Neutron scattering study of magnetic ordering and excitations in the ternary rare-earth diborocarbide Ce^{11}B_2C_2

Neutron scattering experiments have been performed on the ternary rare-earth diborocarbide Ce$^{11}$B$_2$C$_2$. The powder diffraction experiment confirms formation of a long-range magnetic order at $T_{\rm N} = 7.3$ K, where a sinusoidally modulated structure is realized with the modulation vector ${\bm q} = [0.167(3), 0.167(3), 0.114(3)]$. Inelastic excitation spectra in the paramagnetic phase comprise significantly broad quasielastic and inelastic peaks centered at $\hbar \omega \approx 0, 8$ and 65 meV. Crystalline-electric-field (CEF) analysis satisfactorily reproduces the observed spectra, confirming their CEF origin. The broadness of the quasielastic peak indicates strong spin fluctuations due to coupling between localized $4f$ spins and conduction electrons in the paramagnetic phase. A prominent feature is suppression of the quasielastic fluctuations, and concomitant growth of a sharp inelastic peak in a low energy region below $T_{\rm N}$. This suggests dissociation of the conduction and localized $4f$ electrons on ordering, and contrasts the presently observed incommensurate phase with spin-density-wave order frequently seen in heavy fermion compounds, such as Ce(Ru$_{1-x}$La$_x$)$_2$Si$_2$.Comment: accepted for publication in Phys. Rev.

Inhibitory mechanisms of LAG-3–dependent T cell suppression

T cell activation is tightly regulated by both stimulatory and inhibitory co-receptors and has been a focus in the development of interventions for managing cancer or autoimmune diseases. Targeting the inhibitory co-receptors programmed cell death 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4) has successfully eradicated tumors but induced immune-related adverse events in humans and mice. The beneficial and adverse effects of targeting these co-receptors highlight their importance in cancer immunity and also autoimmunity. Although the therapeutic potencies of other inhibitory co-receptors are under extensive investigation, their inhibitory mechanisms and their functional differences are not well understood. Here we analyzed the inhibitory mechanisms of lymphocyte activation gene-3 (LAG-3), another inhibitory co-receptor, by using an in vitro T cell activation system and a high-affinity anti-LAG-3 antibody that strongly interferes with the binding of LAG-3 to its ligand. We found that the expression level of LAG-3 strongly correlates with the inhibitory function of LAG-3, suggesting that LAG-3 functions as a rheostat rather than as a breaker of T cell activation. By evaluating the inhibitory capacities of various LAG-3 variants relative to their expression levels, we found that LAG-3 transduces two independent inhibitory signals through an FXXL motif in the membrane-proximal region and the C-terminal EX repeat. These motifs have not been reported previously for inhibitory co-receptors, suggesting that LAG-3 inhibits T cell activation through a nonredundant inhibitory mechanisms along with the other inhibitory co-receptors. Our findings provide a rationale for combinatorial targeting of LAG-3 and the other inhibitory co-receptors to improve cancer immunotherapy

Thermal conductance across grain boundaries in diamond from molecular dynamics simulation

We determine the dependence of the interfacial conductance on twist angle for (001) symmetric twist grain boundaries (GBs) in diamond. We find that the conductances are extremely large, ranging from 7.7 to 17.6 GW/m(2) K. Nevertheless, when normalized to the single-crystal conductivity, the resulting Kapitza lengths are actually longer in diamond than in Si, indicating that the diamond GBs are relatively worse conductors of heat. This result is consistent with the poorer bonding across the diamond grain boundaries. We find that the interfacial conductance and Kapitza length can be well fitted by an extended Read-Shockley model

Influence of lifestyle choices on risks of CYP1B1 polymorphisms for prostate cancer.

Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5' untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer. Linkage was observed between rs2551188, rs2567206, rs2567207 and rs10175368, and the G-C-T-G haplotype (major allele at respective sites) was decreased in cancer. Interestingly when classified by lifestyle factors, no associations of genotypes were found for non-smokers and non-drinkers, whereas on the contrary, minor type at rs2567206 and rs10175368 increased and major G-C-T-G decreased risk for cancer among smokers and drinkers. Interestingly, rs2551188, rs2567206 and rs10175368 minor genotypes correlated with increased tissue CYP1B1 as determined by immunohistochemistry. Further, rs10175368 enhanced luciferase activity and mobility shift show stronger binding of nuclear factor for the minor allele. These results demonstrate smoking and alcohol consumption to modify the risks of CYP1B1 polymorphisms for prostate cancer which may be through rs10175368, and this is of importance in understanding their role in the pathogenesis and as a biomarker for this disease

Src Homology 2–containing 5-Inositol Phosphatase (SHIP) Suppresses an Early Stage of Lymphoid Cell Development through Elevated Interleukin-6 Production by Myeloid Cells in Bone Marrow

The Src homology (SH)2–containing inositol 5-phosphatase (SHIP) negatively regulates a variety of immune responses through inhibitory immune receptors. In SHIP(−/−) animals, we found that the number of early lymphoid progenitors in the bone marrow was significantly reduced and accompanied by expansion of myeloid cells. We exploited an in vitro system using hematopoietic progenitors that reproduced the in vivo phenotype of SHIP(−/−) mice. Lineage-negative marrow (Lin(−)) cells isolated from wild-type mice failed to differentiate into B cells when cocultured with those of SHIP(−/−) mice. Furthermore, culture supernatants of SHIP(−/−) Lin(−) cells suppressed the B lineage expansion of wild-type lineage-negative cells, suggesting the presence of a suppressive cytokine. SHIP(−/−) Lin(−) cells contained more IL-6 transcripts than wild-type Lin(−) cells, and neutralizing anti–IL-6 antibody rescued the B lineage expansion suppressed by the supernatants of SHIP(−/−) Lin(−) cells. Finally, we found that addition of recombinant IL-6 to cultures of wild-type Lin(−) bone marrow cells reproduced the phenotype of SHIP(−/−) bone marrow cultures: suppression of B cell development and expansion of myeloid cells. The results identify IL-6 as an important regulatory cytokine that can suppress B lineage differentiation and drive excessive myeloid development in bone marrow

Functional role and tobacco smoking effects on methylation of CYP1A1 gene in prostate cancer.

Cytochrome P450 (CYP) 1A1 is a phase I enzyme that can activate various compounds into reactive forms and thus, may contribute to carcinogenesis. In this study, we investigated the expression, methylation status, and functional role of CYP1A1 on prostate cancer cells. Increased expression of CYP1A1 was observed in all cancer lines (PC-3, LNCaP, and DU145) compared to BPH-1 (P < 0.05); and was enhanced further by 5-aza-2'-deoxycytidine treatment (P < 0.01). Methylation-specific PCR (MSP) and sequencing of bisulfite-modified DNA of the xenobiotic response element (XRE) enhancer site XRE-1383 indicated promoter methylation as a regulator of CYP1A1 expression. In tissue, microarrays showed higher immunostaining of CYP1A1 in prostate cancer than normal and benign prostatic hyperplasia (BPH; P < 0.001), and methylation analyses in clinical specimens revealed significantly lower methylation levels in cancer compared to BPH at all enhancer sites analyzed (XRE-1383, XRE-983, XRE-895; P < 0.01). Interestingly, smoking affected the XRE-1383 site where the methylation level was much lower in cancer tissues from smokers than non-smokers (P < 0.05). CYP1A1 levels are thus increased in prostate cancer and to determine the functional effect of CYP1A1 on cells, we depleted the gene in LNCaP and DU145 by siRNA. We observe that CYP1A1 knockdown decreased cell proliferation (P < 0.05) and increased apoptosis (P < 0.01) in both cell lines. We analyzed genes affected by CYP1A1 silencing and found that apoptosis-related BCL2 was significantly down-regulated. This study supports an oncogenic role for CYP1A1 in prostate cancer via promoter hypomethylation that is influenced by tobacco smoking, indicating CYP1A1 to be a promising target for prostate cancer treatment

Defects in ZnO nanoparticles laser-ablated in water-ethanol mixtures at different pressures

The effect of liquid medium and its pressure on the photoluminescence of ZnO nanoparticles prepared via laser ablation of Zn targets in various water-ethanol mixtures is studied. As the ethanol content increases, the photoluminescence of the product changes, while metallic zinc is observed to emerge in nanomaterials prepared in ethanol-rich environments. The applied pressure had a less profound effect, mainly affecting materials produced in water or water-ethanol, and much less those generated in pressurized ethanol. Tuning the reactivity of the liquid and pressurizing it during laser ablation is demonstrated to be promising for tailoring the emission properties of the product

Dust Migration and Morphology in Optically Thin Circumstellar Gas Disks

We analyze the dynamics of gas-dust coupling in the presence of stellar radiation pressure in circumstellar gas disks, which are in a transitional stage between the gas-dominated, optically thick, primordial nebulae, and the dust-dominated, optically thin Vega-type disks. Dust undergo radial migration, seeking a stable equilibrium orbit in corotation with gas. The migration of dust gives rise to radial fractionation of dust and creates a variety of possible observed disk morphologies, which we compute by considering the equilibrium between the dust production and the dust-dust collisions removing particles from their equilibrium orbits. Sand-sized and larger grains are distributed throughout most of the gas disk, with concentration near the gas pressure maximum in the inner disk. Smaller grains (typically in the range of 10 to 200 micron) concentrate in a prominent ring structure in the outer region of the gas disk (presumably at radius 100 AU), where gas density is rapidly declining with radius. The width and density, as well as density contrast of the dust ring with respect to the inner dust disk depend on the distribution of gas. Our results open the prospect for deducing the distribution of gas in circumstellar disks by observing their dust. We have qualitatively compared our models with two observed transitional disks around HR 4796A and HD 141569A. Dust migration can result in observation of a ring or a bimodal radial dust distribution, possibly very similar to the ones produced by gap-opening planet(s) embedded in the disk, or shepherding it from inside or outside. We conclude that a convincing planet detection via dust imaging should include specific non-axisymmetric structure following from the dynamical simulations of perturbed disks.Comment: 27 pages, 16 figures, submitted to Ap

Two-dimensional Lattice Gross-Neveu Model with Wilson Fermion Action at Finite Temperature and Chemical Potential

We investigate the phase structure of the two-dimensional lattice Gross-Neveu model formulated with the Wilson fermion action to leading order of 1/N expansion. Structural change of the parity-broken phase under the influence of finite temperature and chemical potential is studied. The connection between the lattice phase structure and the chiral phase transition of the continuum theory is clarified.Comment: 42 pages, 20 EPS figures, using REVTe