AUK: a simple alternative to the AUC

The area under Receiver Operating Characteristic (ROC) curve, also known as the AUC-index, is commonly used for ranking the performance of data mining models. The AUC has many merits, such as objectivity and ease of interpretation. However, since it is class indifferent, its usefulness while dealing with hig

FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation

Inhibition of spindle microtubule (MT) dynamics has been effectively used in cancer treatment. Although the mechanisms by which MT poisons elicit mitotic arrest are fairly understood, efforts are still needed towards elucidating how cancer cells respond to antimitotic drugs owing to cytotoxicity and resistance side effects. Here, we identified the critical G2/M transcription factor Forkhead box M1 (FOXM1) as a molecular determinant of cell response to antimitotics. We found FOXM1 repression to increase death in mitosis (DiM) due to upregulation of the BCL-2 modifying factor (BMF) gene involved in anoikis, an apoptotic process induced upon cell detachment from the extracellular matrix. FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both the BMF and the neighbor gene BUB1B promoter regions, to oppositely regulate their expression. This mechanism ensures that cells treated with antimitotics repress BMF and avoid DiM when FOXM1 levels are high. In addition, we show that this mechanism is partly disrupted in anoikis/antimitotics-resistant tumor cells, with resistance correlating with lower BMF expression but in a FOXM1-independent manner. These findings provide a stratification biomarker for antimitotic chemotherapy response.This work was supported by: FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020 and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia) in the framework of the project POCI-01-0145-FEDER-031120 (PTDC/BIA-CEL/31120/ 2017); and POCI-01-0145-FEDER-007274 i3S framework project co-funded by COMPETE 2020/ PORTUGAL 2020 through FEDER. S.V. and F.F. were supported by FCT fellowships SFRH/BD/125017/2016 and PD/BD/105745/2014. E.L. was supported by an FCT Investigator Grant (IF/00916/2014). U.B-D. and G.L. were supported by the Azrieli Faculty Fellowship (to U.D.-D.) and the DoD CDMRP Career Development Award (CA191138 to U.B.-D.). J.B. was supported by an FCT Investigator Grant (CEECIND/03482/2018) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC-2015-StG-680156-ZPR)

Smoothed Complexity Theory

Smoothed analysis is a new way of analyzing algorithms introduced by Spielman and Teng (J. ACM, 2004). Classical methods like worst-case or average-case analysis have accompanying complexity classes, like P and AvgP, respectively. While worst-case or average-case analysis give us a means to talk about the running time of a particular algorithm, complexity classes allows us to talk about the inherent difficulty of problems. Smoothed analysis is a hybrid of worst-case and average-case analysis and compensates some of their drawbacks. Despite its success for the analysis of single algorithms and problems, there is no embedding of smoothed analysis into computational complexity theory, which is necessary to classify problems according to their intrinsic difficulty. We propose a framework for smoothed complexity theory, define the relevant classes, and prove some first hardness results (of bounded halting and tiling) and tractability results (binary optimization problems, graph coloring, satisfiability). Furthermore, we discuss extensions and shortcomings of our model and relate it to semi-random models.Comment: to be presented at MFCS 201

Spectral Energy Distributions of Local Luminous And Ultraluminous Infrared Galaxies

Luminous and ultraluminous infrared galaxies ((U)LIRGs) are the most extreme star forming galaxies in the universe. The local (U)LIRGs provide a unique opportunity to study their multi-wavelength properties in detail for comparison to their more numerous counterparts at high redshifts. We present common large aperture photometry at radio through X-ray wavelengths, and spectral energy distributions (SEDs) for a sample of 53 nearby LIRGs and 11 ULIRGs spanning log (LIR/Lsun) = 11.14-12.57 from the flux-limited Great Observatories All-sky LIRG Survey (GOALS). The SEDs for all objects are similar in that they show a broad, thermal stellar peak and a dominant FIR thermal dust peak, where nuLnu(60um) / nuLnu(V) increases from ~2-30 with increasing LIR. When normalized at IRAS-60um, the largest range in the luminosity ratio, R(lambda)=log[nuLnu(lambda)/nuLnu(60um)] observed over the full sample is seen in the Hard X-rays (HX=2-10 keV). A small range is found in the Radio (1.4GHz), where the mean ratio is largest. Total infrared luminosities, LIR(8-1000um), dust temperatures, and dust masses were computed from fitting thermal dust emission modified blackbodies to the mid-infrared (MIR) through submillimeter SEDs. The new results reflect an overall ~0.02 dex lower luminosity than the original IRAS values. Total stellar masses were computed by fitting stellar population synthesis models to the observed near-infrared (NIR) through ultraviolet (UV) SEDs. Mean stellar masses are found to be log(M/Msun) = 10.79+/-0.40. Star formation rates have been determined from the infrared (SFR_IR~45Msun/yr) and from the monochromatic UV luminosities (SFR_UV~1.3Msun/yr), respectively. Multiwavelength AGN indicators have be used to select putative AGN: about 60% of the ULIRGs would have been classified as an AGN by at least one of the selection criteria.Comment: 39 pages, including 12 figures and 11 tables; accepted for publication in ApJ

The Great Observatories All-Sky LIRG Survey: Comparison of Ultraviolet and Far-Infrared Properties

The Great Observatories All-sky LIRG Survey (GOALS) consists of a complete sample of 202 Luminous Infrared Galaxies (LIRGs) selected from the IRAS Revised Bright Galaxy Sample (RBGS). The galaxies span the full range of interaction stages, from isolated galaxies to interacting pairs to late stage mergers. We present a comparison of the UV and infrared properties of 135 galaxies in GOALS observed by GALEX and Spitzer. For interacting galaxies with separations greater than the resolution of GALEX and Spitzer (2-6"), we assess the UV and IR properties of each galaxy individually. The contribution of the FUV to the measured SFR ranges from 0.2% to 17.9%, with a median of 2.8% and a mean of 4.0 +/- 0.4%. The specific star formation rate of the GOALS sample is extremely high, with a median value (3.9*10^{-10} yr^{-1}) that is comparable to the highest specific star formation rates seen in the Spitzer Infrared Nearby Galaxies Survey sample. We examine the position of each galaxy on the IR excess-UV slope (IRX-beta) diagram as a function of galaxy properties, including IR luminosity and interaction stage. The LIRGs on average have greater IR excesses than would be expected based on their UV colors if they obeyed the same relations as starbursts with L_IR < 10^{11}L_0 or normal late-type galaxies. The ratio of L_IR to the value one would estimate from the IRXg-beta relation published for lower luminosity starburst galaxies ranges from 0.2 to 68, with a median value of 2.7. A minimum of 19% of the total IR luminosity in the RBGS is produced in LIRGs and ULIRGs with red UV colors (beta > 0). Among resolved interacting systems, 32% contain one galaxy which dominates the IR emission while the companion dominates the UV emission. Only 21% of the resolved systems contain a single galaxy which dominates both wavelengths.Comment: 37 pages, 10 figures, accepted for publication in Ap

Fluctuations of Matrix Entries of Regular Functions of Wigner Matrices

We study the fluctuations of the matrix entries of regular functions of Wigner random matrices in the limit when the matrix size goes to infinity. In the case of the Gaussian ensembles (GOE and GUE) this problem was considered by A.Lytova and L.Pastur in J. Stat. Phys., v.134, 147-159 (2009). Our results are valid provided the off-diagonal matrix entries have finite fourth moment, the diagonal matrix entries have finite second moment, and the test functions have four continuous derivatives in a neighborhood of the support of the Wigner semicircle law.Comment: minor corrections; the manuscript will appear in the Journal of Statistical Physic

A New Class of Changing-Look LINERs

We report the discovery of six active galactic nuclei (AGN) caught "turning on" during the first nine months of the Zwicky Transient Facility (ZTF) survey. The host galaxies were classified as LINERs by weak narrow forbidden line emission in their archival SDSS spectra, and detected by ZTF as nuclear transients. In five of the cases, we found via follow-up spectroscopy that they had transformed into broad-line AGN, reminiscent of the changing-look LINER iPTF 16bco. In one case, ZTF18aajupnt/AT2018dyk, follow-up HST UV and ground-based optical spectra revealed the transformation into a narrow-line Seyfert 1 (NLS1) with strong [Fe VII, X, XIV] and He II 4686 coronal lines. Swift monitoring observations of this source reveal bright UV emission that tracks the optical flare, accompanied by a luminous soft X-ray flare that peaks ~60 days later. Spitzer follow-up observations also detect a luminous mid-infrared flare implying a large covering fraction of dust. Archival light curves of the entire sample from CRTS, ATLAS, and ASAS-SN constrain the onset of the optical nuclear flaring from a prolonged quiescent state. Here we present the systematic selection and follow-up of this new class of changing-look LINERs, compare their properties to previously reported changing-look Seyfert galaxies, and conclude that they are a unique class of transients well-suited to test the uncertain physical processes associated with the LINER accretion state.Comment: Submitted to ApJ, 31 pages, 17 Figures (excluding Appendix due to file size constraints but will be available in electronic version

Improving rigid fiberoptic intubation: a comparison of the Bonfils Intubating Fiberscope™ with a novel modification

<p>Abstract</p> <p>Background</p> <p>The Bonfils intubating fiberscope has a limited upward tip angle of 40° and requires retromolar entry into the hypopharynx. These factors may make its use less desirable when managing the difficult airway because most anesthesia providers are well versed in midline oral intubation rather than the lateral retromolar approach. The <it>Center for Advanced Technology and Telemedicine </it>at the University of Nebraska Medical Center has developed a novel fiberscope with a more anterior 60° curve to allow for easier midline insertion and intubation. The objective of this work was to evaluate the novel fiberscope, in comparison to the Bonfils intubating fiberscope, in terms of use and function in difficult airway intubation.</p> <p>Methods</p> <p>Twenty-two anesthesia providers participated in simulated intubations of a difficult airway mannequin to compare the Bonfils intubating fiberscope with the novel curved Boedeker intubating fiberscope. The intubations were assessed based upon the following variables: recorded Cormack Lehane airway scores, requests for cricoid pressure, time to intubation, number of intubation attempts and success or failure of the procedure.</p> <p>Results</p> <p>Participants using the Bonfils fiberscope recorded an average Cormack Lehane (CL) airway score of 1.67 ± 1.02 (median = 1); with the novel fiberscope, the recorded average airway grade improved to 1.18 ± 0.50 (median = 1). The difference in airway scores was not statistically significant (p = 0.34; Fishers Exact Test comparing CL grades 1&2 vs. 3&4). There was, however, a statistically significant difference in intubation success rates between the two devices. With the Bonfils fiberscope, 68% (15/22) of participants were successful in intubation compared to a 100% success rate in intubation with the novel fiberscope (22/22) (p = 0.008). After the intubation trial, the majority of participants (95%) indicated a preference for the novel fiberscope (n = 20).</p> <p>Conclusions</p> <p>With this data, we can infer that the novel fiberscope curvature appears to improve or maintain the quality of an intubation attempt (airway score, cricoid pressure requirement, intubation time, number of attempts, placement success). The data indicate that the novel fiberscope offers a superior intubation experience to currently available best practices. The instrument was well received and would be welcomed by most study participants should the device become clinically available in the future.</p

Blood Vitamin C Levels of Patients Receiving Immunotherapy and Relationship to Monocyte Subtype and Epigenetic Modification

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.</p

London Hybrid Exposure Model: Improving Human Exposure Estimates to NO2 and PM2.5 in an Urban Setting.

Here we describe the development of the London Hybrid Exposure Model (LHEM), which calculates exposure of the Greater London population to outdoor air pollution sources, in-buildings, in-vehicles, and outdoors, using survey data of when and where people spend their time. For comparison and to estimate exposure misclassification we compared Londoners LHEM exposure with exposure at the residential address, a commonly used exposure metric in epidemiological research. In 2011, the mean annual LHEM exposure to outdoor sources was estimated to be 37% lower for PM2.5 and 63% lower for NO2 than at the residential address. These decreased estimates reflect the effects of reduced exposure indoors, the amount of time spent indoors (∼95%), and the mode and duration of travel in London. We find that an individual's exposure to PM2.5 and NO2 outside their residential address is highly correlated (Pearson's R of 0.9). In contrast, LHEM exposure estimates for PM2.5 and NO2 suggest that the degree of correlation is influenced by their exposure in different transport modes. Further development of the LHEM has the potential to increase the understanding of exposure error and bias in time-series and cohort studies and thus better distinguish the independent effects of NO2 and PM2.5