T Cells as Vehicles for Cancer Vaccination

The success of cancer vaccines is dependent on the delivery of tumor-associated antigens (TAAs) within lymphoid tissue in the context of costimulatory molecules and immune stimulatory cytokines. Dendritic cells (DCs) are commonly utilized to elicit antitumor immune responses due to their attractive costimulatory molecule and cytokine expression profile. However, the efficacy of DC-based vaccines is limited by the poor viability and lymph-node migration of exogenously generated DCs in vivo. Alternatively, adoptively transferred T cells persist for long periods of time in vivo and readily migrate between the lymphoid and vascular compartments. In addition, T cells may be genetically modified to express both TAA and DC-activating molecules, suggesting that T cells may be ideal candidates to serve as cellular vehicles for antigen delivery to lymph node-resident DCs in vivo. This paper discusses the concept of using T cells to induce tumor-specific immunity for vaccination against cancer

Fundamental principles of rehabilitation and musculoskeletal tissue healing

OBJECTIVE: To review fundamental principles of tissue healing and physical rehabilitation as they apply to dogs recovering from cranial cruciate ligament (CCL) surgery STUDY DESIGN: Invited Review SAMPLE POPULATION: None METHODS: A multidisciplinary group of specialists in small animal surgery, rehabilitation/sports medicine, and human physical and occupational therapy reviewed the currently available evidence for rehabilitation post-CCL surgery. Because current evidence is limited, this group proposes guidelines for rehabilitation after CCL surgery based on the fundamental principles of tissue healing and physical therapy RESULTS: This Review proposes four fundamental principles of small animal physical rehabilitation based on the foundations of tissue healing and patient-centric and goal-oriented therapy. Postoperative rehabilitation programs should be designed such that patient progress is based on individual assessment according to the degree of tissue healing, strength, and achievement of functional goals. Therapists must fully understand phases of tissue healing, reassess the patient frequently, and use clinical reasoning skills to progress treatment appropriately for the individual patient. CONCLUSION: Until more robust evidence is available to guide treatment protocols, fundamental principles of rehabilitation should ideally be adhered to when providing rehabilitation, including after CCL surgery. CLINICAL SIGNIFICANCE: While this Review specifically addresses post-CCL surgery rehabilitation, these fundamental principles should be applied broadly to animals enrolled in rehabilitation programs

T cells enhance gold nanoparticle delivery to tumors in vivo

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation

Mechanized Metatheory for the Masses: The \u3cb\u3ePOPLMARK\u3c/b\u3e Challenge

How close are we to a world where every paper on programming languages is accompanied by an electronic appendix with machinechecked proofs? We propose an initial set of benchmarks for measuring progress in this area. Based on the metatheory of System F, a typed lambda-calculus with second-order polymorphism, subtyping, and records, these benchmarks embody many aspects of programming languages that are challenging to formalize: variable binding at both the term and type levels, syntactic forms with variable numbers of components (including binders), and proofs demanding complex induction principles. We hope that these benchmarks will help clarify the current state of the art, provide a basis for comparing competing technologies, and motivate further research

Galaxy And Mass Assembly (GAMA) : the large-scale structure of galaxies and comparison to mock universes

MA acknowledges funding from the University of St Andrews and the International Centre for Radio Astronomy Research. ASGR is supported by funding from a UWA Fellowship. PN acknowledges the support of the Royal Society through the award of a University Research Fellowship and the European Research Council, through receipt of a Starting Grant (DEGAS-259586). MJIB acknowledges the financial support of the Australian Research Council Future Fellowship 100100280. TMR acknowledges support from a European Research Council Starting Grant (DEGAS-259586).From a volume-limited sample of 45 542 galaxies and 6000 groups with z ≤ 0.213, we use an adapted minimal spanning tree algorithm to identify and classify large-scale structures within the Galaxy And Mass Assembly (GAMA) survey. Using galaxy groups, we identify 643 filaments across the three equatorial GAMA fields that span up to 200 h−1 Mpc in length, each with an average of eight groups within them. By analysing galaxies not belonging to groups, we identify a secondary population of smaller coherent structures composed entirely of galaxies, dubbed ‘tendrils’ that appear to link filaments together, or penetrate into voids, generally measuring around 10 h−1 Mpc in length and containing on average six galaxies. Finally, we are also able to identify a population of isolated void galaxies. By running this algorithm on GAMA mock galaxy catalogues, we compare the characteristics of large-scale structure between observed and mock data, finding that mock filaments reproduce observed ones extremely well. This provides a probe of higher order distribution statistics not captured by the popularly used two-point correlation function.Peer reviewe

Citizen Science 2.0 : Data Management Principles to Harness the Power of the Crowd

Citizen science refers to voluntary participation by the general public in scientific endeavors. Although citizen science has a long tradition, the rise of online communities and user-generated web content has the potential to greatly expand its scope and contributions. Citizens spread across a large area will collect more information than an individual researcher can. Because citizen scientists tend to make observations about areas they know well, data are likely to be very detailed. Although the potential for engaging citizen scientists is extensive, there are challenges as well. In this paper we consider one such challenge – creating an environment in which non-experts in a scientific domain can provide appropriate and accurate data regarding their observations. We describe the problem in the context of a research project that includes the development of a website to collect citizen-generated data on the distribution of plants and animals in a geographic region. We propose an approach that can improve the quantity and quality of data collected in such projects by organizing data using instance-based data structures. Potential implications of this approach are discussed and plans for future research to validate the design are described

Abundance, distribution and population trends of Nile crocodile (Crocodylus niloticus) in Gonarezhou National Park, Zimbabwe

The Nile crocodile (Crocodylus niloticus) is an iconic or keystone species in many aquatic ecosystems. In order to understand the abundance, distribution, and population trends of Nile crocodiles in Gonarezhou National Park (GNP), southeastern Zimbabwe, we carried out 4 annual aerial surveys, using a Super Cub aircraft, along 3 major rivers, namely, Save, Runde and Mwenezi, between 2008 and 2011. Our results show that Runde River was characterised by a significant increase in Nile crocodile abundance whereas both Save and Mwenezi rivers were characterised by non-significant increases in Nile crocodile abundance. Overall, we recorded a significant increase in total Nile crocodile population in the three major rivers of the GNP. The non-significant increase in Nile crocodiles in the Mwenezi and Save rivers was likely due to habitat loss, through siltation of large pools, and conflicts with humans, among other factors. We suggest that GNP management should consider halting crocodile egg collection in rivers with low crocodile populations and continuously monitor the crocodile population in the par

Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

The Precision Array for Probing the Epoch of Reionization: 8 Station Results

We are developing the Precision Array for Probing the Epoch of Reionization (PAPER) to detect 21cm emission from the early Universe, when the first stars and galaxies were forming. We describe the overall experiment strategy and architecture and summarize two PAPER deployments: a 4-antenna array in the low-RFI environment of Western Australia and an 8-antenna array at our prototyping site in Green Bank, WV. From these activities we report on system performance, including primary beam model verification, dependence of system gain on ambient temperature, measurements of receiver and overall system temperatures, and characterization of the RFI environment at each deployment site. We present an all-sky map synthesized between 139 MHz and 174 MHz using data from both arrays that reaches down to 80 mJy (4.9 K, for a beam size of 2.15e-5 steradians at 154 MHz), with a 10 mJy (620 mK) thermal noise level that indicates what would be achievable with better foreground subtraction. We calculate angular power spectra ($C_\ell$) in a cold patch and determine them to be dominated by point sources, but with contributions from galactic synchrotron emission at lower radio frequencies and angular wavemodes. Although the cosmic variance of foregrounds dominates errors in these power spectra, we measure a thermal noise level of 310 mK at $\ell=100$ for a 1.46-MHz band centered at 164.5 MHz. This sensitivity level is approximately three orders of magnitude in temperature above the level of the fluctuations in 21cm emission associated with reionization.Comment: 13 pages, 14 figures, submitted to AJ. Revision 2 corrects a scaling error in the x axis of Fig. 12 that lowers the calculated power spectrum temperatur

The distribution of stellar orbits in eagle galaxies – the effect of mergers, gas accretion, and secular evolution

The merger history of a galaxy is thought to be one of the major factors determining its internal dynamics, with galaxies having undergone different types or mergers (e.g. dry, minor, or major mergers) predicted to show different dynamical properties. We study the instantaneous orbital distribution of galaxies in the EAGLE simulation, colouring the orbits of the stellar particles by their stellar age, in order to understand whether stars form in particular orbits (e.g. in a thin or thick disc). We first show that EAGLE reproduces well the observed stellar mass fractions in different stellar orbital families as a function of stellar mass and spin parameter at z = 0. We find that the youngest stars reside in a thin disc component that can extend to the very inner regions of galaxies, and that older stars have warmer orbits, with the oldest ones showing orbits consistent with both hot and counter-rotating classifications, which is consistent with the trend found in the Milky Way and other disc galaxies. We also show that counter-rotating orbits trace galaxy mergers – in particular dry mergers, and that in the absence of mergers, counter-rotating orbits can also be born from highly misaligned gas accretion that leads to star formation