Cannington Manor, an early settlement community in southeastern Saskatchewan

This project is an analysis of social relationships at Cannington Manor, an early settlement period site in south eastern Saskatchewan. The site earned some fame as a result of the activities of a group of English expatriates who reproduced a round of British upper middle class leisure activities such a fox hunts, dances and musical evenings in the newly-settled West. The town, and the phenomena, lasted only twenty years, but since then, Cannington Manor has captured the imaginations of Saskatchewan residents in both press and literature. Documentary records, oral histories, and archaeological investigations are combined to address the question of the relationship between the upper middle class English and lower middle class farming community that surrounded the English settlement. The dynamics of class are found to be a factor in this relationship, although class differences are mediated to some extent through the mutual interdependencies felt by both groups. In addition, gender is found to be a variable that influences the experience of class dynamics at Cannington Manor. Gender is also found to influence how different Cannington residents participated in the negotiation of class roles. These conclusions are supported by evidence observed in the archaeological record. However, due to the small sample of material culture data available, further research is required to confirm this hypothesis

Linear and Non Linear Effects on the Newtonian Gravitational Constant as deduced from the Torsion Balance

The Newtonian gravitational constant has still 150 parts per million of uncertainty. This paper examines the linear and nonlinear equations governing the rotational dynamics of the torsion gravitational balance. A nonlinear effect modifying the oscillation period of the torsion gravitational balance is carefully explored.Comment: 11 pages, 2 figure

Comparison of the Interactions of Transferrin Receptor and Transferrin Receptor 2 with Transferrin and the Hereditary Hemochromatosis Protein HFE

The transferrin receptor (TfR) interacts with two proteins important for iron metabolism, transferrin (Tf) and HFE, the protein mutated in hereditary hemochromatosis. A second receptor for Tf, TfR2, was recently identified and found to be functional for iron uptake in transfected cells (Kawabata, H., Germain, R. S., Vuong, P. T., Nakamaki, T., Said, J. W., and Koeffler, H. P. (2000) J. Biol. Chem. 275, 16618-16625). TfR2 has a pattern of expression and regulation that is distinct from TfR, and mutations in TfR2 have been recognized as the cause of a non-HFE linked form of hemochromatosis (Camaschella, C., Roetto, A., Cali, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., and Gasparini, P. (2000) Nat. Genet. 25, 14-15). To investigate the relationship between TfR, TfR2, Tf, and HFE, we performed a series of binding experiments using soluble forms of these proteins. We find no detectable binding between TfR2 and HFE by co-immunoprecipitation or using a surface plasmon resonance-based assay. The affinity of TfR2 for iron-loaded Tf was determined to be 27 nM, 25-fold lower than the affinity of TfR for Tf. These results imply that HFE regulates Tf-mediated iron uptake only from the classical TfR and that TfR2 does not compete for HFE binding in cells expressing both forms of TfR

The quality control theory of aging

The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society

Theory of terahertz electric oscillations by supercooled superconductors

We predict that below T_c a regime of negative differential conductivity (NDC) can be reached. The superconductor should be supercooled to T<T_c in the normal phase under DC voltage. In such a nonequilibrium situation the NDC of the superconductor is created by the excess conductivity of the fluctuation Cooper pairs. We propose NDC of supercooled superconductors to be used as an active medium for generation of electric oscillations. Such generators can be used in the superconducting electronics as a new type THz source of radiation. Oscillations can be modulated by the change of the bias voltage, electrostatic doping by a gate electrode when the superconductor is the channel of a field effect transistor, or by light. When small amplitude oscillations are stabilized near the critical temperature T_c the generator can be used as a bolometer. The essential for the applications NDC is predicted by the solution of the Boltzmann kinetic equation for the metastable in the normal phase Cooper pairs. Boltzmann equation for fluctuation Cooper pairs is a result of state-of-the-art application of the microscopic theory of superconductivity. Our theoretical conclusions are based on some approximations like time dependent Ginzburg-Landau theory, but nevertheless can reliably predict appearance of NDC. The maximal frequency at which superconductors can operate as generators is determined by the critical temperature \hbar omega_max ~ k_B T_c. For high-T_c superconductors this maximal frequency falls well inside the terahertz range. Technical conditions to avoid nucleation of the superconducting phase are briefly discussed. We suggest that nanostructured high-T_c superconductors patterned in a single chip can give the best technical performance of the proposed oscillator.Comment: 7 page

The Molecular Mechanism for Receptor-Stimulated Iron Release from the Plasma Iron Transport Protein Transferrin

Human transferrin receptor 1 (TfR) binds iron-loaded transferrin (Fe-Tf) and transports it to acidic endosomes where iron is released in a TfR-facilitated process. Consistent with our hypothesis that TfR binding stimulates iron release from Fe-Tf at acidic pH by stabilizing the apo-Tf conformation, a TfR mutant (W641A/F760A-TfR) that binds Fe-Tf, but not apo-Tf, cannot stimulate iron release from Fe-Tf, and less iron is released from Fe-Tf inside cells expressing W641A/F760A-TfR than cells expressing wild-type TfR (wtTfR). Electron paramagnetic resonance spectroscopy shows that binding at acidic pH to wtTfR, but not W641A/F760A-TfR, changes the Tf iron binding site ≥30 Å from the TfR W641/F760 patch. Mutation of Tf histidine residues predicted to interact with the W641/F760 patch eliminates TfR-dependent acceleration of iron release. Identification of TfR and Tf residues critical for TfR-facilitated iron release, yet distant from a Tf iron binding site, demonstrates that TfR transmits long-range conformational changes and stabilizes the conformation of apo-Tf to accelerate iron release from Fe-Tf

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle

Reproductive performance is the most important component of cattle production from the standpoint of economic sustainability of commercial beef enterprises. Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection tools published by the Red Angus Association of America (RAAA) to assist with improvements in reproductive performance. Given the importance of HPG and STAY to the profitability of commercial beef enterprises, the objective of this study was to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome-wide association study (GWAS) was performed using deregressed HPG and STAY EBV, calculated using a single-trait animal model and a 3-generation pedigree with data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV reliability \u3e 0.05 were merged with the genotype file and marker quality control was performed. Criteria for sifting genotypes consisted of removing those markers where any of the following were found: average call rate less than 0.85, minor allele frequency \u3c 0.01, lack of Hardy–Weinberg equilibrium (P \u3c 0.0001), or extreme linkage disequilibrium (r2 \u3e 0.99). These criteria resulted in 2,664 animals with 62,807 SNP available for GWAS. Association studies were performed using a Bayes Cπ model in the BOLT software package. Marker significance was calculated as the posterior probability of inclusion (PPI), or the number of instances a specific marker was sampled divided by the total number of samples retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI ≥ 3% were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve markers, with a PPI ≥ 75% were identified as QTL associated with STAY on BTA 6, 8, 9, 12, 15, 18, 22, and 23

REVIEW: Life-cycle, total-industry genetic improvement of feed efficiency in beef cattle: Blueprint for the Beef Improvement Federation

On a life-cycle basis, beef animals are able to consume large amounts of low-cost, low-quality forages relative to higher-cost concentrates compared with pigs and chickens. However, of the 3, beef is still more expensive to produce on a cost–per–edible pound basis. Accordingly, there is need for genetic programs and management changes that will improve efficiency, sustainability, and profitability of beef production. Options include improving reproductive rate, reducing feed used for maintenance, or both, while not reducing output. A goal for improving efficiency of feed utilization is to reduce the amount or proportion of feed used for maintenance. Such reduction is a target for genetic improvement, but such a goal does not include defining a single measure of efficiency. A single efficiency measure would likely lead to single-trait selection and not account for any potentially antagonistic effects on other production characteristics. Because we are not able to explain all variation in individual-animal intake from only knowledge of BW maintained and level of production, measuring feed intake is necessary. Therefore, our recommendation is that national cattle evaluation systems analyze feed intake as an economically relevant trait with incorporation of appropriate indicator traits for an EPD for feed intake requirements that could then be used in a multiple-trait setting such as in a selection index. With improvements in technology for measurement of feed intake, individual measures of feed intake should continually be collected to facilitate development of genetic predictors that enhance accuracy of prediction of progeny differences in national cattle evaluations

Microsimulation Modeling for Health Decision Sciences Using R: A Tutorial

Microsimulation models are becoming increasingly common in the field of decision modeling for health. Because microsimulation models are computationally more demanding than traditional Markov cohort models, the use of computer programming languages in their development has become more common. R is a programming language that has gained recognition within the field of decision modeling. It has the capacity to perform microsimulation models more efficiently than software commonly used for decision modeling, incorporate statistical analyses within decision models, and produce more transparent models and reproducible results. However, no clear guidance for the implementation of microsimulation models in R exists. In this tutorial, we provide a step-by-step guide to build microsimulation models in R and illustrate the use of this guide on a simple, but transferable, hypothetical decision problem. We guide the reader through the necessary steps and provide generic R code that is flexible and can be adapted for other models. We also show how this code can be extended to address more complex model structures and provide an efficient microsimulation approach that relies on vectorization solutions