Potential Vorticity Mixing in a Tangled Magnetic Field

A theory of potential vorticity (PV) mixing in a disordered (tangled) magnetic field is presented. The analysis is in the context of $\beta$-plane MHD, with a special focus on the physics of momentum transport in the stably stratified, quasi-2D solar tachocline. A physical picture of mean PV evolution by vorticity advection and tilting of magnetic fields is proposed. In the case of weak-field perturbations, quasi-linear theory predicts that the Reynolds and magnetic stresses balance as turbulence Alfv\'enizes for a larger mean magnetic field. Jet formation is explored quantitatively in the mean field-resistivity parameter space. However, since even a modest mean magnetic field leads to large magnetic perturbations for large magnetic Reynolds number, the physically relevant case is that of a strong but disordered field. We show that numerical calculations indicate that the Reynolds stress is modified well before Alfv\'enization -- i.e. before fluid and magnetic energies balance. To understand these trends, a double-average model of PV mixing in a stochastic magnetic field is developed. Calculations indicate that mean-square fields strongly modify Reynolds stress phase coherence and also induce a magnetic drag on zonal flows. The physics of transport reduction by tangled fields is elucidated and linked to the related quench of turbulent resistivity. We propose a physical picture of the system as a resisto-elastic medium threaded by a tangled magnetic network. Applications of the theory to momentum transport in the tachocline and other systems are discussed in detail.Comment: 17 pages, 10 figures, 2 table

Phenomenology of the Littlest Higgs with T-Parity

Little Higgs models offer an interesting approach to weakly coupled electroweak symmetry breaking without fine tuning. The original little Higgs models were plagued by strong constraints from electroweak precision data which required a fine tuning to be reintroduced. An economical solution to this problem is to introduce a discrete symmetry (analogous to R-parity of SUSY) called T-parity. T-parity not only eliminates most constraints from electroweak precision data, but it also leads to a promising dark matter candidate. In this paper we investigate the dark matter candidate in the littlest Higgs model with T-parity. We find bounds on the symmetry breaking scale f as a function of the Higgs mass by calculating the relic density. We begin the study of the LHC phenomenology of the littlest Higgs model with T-parity. We find that the model offers an interesting collider signature that has a generic missing energy signal which could "fake" SUSY at the LHC. We also investigate the properties of the heavy partner of the top quark which is common to all littlest Higgs models, and how its properties are modified with the introduction of T-parity. We include an appendix with a list of Feynman rules specific to the littlest Higgs with T-parity to facilitate further study.Comment: 32 pages, 8 figures; dark matter bounds revised; comphep model files made publicly available at http://www.lns.cornell.edu/public/theory/tparity

Predicting Clinical Response to Everolimus in ER+ Breast Cancers Using Machine-Learning

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and 23 patients treated with everolimus to develop and validate an integrative machine learning biomarker of mTOR inhibitor response. Our results show that the machine learning biomarker can successfully distinguish responders from non-responders and can be applied to identify patients that will most likely benefit from everolimus treatment

Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells. Moreover, selective proteasome inhibition enabled mammary epithelial cells to acquire certain morphologic and functional characteristics reminiscent of cancer stem cells, including CD44 expression, self-renewal, and tumor formation. Transcriptomic analyses suggested that proteasome-inhibited cells share gene expression signatures with cells that have undergone EMT, in part, through modulation of the TGF-β signaling pathway. These findings suggest that selective downregulation of proteasome activity in mammary epithelial cells can initiate the EMT program and acquisition of a cancer stem cell-like phenotype. As proteasome inhibitors become increasingly used in cancer treatment, our findings highlight a potential risk of these therapeutic strategies and suggest a possible mechanism by which carcinoma cells may escape from proteasome inhibitor-based therapy

Gut bacteria responding to dietary change encode sialidases that exhibit preference for red meat-associated carbohydrates.

Dietary habits have been associated with alterations of the human gut resident microorganisms contributing to obesity, diabetes and cancer1. In Western diets, red meat is a frequently eaten food2, but long-term consumption has been associated with increased risk of disease3,4. Red meat is enriched in N-glycolylneuraminic acid (Neu5Gc) that cannot be synthesized by humans5. However, consumption can cause Neu5Gc incorporation into cell surface glycans6, especially in carcinomas4,7. As a consequence, an inflammatory response is triggered when Neu5Gc-containing glycans encounter circulating anti-Neu5Gc antibodies8,9. Although bacteria can use free sialic acids as a nutrient source10-12, it is currently unknown if gut microorganisms contribute to releasing Neu5Gc from food. We found that a Neu5Gc-rich diet induces changes in the gut microbiota, with Bacteroidales and Clostridiales responding the most. Genome assembling of mouse and human shotgun metagenomic sequencing identified bacterial sialidases with previously unobserved substrate preference for Neu5Gc-containing glycans. X-ray crystallography revealed key amino acids potentially contributing to substrate preference. Additionally, we verified that mouse and human sialidases were able to release Neu5Gc from red meat. The release of Neu5Gc from red meat using bacterial sialidases could reduce the risk of inflammatory diseases associated with red meat consumption, including colorectal cancer4 and atherosclerosis13

Two New Gravitationally Lensed Double Quasars from the Sloan Digital Sky Survey

We report the discoveries of the two-image gravitationally lensed quasars, SDSS J0746+4403 and SDSS J1406+6126, selected from the Sloan Digital Sky Survey (SDSS). SDSS J0746+4403, which will be included in our lens sample for statistics and cosmology, has a source redshift of z_s=2.00, an estimated lens redshift of z_l~0.3, and an image separation of 1.08". SDSS J1406+6126 has a source redshift of z_s=2.13, a spectroscopically measured lens redshift of z_l=0.27, and an image separation of 1.98". We find that the two quasar images of SDSS J1406+6126 have different intervening MgII absorption strengths, which are suggestive of large variations of absorbers on kpc scales. The positions and fluxes of both the lensed quasar systems are easily reproduced by simple mass models with reasonable parameter values. These objects bring to 18 the number of lensed quasars that have been discovered from the SDSS data.Comment: 25 pages, 6 figures, The Astronomical Journal accepte

Scalable continuous evolution for the generation of diverse enzyme variants encompassing promiscuous activities

Enzyme orthologs sharing identical primary functions can have different promiscuous activities. While it is possible to mine this natural diversity to obtain useful biocatalysts, generating comparably rich ortholog diversity is difficult, as it is the product of deep evolutionary processes occurring in a multitude of separate species and populations. Here, we take a first step in recapitulating the depth and scale of natural ortholog evolution on laboratory timescales. Using a continuous directed evolution platform called OrthoRep, we rapidly evolve the Thermotoga maritima tryptophan synthase β-subunit (TmTrpB) through multi-mutation pathways in many independent replicates, selecting only on TmTrpB’s primary activity of synthesizing L-tryptophan from indole and L-serine. We find that the resulting sequence-diverse TmTrpB variants span a range of substrate profiles useful in industrial biocatalysis and suggest that the depth and scale of evolution that OrthoRep affords will be generally valuable in enzyme engineering and the evolution of biomolecular functions

Reliable Optical Pump Architecture for Highly Coherent Lasers Used in Space Metrology Applications

The design and initial demonstration of a laser pump module (LPM) incorporating single-mode, grating-stabilized 808-nm diode lasers and a low-loss, high-port-count optical combiner are completed. The purpose of the developed LPM is to reliably pump an Nd:YAG crystal in the laser head (LH), which serves as the optical metrology source for SIMLite mission. Using the narrow-linewidth, single-mode laser diodes enables placement of the pump power near Nd adsorption peak, which enhances pumping efficiency. Grating stabilization allows for stable pump spectra as diode operating temperature and bias current change. The low-loss, high-port-count optical combiner enables efficient combining of tens of pumps. Overall, the module supports 5+ years of continuous operation at 2 W of pump power with reliability approaching 100 percent. The LPM consists of a laser diode farm (LDF) and a pump beam combiner (PBC). An array of 807- to 808-nm fiber-pigtailed laser diodes makes up the LDF. A Bragg grating in each 5- m core single-mode (SM) fiber pigtail acts to stabilize the lasing spectra over a range of diode operating conditions. These commercially available single-mode laser diodes can deliver up to 150 mW of optical power. The outputs from the multiple pumps in the LDF are routed to the PBC, which is a 37-input by 1-output all-fiber device. The input ports consist of 5- m core SM fiber, while the output port consists of 105- m core, 0.15 NA (numerical aperture) multi-mode (MM) fiber. The combiner is fabricated by fusing the 37 input fibers while simultaneously tapering the fused region. At the completion of this process, the MM fiber is spliced to the end of the adiabatic taper, and, for protection, the combiner is sheathed by a capillary tube. A compact and robust metal housing was designed and fabricated to protect the PBC during space deployment