Abstract
We report results from 21-cm intensity maps acquired from the Parkes radio telescope and cross-correlated with galaxy maps from the 2dF galaxy survey. The data span the redshift range ...0.057 < z < 0.098 and cover approximately 1300 deg2 over two long fields. Cross-correlation is detected at a significance of 5.7 σ. The amplitude of the cross-power spectrum is low relative to the expected dark matter power spectrum, assuming a neutral hydrogen (H i) bias and mass density equal to measurements from the ALFALFA survey. The decrement is pronounced and statistically significant at small scales. At k ∼ 1.5 h Mpc−1, the cross-power spectrum is more than a factor of 6 lower than expected, with a significance of 15.3 σ. This decrement indicates a lack of clustering of neutral hydrogen (H i), a small correlation coefficient between optical galaxies and H i, or some combination of the two. Separating 2dF into red and blue galaxies, we find that red galaxies are much more weakly correlated with H i on k ∼ 1.5 h Mpc−1 scales, suggesting that H i is more associated with blue star-forming galaxies and tends to avoid red galaxies.
Phages shape the structure of natural bacterial communities and can be effective therapeutic agents. Bacterial resistance to phage infection, however, limits the usefulness of phage therapies and ...could destabilise community structures, especially if individual resistance mutations provide cross-resistance against multiple phages. We currently understand very little about the evolution of cross-resistance in bacteria-phage interactions. Here we show that the network structure of cross-resistance among spontaneous resistance mutants of Pseudomonas aeruginosa evolved against each of 27 phages is highly modular. The cross-resistance network contained both symmetric (reciprocal) and asymmetric (nonreciprocal) cross-resistance, forming two cross-resistance modules defined by high within- but low between-module cross-resistance. Mutations conferring cross-resistance within modules targeted either lipopolysaccharide or type IV pilus biosynthesis, suggesting that the modularity of cross-resistance was structured by distinct phage receptors. In contrast, between-module cross-resistance was provided by mutations affecting the alternative sigma factor, RpoN, which controls many lifestyle-associated functions, including motility, biofilm formation, and quorum sensing. Broader cross-resistance range was not associated with higher fitness costs or weaker resistance against the focal phage used to select resistance. However, mutations in rpoN, providing between-module cross-resistance, were associated with higher fitness costs than mutations associated with within-module cross-resistance, i.e., in genes encoding either lipopolysaccharide or type IV pilus biosynthesis. The observed structure of cross-resistance predicted both the frequency of resistance mutations and the ability of phage combinations to suppress bacterial growth. These findings suggest that the evolution of cross-resistance is common, is likely to play an important role in the dynamic structure of bacteria-phage communities, and could inform the design principles for phage therapy treatments.
We derive new constraints on the mass of the Milky Way's dark matter halo, based on 2401 rigorously selected blue horizontal-branch halo stars from SDSS DR6. This sample enables construction of the ...full line-of-sight velocity distribution at different galactocentric radii. To interpret these distributions, we compare them to matched mock observations drawn from two different cosmological galaxy formation simulations designed to resemble the Milky Way. This procedure results in an estimate of the Milky Way's circular velocity curve to image60 kpc, which is found to be slightly falling from the adopted value of 220 km s super(-1) at the Sun's location, and implies image M sub(image). The radial dependence of image, derived in statistically independent bins, is found to be consistent with the expectations from an NFW dark matter halo with the established stellar mass components at its center. If we assume that an NFW halo profile of characteristic concentration holds, we can use the observations to estimate the virial mass of the Milky Way's dark matter halo, image M sub(image), which is lower than many previous estimates. We have checked that the particulars of the cosmological simulations are unlikely to introduce systematics larger than the statistical uncertainties. This estimate implies that nearly 40% of the baryons within the virial radius of the Milky Way's dark matter halo reside in the stellar components of our Galaxy. A value for image of only image M sub(image) also (re)opens the question of whether all of the Milky Way's satellite galaxies are on bound orbits.
We have conducted quantum chemistry calculations and gas- and solution-phase reactive molecular dynamics simulation studies of reactions involving the ethylene carbonate (EC) radical anion EC– using ...the reactive force field ReaxFF. Our studies reveal that the substantial barrier for transition from the closed (cyclic) form, denoted c-EC–, of the radical anion to the linear (open) form, denoted o-EC–, results in a relatively long lifetime of the c-EC– allowing this compound to react with other singly reduced alkyl carbonates. Using ReaxFF, we systematically investigate the fate of both c-EC– and o-EC– in the gas phase and EC solution. In the gas phase and EC solutions with a relatively low concentration of Li+/x-EC– (where x = o or c), radical termination reactions between radical pairs to form either dilithium butylene dicarbonate (CH2CH2OCO2Li)2 (by reacting two Li+/o-EC–) or ester-carbonate compound (by reacting Li+/o-EC– with Li+/c-EC–) are observed. At higher concentrations of Li+/x-EC– in solution, we observe the formation of diradicals which subsequently lead to formation of longer alkyl carbonates oligomers through reaction with other radicals or, in some cases, formation of (CH2OCO2Li)2 through elimination of C2H4. We conclude that the local ionic concentration is important in determining the fate of x-EC– and that the reaction of c-EC– with o-EC– may compete with the formation of various alkyl carbonates from o-EC–/o-EC– reactions.
The quest to develop materials that enable the manufacture of dimensionally ultra-stable structures for critical-dimension components in spacecraft has led to much research over many decades and the ...evolution of carbon fibre reinforced polymer materials. This has resulted in structural designs that feature a near-zero coefficient of thermal expansion. However, the dimensional instabilities that result from moisture ingression and release remain the fundamental vulnerability of the matrix, which restricts many applications. Here, we address this challenge by developing a space-qualifiable physical surface barrier that blends within the mechanical properties of the composite, thus becoming part of the composite itself. The resulting enhanced composite features mechanical integrity and a strength that is superior to the underlying composite, while remaining impervious to moisture and outgassing. We demonstrate production capability for a model-sized component for the Sentinel-5 mission and demonstrate such capability for future European Space Agency (ESA) and National Aeronautics and Space Administration (NASA) programmes such as Copernicus Extension, Earth Explorer and Science Cosmic Visions.
Background
Cannabis has a long history of medicinal use. Cannabis‐based medications (cannabinoids) are based on its active element, delta‐9‐tetrahydrocannabinol (THC), and have been approved for ...medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy‐induced nausea and vomiting that respond poorly to commonly used anti‐emetic agents (anti‐sickness drugs). However, unpleasant adverse effects may limit their widespread use.
Objectives
To evaluate the effectiveness and tolerability of cannabis‐based medications for chemotherapy‐induced nausea and vomiting in adults with cancer.
Search methods
We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication.
Selection criteria
We included randomised controlled trials (RCTs) that compared a cannabis‐based medication with either placebo or with a conventional anti‐emetic in adults receiving chemotherapy.
Data collection and analysis
At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta‐analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI).
Main results
We included 23 RCTs. Most were of cross‐over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti‐emetic drugs such as ondansetron.
Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I2 = 0% in both analyses).
People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I2 = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I2 = 0%).
People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence).
Comparison with other anti‐emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I2 = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I2 = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I2 = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross‐over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I2 = 0%).
People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I2 = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.
People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I2 = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I2 = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I2 = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I2 = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I2 = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.
People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I2 = 51%; low quality evidence).
In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.
Two trials with 141 participants compared an anti‐emetic drug alone with a cannabinoid added to the anti‐emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events.
Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti‐emetic treatment regimens. Furthermore, the quality of evidence arising from meta‐analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results.
Authors' conclusions
Cannabis‐based medications may be useful for treating refractory chemotherapy‐induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti‐emetic drugs is likely to modify these conclusions.
To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that ...truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness
than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans.
During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.
Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the ...observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.
Dawn at Vesta: Testing the Protoplanetary Paradigm Russell, C. T.; Raymond, C. A.; Coradini, A. ...
Science (American Association for the Advancement of Science),
05/2012, Letnik:
336, Številka:
6082
Journal Article
Recenzirano
The Dawn spacecraft targeted 4 Vesta, believed to be a remnant intact protoplanet from the earliest epoch of solar system formation, based on analyses of howardite-eucrite-diogenite (HED) meteorites ...that indicate a differentiated parent body. Dawn observations reveal a giant basin at Vesta's south pole, whose excavation was sufficient to produce Vesta-family asteroids (Vestoids) and HED meteorites. The spatially resolved mineralogy of the surface reflects the composition of the HED meteorites, confirming the formation of Vesta's crust by melting of a chondritic parent body. Vesta's mass, volume, and gravitational field are consistent with a core having an average radius of 107 to 113 kilometers, indicating sufficient internal melting to segregate iron. Dawn's results confirm predictions that Vesta differentiated and support its identification as the parent body of the HEDs.
Necrostatin (Nec-1) protects against ischemia-reperfusion (IR) injury in both brain and heart. We have previously reported in this journal that necrostatin can delay opening of the mitochondrial ...permeability transition pore (MPTP) in isolated cardiomyocytes.
The aim of the present study was to investigate in more detail the role played by the MPTP in necrostatin-mediated cardioprotection employing mice lacking a key component of the MPTP, namely cyclophilin-D.
Anaesthetized wild type (WT) and cyclophilin-D knockout (Cyp-D-/-) mice underwent an open-chest procedure involving 30 min of myocardial ischemia and 2 h of reperfusion, with subsequent infarct size assessed by triphenyltetrazolium staining. Nec-1, given at reperfusion, significantly limited infarct size in WT mice (17.7 +/- 3% vs. 54.3 +/- 3%, P < 0.05) but not in Cyp-D-/- mice (28.3 +/- 7% vs. 30.8 +/- 6%, P > 0.05).
The data obtained in Cyp-D-/- mice provide further evidence that Nec-1 protects against myocardial IR injury by modulating MPTP opening at reperfusion.
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