The increasing richness of data related to cold dense matter, from laboratory experiments to neutron-star observations, requires a framework for constraining the properties of such matter that makes ...use of all relevant information. Here, we present a rigorous but practical Bayesian approach that can include diverse evidence, such as nuclear data and the inferred masses, radii, tidal deformabilities, moments of inertia, and gravitational binding energies of neutron stars. We emphasize that the full posterior probability distributions of measurements should be used rather than, as is common, imposing a cut on the maximum mass or other quantities. Our method can be used with any parameterization of the equation of state (EOS). We use both a spectral parameterization and a piecewise polytropic parameterization with variable transition densities to illustrate the implications of current measurements and show how future measurements in many domains could improve our understanding of cold catalyzed matter. We find that different types of measurements will play distinct roles in constraining the EOS in different density ranges. For example, better symmetry energy measurements will have a major influence on our understanding of matter somewhat below nuclear saturation density but little influence above that density. In contrast, precise radius measurements or multiple tidal deformability measurements of the quality of those from GW170817 or better will improve our knowledge of the EOS over a broader density range.
Abstract
PSR J0740+6620 has a gravitational mass of 2.08 ± 0.07
M
⊙
, which is the highest reliably determined mass of any neutron star. As a result, a measurement of its radius will provide unique ...insight into the properties of neutron star core matter at high densities. Here we report a radius measurement based on fits of rotating hot spot patterns to Neutron Star Interior Composition Explorer (NICER) and X-ray Multi-Mirror (XMM-Newton) X-ray observations. We find that the equatorial circumferential radius of PSR J0740+6620 is
13.7
−
1.5
+
2.6
km (68%). We apply our measurement, combined with the previous NICER mass and radius measurement of PSR J0030+0451, the masses of two other ∼2
M
⊙
pulsars, and the tidal deformability constraints from two gravitational wave events, to three different frameworks for equation-of-state modeling, and find consistent results at ∼1.5–5 times nuclear saturation density. For a given framework, when all measurements are included, the radius of a 1.4
M
⊙
neutron star is known to ±4% (68% credibility) and the radius of a 2.08
M
⊙
neutron star is known to ±5%. The full radius range that spans the ±1
σ
credible intervals of all the radius estimates in the three frameworks is 12.45 ± 0.65 km for a 1.4
M
⊙
neutron star and 12.35 ± 0.75 km for a 2.08
M
⊙
neutron star.
In preparation for bidirectional DNA replication, the origin recognition complex (ORC) loads two hexameric MCM helicases to form a head-to-head double hexamer around DNA
. The mechanism of MCM ...double-hexamer formation is debated. Single-molecule experiments have suggested a sequential mechanism, in which the ORC-dependent loading of the first hexamer drives the recruitment of the second hexamer
. By contrast, biochemical data have shown that two rings are loaded independently via the same ORC-mediated mechanism, at two inverted DNA sites
. Here we visualize MCM loading using time-resolved electron microscopy, and identify intermediates in the formation of the double hexamer. We confirm that both hexamers are recruited via the same interaction that occurs between ORC and the C-terminal domains of the MCM helicases. Moreover, we identify the mechanism of coupled MCM loading. The loading of the first MCM hexamer around DNA creates a distinct interaction site, which promotes the engagement of ORC at the N-terminal homodimerization interface of MCM. In this configuration, ORC is poised to direct the recruitment of the second hexamer in an inverted orientation, which is suitable for the formation of the double hexamer. Our results therefore reconcile the two apparently contrasting models derived from single-molecule experiments and biochemical data.
Hundreds of stellar-mass black holes probably form in a typical globular star cluster, with all but one predicted to be ejected through dynamical interactions. Some observational support for this ...idea is provided by the lack of X-ray-emitting binary stars comprising one black hole and one other star ('black-hole/X-ray binaries') in Milky Way globular clusters, even though many neutron-star/X-ray binaries are known. Although a few black holes have been seen in globular clusters around other galaxies, the masses of these cannot be determined, and some may be intermediate-mass black holes that form through exotic mechanisms. Here we report the presence of two flat-spectrum radio sources in the Milky Way globular cluster M22, and we argue that these objects are black holes of stellar mass (each ∼10-20 times more massive than the Sun) that are accreting matter. We find a high ratio of radio-to-X-ray flux for these black holes, consistent with the larger predicted masses of black holes in globular clusters compared to those outside. The identification of two black holes in one cluster shows that ejection of black holes is not as efficient as predicted by most models, and we argue that M22 may contain a total population of ∼5-100 black holes. The large core radius of M22 could arise from heating produced by the black holes.
Chemokines from a Structural Perspective Miller, Michelle C; Mayo, Kevin H
International journal of molecular sciences,
10/2017, Letnik:
18, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Chemokines are a family of small, highly conserved cytokines that mediate various biological processes, including chemotaxis, hematopoiesis, and angiogenesis, and that function by interacting with ...cell surface G-Protein Coupled Receptors (GPCRs). Because of their significant involvement in various biological functions and pathologies, chemokines and their receptors have been the focus of therapeutic discovery for clinical intervention. There are several sub-families of chemokines (e.g., CXC, CC, C, and CX3C) defined by the positions of sequentially conserved cysteine residues. Even though all chemokines also have a highly conserved, three-stranded β-sheet/α-helix tertiary structural fold, their quarternary structures vary significantly with their sub-family. Moreover, their conserved tertiary structures allow for subunit swapping within and between sub-family members, thus promoting the concept of a "chemokine interactome". This review is focused on structural aspects of CXC and CC chemokines, their functional synergy and ability to form heterodimers within the chemokine interactome, and some recent developments in structure-based chemokine-targeted drug discovery.
We discuss residual finiteness and several related separability conditions for the class of monoid acts, namely weak subact separability, strong subact separability and complete separability. For ...each of these four separability conditions, we investigate which monoids have the property that all their (finitely generated) acts satisfy the condition. In particular, we prove that: all acts over a finite monoid are completely separable (and hence satisfy the other three separability conditions); all finitely generated acts over a finitely generated commutative monoid are residually finite and strongly subact separable (and hence weakly subact separable); all acts over a commutative idempotent monoid are residually finite and strongly subact separable; and all acts over a Clifford monoid are strongly subact separable.
Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. ...The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Löffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are relentlessly progressive neurodegenerative disorders with overlapping clinical, genetic and pathological features. ...Cytoplasmic inclusions of fused in sarcoma (FUS) are the hallmark of several forms of FTLD and ALS patients with mutations in the
FUS
gene. FUS is a multifunctional, predominantly nuclear, DNA and RNA binding protein. Here, we report that transgenic mice overexpressing wild-type human FUS develop an aggressive phenotype with an early onset tremor followed by progressive hind limb paralysis and death by 12 weeks in homozygous animals. Large motor neurons were lost from the spinal cord accompanied by neurophysiological evidence of denervation and focal muscle atrophy. Surviving motor neurons in the spinal cord had greatly increased cytoplasmic expression of FUS, with globular and skein-like FUS-positive and ubiquitin-negative inclusions associated with astroglial and microglial reactivity. Cytoplasmic FUS inclusions were also detected in the brain of transgenic mice without apparent neuronal loss and little astroglial or microglial activation. Hemizygous FUS overexpressing mice showed no evidence of a motor phenotype or pathology. These findings recapitulate several pathological features seen in human ALS and FTLD patients, and suggest that overexpression of wild-type FUS in vulnerable neurons may be one of the root causes of disease. Furthermore, these mice will provide a new model to study disease mechanism, and test therapies.
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