Specimen collection: An essential tool Rocha, L. A.; Aleixo, A.; Allen, G. ...
Science (American Association for the Advancement of Science),
05/2014, Letnik:
344, Številka:
6186
Journal Article
•MPLA administration can trigger expression of sickness behaviors in C57BL/6J mice.•Treatment with MPLA for two consecutive days prior to LPS administration is sufficient to prevent LPS-induced ...sickness behaviors.•Treatment with MPLA for two consecutive days prior to LPS administration is sufficient to prevent LPS-induced elevations in IL-1β in the dorsal hippocampus.•MPLA protection from LPS-induced sickness behaviors appears to be independent of effects on IL-4 expression in the dorsal hippocampus.
Peripheral administration of lipopolysaccharide (LPS) elevates production of pro-inflammatory cytokines, and motivates the expression of sickness behaviors. In this study, we tested the ability of an LPS-derived adjuvant, monophosphoryl lipid A (MPLA), to prevent LPS-induced sickness behaviors in a burrowing paradigm. Testing occurred over a three-day period. Animals received a single injection of either MPLA or saline the first two days of testing. On day three, animals received either LPS or saline. Tissue from the dorsal hippocampus was collected for qRT-PCR to assess expression of IL-1β and IL-4. Results indicate that, during the pre-treatment phase, administration of MPLA induces an immune response sufficient to trigger sickness behaviors. However, we observed that animals pre-treated with MPLA for two days were resistant to LPS-induced sickness behaviors on day three. Results from the qRT-PCR analysis indicated that LPS-treated animals pre-treated with MPLA expressed significantly less IL-1β compared to LPS-treated animals pre-treated with saline. However, we did not observe a significant difference in IL-4 expression between groups. Therefore, results indicate that under the given parameters of the study, MPLA pre-treatment protects against LPS-induced sickness behaviors, at least in part, by decreasing expression of the pro-inflammatory cytokine IL-1β.
The LOFAR Two-metre Sky Survey Shimwell, T. W.; Hardcastle, M. J.; Tasse, C. ...
Astronomy and astrophysics (Berlin),
03/2022, Letnik:
659
Journal Article
Recenzirano
Odprti dostop
In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120–168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred ...at approximately 12h45m +44°30′ and 1h00m +28°00′ and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes
I
) maps, where the majority of these have never been detected at radio wavelengths before. At 6″ resolution, our full bandwidth Stokes
I
continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beam
−1
; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2″; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beam
−1
. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > ± 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes
V
) 20″ resolution 120–168 MHz continuum images have a median rms sensitivity of 95 μJy beam
−1
, and we estimate a Stokes
I
to Stokes
V
leakage of 0.056%. Our linear polarisation (Stokes
Q
and Stokes
U
) image cubes consist of 480 × 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beam
−1
at 4′ and 2.2 mJy beam
−1
at 20″; we estimate the Stokes
I
to Stokes
Q
/
U
leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes
I
,
Q
,
U
and
V
images in addition to the calibrated
uv
-data to facilitate the thorough scientific exploitation of this unique dataset.
The RENEW Trial Povsic, Thomas J., MD, PhD; Henry, Timothy D., MD; Traverse, Jay H., MD ...
JACC. Cardiovascular interventions,
08/2016, Letnik:
9, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34+ cells would improve total exercise time (TET) and angina frequency in ...patients with refractory angina. Background IM administration of autologous CD34+ cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials. Methods RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM CD34+ administration with no intervention (open-label standard of care) or IM placebo injections (active control). The primary efficacy endpoint was change in TET at 12 months. Key secondary endpoints include changes in angina frequency at 3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the incidence of major adverse cardiovascular events through 24 months. Results The sponsor terminated the study for strategic considerations after enrollment of 112 of planned 444 patients. The difference in TET between patients treated with cell therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9 to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and 36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34+ cell therapy seemed to be safe compared with both open-label standard of care and active control (major adverse cardiovascular events 67.9% standard of care, 42.9% (active control), 46.0% CD34+ ). Conclusions Due to early termination, RENEW was an incomplete experiment; however, the results were consistent with observations from earlier phase studies. These findings underscore the need for a definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina RENEW: NCT01508910 )
Two narrow resonant states are observed in the Λ_{b}^{0}K^{-}π^{+} mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment ...and corresponding to an integrated luminosity of 6 fb^{-1}. The minimal quark content of the Λ_{b}^{0}K^{-}π^{+} system indicates that these are excited Ξ_{b}^{0} baryons. The masses of the Ξ_{b}(6327)^{0} and Ξ_{b}(6333)^{0} states are mΞ_{b}(6327)^{0}=6327.28_{-0.21}^{+0.23}±0.12±0.24 and mΞ_{b}(6333)^{0}=6332.69_{-0.18}^{+0.17}±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41_{-0.27}^{+0.26}±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λ_{b}^{0} mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of ΓΞ_{b}(6327)^{0}<2.20(2.56) and ΓΞ_{b}(6333)^{0}<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξ_{b}^{0} resonances.
Abstract
The Dark Energy Spectroscopic Instrument (DESI) was designed to conduct a survey covering 14,000 deg
2
over 5 yr to constrain the cosmic expansion history through precise measurements of ...baryon acoustic oscillations (BAO). The scientific program for DESI was evaluated during a 5 month survey validation (SV) campaign before beginning full operations. This program produced deep spectra of tens of thousands of objects from each of the stellar Milky Way Survey (MWS), Bright Galaxy Survey (BGS), luminous red galaxy (LRG), emission line galaxy (ELG), and quasar target classes. These SV spectra were used to optimize redshift distributions, characterize exposure times, determine calibration procedures, and assess observational overheads for the 5 yr program. In this paper, we present the final target selection algorithms, redshift distributions, and projected cosmology constraints resulting from those studies. We also present a One-Percent Survey conducted at the conclusion of SV covering 140 deg
2
using the final target selection algorithms with exposures of a depth typical of the main survey. The SV indicates that DESI will be able to complete the full 14,000 deg
2
program with spectroscopically confirmed targets from the MWS, BGS, LRG, ELG, and quasar programs with total sample sizes of 7.2, 13.8, 7.46, 15.7, and 2.87 million, respectively. These samples will allow exploration of the Milky Way halo, clustering on all scales, and BAO measurements with a statistical precision of 0.28% over the redshift interval
z
< 1.1, 0.39% over the redshift interval 1.1 <
z
< 1.9, and 0.46% over the redshift interval 1.9 <
z
< 3.5.
Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that ...adequate cleavage of ACTH to α-melanocortin-stimulating hormone (α-MSH) and desacetyl-α-melanocortin-stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance.
We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant.
The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism.
The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control.
Abstract Background The α2 adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, ...analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. Methods This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3 h of dexmedetomidine infusion to the ewe at a rate of 1 μg/kg/h. Results Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3-h infusion, glucose increased from 49 ± 10 to 104 ± 33 mg/dL in the ewe and from 22 ± 3 to 48 ± 16 mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63 ± 12 mg/dL, P = 0.0497; and fetal, 24 ± 4 mg/dL, P = 0.012). With respect to cardiovascular status, dexmedetomidine produced a decrease in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. Conclusions Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.
Abstract Background Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and ...psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders. Methods Here, 2D digital photographs were collected from 22q11DS ( n = 150), PS ( n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics—a semi-automated machine learning technique that localizes and measures facial features. Results F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements. Conclusions The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.
The tsunami generation potential of pyroclastic density currents (PDCs) entering the sea is poorly understood, due to limited data and observations. Thus far, tsunami generation by PDCs has been ...modeled in a similar manner to tsunami generation associated with landslides or debris flows, using two‐layer depth‐averaged approaches. Using the adaptive partial differential equation solver Basilisk and benchmarking with published laboratory experiments, this work explores some of the important parameters not yet accounted for in numerical models of PDC‐generated tsunamis. We use assumptions derived from experimental literature to approximate the granular, basal flow component of a PDC as a dense Newtonian fluid flowing down an inclined plane. This modeling provides insight into how the boundary condition of the slope and the viscosity of the dense granular‐fluid influence the characteristics of the waves generated. It is shown that the boundary condition of the slope has a first‐order impact on the interaction dynamics between the fluidized granular flow and water, as well as the energy transfer from the flow to the generated wave. The experimental physics is captured well in the numerical model, which confirms the underlying assumption of Newtonian fluid‐like behavior in the context of wave generation. The results from this study suggest the importance of considering vertical density and velocity stratification in wave generation models. Furthermore, we demonstrate that granular‐fluids denser than water are capable of shearing the water surface and generating significant amplitude waves, despite vigorous overturning.
Plain Language Summary
When a volcano erupts, it ejects large quantities of volcanic rock, gas, ash, and debris. These ejected materials can flow very rapidly down the side slopes of the volcano; these flows are called pyroclastic density currents (PDCs). When PDCs enter the sea, they displace water and can generate tsunami waves with enormous destructive potential. One method of understanding this potential is by mathematically modeling the flow and its interactions with water, and confirming these model results against laboratory data. The present study compares numerical model results with published laboratory experiments of PDC generated tsunamis, to understand how our assumptions about the flow and its motion along the boundary can affect the amount of energy transferred to the generated waves. We approximate a PDC generated tsunami as a dense, viscous fluid moving down a slope into the water. The amount of friction on the slope and the properties of the dense fluid lead to different interaction dynamics between the PDC and the water. The interaction dynamics lead to a wide range of wave breaking behaviors. Our results show the importance of the boundary conditions and fluid properties in correctly capturing experimental observations and in predicting how PDCs generate tsunamis.
Key Points
Numerical experiments of fluidized granular flows entering water are performed to study tsunamis generated by pyroclastic density currents
A Newtonian fluid model is able to reproduce the wave generation mechanism at the interaction between a fluidized granular flow and water
The basal shear stress has a first‐order control on the interaction dynamics and flow/wave energetics
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