Notes on the Oceanography of d'Iberville Fiord

The oceanography of a small arctic fiord has been studied over a period of three years. The shallow water structure is determined by convection in the fiord, as is shown by temperature-time series and budget studies. The fiord contains temperature inversions at shallow depths, which have been present in observations over several years. The deeper water structure is determined by the sill across the fiord mouth and similar sills in Nansen Sound that restrict free access at depth of water layers from the Arctic Ocean

Characteristics of TCR repertoire associated with successful immune checkpoint therapy responses

Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding immune mechanisms that underlie responsiveness to ICT will help identify predictive biomarkers of response and develop treatments to convert non-responding patients to responding ones. ICT primarily acts at the level of adaptive immunity. The specificity of adaptive immune cells, such as T and B cells, is determined by antigen-specific receptors. T cell repertoires can be comprehensively profiled by high-throughput sequencing at the bulk and single-cell level. T cell receptor (TCR) sequencing allows for sensitive tracking of dynamic changes in antigen-specific T cells at the clonal level, giving unprecedented insight into the mechanisms by which ICT alters T cell responses. Here, we review how the repertoire influences response to ICT and conversely how ICT affects repertoire diversity. We will also explore how changes to the repertoire in different anatomical locations can better correlate and perhaps predict treatment outcome. We discuss the advantages and limitations of current metrics used to characterize and represent TCR repertoire diversity. Discovery of predictive biomarkers could lie in novel analysis approaches, such as network analysis of amino acids similarities between TCR sequences. Single-cell sequencing is a breakthrough technology that can link phenotype with specificity, identifying T cell clones that are crucial for successful ICT. The field of immuno-sequencing is rapidly developing and cross-disciplinary efforts are required to maximize the analysis, application, and validation of sequencing data. Unravelling the dynamic behavior of the TCR repertoire during ICT will be highly valuable for tracking and understanding anti-tumor immunity, biomarker discovery, and ultimately for the development of novel strategies to improve patient outcomes

Actions of Camptothecin Derivatives on Larvae and Adults of the Arboviral Vector Aedes aegypti

Mosquito-borne viruses including dengue, Zika, and Chikungunya viruses, and parasites such as malaria and Onchocerca volvulus endanger health and economic security around the globe, and emerging mosquito-borne pathogens have pandemic potential. However, the rapid spread of insecticide resistance threatens our ability to control mosquito vectors. Larvae of Aedes aegypti were screened with the Medicines for Malaria Venture Pandemic Response Box, an open-source compound library, using INVAPP, an invertebrate automated phenotyping platform suited to high-throughput chemical screening of larval motility. We identified rubitecan (a synthetic derivative of camptothecin) as a hit compound that reduced A. aegypti larval motility. Both rubitecan and camptothecin displayed concentration dependent reduction in larval motility with estimated EC50 of 25.5 ± 5.0 µM and 22.3 ± 5.4 µM, respectively. We extended our investigation to adult mosquitoes and found that camptothecin increased lethality when delivered in a blood meal to A. aegypti adults at 100 µM and 10 µM, and completely blocked egg laying when fed at 100 µM. Camptothecin and its derivatives are inhibitors of topoisomerase I, have known activity against several agricultural pests, and are also approved for the treatment of several cancers. Crucially, they can inhibit Zika virus replication in human cells, so there is potential for dual targeting of both the vector and an important arbovirus that it carries

An inverse approach to Einstein's equations for non-conducting fluids

We show that a flow (timelike congruence) in any type $B_{1}$ warped product spacetime is uniquely and algorithmically determined by the condition of zero flux. (Though restricted, these spaces include many cases of interest.) The flow is written out explicitly for canonical representations of the spacetimes. With the flow determined, we explore an inverse approach to Einstein's equations where a phenomenological fluid interpretation of a spacetime follows directly from the metric irrespective of the choice of coordinates. This approach is pursued for fluids with anisotropic pressure and shear viscosity. In certain degenerate cases this interpretation is shown to be generically not unique. The framework developed allows the study of exact solutions in any frame without transformations. We provide a number of examples, in various coordinates, including spacetimes with and without unique interpretations. The results and algorithmic procedure developed are implemented as a computer algebra program called GRSource.Comment: 9 pages revtex4. Final form to appear in Phys Rev

A subset of malignant mesothelioma tumors retain osteogenic potential

Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors

Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy

Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT. We tracked tumor antigen-specific CTL frequencies and phenotype before and after ICT in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICT, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T-bet, and granzyme B. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICT response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICT

Spherically Symmetric Solutions in Macroscopic Gravity

Schwarzschild's solution to the Einstein Field Equations was one of the first and most important solutions that lead to the understanding and important experimental tests of Einstein's theory of General Relativity. However, Schwarzschild's solution is essentially based on an ideal theory of gravitation, where all inhomogeneities are ignored. Therefore, any generalization of the Schwarzschild solution should take into account the effects of small perturbations that may be present in the gravitational field. The theory of Macroscopic Gravity characterizes the effects of the inhomogeneities through a non-perturbative and covariant averaging procedure. With similar assumptions on the geometry and matter content, a solution to the averaged field equations as dictated by Macroscopic Gravity are derived. The resulting solution provides a possible explanation for the flattening of galactic rotation curves, illustrating that Dark Matter is not real but may only be the result of averaging inhomogeneities in a spherically symmetric background.Comment: 14 pages, added and updated references, some paragraphs rewritten for clarity, typographical errors fixed, results have not change

Thermodynamic properties of excess-oxygen-doped La2CuO4.11 near a simultaneous transition to superconductivity and long-range magnetic order

We have measured the specific heat and magnetization {\it versus} temperature in a single crystal sample of superconducting La$_{2}$CuO$_{4.11}$ and in a sample of the same material after removing the excess oxygen, in magnetic fields up to 15 T. Using the deoxygenated sample to subtract the phonon contribution, we find a broad peak in the specific heat, centered at 50 K. This excess specific heat is attributed to fluctuations of the Cu spins possibly enhanced by an interplay with the charge degrees of freedom, and appears to be independent of magnetic field, up to 15 T. Near the superconducting transition $T_{c}$($H$=0)= 43 K, we find a sharp feature that is strongly suppressed when the magnetic field is applied parallel to the crystallographic c-axis. A model for 3D vortex fluctuations is used to scale magnetization measured at several magnetic fields. When the magnetic field is applied perpendicular to the c-axis, the only observed effect is a slight shift in the superconducting transition temperature.Comment: 8 pages, 8 figure

The Influence of Free Quintessence on Gravitational Frequency Shift and Deflection of Light with 4D momentum

Based on the 4D momentum, the influence of quintessence on the gravitational frequency shift and the deflection of light are examined in modified Schwarzschild space. We find that the frequency of photon depends on the state parameter of quintessence $w_q$: the frequency increases for $-1<w_q<-1/3$ and decreases for $-1/3<w_q<0$. Meanwhile, we adopt an integral power number $a$ ($a = 3\omega_q + 2$) to solve the orbital equation of photon. The photon's potentials become higher with the decrease of $\omega_q$. The behavior of bending light depends on the state parameter $\omega_q$ sensitively. In particular, for the case of $\omega_q = -1$, there is no influence on the deflection of light by quintessence. Else, according to the H-masers of GP-A redshift experiment and the long-baseline interferometry, the constraints on the quintessence field in Solar system are presented here.Comment: 12 pages, 2 figures, 4 tables. European Physical Journal C in pres

Identification of the bulk pairing symmetry in high-temperature superconductors: Evidence for an extended s-wave with eight line nodes

we identify the intrinsic bulk pairing symmetry for both electron and hole-doped cuprates from the existing bulk- and nearly bulk-sensitive experimental results such as magnetic penetration depth, Raman scattering, single-particle tunneling, Andreev reflection, nonlinear Meissner effect, neutron scattering, thermal conductivity, specific heat, and angle-resolved photoemission spectroscopy. These experiments consistently show that the dominant bulk pairing symmetry in hole-doped cuprates is of extended s-wave with eight line nodes, and of anisotropic s-wave in electron-doped cuprates. The proposed pairing symmetries do not contradict some surface- and phase-sensitive experiments which show a predominant d-wave pairing symmetry at the degraded surfaces. We also quantitatively explain the phase-sensitive experiments along the c-axis for both Bi_{2}Sr_{2}CaCu_{2}O_{8+y} and YBa_{2}Cu_{3}O_{7-y}.Comment: 11 pages, 9 figure