Impacts of Salt Production on Pemba

The economic, social, and environmental impacts of salt production were studied on the eastern coast of Pemba Island. Solar salt production is associated with the clear cutting of mangrove forests, which are significant as soil stabilizers, animal habitats, and as an economic resource. An environmental assessment of this industry is necessary to determine whether the socio-economic gains from salt production justify the environmental costs. Interviews with owners, employees, and day laborers from 20 salt farms were conducted to assess the general sustainability of the industry. The average annual owner income was determined to be approximately 570 000 Tsh, while employees and day laborers, usually paid in salt, earned the monetary equivalent of 245 000 Tsh and 70 000 Tsh, respectively. Field visits to salt farms were done study the surrounding mangroves and measure salinity, which was found to be 0 Be at the farms. Mangrove transects were studied in both salt farm and non-salt farm areas to determine species diversity, distribution, and average height. Avicennia marina, Ceriops tagal, and Rhizophora mucronata were present in all transects through salt farm and non-salt areas. Suggestions for improving salt production and quality while minimizing adverse environmental effects were recommended

Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

Preclinical animal studies have convincingly demonstrated that tumor immunity to self antigens can be actively induced and can translate into an effective anti-tumor response. Several of these observations are being tested in clinical trials. Immunization with xenogeneic DNA is an attractive approach to treat cancer since it generates T cell and antibody responses. When working in concert, these mechanisms may improve the efficacy of vaccines. The use of xenogeneic DNA in overcoming immune tolerance has been promising not only in inbred mice with transplanted tumors but also in outbred canines, which present with spontaneous tumors, as in the case of human. Use of this strategy also overcomes limitations seen in other types of cancer vaccines. Immunization against defined tumor antigens using a xenogeneic DNA vaccine is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers, with proposed trials for breast cancer and Non-Hodgkin's Lymphoma

Covert Ephemeral Communication in Named Data Networking

In the last decade, there has been a growing realization that the current Internet Protocol is reaching the limits of its senescence. This has prompted several research efforts that aim to design potential next-generation Internet architectures. Named Data Networking (NDN), an instantiation of the content-centric approach to networking, is one such effort. In contrast with IP, NDN routers maintain a significant amount of user-driven state. In this paper we investigate how to use this state for covert ephemeral communication (CEC). CEC allows two or more parties to covertly exchange ephemeral messages, i.e., messages that become unavailable after a certain amount of time. Our techniques rely only on network-layer, rather than application-layer, services. This makes our protocols robust, and communication difficult to uncover. We show that users can build high-bandwidth CECs exploiting features unique to NDN: in-network caches, routers' forwarding state and name matching rules. We assess feasibility and performance of proposed cover channels using a local setup and the official NDN testbed

Engineering of extracellular matrix scaffolds via hollow fiber cell culture

Extracellular matrix (ECM) tissue scaffolds are seeing increased use for clinical applications, as they significantly decrease the time course of healing for injured tissues; however, the use of animal-sourced matrix for these scaffolds introduces xenogeneic epitopes into the patient toward which deleterious immune responses are directed, decreasing the effectiveness of the scaffold. ECM scaffolds produced in vitro have potential to minimize the foreign body response, as ECM can be cultured using human cell lines and decellularized to produce an allogeneic scaffold with high biocompatibility. The primary challenge of producing ECM-based therapeutics in vitro is fabricating such material in a manner which approximates the composition and architecture of native matrix while maintaining high yield and ease-of-handling. In previous work, we have demonstrated that sacrificial open-cell foams can be used for the production of ECM scaffolds with properties approximating those of native tissues.1 Herein we demonstrate a novel approach for the production of continuous threads of extracellular matrix by statically culturing ECM-secreting fibroblasts in the lumina of mesoporous hollow fiber membranes (HFMs). This approach exploits the fact that mesoporous HFMs prevent cross-membrane transport of high molecular weight proteins produced by cells in their lumina, while allowing for diffusion of low molecular weight cell medium components. Please click Additional Files below to see the full abstract

Blockade of Treg derived TGF-β abrogates suppression of effector T cell function within the tumor microenvironment

Regulatory T cells (Treg) play a role in suppression of anti-melanoma immunity; however, the exact mechanism is poorly understood. Through intravital two photon microscopy, we found that Pmel-1 effectors engage in cell-cell interactions with tumor resident Tregs. To determine if contact between Tregs and T effectors (Teff) hinders killing of tumor cells in vivo, we utilized ex-vivo three-dimensional collagen-fibrin gel cultures of B16 melanoma cells. Collagen-fibrin gel cultures recapitulated the in vivo suppression, rendering the dissociated tumor resistant to killing by in vitro activated antigen specific Teff. In vivo depletion of Tregs in foxp3-DTR mice prior to tumor excision reversed the suppression. Additionally, In vivo modulation of intra-tumor Tregs suppressive function by GITR ligation had a similar effect, leading to ex-vivo tumor killing. Using neutralizing antibodies, we found that blocking TGF-β reversed the suppression. In addition, soluble factors from collagen-fibrin gel tumors do not inhibit killing suggesting that suppression is contact or proximity dependent. The CD8 Teff recovered from these gels exhibit a decrease in Granzyme B expression and an increase in expression of T cell exhaustion marker PD-1. These findings support the conclusion that intra-tumor contact with Tregs during the effector phase of the immune response is responsible for inhibiting anti-melanoma immunity in a TGF-β dependent manner, elucidating a novel way to target intratumoral Tregs

Meeting Report: Fourth International Congress of the Society for Melanoma Research

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73384/1/j.1755-148X.2007.00437.x.pd

Improved Endpoints for Cancer Immunotherapy Trials

Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation

Alphavirus Replicon Particles Expressing TRP-2 Provide Potent Therapeutic Effect on Melanoma through Activation of Humoral and Cellular Immunity

Malignant melanoma is the deadliest form of skin cancer and is refractory to conventional chemotherapy and radiotherapy. Therefore alternative approaches to treat this disease, such as immunotherapy, are needed. Melanoma vaccine design has mainly focused on targeting CD8+ T cells. Activation of effector CD8+ T cells has been achieved in patients, but provided limited clinical benefit, due to immune-escape mechanisms established by advanced tumors. We have previously shown that alphavirus-based virus-like replicon particles (VRP) simultaneously activate strong cellular and humoral immunity against the weakly immunogenic melanoma differentiation antigen (MDA) tyrosinase. Here we further investigate the antitumor effect and the immune mechanisms of VRP encoding different MDAs.VRP encoding different MDAs were screened for their ability to prevent the growth of the B16 mouse transplantable melanoma. The immunologic mechanisms of efficacy were investigated for the most effective vaccine identified, focusing on CD8+ T cells and humoral responses. To this end, ex vivo immune assays and transgenic mice lacking specific immune effector functions were used. The studies identified a potent therapeutic VRP vaccine, encoding tyrosinase related protein 2 (TRP-2), which provided a durable anti-tumor effect. The efficacy of VRP-TRP2 relies on a novel immune mechanism of action requiring the activation of both IgG and CD8+ T cell effector responses, and depends on signaling through activating Fcγ receptors.This study identifies a VRP-based vaccine able to elicit humoral immunity against TRP-2, which plays a role in melanoma immunotherapy and synergizes with tumor-specific CD8+ T cell responses. These findings will aid in the rational design of future immunotherapy clinical trials