Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.https://scholarscompass.vcu.edu/gradposters/1078/thumbnail.jp

BUSINESS, HUMAN RIGHTS AND CHILDREN: THE DEVELOPING INTERNATIONAL AGENDA

The consideration of the role of the private business sector with regards to the fulfilment of children’s rights is relatively recent. International attention on the effects of business activities have on children has been fragmented until now, focussing on specific sectors, mainly child labour and economic exploitation. Recent international developments, addressed both to states and business enterprises, propose a more comprehensive approach. This article focuses on two of them: the UNICEF-Global Compact and Save the Children Children’s Rights and Business Principles (CRB Principles), launched in May 2012, and the Committee on the Rights of the Child’s General Comment No. 16 on state obligations regarding the impact of the business sector on children’s rights, published in April 2013.  Both documents represent an important step in the consolidation of an international agenda for the protection of the rights of the child that takes into account the different challenges faced by children in the current economic system

Confinement of the Sun's interior magnetic field: some exact boundary-layer solutions

High-latitude laminar confinement of the Sun's interior magnetic field is shown to be possible, as originally proposed by Gough and McIntyre (1998) but contrary to a recent claim by Brun and Zahn (A&A 2006). Mean downwelling as weak as 2x10^-6cm/s -- gyroscopically pumped by turbulent stresses in the overlying convection zone and/or tachocline -- can hold the field in advective-diffusive balance within a confinement layer of thickness scale ~ 1.5Mm ~ 0.002 x (solar radius) while transmitting a retrograde torque to the Ferraro-constrained interior. The confinement layer sits at the base of the high-latitude tachocline, near the top of the radiative envelope and just above the `tachopause' marking the top of the helium settling layer. A family of exact, laminar, frictionless, axisymmetric confinement-layer solutions is obtained for uniform downwelling in the limit of strong rotation and stratification. A scale analysis shows that the flow is dynamically stable and the assumption of laminar flow realistic. The solution remains valid for downwelling values of the order of 10^-5cm/s but not much larger. This suggests that the confinement layer may be unable to accept a much larger mass throughput. Such a restriction would imply an upper limit on possible internal field strengths, perhaps of the order of hundreds of gauss, and would have implications also for ventilation and lithium burning. The solutions have interesting chirality properties not mentioned in the paper owing to space restrictions, but described at http://www.atmos-dynamics.damtp.cam.ac.uk/people/mem/papers/SQBO/solarfigure.htmlComment: 6 pages, 3 figures, to appear in conference proceedings: Unsolved Problems in Stellar Physic

Long GRBs from binary stars: runaway, Wolf-Rayet progenitors

The collapsar model for long gamma-ray bursts requires a rapidly rotating Wolf-Rayet star as progenitor. We test the idea of producing rapidly rotating Wolf-Rayet stars in massive close binaries through mass accretion and consecutive quasi-chemically homogeneous evolution; the latter had previously been shown to provide collapsars below a certain metallicity threshold for single stars. The binary channel presented here may provide a means for massive stars to obtain the high rotation rates required to evolve quasi-chemically homogeneous and fulfill the collapsar scenario. Moreover, it suggests that a possibly large fraction of long gamma-ray bursts occurs in runaway stars.Comment: To appear in the proceedings of the conference "Unsolved problems in stellar physics" - Cambridge, July 200

Space spider crane

A space spider crane for the movement, placement, and or assembly of various components on or in the vicinity of a space structure is described. As permanent space structures are utilized by the space program, a means will be required to transport cargo and perform various repair tasks. A space spider crane comprising a small central body with attached manipulators and legs fulfills this requirement. The manipulators may be equipped with constant pressure gripping end effectors or tools to accomplish various repair tasks. The legs are also equipped with constant pressure gripping end effectors to grip the space structure. Control of the space spider crane may be achieved either by computer software or a remotely situated human operator, who maintains visual contact via television cameras mounted on the space spider crane. One possible walking program consists of a parallel motion walking program whereby the small central body alternatively leans forward and backward relative to end effectors

The effect of different opacity data and chemical element mixture on the Petersen diagram

The Petersen diagram is a frequently used tool to constrain model parameters such as metallicity of radial double-mode pulsators. In this diagram the period ratio of the radial first overtone to the fundamental mode, P_1/P_0, is plotted against the period of the fundamental mode. The period ratio is sensitive to the chemical composition as well as to the rotational velocity of a star. In the present study we compute stellar pulsation models to demonstrate the sensitivity of the radial period ratio to the opacity data (OPAL and OP tables) and we also examine the effect of different relative abundances of heavy elements. We conclude that the comparison with observed period ratios could be used successfully to test the opacity data.Comment: 5 pages, 5 figures, 1 table; to be published in the Proceedings of the Conference 'Unsolved Problems in Stellar Physics', Cambridge, 2-6 July 200

IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels

The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at "http://www.iuphar-db.org":http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support

Thermohaline mixing in low-mass giants: RGB and beyond

Thermohaline mixing has recently been proposed to occur in low mass red giants, with large consequence for the chemical yields of low mass stars. We investigate the role of thermohaline mixing during the evolution of stars between 1 Msun and 3 Msun. We use a stellar evolution code which includes rotational mixing and internal magnetic fields. We confirm that thermohaline mixing has the potential to destroy most of the helium 3 which is produced earlier on the main sequence during the red giant stage, in stars below 1.5Msun. We find this process to continue during core helium burning and beyond. We find rotational and magnetic mixing to be negligible compared to the thermohaline mixing in the relevant layers, even if the interaction of thermohaline motions with the differential rotation may be essential to establish the time scale of thermohaline mixing in red giants.Comment: Proceedings of the Conference "Unsolved problems in stellar physics" - Cambridge, July 200