The last century of food animal agriculture is a remarkable triumph of scientific research. Knowledge derived through research has resulted in the development and use of new technologies that have ...increased the efficiency of food production and created a huge animal production and food manufacturing industry capable of feeding the US population while also providing significant quantities of high-quality food for export to other countries. Although the US food supply is among the safest in the world, the US Center for Disease Prevention and Control estimates that 76 million people get sick, more than 300,000 are hospitalized, and 5,000 die each year from foodborne illness. Consequently, preventing foodborne illness and death remains a major public health concern. Challenges to providing a safe, abundant, and nutritious food supply are complex because all aspects of food production, from farm to fork, must be considered. Given the national and international demand and expectations for food safety as well as the formidable challenges of producing and maintaining a safe food supply, food safety research and educational programs have taken on a new urgency. Remarkable progress has been made during the last century. Wisdom from a century of animal agriculture research now includes the realization that on-farm pathogens are intricately associated with animal health and well-being, the production of high-quality food, and profitability. In this review, some of the developments that have occurred over the last few decades are summarized, including types, sources, and concentrations of disease-causing pathogens encountered in food-producing animal environments and their association with food safety; current and future methods to control or reduce foodborne pathogens on the farm; and present and future preharvest food safety research directions. Future scientific breakthroughs will no doubt have a profound impact on animal agriculture and the production of high-quality food, but we will also be faced with moral, ethical, and societal dilemmas that must be reconciled. A strong, science-based approach that addresses all the complex issues involved in continuing to improve food safety and public health is necessary to prevent foodborne illnesses. Not only must research be conducted to solve complex food safety issues, but results of that research must also be communicated effectively to producers and consumers.
mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of ...mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis. In TSC2-deficient cells and tumors, we find that mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2 and BCL-XL for survival, thereby altering susceptibility to BH3 mimetics that target specific pro-survival BCL-2 proteins. The BCL-2/BCL-XL inhibitor ABT-263 synergizes with rapamycin to induce apoptosis in TSC-deficient cells and in a mouse tumor model of TSC, resulting in a more complete and durable response. These data expose a therapeutic vulnerability in regulation of the apoptotic machinery downstream of mTORC1 that promotes a cytotoxic response to rapamycin.
Display omitted
•mTORC1 inhibition alters expression of BCL-2 family proteins in TSC-deficient cells•mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2/BCL-XL for survival•ABT-263 synergizes with mTORC1 inhibitors in TSC-deficient mouse and human cells•ABT-263 improves the anti-tumor durability of rapamycin in a TSC tumor model
Biological sciences; Cancer; Cell biology; Molecular biology
Display omitted
•This work identifies asperities, also called local maxima, on a particle's surface.•A novel method uses asperities to identify overlap between two irregular particles.•Run time was ...cut by over 90 % on average for a 40 % volume fraction microstructure.
A novel method of detecting overlap between two irregularly shaped virtual particles whose surfaces are described by analytical functions is presented in this study. Utilizing the analytical equation that describes the surface of the particle, the first and second spatial derivatives are used to locate the major surface asperities via the surface curvature. During the particle placement process, detecting overlap between two particles is a crucial, but slow, step. While the asperity check does not detect all cases of overlap between two particles, it leverages the probability that overlap is most likely to occur at a surface asperity. Microstructures are generated using four particle size gradations and three volume fractions to demonstrate the decreased computational time associated with using the asperity overlap detection versus a brute force method. This overlap detection method provides significant increases in efficiency, averaging a speedup of 10 when generating a 40% volume fraction microstructure.
Concrete creep research has focused primarily on uniaxial response. However, biaxially prestressed concrete structures are common, resulting in a multiaxial stress state that can complicate the ...behavior of a viscoelastic material like concrete. Significant creep strains may be induced in directions transverse to each principle stress due to Poisson’s effect. Past research is unclear regarding the viscoelastic or viscoplastic properties of concrete outside of uniaxial response. It has been reported in separate studies that concrete viscoelastic/viscoplastic Poisson’s ratio (VPR) is an increasing, decreasing and constant function with time, with all reported measurements performed at room temperature. In this paper, the 3D basic creep response of mature cement mortar is examined using a confined compression experiment that allows direct determination of the full stress and infinitesimal strain tensors in a single test, which enables the determination of VPR under a multiaxial stress state. For this purpose, a unique, miniature version of the standardized concrete creep frame is designed that is amenable to placing in climate chambers and temperature ovens. The experimental results indicate that the VPR of sealed, mature cement mortar is nearly constant and equal to the elastic at room temperature, while the VPR gradually increases with time when measured at 60 °C.
Creep is a long-term deformation that can cause redistribution of stresses, large deformations, and prestress or post-tensioning losses in prestressed or post-tensioned structures, respectively. A ...major challenge in quantifying the effect of creep in such structures is that creep of concrete is known to continue for decades. In this paper, we examine the time-temperature superposition principle as a method to predict long-term basic creep of mature portland cement mortar from short-term creep experiments conducted at multiple elevated temperatures. For this purpose, we design a unique, miniature version of the standardized concrete creep frame to be amenable to placing in climatic chambers. We use Bažant’s B4 model to verify that the drying creep component of the measured creep behavior is negligible in comparison to the basic creep component. We develop a basic creep compliance master curve for nearly 60 years of deformation at 20 °C using experimental creep data obtained at higher temperatures for test durations of 600 days.
Summary
The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. A consensus meeting of ...experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare and food safety outcomes. The consensus meeting was held 11–13 May 2014 in Mississauga, Ontario, Canada. Seventeen experts from North America, Europe and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and whether items should be added to address unique issues related to observational studies in animal species with health, production, welfare or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re‐wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered as follows: 1 (title and ), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations) and 22 (funding). Published literature was not always available to support modification to, or inclusion of, an item. The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare or food safety outcomes by recognizing the unique features of observational studies involving food‐producing and companion animals, products of animal origin, aquaculture and wildlife.
In this study, we used a series of immunohistochemical measurements of 2 cell cycle regulators, p16 and p21, to evaluate their prognostic value, separately and in combination, for the disease ...outcomes.
A total of 101 patients with high-grade osteosarcoma were included in this study. Clinicopathologic data were collected, and immunohistochemistry for p16 and p21 was performed and interpreted by 3 independent pathologists. Statistical analysis was performed to assess the strength of each of these markers relative to disease outcome.
Our results indicate that more than 90% expression (high) of p16 by immunohistochemistry on the initial biopsy has a strong predictive value for good histologic response to chemotherapy. The patients are also more likely to survive the past 5 years and less likely to develop metastasis than patients with less than 90% p16 (low) expression. The results for p21, on the other hand, show a unique pattern of relationship to the clinicopathologic outcomes of the disease. Patients with less than 1% (low) or more than 50% (high) expression of p21 by immunohistochemistry show a higher chance of metastasis, poor necrotic response to chemotherapy, and an overall decreased survival rate when compared with p21 expression between 1% and 50% (moderate). Our results also showed that the expression of p16 and combined p16 and p21 demonstrates a stronger predictive relationship to 5-year survival than tumor histologic necrosis and p21 alone.
The results of this study, once proven to be reproducible by a larger number of patients, will be valuable in the initial assessment and risk stratification of the patients for treatment and possibly the clinical trials.
•This work efficiently generates highly realistic, 3D virtual concrete microstructures.•Over 27 y of concrete creep data was simulated with excellent agreement with concrete experimental data.•This ...work can assess a wide variety of concrete parameters in relation to creep.
Nearly all nuclear power plants in the United States are operating past their intended lifetimes or are requesting lifetime extensions. Therefore, understanding changes to the concrete containment structure over time is crucial to evaluate the structure’s continued viability. Concrete materials are heterogeneous particulate composites that exhibit viscoelastic material properties, which can lead to slow deformation over time, causing stress redistribution and the potential for creep cracking. A code to generate random, three dimensional (3D) concrete microstructures has been developed and paired with finite element analysis to predict the long-term viscoelastic properties of concrete. Data from these simulations are used to develop constitutive equations for the viscoelastic behavior of the homogenized concrete. The codes in this work are used to virtualize laboratory experiments, to obtain long-term creep data in a faster, cheaper manner. To validate this work, the simulated creep behavior of concrete is compared to 800 d of experimental data that has been extended to 27 y of data using the Time-Temperature superposition (TTS) principal. Excellent agreement between the simulation results and experimental data is seen.
The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines.
To develop an extension of the STROBE ...(Strengthening the Reporting of Observational Studies in Epidemiology) statement that addresses unique reporting requirements for observational studies in veterinary medicine related to health, production, welfare, and food safety.
A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare, and food safety outcomes.
Consensus meeting May 11–13, 2014 in Mississauga, Ontario, Canada.
Seventeen experts from North America, Europe, and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals.
Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and if items should be added to address unique issues related to observational studies in animal species with health, production, welfare, or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re-wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition.
The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations), and 22 (funding).
Published literature was not always available to support modification to, or inclusion of, an item.
The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare, or food safety outcomes by recognizing the unique features of observational studies involving food-producing and companion animals, products of animal origin, aquaculture, and wildlife.
PDF
