12,141 research outputs found
The spectral variability of FSRQs
The optical variability of 29 flat spectrum radio quasars in SDSS Stripe 82
region are investigated by using DR7 released multi-epoch data. All FSRQs show
variations with overall amplitude ranging from 0.24 mag to 3.46 mag in
different sources. About half of FSRQs show a bluer-when-brighter trend, which
is commonly observed for blazars. However, only one source shows a
redder-when-brighter trend, which implies it is rare in FSRQs. In this source,
the thermal emission may likely be responsible for the spectral behavior.Comment: 4 pages, 1 figure, to be published in Journal of Astrophysics and
Astronomy, as a proceeding paper of the conference "Multiwavelength
Variability of Blazars", Guangzhou, China, September 22-24, 201
Functional properties, structural studies and chemoenzymatic synthesis of oligosaccharides
Oligosaccharides offer beneficial effects on immune system and gut health, such as anticancer activity, immunomodulatory activity, and complement activation. Functional oligosaccharides are widely found in plants, algae, bacteria and higher fungi. Milk oligosaccharides, especially human milk oligosaccharides, have considerable health benefits, such as the growth-promotion of the beneficial bacterial flora in the intestines, and developing resistance to bactertial and viral infections. Recent developments in high performance liquid chromatography, mass spectrometry, nuclear magnetic resonance and capillary electrophoresis techniques contribute to the analysis of the oligosaccharide identification and mixture quantification. Synthesis of oligosaccharides is becoming increasingly important to pharmaceutical industries, in which chemo-enzymatic synthesis is considered as an effective method. This article gives a brief summary of structures, accessible sources, physiological and chemical characteristics, and potential health benefits of functional oligosaccharides
Atrial fibrillation impairs the diagnostic performance of cardiac natriuretic peptides in dyspneic patients. results from the BACH Study (Biomarkers in ACute Heart Failure)
Objectives: The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance of mid-region amino terminal pro-atrial natriuretic peptide (MR-proANP) in comparison with the B-type peptides (BNP and NT-proBNP) for diagnosis of acute heart failure (HF) in dyspneic patients. Background: The effects of AF on the diagnostic and prognostic performance of MR-proANP in comparison with the B type natriuretic peptides have not been previously reported. Methods: A total of 1,445 patients attending the emergency department with acute dyspnea had measurements taken of MR-proANP, BNP, and NT-proBNP values on enrollment to the BACH trial and were grouped according to presence or absence of AF and HF. Results: AF was present in 242 patients. Plasma concentrations of all three peptides were lowest in those with neither AF nor HF and AF without HF was associated with markedly increased levels (p < 0.00001). HF with or without AF was associated with a significant further increment (p < 0.00001 for all three markers). Areas under receiver operator characteristic curves (AUCs) for discrimination of acute HF were similar and powerful for all peptides without AF (0.893 to 0.912; all p < 0.001) with substantial and similar reductions (0.701 to 0.757) in the presence of AF. All 3 peptides were independently prognostic but there was no interaction between any peptide and AF for prediction of all-cause mortality. Conclusions: AF is associated with increased plasma natriuretic peptide (MR-proANP, BNP and NT-proBNP) levels in the absence of HF. The diagnostic performance of all three peptides is impaired by AF. This warrants consideration of adjusted peptide thresholds for diagnostic use in AF and mandates the continued search for markers free of confounding by AF
An SU(N) Mott insulator of an atomic Fermi gas realized by large-spin Pomeranchuk cooling
The Hubbard model, containing only the minimum ingredients of nearest
neighbor hopping and on-site interaction for correlated electrons, has
succeeded in accounting for diverse phenomena observed in solid-state
materials. One of the interesting extensions is to enlarge its spin symmetry to
SU(N>2), which is closely related to systems with orbital degeneracy. Here we
report a successful formation of the SU(6) symmetric Mott insulator state with
an atomic Fermi gas of ytterbium (173Yb) in a three-dimensional optical
lattice. Besides the suppression of compressibility and the existence of charge
excitation gap which characterize a Mott insulating phase, we reveal an
important difference between the cases of SU(6) and SU(2) in the achievable
temperature as the consequence of different entropy carried by an isolated
spin. This is analogous to Pomeranchuk cooling in solid 3He and will be helpful
for investigating exotic quantum phases of SU(N) Hubbard system at extremely
low temperatures.Comment: 20 pages, 6 figures, to appear in Nature Physic
Social interactions through the eyes of macaques and humans
Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions) to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression). Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys’ gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of social attention between rhesus macaques and humans
Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.
BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity
Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle
Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time
Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial
Background
Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges.
Methods
We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented).
Results
At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points.
Conclusion
In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes
Structure of the hDmc1-ssDNA filament reveals the principles of its architecture
In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination
Many-body Landau-Zener dynamics in coupled 1D Bose liquids
The Landau-Zener model of a quantum mechanical two-level system driven with a
linearly time dependent detuning has served over decades as a textbook paradigm
of quantum dynamics. In their seminal work [L. D. Landau, Physik. Z. Sowjet. 2,
46 (1932); C. Zener, Proc. Royal Soc. London 137, 696 (1932)], Landau and Zener
derived a non-perturbative prediction for the transition probability between
two states, which often serves as a reference point for the analysis of more
complex systems. A particularly intriguing question is whether that framework
can be extended to describe many-body quantum dynamics. Here we report an
experimental and theoretical study of a system of ultracold atoms, offering a
direct many-body generalization of the Landau-Zener problem. In a system of
pairwise tunnel-coupled 1D Bose liquids we show how tuning the correlations of
the 1D gases, the tunnel coupling between the tubes and the inter-tube
interactions strongly modify the original Landau-Zener picture. The results are
explained using a mean-field description of the inter-tube condensate
wave-function, coupled to the low-energy phonons of the 1D Bose liquid.Comment: 13 pages, 10 figures
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