Marginally unstable Holmboe modes

Marginally unstable Holmboe modes for smooth density and velocity profiles are studied. For a large family of flows and stratification that exhibit Holmboe instability, we show that the modes with phase velocity equal to the maximum or the minimum velocity of the shear are marginally unstable. This allows us to determine the critical value of the control parameter R (expressing the ratio of the velocity variation length scale to the density variation length scale) that Holmboe instability appears R=2. We then examine systems for which the parameter R is very close to this critical value. For this case we derive an analytical expression for the dispersion relation of the complex phase speed c(k) in the unstable region. The growth rate and the width of the region of unstable wave numbers has a very strong (exponential) dependence on the deviation of R from the critical value. Two specific examples are examined and the implications of the results are discussed.Comment: Submitted to Physics of Fluid

Local ocean response to a multiphase westerly wind burst: 1. Dynamic response

The dynamic response to a westerly wind burst which occurred during the Coupled Ocean Atmosphere Response Experiment in the warm pool of the equatorial Pacific Ocean is described using velocity, hydrography, and microstructure measurements. Turbulent fluxes distributed momentum input from the wind over a near‐surface layer of variable thickness. Coriolis and pressure gradient terms combined to induce a wavelike response whose frequency was close to the local inertial frequency. Wind stress variations on near‐inertial timescales interfered both constructively and destructively with the wave response, exerting considerable influence on the observed currents

Stratified shear flow instabilities at large Richardson numbers

Numerical simulations of stratified shear flow instabilities are performed in two dimensions in the Boussinesq limit. The density variation length scale is chosen to be four times smaller than the velocity variation length scale so that Holmboe or Kelvin-Helmholtz unstable modes are present depending on the choice of the global Richardson number Ri. Three different values of Ri were examined Ri =0.2, 2, 20. The flows for the three examined values are all unstable due to different modes namely: the Kelvin-Helmholtz mode for Ri=0.2, the first Holmboe mode for Ri=2, and the second Holmboe mode for Ri=20 that has been discovered recently and it is the first time that it is examined in the non-linear stage. It is found that the amplitude of the velocity perturbation of the second Holmboe mode at the non-linear stage is smaller but comparable to first Holmboe mode. The increase of the potential energy however due to the second Holmboe modes is greater than that of the first mode. The Kelvin-Helmholtz mode is larger by two orders of magnitude in kinetic energy than the Holmboe modes and about ten times larger in potential energy than the Holmboe modes. The results in this paper suggest that although mixing is suppressed at large Richardson numbers it is not negligible, and turbulent mixing processes in strongly stratified environments can not be excluded.Comment: Submitted to Physics of Fluid

Acquired resistance to anti-PD1 therapy: checkmate to checkpoint blockade?

Editorial summary Anti-programmed cell death 1 (PD1) immunotherapies are among the most effective anti-cancer immunotherapies available; however, a large number of patients present with or develop resistance to them. Unfortunately, very little is known regarding the mechanisms of resistance to such therapies. A recent study sought to identify mutations associated with resistance to anti-PD1 therapy. Results from this study demonstrated that mutations which affected the sensitivity of tumor cells to T-cell-derived interferons, and mutations limiting tumor-cell antigen presentation, could cause acquired resistance. These findings have significant implications for understanding the mechanisms by which anti-PD1 therapies exert their efficacy, comprehending why and how some patients acquire resistance over time, and ultimately guiding the development of combination therapies designed to overcome, or potentially prevent, the development of acquired immunotherapeutic resistance

The combination of histone deacetylase inhibitors with immune-stimulating antibodies has potent anti-cancer effects

The use of immunotherapy to treat cancer is rapidly gaining momentum. Using pre-clinical mouse models, we have recently demonstrated potent and long lasting tumor regression can be elicited by immune-stimulating monoclonal antibodies (mAbs) when combined with histone deacetylase inhibitors (HDACi) and believe this therapy will have broad application in humans

Final Technical Report for "Collaborative Research: Regional climate-change projections through next-generation empirical and dynamical models"

This project was a continuation of previous work under DOE CCPP funding in which we developed a twin approach of non-homogeneous hidden Markov models (NHMMs) and coupled ocean-atmosphere (O-A) intermediate-complexity models (ICMs) to identify the potentially predictable modes of climate variability, and to investigate their impacts on the regional-scale. We have developed a family of latent-variable NHMMs to simulate historical records of daily rainfall, and used them to downscale seasonal predictions. We have also developed empirical mode reduction (EMR) models for gaining insight into the underlying dynamics in observational data and general circulation model (GCM) simulations. Using coupled O-A ICMs, we have identified a new mechanism of interdecadal climate variability, involving the midlatitude oceans mesoscale eddy field and nonlinear, persistent atmospheric response to the oceanic anomalies. A related decadal mode is also identified, associated with the oceans thermohaline circulation. The goal of the continuation was to build on these ICM results and NHMM/EMR model developments and software to strengthen two key pillars of support for the development and application of climate models for climate change projections on time scales of decades to centuries, namely: (a) dynamical and theoretical understanding of decadal-to-interdecadal oscillations and their predictability; and (b) an interface from climate models to applications, in order to inform societal adaptation strategies to climate change at the regional scale, including model calibration, correction, downscaling and, most importantly, assessment and interpretation of spread and uncertainties in multi-model ensembles. Our main results from the grant consist of extensive further development of the hidden Markov models for rainfall simulation and downscaling specifically within the non-stationary climate change context together with the development of parallelized software; application of NHMMs to downscaling of rainfall projections over India; identification and analysis of decadal climate signals in data and models; and, studies of climate variability in terms of the dynamics of atmospheric flow regimes. Each of these project components is elaborated on below, followed by a list of publications resulting from the grant

Binomial coefficients, Catalan numbers and Lucas quotients

Let $p$ be an odd prime and let $a,m$ be integers with $a>0$ and $m \not\equiv0\pmod p$. In this paper we determine $\sum_{k=0}^{p^a-1}\binom{2k}{k+d}/m^k$ mod $p^2$ for $d=0,1$; for example, $$\sum_{k=0}^{p^a-1}\frac{\binom{2k}k}{m^k}\equiv\left(\frac{m^2-4m}{p^a}\right)+\left(\frac{m^2-4m}{p^{a-1}}\right)u_{p-(\frac{m^2-4m}{p})}\pmod{p^2},$$ where $(-)$ is the Jacobi symbol, and $\{u_n\}_{n\geqslant0}$ is the Lucas sequence given by $u_0=0$, $u_1=1$ and $u_{n+1}=(m-2)u_n-u_{n-1}$ for $n=1,2,3,\ldots$. As an application, we determine $\sum_{0<k<p^a,\, k\equiv r\pmod{p-1}}C_k$ modulo $p^2$ for any integer $r$, where $C_k$ denotes the Catalan number $\binom{2k}k/(k+1)$. We also pose some related conjectures.Comment: 24 pages. Correct few typo

Cluster Analysis of Typhoon Tracks. Part II: Large-Scale Circulation and ENSO

A new probabilistic clustering method, based on a regression mixture model, is used to describe tropical cyclone (TC) propagation in the western North Pacific (WNP). Seven clusters were obtained and described in Part I of this two-part study. In Part II, the present paper, the large-scale patterns of atmospheric circulation and sea surface temperature associated with each of the clusters are investigated, as well as associations with the phase of the El Niño–Southern Oscillation (ENSO). Composite wind field maps over the WNP provide a physically consistent picture of each TC type, and of its seasonality. Anomalous vorticity and outgoing longwave radiation indicate changes in the monsoon trough associated with different types of TC genesis and trajectory. The steering winds at 500 hPa are more zonal in the straight-moving clusters, with larger meridional components in the recurving ones. Higher values of vertical wind shear in the midlatitudes also accompany the straight-moving tracks, compared to the recurving ones. The influence of ENSO on TC activity over the WNP is clearly discerned in specific clusters. Two of the seven clusters are typical of El Niño events; their genesis locations are shifted southeastward and they are more intense. The largest cluster is recurving, located northwestward, and occurs more often during La Niña events. Two types of recurving and one of straight-moving tracks occur preferentially when the Madden–Julian oscillation is active over the WNP region