Selection for Catalytic Function with Nucleic Acids

For in vitro selection of catalytic polynucleotides, each new protocol must be designed to harness the desired catalytic activity to help propel the selection process itself. This unit gives guidelines for design of in vitro selection experiments for catalytic function. It outlines several representative protocols as examples of successful selection experiments, providing a conceptual basis for the design and implementation of new selective‐amplification protocols for nucleic acids.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143687/1/cpnc0904.pd

Photonuclear reactions of actinides in the giant dipole resonance region

Photonuclear reactions at energies covering the giant dipole resonance (GDR) region are analyzed with an approach based on nuclear photoabsorption followed by the process of competition between light particle evaporation and fission for the excited nucleus. The photoabsorption cross section at energies covering the GDR region is contributed by both the Lorentz type GDR cross section and the quasideuteron cross section. The evaporation-fission process of the compound nucleus is simulated in a Monte-Carlo framework. Photofission reaction cross sections are analyzed in a systematic manner in the energy range of $\sim$ 10-20 MeV for the actinides $^{232}$Th, $^{238}$U and $^{237}$Np. Photonuclear cross sections for the medium-mass nuclei $^{63}$Cu and $^{64}$Zn, for which there are no fission events, are also presented. The study reproduces satisfactorily the available experimental data of photofission cross sections at GDR energy region and the increasing trend of nuclear fissility with the fissility parameter $Z^2/A$ for the actinides.Comment: 4 pages including 2 tables and 1 figur

Evaluating synergy between marbofloxacin and gentamicin in Pseudomonas aeruginosa strains isolated from dogs with otitis externa

The aim of this study was to determine antimicrobial susceptibility of Pseudomonas aeruginosa strains to marbofloxacin and gentamicin, and investigate the possible synergistic, additive, indifferent or antagonistic effects between the two agents. P. aeruginosa strains can develop resistance quickly against certain antibiotics if used alone, thus the need emerges to find synergistic combinations. A total of 68 P. aeruginosa strains isolated from dogs were examined. In order to describe interactions between marbofloxacin and gentamicin the checkerboard microdilution method was utilized. The MICs (minimum inhibitory concentrations) for marbofloxacin and gentamicin were in the range 0.25–64 mg/L and 0.25–32 mg/L, respectively. The combination of marbofloxacin and gentamicin was more effective with a MIC range of 0.031–8 mg/L and a MIC90 of 1 mg/L, compared to 16 mg/L for marbofloxacin alone and 8 mg/L for gentamicin alone. The FIC (fractional inhibitory concentration) indices ranged from 0.0945 (pronounced synergy) to 1.0625 (indifference). Synergy between marbofloxacin and gentamicin was found in 33 isolates. The mean FIC index is 0.546, which represents a partial synergistic/additive effect close to the full synergy threshold. In vitro results indicate that marbofloxacin and gentamicin as partially synergistic agents may prove clinically useful in combination therapy against P. aeruginosa infections. Although marbofloxacin is not used in the human practice, the interactions between fluoroquinolones and aminoglycosides may have importance outside the veterinary field

Observers and Locality in Everett Quantum Field Theory

A model for measurement in collapse-free nonrelativistic fermionic quantum field theory is presented. In addition to local propagation and effectively-local interactions, the model incorporates explicit representations of localized observers, thus extending an earlier model of entanglement generation in Everett quantum field theory [M. A. Rubin, Found. Phys. 32, 1495-1523 (2002)]. Transformations of the field operators from the Heisenberg picture to the Deutsch-Hayden picture, involving fictitious auxiliary fields, establish the locality of the model. The model is applied to manifestly-local calculations of the results of measurements, using a type of sudden approximation and in the limit of massive systems in narrow-wavepacket states. Detection of the presence of a spin-1/2 system in a given spin state by a freely-moving two-state observer illustrates the features of the model and the nonperturbative computational methodology. With the help of perturbation theory the model is applied to a calculation of the quintessential "nonlocal" quantum phenomenon, spin correlations in the Einstein-Podolsky-Rosen-Bohm experiment.Comment: Some changes to introduction and discussion sections, typos corrected, conclusions unchanged. To appear in Foundations of Physic

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The interplay between total mercury, methylmercury and dissolved organic matter in fluvial systems: A latitudinal study across Europe.

Large-scale studies are needed to identify the drivers of total mercury (THg) and monomethyl-mercury (MeHg) concentrations in aquatic ecosystems. Studies attempting to link dissolved organic matter (DOM) to levels of THg or MeHg are few and geographically constrained. Additionally, stream and river systems have been understudied as compared to lakes. Hence, the aim of this study was to examine the influence of DOM concentration and composition, morphological descriptors, land uses and water chemistry on THg and MeHg concentrations and the percentage of THg as MeHg (%MeHg) in 29 streams across Europe spanning from 41°N to 64 °N. THg concentrations (0.06-2.78 ng L-1) were highest in streams characterized by DOM with a high terrestrial soil signature and low nutrient content. MeHg concentrations (7.8-159 pg L-1) varied non-systematically across systems. Relationships between DOM bulk characteristics and THg and MeHg suggest that while soil derived DOM inputs control THg concentrations, autochthonous DOM (aquatically produced) and the availability of electron acceptors for Hg methylating microorganisms (e.g. sulfate) drive %MeHg and potentially MeHg concentration. Overall, these results highlight the large spatial variability in THg and MeHg concentrations at the European scale, and underscore the importance of DOM composition on mercury cycling in fluvial systems

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group