4,665 research outputs found
Q
© International Union of Crystallography, 2017. Quantum-based refinement utilizes chemical restraints derived from quantum-chemical methods instead of the standard parameterized library-based restraints used in refinement packages. The motivation is twofold: firstly, the restraints have the potential to be more accurate, and secondly, the restraints can be more easily applied to new molecules such as drugs or novel cofactors. Here, a new project called Q|R aimed at developing quantum-based refinement of biomacromolecules is under active development by researchers at Shanghai University together with PHENIX developers. The central focus of this long-term project is to develop software that is built on top of open-source components. A development version of Q|R was used to compare quantum-based refinements with standard refinement using a small model system.Quantum-based refinement software is being developed to refine biomacromolecules against crystallographic or cryo-electron microscopy data
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Dynamic Covalent Synthesis of Crystalline Porous Graphitic Frameworks
Porous graphitic framework (PGF) is a two-dimensional (2D) material that has emerging energy applications. An archetype contains stacked 2D layers, the structure of which features a fully annulated aromatic skeleton with embedded heteroatoms and periodic pores. Due to the lack of a rational approach in establishing in-plane order under mild synthetic conditions, the structural integrity of PGF has remained elusive and ultimately limited its material performance. Here, we report the discovery of the unusual dynamic character of the C=N bonds in the aromatic pyrazine ring system under basic aqueous conditions, which enables the successful synthesis of a crystalline porous nitrogenous graphitic framework with remarkable in-plane order, as evidenced by powder X-ray diffraction studies and direct visualization using high-resolution transmission electron microscopy. The crystalline framework displays superior performance as a cathode material for lithium-ion batteries, outperforming the amorphous counterparts in terms of capacity and cycle stability. Insertion of well-defined, evenly spaced nanoscale pores into the two-dimensional (2D) layers of graphene invokes exciting properties due to the modulation of its electronic band gaps and surface functionalities. A bottom-up synthesis approach to such porous graphitic frameworks (PGFs) is appealing but also remains a great challenge. The current methods of building covalent organic frameworks rely on a small collection of thermodynamically reversible reactions. Such reactions are, however, inadequate in generating a fully annulated aromatic skeleton in PGFs. With the discovery of dynamic pyrazine formation, we succeeded in applying this linking chemistry to obtain a crystalline PGF material, which has displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries. We envision that the demonstrated success will open the door to a wide array of fully annulated 2D porous frameworks, which hold immense potential for clean energy applications. We report the unusual dynamic characteristics of the C=N bonds in the pyrazine ring promoted under basic aqueous conditions, which enables the successful synthesis of two-dimensional porous graphitic frameworks (PGFs) featuring fully annulated aromatic skeletons and periodic pores. The PGF displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries, far outperforming the amorphous counterparts in terms of capacity and cycle stability
Unary probabilistic and quantum automata on promise problems
We continue the systematic investigation of probabilistic and quantum finite
automata (PFAs and QFAs) on promise problems by focusing on unary languages. We
show that bounded-error QFAs are more powerful than PFAs. But, in contrary to
the binary problems, the computational powers of Las-Vegas QFAs and
bounded-error PFAs are equivalent to deterministic finite automata (DFAs).
Lastly, we present a new family of unary promise problems with two parameters
such that when fixing one parameter QFAs can be exponentially more succinct
than PFAs and when fixing the other parameter PFAs can be exponentially more
succinct than DFAs.Comment: Minor correction
Unified force law for granular impact cratering
Experiments on the low-speed impact of solid objects into granular media have
been used both to mimic geophysical events and to probe the unusual nature of
the granular state of matter. Observations have been interpreted in terms of
conflicting stopping forces: product of powers of projectile depth and speed;
linear in speed; constant, proportional to the initial impact speed; and
proportional to depth. This is reminiscent of high-speed ballistics impact in
the 19th and 20th centuries, when a plethora of empirical rules were proposed.
To make progress, we developed a means to measure projectile dynamics with 100
nm and 20 us precision. For a 1-inch diameter steel sphere dropped from a wide
range of heights into non-cohesive glass beads, we reproduce prior observations
either as reasonable approximations or as limiting behaviours. Furthermore, we
demonstrate that the interaction between projectile and medium can be
decomposed into the sum of velocity-dependent inertial drag plus
depth-dependent friction. Thus we achieve a unified description of low-speed
impact phenomena and show that the complex response of granular materials to
impact, while fundamentally different from that of liquids and solids, can be
simply understood
Quantum spin liquid states in the two dimensional kagome antiferromagnets, ZnxCu4-x(OD)6Cl2
A three-dimensional system of interacting spins typically develops static
long-range order when it is cooled. If the spins are quantum (S = 1/2),
however, novel quantum paramagnetic states may appear. The most highly sought
state among them is the resonating valence bond (RVB) state in which every pair
of neighboring quantum spins form entangled spin singlets (valence bonds) and
the singlets are quantum mechanically resonating amongst all the possible
highly degenerate pairing states. Here we provide experimental evidence for
such quantum paramagnetic states existing in frustrated antiferromagnets,
ZnxCu4-x(OD)6Cl2, where the S = 1/2 magnetic Cu2+ moments form layers of a
two-dimensional kagome lattice. We find that in Cu4(OD)6Cl2, where distorted
kagome planes are weakly coupled to each other, a dispersionless excitation
mode appears in the magnetic excitation spectrum below ~ 20 K, whose
characteristics resemble those of quantum spin singlets in a solid state, known
as a valence bond solid (VBS), that breaks translational symmetry. Doping
nonmagnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens
the interplane coupling but also dilutes the magnetic occupancy of the kagome
lattice. The VBS state is suppressed and for ZnCu3(OD)6Cl2 where the kagome
planes are undistorted and 90% occupied by the Cu2+ ions, the low energy spin
fluctuations in the spin liquid phase become featureless
CXD101 and nivolumab in patients with metastatic microsatellite-stable colorectal cancer (CAROSELL): a multicentre, open-label, single-arm, phase II trial.
BACKGROUND: Patients with microsatellite stable (MSS) colorectal carcinoma (CRC) do not respond to immune checkpoint inhibitors. Preclinical models suggested synergistic anti-tumour activity combining CXD101 and anti-programmed cell death protein 1 treatment; therefore, we assessed the clinical combination of CXD101 and nivolumab in heavily pre-treated patients with MSS metastatic CRC (mCRC). PATIENTS AND METHODS: This single-arm, open-label study enrolled patients aged 18 years or older with biopsy-confirmed MSS CRC; at least two lines of systemic anticancer therapies (including oxaliplatin and irinotecan); at least one measurable lesion; Eastern Cooperative Oncology Group performance status of 0, 1 or 2; predicted life expectancy above 3 months; and adequate organ and bone marrow function. Nine patients were enrolled in a safety run-in study to define a tolerable combination schedule of CXD101 and nivolumab, followed by 46 patients in the efficacy assessment phase. Patients in the efficacy assessment cohort were treated orally with 20 mg CXD101 twice daily for 5 consecutive days every 3 weeks, and intravenously with 240 mg nivolumab every 2 weeks. The primary endpoint was immune disease control rate (iDCR). RESULTS: Between 2018 and 2020, 55 patients were treated with CXD101 and nivolumab. The combination therapy was well tolerated with the most frequent grade 3 or 4 adverse events being neutropenia (18%) and anaemia (7%). Immune-related adverse reactions commonly ascribed to checkpoint inhibitors were surprisingly rare although we did see single cases of pneumonitis, hypothyroidism and hypopituitarism. There were no treatment-related deaths. Of 46 patients assessable for efficacy, 4 (9%) achieved partial response and 18 (39%) achieved stable disease, translating to an immune disease control rate of 48%. The median overall survival (OS) was 7.0 months (95% confidence interval 5.13-10.22 months). CONCLUSIONS: The primary endpoint was met in this phase II study, which showed that the combination of CXD101 and nivolumab, at full individual doses in the treatment of advanced or metastatic MSS CRC, was both well tolerated and efficacious
Direct observation of local K variation and its correlation to electronic inhomogeneity in (Ba1-xKx)Fe2As2 Pnictide
Local fluctuations in the distribution of dopant atoms are a suspected cause
of nanoscale electronic disorder or phase separation observed within the
pnictide superconductors. Atom probe tomography results present the first
direct observations of dopant nano-clustering in a K-doped 122-phase pnictides.
First-principles calculations suggest the coexistence of static magnetism and
superconductivity on a lattice parameter length scale over a large range of
doping concentrations. Collectively, our results provide evidence for a mixed
scenario of phase coexistence and phase separation originating from variation
of dopant atom experiments distroibutions.Comment: 4 pages, 4 figures and 1 table, accepted by Physical Review Letter
201
Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1
We investigate the evolution in the distribution of surface brightness, as a
function of size, for elliptical and S0 galaxies in the two clusters RDCS
J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging
with the Advanced Camera for Surveys on the Hubble Space Telescope to determine
these sizes and surface brightnesses. Using three different estimates of the
surface brightnesses, we find that we reliably estimate the surface brightness
for the galaxies in our sample with a scatter of < 0.2 mag and with systematic
shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type
morphologies in both clusters. For each cluster, we use a magnitude limit in a
band which closely corresponds to the rest-frame B, to magnitude limit of M_B =
-18.8 at z=0, and select only those galaxies within the color-magnitude
sequence of the cluster or by using our spectroscopic redshifts. We measure
evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag
from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag
of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15)
z mag. Our statistical errors are dominated by the observed scatter in the
size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX
J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no
statistically significant evolution in this scatter, though an increase in the
scatter could be expected. Overall, the pace of luminosity evolution we measure
agrees with that of the Fundamental Plane of early-type galaxies, implying that
the majority of massive early-type galaxies observed at z =~ 1 formed at high
redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6
in colo
Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.
Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives
Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer
BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com
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