Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

Endocrine disruption in fish: An assessment of recent research and results

This report provides an assessment of recent investigations into endocrine disruption in fresh and saltwater species of fish. Most work to date has concen-trated on reproductive endocrine disruption. Laboratory studies have shown a variety of synthetic and natural chemicals including certain industrial intermediates, PAHs, PCBs, pesticides, dioxins, trace elements and plant sterols can interfere with the endocrine system in fish. The potency of most of these chemicals, however, is typically hundreds to thousands of times less than that of endog-enous hormones. Evidence of environmental endocrine disruption ranges from the presence of female egg proteins in males and reduced levels of endogenous hormones in both males and females, to gonadal histopathologies and intersex (presence of ovotestes) fish. Overt endocrine disruption in fish does not appear to be a ubiquitous environmental phenomenon, but rather more likely to occur near sewage treatment plants, pulp and paper mills, and in areas of high organic chemical contamination. However, more wide-spread endocrine disruption can occur in rivers with smaller flows and correspondingly large or numerous wastewater inputs. Some of the most severe examples of endocrine disruption in fish have been found adjacent to sewage treatment plants. Effects are thought to be caused prima-rily by natural and synthetic estrogens and to a lesser extent by the degradation products of alkylphenol poly-ethoxylate surfactants. Effects found in fish near pulp and paper mills include reduced levels of estrogens and androgens as well as masculinization of females, and has been linked to the presence of β-sitosterol, a plant sterol. Effects seen in areas of heavy industrial activity typically include depressed levels of estrogens and androgens as well as reduced gonadal growth, and may be linked to the presence of PAHs, PCBs, and possibly dioxins. At this time, however, there is no clear indication that large populations of fish are being seriously impacted as a result of endocrine disruption, although additional work is needed to address this possibility. (PDF contains 63 pages)

Design considerations for a micro aerial vehicle aerodynamic characterization facility at the University of Florida research and engineering education facility

This paper describes the design considerations for a proposed aerodynamic characterization facility (ACF) for micro aerial vehicles (MAVs). This is a collaborative effort between the Air Force Research Laboratory Munitions Directorate (AFRL/MN) and the University of Florida Research and Engineering Education Facility (UF/REEF). The ACF is expected to provide a capability for the characterization of the aerodynamic performance of future MAVs. This includes the ability to gather the data necessary to devise control strategies as well as the potential to investigate aerodynamic 'problem areas' or specific failings. Since it is likely that future MAVs will incorporate advanced control strategies, the facility must enable researchers to critically assess such novel methods. Furthermore, the aerodynamic issues should not be seen (and tested) in isolation, but rather the facility should be able to also provide information on structural responses (such as aeroelasticity) as well as integration issues (say, thrust integration or sensor integration). Therefore the mission for the proposed facility ranges form fairly basic investigations of individual technical issues encountered by MAVs (for example an evaluation of wing shapes or control effectiveness) all the way to testing a fully integrated vehicle in a flight configuration for performance evaluation throughout the mission envelope.

Quantitative Particle Characterization by Scattered Ultrasound

The topic of this thesis is an acoustic scattering technique for detennining the compressibility and density of individual particles. The particles, which have diameters on the order of 10 µm, are modeled as fluid spheres. Ultrasonic tone bursts of 2 µsec duration and 30 MHz center frequency scatter from individual particles as they traverse the focal region of two confocally positioned transducers. One transducer acts as a receiver while the other both transmits and receives acoustic signals. The resulting scattered bursts are detected at 90° and at 180° (backscattered). Using either the long wavelength (Rayleigh) or the weak scatterer (Born) approximations, it is possible to detennine the compressibility and density of the particle provided we possess a priori knowledge of the particle size and the host properties. The detected scattered signals are digitized and stored in computer memory. With this information we can compute the mean compressibility and density averaged over a population of particles ( typically 1000 particles) or display histograms of scattered amplitude statistics. An experiment was run first run to assess the feasibility of using polystyrene polymer microspheres to calibrate the instrument. A second study was performed on the buffy coat harvested from whole human blood. Finally, chinese hamster ovary cells which were subject to hyperthermia treatment were studied in order to see if the instrument could detect heat induced membrane blebbing.

Climate change and marine benthos: a review of existing research and future directions in the North Atlantic

There is growing evidence that climate change could affect marine benthic systems. This review provides information of climate change‐related impacts on the marine benthos in the North Atlantic. We cover a number of related research aspects, mainly in connection to two key issues. First, is the relationship between different physical aspects of climate change and the marine benthos. This section covers: (a) the responses to changes in seawater temperature (biogeographic shifts and phenology); (b) altered Hydrodynamics; (c) ocean acidification (OA); and (d) sea‐level rise‐coastal squeeze. The second major issue addressed is the possible integrated impact of climate change on the benthos. This work is based on relationships between proxies for climate variability, notably the North Atlantic Oscillation (NAO) index, and the long‐term marine benthos. The final section of our review provides a series of conclusions and future directions to support climate change research on marine benthic systems. WIREs Clim Change 2015, 6:203–223. doi: 10.1002/wcc.330

Clipping from a Town Council meeting at which estimates of the costs of Railway Line no. 1 and Line no. 2 were submitted by the office of Port Dalhousie and Thorold Railway

Clipping from a Town Council meeting at which estimates of the costs of Railway Line no. 1 and Line no. 2 were submitted by the office of Port Dalhousie and Thorold Railway. The estimate was submitted by S.D. Woodruff and George Rykert, president. There is also a disclaimer in which Calvin Phelps claims to have resigned as director of the Port Dalhousie and Thorold Railway when he discovered that the company had no intention to adhere to the original plan for building and running the road, Aug. 1854.

Letter from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines, Ont.

Letter (2 pages, handwritten) from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines, Ont. proposing work to be done regarding the hot water heating of the building. The owner of the building is expected to pay the railway fare of the men and to pay their board while they are in St. Catharines, July 8, 1876.