Lattice extraction of K→ππ K \to \pi \pi amplitudes to NLO in partially quenched and in full chiral perturbation theory

We show that it is possible to construct $\epsilon^\prime/\epsilon$ to NLO using partially quenched chiral perturbation theory (PQChPT) from amplitudes that are computable on the lattice. We demonstrate that none of the needed amplitudes require three-momentum on the lattice for either the full theory or the partially quenched theory; non-degenerate quark masses suffice. Furthermore, we find that the electro-weak penguin ($\Delta I=3/2$ and 1/2) contributions to $\epsilon^\prime/\epsilon$ in PQChPT can be determined to NLO using only degenerate ($m_K=m_\pi$) $K\to\pi$ computations without momentum insertion. Issues pertaining to power divergent contributions, originating from mixing with lower dimensional operators, are addressed. Direct calculations of $K\to\pi\pi$ at unphysical kinematics are plagued with enhanced finite volume effects in the (partially) quenched theory, but in simulations when the sea quark mass is equal to the up and down quark mass the enhanced finite volume effects vanish to NLO in PQChPT. In embedding the QCD penguin left-right operator onto PQChPT an ambiguity arises, as first emphasized by Golterman and Pallante. With one version (the "PQS") of the QCD penguin, the inputs needed from the lattice for constructing $K\to\pi\pi$ at NLO in PQChPT coincide with those needed for the full theory. Explicit expressions for the finite logarithms emerging from our NLO analysis to the above amplitudes are also given.Comment: 54 pages, 3 figures; Important revisions: Corrections to formulas for K->pi pi with degenerate quark masses have been mad

UV-light-driven prebiotic synthesis of iron–sulfur clusters

Iron–sulfur clusters are ancient cofactors that play a fundamental role in metabolism and may have impacted the prebiotic chemistry that led to life. However, it is unclear whether iron–sulfur clusters could have been synthesized on prebiotic Earth. Dissolved iron on early Earth was predominantly in the reduced ferrous state, but ferrous ions alone cannot form polynuclear iron–sulfur clusters. Similarly, free sulfide may not have been readily available. Here we show that UV light drives the synthesis of [2Fe–2S] and [4Fe–4S] clusters through the photooxidation of ferrous ions and the photolysis of organic thiols. Iron–sulfur clusters coordinate to and are stabilized by a wide range of cysteine-containing peptides and the assembly of iron–sulfur cluster-peptide complexes can take place within model protocells in a process that parallels extant pathways. Our experiments suggest that iron–sulfur clusters may have formed easily on early Earth, facilitating the emergence of an iron–sulfur-cluster-dependent metabolism

Nitric acid scavenging by mineral and biomass burning aerosols

The abundance of gas phase nitric acid in the upper troposphere is overestimated by global chemistry-transport models, especially during the spring and summer seasons. Recent aircraft data obtained over the central US show that mineral aerosols were abundant in the upper troposphere during spring. Chemical reactions on mineral dust may provide an important sink for nitric acid. In regions where the mineral dust abundance is low in the upper troposphere similar HNO3 removal processes may occur on biomass burning aerosols. We propose that mineral and biomass burning aerosols may provide an important global sink for gas phase nitric acid, particularly during spring and summer when aerosol composition in the upper troposphere may be greatly affected by dust storms from east Asia or tropical biomass burning plumes

Mir-434-5p mediates skin whitening and lightening

Utilization of gene silencing effectors, such as microRNA (miRNA) and small hairpin RNA (shRNA), provides a powerful new strategy for human skin care in vivo, particularly for hyperpigmentation treatment and aging prevention. In this study, tyrosinase (Tyr), the rate-limiting enzyme of melanin (black pigment) biosynthesis, was served as a target for treatment of hyperpigmentation in mouse and human skins. There are over 54 native microRNA capable of silencing human tyrosinase for skin whitening and lightening. To this, we have designed a mir-434-5p homologue and used it to successfully demonstrate the feasibility of miRNA-mediated skin whitening and lightening in vitro and in vivo. Under the same experimental condition in the trials, Pol-II-directed intronic mir-434-5p expression did not cause any detectable sign of cytotoxicity, whereas siRNAs targeting the same sequence often induced certain nonspecific mRNA degradation as previously reported. Because the intronic miRNA-mediated gene silencing pathway is tightly regulated by multiple intracellular surveillance systems, including Pol-II transcription, RNA splicing, exosomal digestion and nonsense-mediated RNA decay (NMD), the current findings underscore the fact that intronic miRNA agents, such as manually re-designed mir-434-5p homologues, are effective, target-specific and safe to be used for skin whitening without any detectable cytotoxic effect. Given that the human skins also express a variety of other native miRNAs, we may re-design these miRNAs based on their individual functions for skin care, which may provide significant insights into areas of opportunity for new cosmetic and/or therapeutical applications

Turbulence spectra in the buoyancy subrange of thermally stratified shear flows

CER68-69JTL21.February 1969.Originally presented as the author's thesis, Colorado State University.Includes bibliographical references (pages 94-97).Prepared under Office of Naval Research, project no. NR 062-414/6-6-68(Code 438), U.S. Department of Defense.A generalized eddy-viscosity approximation is used to study the turbulence spectra of thermally stratified shear flows. For a stationary process in the wave number range investigated--the buoyancy subrange--under the assumption of local homogeneity of the flow, two governing spectral equations with six unknowns are derived from the equations of motion and energy. In order to reduce the number of unknowns to two so that the spectral equations can be solved, a generalized eddy-viscosity is used for expressing the integrated forms of the inertial transfers of energy and temperature inhomogeneity, the shear stress and vertical heat flux in terms of velocity spectrum ¢(k) and temperature spectrum ¢TT(k). Asymptotic solutions are obtained in the buoyancy subrange where the local production and local dissipation of turbulent energy is negligible as compared to the inertial transfer and vertical heat flux terms when the flow conditions satisfy the criterion ε|dT'/dz| << N g/T' or g/T'. |dT'/dz| << N/ε.(g/T)^2. In the buoyancy subrange of stably stratified turbulent flow, the power law for the velocity and temperature spectra is not universal but varies with the flow conditions in the way ¢(k) ~ k^n and ¢TT(k) ~ k^m where 11/5 ≥ n ≥ -3 and -1 ≥ m ≥ -7/5. According to the measurements of velocity spectra in the atmosphere (Pinus and Schcherbakova, 1966; Myrup, 1968), the dependence of the power law on the flow conditions was confirmed. The solutions of Bolgiano (1959) and Luialey-Shur (1964) are only two particular cases of the present results under cert ain flow conditions. In the case of the unstably stratified turbulent flow, the velocity spectrum exhibits a hump in the buoyancy subrange as a result of the energy input from the temperature field to the velocity field. In the left side of this hump the velocity spectrum approaches a +1 slope and the temperature spectrum shows a -3 slope. The measurements of the velocity spectra in the atmosphere (Ivanov and Ordanovich, 1967) confirms this tendency.Under contract no. N00014-68-A-0493-0001

Dynamic Phase-Control of a Rising Sun Magnetron Using Modulated and Continuous Current

Phase-control of a magnetron is studied via simulation using a combination of a continuous current source and a modulated current source. The addressable, modulated current source is turned ON and OFF at the magnetron operating frequency in order to control the electron injection and the spoke phase. Prior simulation work using a 2D model of a Rising Sun magnetron showed that the use of 100% modulated current controlled the magnetron phase and allowed for dynamic phase control. In this work, the minimum fraction of modulated current source needed to achieve a phase control is studied. The current fractions (modulated versus continuous) were varied from 10% modulated current to 100% modulated current to study the effects on phase control. Dynamic phase-control, stability, and start up time of the device were studied for all these cases showing that with 10% modulated current and 90% continuous current, a phase shift of 180˚ can be achieved demonstrating dynamic phase control

Photonic Clusters

We show through rigorous calculations that dielectric microspheres can be organized by an incident electromagnetic plane wave into stable cluster configurations, which we call photonic molecules. The long-range optical binding force arises from multiple scattering between the spheres. A photonic molecule can exhibit a multiplicity of distinct geometries, including quasicrystal-like configurations, with exotic dynamics. Linear stability analysis and dynamical simulations show that the equilibrium configurations can correspond with either stable or a type of quasi-stable states exhibiting periodic particle motion in the presence of frictional dissipation.Comment: 4 pages, 3 figure

Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.

The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Activation of JAK/STAT signaling is thought to be a central component of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor Food and Drug Administration (FDA) approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Herein, we validated in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated xenograft models of myeloma, that tofacitinib showed efficacy in myeloma models. Furthermore, tofacitinib strongly synergized with venetoclax in coculture with bone marrow stromal cells but not in monoculture. Surprisingly, we found that ruxolitinib, an FDA approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. Transcriptome analysis and unbiased phosphoproteomics revealed that bone marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib reverses the growth-promoting effects of the tumor microenvironment. As tofacitinib is already FDA approved, these results can be rapidly translated into potential clinical benefits for myeloma patients