1,451 research outputs found
Ultraviolet Complete Quantum Gravity
An ultraviolet complete quantum gravity theory is formulated in which vertex
functions in Feynman graphs are entire functions and the propagating graviton
is described by a local, causal propagator. The cosmological constant problem
is investigated in the context of the ultraviolet complete quantum gravity.Comment: 11 pages, no figures. Changes to text. Results remain the same.
References added. To be published in European Physics Journal Plu
Evolution of Protein-Mediated Biomineralization in Scleractinian Corals
While recent strides have been made in understanding the biological process by which stony corals calcify, much remains to be revealed, including the ubiquity across taxa of specific biomolecules involved. Several proteins associated with this process have been identified through proteomic profiling of the skeletal organic matrix (SOM) extracted from three scleractinian species. However, the evolutionary history of this putative âbiomineralization toolkit,â including the appearance of these proteinsâ throughout metazoan evolution, remains to be resolved. Here we used a phylogenetic approach to examine the evolution of the known scleractiniansâ SOM proteins across the Metazoa. Our analysis reveals an evolutionary process dominated by the co-option of genes that originated before the cnidarian diversification. Each one of the three species appears to express a unique set of the more ancient genes, representing the independent co-option of SOM proteins, as well as a substantial proportion of proteins that evolved independently. In addition, in some instances, the different species expressed multiple orthologous proteins sharing the same evolutionary history. Furthermore, the non-random clustering of multiple SOM proteins within scleractinian-specific branches suggests the conservation of protein function between distinct species for what we posit is part of the scleractinian âcore biomineralization toolkit.â This âcore setâ contains proteins that are likely fundamental to the scleractinian biomineralization mechanism. From this analysis, we infer that the scleractiniansâ ability to calcify was achieved primarily through multiple lineage-specific protein expansions, which resulted in a new functional role that was not present in the parent gene
Ex post aggregate real rates of return in Canada: 1947-1976
Cover title"June 1981."Series statement handwritten on cover"This is a draft of a study to be published by the Economic Council of Canada. It is made available to participants in the Rates of Return Conference on the strict understanding that it is not to be circulated or quoted without permission from the Economic Council of Canada."Includes bibliographical references (p. 77-80
Evaluation of the Energy Value and Nutrient Digestibility of Distillers Grains That Have Undergone a Fiber Separation Process in Finishing Diets
A digestion study was conducted to determine the effects of feeding a new, high protein distillers grains and corn bran plus solubles on nutrient digestibility. Treatments included a corn-based control, high protein distillers at both 20% and 40%, corn bran plus solubles, traditional wet distillers grains and traditional dry distillers grains all at 40% of diet DM. Feeding high protein distillers grains or corn bran plus solubles resulted in decreased digestibility compared to corn or traditional wet and dry distillers grains, but increased energy intake. Traditional wet and dry distillers grains also resulted in decreased digestibilities while energy intake was increased. Volatile fatty acid profiles and pH parameters were not different across treatments. Overall, nutrient digestibility for high protein distillers grains and corn bran plus solubles is similar to traditional wet or dry distillers grains
Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery
Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 ΌM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening
HER2 testing in breast cancer: Opportunities and challenges
Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results
Integrate and Fire Neural Networks, Piecewise Contractive Maps and Limit Cycles
We study the global dynamics of integrate and fire neural networks composed
of an arbitrary number of identical neurons interacting by inhibition and
excitation. We prove that if the interactions are strong enough, then the
support of the stable asymptotic dynamics consists of limit cycles. We also
find sufficient conditions for the synchronization of networks containing
excitatory neurons. The proofs are based on the analysis of the equivalent
dynamics of a piecewise continuous Poincar\'e map associated to the system. We
show that for strong interactions the Poincar\'e map is piecewise contractive.
Using this contraction property, we prove that there exist a countable number
of limit cycles attracting all the orbits dropping into the stable subset of
the phase space. This result applies not only to the Poincar\'e map under
study, but also to a wide class of general n-dimensional piecewise contractive
maps.Comment: 46 pages. In this version we added many comments suggested by the
referees all along the paper, we changed the introduction and the section
containing the conclusions. The final version will appear in Journal of
Mathematical Biology of SPRINGER and will be available at
http://www.springerlink.com/content/0303-681
Non-equilibrium stationary state of a two-temperature spin chain
A kinetic one-dimensional Ising model is coupled to two heat baths, such that
spins at even (odd) lattice sites experience a temperature ().
Spin flips occur with Glauber-type rates generalised to the case of two
temperatures. Driven by the temperature differential, the spin chain settles
into a non-equilibrium steady state which corresponds to the stationary
solution of a master equation. We construct a perturbation expansion of this
master equation in terms of the temperature difference and compute explicitly
the first two corrections to the equilibrium Boltzmann distribution. The key
result is the emergence of additional spin operators in the steady state,
increasing in spatial range and order of spin products. We comment on the
violation of detailed balance and entropy production in the steady state.Comment: 11 pages, 1 figure, Revte
Ă-Methylphenylethylamines: Common fragmentation pathways with amphetamines in electrospray ionization collision-induced dissociation
ÎČ-Methylphenylethylamines are positional isomers of amphetamines and have been discovered in sporting supplements. Although the fragmentation of the ÎČ-methylphenylethylamine and N-methyl-ÎČ-methylphenylethylamine in gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) systems is significantly different to their amphetamine and methylamphetamine isomers, under electrospray ionization commonly used in liquid chromatography-mass spectrometry (LC-MS) systems, the fragmentation of each of the isomeric pairs is almost identical. The similarities in fragmentation make it possible for the misidentification of the ÎČ-methylphenylethylamines as the illicit amphetamines. It is proposed that the similarities are due to a fragmentation pathway involving a common phenonium ion intermediate. By careful control of fragmentation energies in liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems and/or close examination of the relative abundances of product ions formed by collision-induced dissociation (qualifier ratios), it is possible to distinguish the ÎČ-methylphenylethylamines from the amphetamines, even if significant retention time separation is not achieved. In liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF) systems the mass spectra of the ÎČ-methylphenylethylamines are identical to their amphetamine isomers. In such systems, retention time separation of the isomers is critical to avoid misidentification. During this study ÎČ-methylphenylethylamine and N-methyl-ÎČ-methylphenylethylamine have been identified in commercially available sporting supplements and oral fluid samples taken during the course of road-side drugs-in-drivers and workplace testing programmes
Light quark masses and pseudoscalar decay constants from Nf=2 Lattice QCD with twisted mass fermions
We present the results of a lattice QCD calculation of the average up-down
and strange quark masses and of the light meson pseudoscalar decay constants
with Nf=2 dynamical fermions. The simulation is carried out at a single value
of the lattice spacing with the twisted mass fermionic action at maximal twist,
which guarantees automatic O(a)-improvement of the physical quantities. Quark
masses are renormalized by implementing the non-perturbative RI-MOM
renormalization procedure. Our results for the light quark masses are
m_ud^{msbar}(2 GeV)= 3.85 +- 0.12 +- 0.40 MeV, m_s^{msbar}(2 GeV) = 105 +- 3 +-
9 MeV and m_s/m_ud = 27.3 +- 0.3 +- 1.2. We also obtain fK = 161.7 +- 1.2 +-
3.1 MeV and the ratio fK/fpi=1.227 +- 0.009 +- 0.024. From this ratio, by using
the experimental determination of Gamma(K-> mu nu (gamma))/Gamma(pi -> mu nu
(gamma)) and the average value of |Vud| from nuclear beta decays, we obtain
|Vus|=0.2192(5)(45), in agreement with the determination from Kl3 decays and
the unitarity constraint.Comment: 20 pages, 5 figure
- âŠ