Deep Learning-Based Prediction of Molecular Tumor Biomarkers from H&E: A Practical Review

Molecular and genomic properties are critical in selecting cancer treatments to target individual tumors, particularly for immunotherapy. However, the methods to assess such properties are expensive, time-consuming, and often not routinely performed. Applying machine learning to H&E images can provide a more cost-effective screening method. Dozens of studies over the last few years have demonstrated that a variety of molecular biomarkers can be predicted from H&E alone using the advancements of deep learning: molecular alterations, genomic subtypes, protein biomarkers, and even the presence of viruses. This article reviews the diverse applications across cancer types and the methodology to train and validate these models on whole slide images. From bottom-up to pathologist-driven to hybrid approaches, the leading trends include a variety of weakly supervised deep learning-based approaches, as well as mechanisms for training strongly supervised models in select situations. While results of these algorithms look promising, some challenges still persist, including small training sets, rigorous validation, and model explainability. Biomarker prediction models may yield a screening method to determine when to run molecular tests or an alternative when molecular tests are not possible. They also create new opportunities in quantifying intratumoral heterogeneity and predicting patient outcomes.Comment: 20 pages, 2 figure

Innovative Feed-In Tariff Designs that Limit Policy Costs

Feed-in tariffs (FITs) are the most prevalent renewable energy policy used globally to date, and there are many benefits to the certainty offered in the marketplace to reduce development risks and associated financing costs and to grow the renewable energy industry. However, concerns over escalating costs in jurisdictions with FIT policies have led to increased attention on cost control in renewable energy policy design. In recent years, policy mechanisms for containing FIT costs have become more refined, allowing policymakers to exert greater control on policy outcomes and on the resulting costs to ratepayers. As policymakers and regulators in the United States begin to explore the use of FITs, careful consideration must be given to the ways in which policy design can be used to balance the policies' advantages while bounding its costs. This report explores mechanisms that policymakers have implemented to limit FIT policy costs. If designed clearly and transparently, such mechanisms can align policymaker and market expectations for project deployment. Three different policy tools are evaluated: (1) caps, (2) payment level adjustment mechanisms, and (3) auction-based designs. The report employs case studies to explore the strengths and weaknesses of these three cost containment tools. These tools are then evaluated with a set of criteria including predictability for policymakers and the marketplace and the potential for unintended consequences

Occurrence of the orange wheat blossom midge [Diptera :Cecidomyiidae] in Quebec and its incidence on wheat grain microflora

À l'été 1995, on a prélevé des échantillons de blé (Triticum aestivum) dans des champs de diverses régions agricoles du Québec. La présence de larves de la cécidomyie orangée du blé (Sitodiplosis mosellana) fut quantifiée et une évaluation qualitative et quantitative de la microflore des grains fut réalisée. Les pertes moyennes de rendement causées par les larves de la cécidomyie du blé furent estimée à 6,3%. Le pourcentage des épis infestés fut significativement corrélé avec la contamination bactérienne et fongique des grains (r = 0,79). La présence spécifique du Fusarium graminearum dans les grains de blé fut aussi significativement corrélée avec le nombre de larves par épi (r= 0,67) ou par épillet (r= 0,67). Il appert que la cécidomyie du blé pourrait jouer un rôle dans la dissémination du F. graminearum.Samples of wheat spikes (Triticum aestivum) were collected in the summer of 1995 from different crop districts in Quebec and the occurrence of orange wheat blossom midge (Sitodiplosis mosellana) and seed microflora were determined. Estimated yield loss caused by wheat midge larvae averaged 6.3%. The percentage of infested spikes was significantly correlated with total seed contamination by fungi and bacteria (r = 0.79). The specific occurrence of Fusarium graminearum in grains was also significantly correlated with number of larvae per spike (r = 0.67) or per spikelet (r = 0.67). Consequently, the wheat midge might play a role in dissemination of F. graminearum

Globular Clusters in the dE,N galaxy NGC 3115 DW1: New Insights from Spectroscopy and HST Photometry

The properties of globular clusters in dwarf galaxies are key to understanding the formation of globular cluster systems, and in particular in verifying scenarios in which globular cluster systems of larger galaxies formed (at least partly) from the accretion of dwarf galaxies. Here, we revisit the globular cluster system of the dE,N galaxy NGC 3115 DW1 - a companion of the nearby S0 galaxy NGC 3115 - adding Keck/LRIS spectroscopy and HST/WFPC2 imaging to previous ground-based photometry. Spectra for seven globular clusters reveal normal abundance ratios with respect to the Milky Way and M31 clusters, as well as a relatively high mean metallicity ([Fe/H] = -1.0+/-0.1 dex). Crude kinematics indicate a high velocity dispersion within 10 kpc which could either be caused by dark matter dominated outer regions, or by the stripping of outer globular clusters by the nearby giant galaxy NGC 3115. The total galaxy mass out to 3 and 10 kpc lies between 10^10 and 10^11 solar masses and 2*10^10 and 4*10^11 solar masses, respectively, depending on the mass estimator used and the assumptions on cluster orbits and systemic velocity. The HST imaging allows measurement of sizes for two clusters, returning core radii around 2.0 pc, similar to the sizes observed in other galaxies. Spectroscopy allows an estimate of the degree of contamination by foreground stars or background galaxies for the previous ground-based photometry, but does not require a revision of previous results: NGC 3115 DW1 hosts around 60+/-20 clusters which corresponds to a specific frequency of 4.9+/-1.9, on the high end for massive dEs. Given its absolute magnitude (M_V=-17.7 mag) and the properties of its cluster system, NGC 3115 DW1 appears to be a transition between a luminous dE and low-luminosity E galaxy.Comment: 25 pages, 8 figures, accepted for publication in The Astronomical Journal, August 2000 issu

Supersymmetric QCD flavor changing top quark decay

We present a detailed and complete calculation of the gluino and scalar quarks contribution to the flavour-changing top quark decay into a charm quark and a photon, gluon, or a Z boson within the minimal supersymmetric standard model including flavour changing gluino-quarks-scalar quarks couplings in the right-handed sector. We compare the results with the ones presented in an earlier paper where we considered flavour changing couplings only in the left-handed sector. We show that these new couplings have important consequences leading to a large enhancement when the mixing of the scalar partners of the left- and right-handed top quark is included. Furthermore CP violation in the flavour changing top quark decay will occur when a SUSY phase is taken into account.Comment: 14 pages, latex, 3 figure

Radiative lepton flavor violating decays in the Randall Sundrum background with localized leptons

We study the radiative lepton flavor violating l_i -> l_j\gamma decays in the two Higgs doublet model, respecting the Randall Sundrum scenario and estimate the contributions of the KK modes of left (right) handed charged lepton doublets (singlets) on the branching ratios. We observe that the branching ratios are sensitive to the contributions of the charged lepton KK modes.Comment: 23 pages, 10 figures, 2 table

Searching for Anomalous Weak Couplings of Heavy Flavors at the SLC and LEP

The existence of anomalous electric($\tilde \kappa$) and/or magnetic($\kappa$) dipole moment couplings between the heavy flavor fermions ($c,b,\tau$) and the $Z$ boson can cause significant shifts in the values of several electroweak observables currently being probed at both the SLC and LEP. Using the good agreement between existing data and the predictions of the Standard Model we obtain strict bounds on the possible strength of these new interactions for all of the heavy flavors. The decay $Z\rightarrow b\bar b$, however, provides some possible hint of new physics. The corresponding anomalous couplings of $\tau$'s to photons is briefly examined.Comment: 21 pages, 14 figs(available on request), LaTex, SLAC-PUB-667

Applying dissipative dynamical systems to pseudorandom number generation: Equidistribution property and statistical independence of bits at distances up to logarithm of mesh size

The behavior of a family of dissipative dynamical systems representing transformations of two-dimensional torus is studied on a discrete lattice and compared with that of conservative hyperbolic automorphisms of the torus. Applying dissipative dynamical systems to generation of pseudorandom numbers is shown to be advantageous and equidistribution of probabilities for the sequences of bits can be achieved. A new algorithm for generating uniform pseudorandom numbers is proposed. The theory of the generator, which includes proofs of periodic properties and of statistical independence of bits at distances up to logarithm of mesh size, is presented. Extensive statistical testing using available test packages demonstrates excellent results, while the speed of the generator is comparable to other modern generators.Comment: 6 pages, 3 figures, 3 table

Analytical evidence of enamel hypomineralisation on permanent and primary molars amongst past populations /631/181/19/2471 /692/699 /123 article

Molar Incisor Hypomineralisation (MIH) and Hypomineralised Second Primary Molars (HSPM) involve prevalent qualitative structural developmental anomalies of tooth enamel affecting the first permanent molars (and often incisors) and the second primary molars, respectively. These demarcated hypomineralised lesions of enamel manifest as white-cream or yellow-brown opacities, with possible post-eruptive localised loss of enamel. Aetiological hypotheses have involved contemporary life factors (i.e. environmental pollutant exposure or early childhood medications) in contrast to factors not limited to a specific time period (i.e. hypoxia at birth or genetic predisposition). Evidence of MIH in ancient populations would reinforce aetiological factors present for many centuries. By means of microtomographic and X-ray fluorescence analyses the present study provides evidence that (i) two archaeological specimens: "S407" (Sains-en-Gohelle, France, 12th-16th centuries) and "B335" (Beauvais, France, 15th-18th centuries) were MIH-affected, and (ii) one individual "S323" was affected by HSPM and MIH (Sains-en-Gohelle, France, 7th-11th centuries)