Pathway-Based Genomics Prediction using Generalized Elastic Net.

We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach

AlGaAs heterojunction lasers

The characterization of 8300 A lasers was broadened, especially in the area of beam quality. Modulation rates up to 2 Gbit/sec at output powers of 20 mW were observed, waveform fidelity was fully adequate for low BER data transmission, and wavefront measurements showed that phase aberrations were less than lamda/50. Also, individually addressable arrays of up to ten contiguous diode lasers were fabricated and tested. Each laser operates at powers up to 30 mW CW in single spatial mode. Shifting the operating wavelength of the basic CSP laser from 8300 A to 8650 A was accomplished by the addition of Si to the active region. Output power has reached 100 mW single mode, with excellent far field wave front properties. Operating life is currently approx. 1000 hrs at 35 mW CW. In addition, laser reliability, for operation at both 8300 A and 8650 A, has profited significantly from several developments in the processing procedures

High-power AlGaAs channeled substrate planar diode lasers for spaceborne communications

A high power channeled substrate planar AlGaAs diode laser with an emission wavelength of 8600 to 8800 A was developed. The optoelectronic behavior (power current, single spatial and spectral behavior, far field characteristics, modulation, and astigmatism properties) and results of computer modeling studies on the performance of the laser are discussed. Lifetest data on these devices at high output power levels is also included. In addition, a new type of channeled substrate planar laser utilizing a Bragg grating to stabilize the longitudinal mode was demonstrated. The fabrication procedures and optoelectronic properties of this new diode laser are described

Large K-exciton dynamics in GaN epilayers: the non-thermal and thermal regime

We present a detailed investigation concerning the exciton dynamics in GaN epilayers grown on c-plane sapphire substrates, focussing on the exciton formation and the transition from the nonthermal to the thermal regime. The time-resolved kinetics of LO-phonon replicas is used to address the energy relaxation in the excitonic band. From ps time-resolved spectra we bring evidence for a long lasting non-thermal excitonic distribution which accounts for the rst 50 ps. Such a behavior is con rmed in di erent experimental conditions, both when non-resonant and resonant excitation are used. At low excitation power density the exciton formation and their subsequent thermalization is dominated by impurity scattering rather than by acoustic phonon scattering. The estimate of the average energy of the excitons as a function of delay after the excitation pulse provides information on the relaxation time, which describes the evolution of the exciton population to the thermal regime.Comment: 9 pages,8 figure

Affective Polarization in Multiparty Systems? Comparing Affective Polarization Towards Voters and Parties in Norway and the United States

A growing body of comparative studies on partisan hostility – a phenomenon known as affective polarization – is providing evidence that partisan affective polarization is generally no greater in the United States than it is in many European multiparty systems. This article takes the comparative literature on affective polarization one step further by presenting the first comparative study on affective polarization that simultaneously uses, compares and combines a direct measure of affective polarization towards voters (using the inter-party marriage measure) and an indirect measure of affective polarization towards parties (using the like/dislike of party measure) while accounting for the fact that multiparty systems have numerous political parties. This is done by comparing the levels of affective polarization in the United States and Norway. The results show greater affective polarization in the United States relating to parties, but the differences between these two countries are indistinguishable from chance when focusing on the affect relating to voters. This provides empirical evidence that comparative evidence of negative affect towards parties cannot necessarily be generalized to suggest that there is comparative evidence of negative affect towards voters. Yet the results also suggest that negative feelings towards out-parties move to some extent to the personal level in terms of negative feelings towards voters of these out-parties.publishedVersio

A Deep Proper-Motion Survey in Kapteyn Selected Areas: I. Survey Description and First Results for Stars in the Tidal Tail of Sagittarius and in the Monoceros Ring

We describe a high-precision, deep (to V ~ 19-21) absolute proper-motion survey that samples ~50 lines of sight in the Kapteyn Selected Areas along declination zones -15, 0 and 15 degrees. In many fields the astrometric baseline reaches nearly a century. We demonstrate that these data provide typical per star precisions between ~ 1 and 3 mas/yr to the above magnitude limits, with the absolute reference frame established by numerous extragalactic sources in each survey field. Combined with existing and ongoing photometric and radial velocity surveys in these fields, these astrometric data will enable, among other things, accurate, detailed dynamical modeling of satellite interactions with our Galaxy. In this contribution we describe the astrometric part of our survey and show preliminary results along the trailing tail of the Sagittarius dwarf galaxy, and in the Monoceros ring region.Comment: Accepter for publication in the Astronomical Journa

Bayesian Optimization for Personalized Dose-Finding Trials with Combination Therapies

Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the dose-response surface, and the small sample sizes in early phase trials. Existing methods often restrict the search to pre-defined dose combinations, which may fail to identify regions of optimality in the dose combination space. These difficulties are even more pertinent in the context of personalized dose-finding, where patient characteristics are used to identify tailored optimal dose combinations. To overcome these challenges, we propose the use of Bayesian optimization for finding optimal dose combinations in standard ("one size fits all") and personalized multi-agent dose-finding trials. Bayesian optimization is a method for estimating the global optima of expensive-to-evaluate objective functions. The objective function is approximated by a surrogate model, commonly a Gaussian process, paired with a sequential design strategy to select the next point via an acquisition function. This work is motivated by an industry-sponsored problem, where focus is on optimizing a dual-agent therapy in a setting featuring minimal toxicity. To compare the performance of the standard and personalized methods under this setting, simulation studies are performed for a variety of scenarios. Our study concludes that taking a personalized approach is highly beneficial in the presence of heterogeneity.Comment: 26 pages, 4 figures, 1 tabl