The observation of neutron stars with masses greater than one solar mass places severe demands on any exotic neutron decay mode that could explain the discrepancy between beam and bottle measurements ...of the neutron lifetime. If the neutron can decay to a stable, feebly interacting dark fermion, the maximum possible mass of a neutron star is 0.7M_{⊙}, while all well-measured neutron star masses exceed one M_{⊙}. The existence of 2M_{⊙} neutron stars further indicates that any explanation beyond the standard model for the neutron lifetime puzzle requires dark matter to be part of a multiparticle dark sector with highly constrained interactions. Beyond the neutron lifetime puzzle, our results indicate that neutron stars provide unique and useful probes of GeV-scale dark sectors coupled to the standard model via baryon-number-violating interactions.
Parasite attachment structures are critical traits that influence effective host exploitation and survival. Morphology of attachment structures can reinforce host specificity and niche ...specialisation, or even enable host switching. Therefore, it is important to understand the determinants of variation in attachment structures. Cymothoid isopods are striking ectoparasites of fishes that include the infamous 'tongue-biters.' They are known to parasitise hosts in one of four qualitatively distinct anatomical regions. Here, we quantify variation in cymothoid attachment structures - hook-like appendages called dactyli - and test whether differences in dactylus shape are correlated with parasite mode (where they attach), allometry, or both, using multivariate ordinary least squares regression. We also assess the influence of shared ancestry on shape using a molecular phylogeny to weight our models using phylogenetic generalised least squares regression.
We find clear differences in shape between externally-attaching and internally-attaching cymothoids but also between anterior and posterior dactyli across various species with the same attachment mode. Allometric effects are significant for anterior but not posterior dactyli. Mouth-attaching species show greater shape variability than gill- and mouth-attaching species. We find no evidence that there are clade-specific patterns of association between parasite mode and dactylus shape.
Parasite mode appears to be the main driver of attachment morphology. This likely reflects several components of parasite ecology including feeding and functional demands of attachment in different microhabitats. Geometric morphometric approaches to the quantification of shape variation of simple structures is an effective tool that provides new insights into the evolvability of parasite attachment.
Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities ...of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Nucleoside modification and elimination of double-stranded RNA can reduce the immunomodulatory activity of mRNA and increase and prolong protein production. In combination with nanoparticle-based formulations that increase transfection efficiency and facilitate lymphatic system targeting, nucleoside-modified mRNA enables efficient delivery of cytokines, costimulatory receptors, or therapeutic antibodies. Steady but transient production of the encoded bioactive molecule from the mRNA template can improve the pharmacokinetic, pharmacodynamic and safety properties as compared to the respective recombinant proteins. This may be harnessed for applications that benefit from a higher level of expression control, such as chimeric antigen receptor (CAR)-modified adoptive T-cell therapies. This review highlights the advancements in the field of mRNA-based cancer therapeutics, providing insights into key preclinical developments and the evolving clinical landscape.
Water dissociation on transition-metal catalysts is an important step in steam reforming and the water-gas shift reaction. To probe the effect of translational and vibrational activation on this ...important heterogeneous reaction, we performed state-resolved gas/surface reactivity measurements for the dissociative chemisorption of D2O on Ni(111), using molecular beam techniques. The reaction occurs via a direct pathway, because both the translational and vibrational energies promote the dissociation. The experimentally measured initial sticking probabilities were used to calibrate a first-principles potential energy surface based on density functional theory. Quantum dynamical calculations on the scaled potential energy surface reproduced the experimental results semiquantitatively. The larger increase of the dissociation probability by vibrational excitation than by translation per unit of energy is consistent with a late barrier along the O-D stretch reaction coordinate.
Methane is an essential component of the global carbon cycle and one of the most powerful greenhouse gases, yet it is also a promising alternative source of carbon for the biological production of ...value-added chemicals. Aerobic methane-consuming bacteria (methanotrophs) represent a potential biological platform for methane-based biocatalysis. Here we use a multi-pronged systems-level approach to reassess the metabolic functions for methane utilization in a promising bacterial biocatalyst. We demonstrate that methane assimilation is coupled with a highly efficient pyrophosphate-mediated glycolytic pathway, which under oxygen limitation participates in a novel form of fermentation-based methanotrophy. This surprising discovery suggests a novel mode of methane utilization in oxygen-limited environments, and opens new opportunities for a modular approach towards producing a variety of excreted chemical products using methane as a feedstock.
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the ...past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
The properties of exotic nuclei on the verge of existence play a fundamental part in our understanding of nuclear interactions. Exceedingly neutron-rich nuclei become sensitive to new aspects of ...nuclear forces. Calcium, with its doubly magic isotopes (40)Ca and (48)Ca, is an ideal test for nuclear shell evolution, from the valley of stability to the limits of existence. With a closed proton shell, the calcium isotopes mark the frontier for calculations with three-nucleon forces from chiral effective field theory. Whereas predictions for the masses of (51)Ca and (52)Ca have been validated by direct measurements, it is an open question as to how nuclear masses evolve for heavier calcium isotopes. Here we report the mass determination of the exotic calcium isotopes (53)Ca and (54)Ca, using the multi-reflection time-of-flight mass spectrometer of ISOLTRAP at CERN. The measured masses unambiguously establish a prominent shell closure at neutron number N = 32, in excellent agreement with our theoretical calculations. These results increase our understanding of neutron-rich matter and pin down the subtle components of nuclear forces that are at the forefront of theoretical developments constrained by quantum chromodynamics.
This report describes prevalence, severity, and extent of periodontitis in the US adult population using combined data from the 2009 to 2010 and 2011 to 2012 cycles of the National Health and ...Nutrition Examination Survey (NHANES).
Estimates were derived for dentate adults, aged ≥30 years, from the US civilian non-institutionalized population. Periodontitis was defined by combinations of clinical attachment loss (AL) and periodontal probing depth (PD) from six sites per tooth on all teeth, except third molars, using standard surveillance case definitions. For the first time in NHANES history, sufficient numbers of non-Hispanic Asians were sampled in 2011 to 2012 to provide reliable estimates of their periodontitis prevalence.
In 2009 to 2012, 46% of US adults, representing 64.7 million people, had periodontitis, with 8.9% having severe periodontitis. Overall, 3.8% of all periodontal sites (10.6% of all teeth) had PD ≥4 mm, and 19.3% of sites (37.4% teeth) had AL ≥3 mm. Periodontitis prevalence was positively associated with increasing age and was higher among males. Periodontitis prevalence was highest in Hispanics (63.5%) and non-Hispanic blacks (59.1%), followed by non-Hispanic Asian Americans (50.0%), and lowest in non-Hispanic whites (40.8%). Prevalence varied two-fold between the lowest and highest levels of socioeconomic status, whether defined by poverty or education.
This study confirms a high prevalence of periodontitis in US adults aged ≥30 years, with almost fifty-percent affected. The prevalence was greater in non-Hispanic Asians than non-Hispanic whites, although lower than other minorities. The distribution provides valuable information for population-based action to prevent or manage periodontitis in US adults.
Abstract
Background
To review the validated instruments that assess gait, balance, and functional mobility to predict falls in older adults across different settings.
Methods
Umbrella review of ...narrative- and systematic reviews with or without meta-analyses of all study types. Reviews that focused on older adults in any settings and included validated instruments assessing gait, balance, and functional mobility were included. Medical and allied health professional databases (MEDLINE, PsychINFO, Embase, and Cochrane) were searched from inception to April 2022. Two reviewers undertook title, abstract, and full text screening independently. Review quality was assessed through the Risk of Bias Assessment Tool for Systematic Reviews (ROBIS). Data extraction was completed in duplicate using a standardised spreadsheet and a narrative synthesis presented for each assessment tool.
Results
Among 2736 articles initially identified, 31 reviews were included; 11 were meta-analyses. Reviews were primarily of low quality, thus at high risk of potential bias. The most frequently reported assessments were: Timed Up and Go, Berg Balance Scale, gait speed, dual task assessments, single leg stance, functional Reach Test, tandem gait and stance and the chair stand test. Findings on the predictive ability of these tests were inconsistent across the reviews.
Conclusions
In conclusion, we found that no single gait, balance or functional mobility assessment in isolation can be used to predict fall risk in older adults with high certainty. Moderate evidence suggests gait speed can be useful in predicting falls and might be included as part of a comprehensive evaluation for older adults.
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