discrimination ability. The current results also reveal a significant effect of age: older adults' shape discrimination abilities are moderately reduced relative to younger adults, regardless of how objects are manipulated (left hand only, right hand only, or bimanual exploration).
Dynamic radio spectra from two fireballs Obenberger, K. S.; Taylor, G. B.; Lin, C. S. ...
Journal of geophysical research. Space physics,
November 2015, Letnik:
120, Številka:
11
Journal Article
Recenzirano
Odprti dostop
We present dynamic spectra from the Long Wavelength Array telescope of two large meteors (fireballs) observed to emit between 37 and 54 MHz. These spectra show the first ever recorded broadband ...measurements of this newly discovered VHF emission. The spectra show that the emission is smooth and steep, getting very bright at lower frequencies. We suggest that this signal is possibly emission of Langmuir waves and that these waves could be excited by a bump‐on‐tail instability within the trail. The spectra of one fireball display broadband temporal frequency sweeps. We suggest that these sweeps are evidence of individual expanding clumps of emitting plasma. While some of these proposed clumps may have formed at the very beginning of the fireball event, others must have formed seconds after the initial event.
Key Points
We have made broadband measurements of the newly discovered HF and VHF radio emission from meteors
The spectra are broad and very steep
The emission is likely due to the radiation of plasma waves, possibly Langmuir waves.
GPR55 is a G protein-coupled receptor activated by L-α-lysophosphatidylinositol and suggested to have roles in pain signaling, bone morphogenesis, and possibly in vascular endothelial cells. It has ...affinity for certain cannabinoids (molecules that interact with the cannabinoid CB(1) and CB(2) receptors), but investigation of its functional role in cell-based systems and in tissue has been limited by a lack of selective pharmacological tools. Here, we present our characterization of GPR55 in the yeast Saccharomyces cerevisiae and in human embryonic kidney (HEK293) cells. We describe GSK494581A (1-{2-fluoro-4-1-(methyloxy)ethylphenyl}-4-{4'-fluoro-4-(methylsulfonyl)-2-biphenylylcarbonyl}piperazine), a selective small-molecule ligand of GPR55 identified through diversity screening. GSK494581A is one of a series of benzoylpiperazines originally identified and patented as inhibitors of the glycine transporter subtype 1 (GlyT1). The structure-activity relationship between GPR55 and GlyT1 is divergent across this series. The most GPR55-selective example is GSK575594A (3-fluoro-4-(4-{4'-fluoro-4-(methylsulfonyl)-2-biphenylylcarbonyl}-1-piperazinyl)aniline), which is approximately 60-fold selective for GPR55 (pEC(50) = 6.8) over GlyT1 (pIC(50) = 5.0). Several exemplars with activity at GPR55 and GlyT1 have been profiled at a broad range of other molecular targets and are inactive at cannabinoid receptors and all other targets tested. The benzoylpiperazine agonists activate human GPR55 but not rodent GPR55, suggesting that the relatively low level of sequence identity between these orthologs (75%) translates to important functional differences in the ligand-binding site.
DETECTION OF RADIO EMISSION FROM FIREBALLS Obenberger, K S; Taylor, G B; Hartman, J M ...
Astrophysical journal. Letters,
06/2014, Letnik:
788, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present the findings from the Prototype All-Sky Imager, a back end correlator of the first station of the Long Wavelength Array, which has recorded over 11,000 hr of all-sky images at frequencies ...between 25 and 75 MHz. In a search of this data for radio transients, we have found 49 long-duration (10 s of seconds) transients. Ten of these transients correlate both spatially and temporally with large meteors (fireballs), and their signatures suggest that fireballs emit a previously undiscovered low frequency, non-thermal pulse. This emission provides a new probe into the physics of meteors and identifies a new form of naturally occurring radio transient foreground.
A previous study has shown that shorter bevacizumab infusions (0.5 mg/kg/min) can be safely administered without increasing the risk of infusion-related hypersensitivity reactions (HSRs). However, ...the risk of proteinuria and hypertension in patients receiving shorter infusions of bevacizumab is undetermined.
This was a multicenter, prospective, observational study in patients receiving <10 mg/kg of bevacizumab infused over 0.5 mg/kg/min. Patients were observed until discontinuation of bevacizumab for progression of cancer or toxicity. The incidence of hypertension and proteinuria was compared with a prior cohort of patients who had received standard duration infusions of bevacizumab.
Sixty-three patients received a total of 392 doses of shorter bevacizumab infusions. Nineteen (30.2%) patients experienced proteinuria while receiving bevacizumab. Out of 19 patients, 13 had grade 1 and 6 had grade 2 proteinuria. None of the patients experienced grade 3 or 4 proteinuria. Hypertension was reported in 32 (50.8%) patients receiving bevacizumab. Twelve (19%) patients developed grade 3 or greater hypertension on bevacizumab. The incidence of proteinuria and hypertension was 38.3% and 56.6%, respectively, in patients (N = 120, 1347 infusions) receiving standard duration infusions of bevacizumab.
Shorter bevacizumab infusions (0.5 mg/kg/min) do not increase the risk of proteinuria and hypertension.
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