Multi-wavelength observations of 2HWC J1928+177: dark accelerator or new TeV gamma-ray binary?

2HWC J1928+177 is a Galactic TeV gamma-ray source detected by the High Altitude Water Cherenkov (HAWC) Observatory up to ~ 56 TeV. The HAWC source, later confirmed by H.E.S.S., still remains unidentified as a dark accelerator since there is no apparent supernova remnant or pulsar wind nebula detected in the lower energy bands. The radio pulsar PSR J1928+1746, coinciding with the HAWC source position, has no X-ray counterpart. Our SED modeling shows that inverse Compton scattering in the putative pulsar wind nebula can account for the TeV emission only if the unseen nebula is extended beyond r ~ 4 [arcmin]. Alternatively, TeV gamma rays may be produced by hadronic interactions between relativistic protons from an undetected supernova remnant associated with the radio pulsar and a nearby molecular cloud G52.9+0.1. NuSTAR and Chandra observations detected a variable X-ray point source within the HAWC error circle, potentially associated with a bright IR source. The X-ray spectra can be fitted with an absorbed power-law model with $N_{\rm H} = (9\pm3)\times10^{22}$ cm$^{-2}$ and $\Gamma_X = 1.6\pm0.3$ and exhibit long-term X-ray flux variability over the last decade. If the X-ray source, possibly associated with the IR source (likely an O star), is the counterpart of the HAWC source, it may be a new TeV gamma-ray binary powered by collisions between the pulsar wind and stellar wind. Follow-up X-ray observations are warranted to search for diffuse X-ray emission and determine the nature of the HAWC source.Comment: accepted to ApJ, 8 pages, 7 figure

Novel Likelihood Ratio Tests for Screening Gene‐Gene and Gene‐Environment Interactions With Unbalanced Repeated‐Measures Data

There has been extensive literature on modeling gene‐gene interaction (GGI) and gene‐environment interaction (GEI) in case‐control studies with limited literature on statistical methods for GGI and GEI in longitudinal cohort studies. We borrow ideas from the classical two‐way analysis of variance literature to address the issue of robust modeling of interactions in repeated‐measures studies. While classical interaction models proposed by Tukey and Mandel have interaction structures as a function of main effects, a newer class of models, additive main effects and multiplicative interaction (AMMI) models, do not have similar restrictive assumptions on the interaction structure. AMMI entails a singular value decomposition of the cell residual matrix after fitting the additive main effects and has been shown to perform well across various interaction structures. We consider these models for testing GGI and GEI from two perspectives: likelihood ratio test based on cell means and a regression‐based approach using individual observations. Simulation results indicate that both approaches for AMMI models lead to valid tests in terms of maintaining the type I error rate, with the regression approach having better power properties. The performance of these models was evaluated across different interaction structures and 12 common epistasis patterns. In summary, AMMI model is robust with respect to misspecified interaction structure and is a useful screening tool for interaction even in the absence of main effects. We use the proposed methods to examine the interplay between the hemochromatosis gene and cumulative lead exposure on pulse pressure in the Normative Aging Study.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99643/1/gepi21744-sup-0001-si.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99643/2/gepi21744.pd

Hard X-ray observation and multiwavelength study of the PeVatron candidate pulsar wind nebula "Dragonfly"

We studied the PeVatron nature of the pulsar wind nebula G75.2+0.1 ("Dragonfly") as part of our NuSTAR observational campaign of energetic PWNe. The Dragonfly is spatially coincident with LHAASO J2018+3651 whose maximum photon energy is 0.27 PeV. We detected a compact (radius 1') inner nebula of the Dragonfly without a spectral break in 3 $-$ 20 keV using NuSTAR. A joint analysis of the inner nebula with the archival Chandra and XMM-Newton observations yields a power-law spectrum with $\Gamma=1.49\pm0.03$. Synchrotron burnoff is observed from the shrinkage of the NuSTAR nebula at higher energies, from which we infer the magnetic field in the inner nebula of 24 $\mu$G at 3.5 kpc. Our analysis of archival XMM data and 13 years of Fermi-LAT data confirms the detection of an extended (~10') outer nebula in 2 $-$ 6 keV ($\Gamma=1.82\pm0.03$) and non-detection of a GeV nebula, respectively. Using the VLA, XMM, and HAWC data, we modeled a multi-wavelength spectral energy distribution of the Dragonfly as a leptonic PeVatron. The maximum injected particle energy of 1.4 PeV from our model suggests that the Dragonfly is likely a PeVatron. Our model prediction of the low magnetic field (2.7 $\mu$G) in the outer nebula and recent interaction with the host supernova remnant's reverse shock (4 kyrs ago) align with common features of PeVatron PWNe. The origin of its highly asymmetric morphology, pulsar proper motion, PWN-SNR interaction, and source distance will require further investigations in the future including a multi-wavelength study using radio, X-ray, and gamma-ray observations.Comment: 18 pages, 11 figures, ApJ accepte

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases

Testing departure from additivity in Tukey's model using shrinkage: application to a longitudinal setting

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109558/1/sim6281-sup-0001-WebBased.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109558/2/sim6281.pd

Integration of Liquid Biopsy and Pharmacogenomics for Precision Therapy of EGFR Mutant and Resistant Lung Cancers

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases of lung cancer treatment. This selection will be based on the driver EGFR mutational status, as well as monitoring the development of potential EGFR mutations arising during or after TKIs treatment, since some of these new mutations may be druggable targets for alternative TKIs. Several studies have identified the utility of liquid biopsy in the identification of EGFR driver and acquired resistance with good sensitivities for various blood-based biomarkers. With a plethora of sequencing technologies and platforms available currently, further evaluations using randomized controlled trials (RCTs) in multicentric, multiethnic and larger patient cohorts could enable optimization of liquid-based assays for the detection of EGFR mutations, and support testing of CYP450 enzymes and drug transporter polymorphisms to guide precise dosing of EGFR TKIs

Probing the fuzzy sphere regularisation in simulations of the 3d \lambda \phi^4 model

We regularise the 3d \lambda \phi^4 model by discretising the Euclidean time and representing the spatial part on a fuzzy sphere. The latter involves a truncated expansion of the field in spherical harmonics. This yields a numerically tractable formulation, which constitutes an unconventional alternative to the lattice. In contrast to the 2d version, the radius R plays an independent r\^{o}le. We explore the phase diagram in terms of R and the cutoff, as well as the parameters m^2 and \lambda. Thus we identify the phases of disorder, uniform order and non-uniform order. We compare the result to the phase diagrams of the 3d model on a non-commutative torus, and of the 2d model on a fuzzy sphere. Our data at strong coupling reproduce accurately the behaviour of a matrix chain, which corresponds to the c=1-model in string theory. This observation enables a conjecture about the thermodynamic limit.Comment: 31 pages, 15 figure

Exercise therapy in adults with serious mental illness: a systematic review and meta-analysis

Background: Individuals with serious mental illness are at a higher risk of physical ill health. Mortality rates are at least twice those of the general population with higher levels of cardiovascular disease, metabolic disease, diabetes, and respiratory illness. Although genetics may have a role in the physical health problems of these patients, lifestyle and environmental factors such as levels of smoking, obesity, poor diet, and low levels of physical activity also play a prominent part.<p></p> Objective: To conduct a systematic review and meta-analysis of randomised controlled trials comparing the effect of exercise interventions on individuals with serious mental illness.<p></p> Methods: Searches were made in Ovid MEDLINE, Embase, CINAHL, PsycINFO, Biological Abstracts on Ovid, and The Cochrane Library (January 2009, repeated January 2013) through to February 2013.<p></p> Results: Eight RCTs were identified in the systematic search. Six compared exercise versus usual care. One study assessed the effect of a cycling programme versus muscle strengthening and toning exercises. The final study compared the effect of adding specific exercise advice and motivational skills to a simple walking programme. Exercise programmes were noted by their heterogeneity in terms of the type of exercise intervention, setting, and outcome measures. The review found that exercise improved levels of exercise activity (n=13, standard mean difference [SMD] 1.81, CI 0.44 to 3.18, p = 0.01). No beneficial effect was found on negative (n = 84, SMD = -0.54, CI -1.79 to 0.71, p = 0.40) or positive symptoms of schizophrenia (n = 84, SMD = -1.66, CI -3.78 to 0.45, p = 0.12). No change was found on body mass index compared with usual care (n= 151, SMD = -0.24, CI -0.56 to 0.08, p = 0.14), or body weight (n = 77, SMD = 0.13, CI -0.32 to 0.58, p = 0.57). No beneficial effect was found on anxiety and depressive symptoms (n = 94, SMD = -0.26, CI -0.91 to 0.39, p = 0.43), or quality of life in respect of physical and mental domains. One RCT measured the effect of exercise on exercise intensity, attendance, and persistence at a programme. No significant effect was found on these measures.<p></p> Conclusions: This systematic review showed that exercise therapies can lead to a modest increase in levels of exercise activity but overall there was no noticeable change for symptoms of mental health, body mass index, and body weight.<p></p&gt

A new multistage lattice vector quantization with adaptive subband thresholding for image compression

Lattice vector quantization (LVQ) reduces coding complexity and computation due to its regular structure. A new multistage LVQ (MLVQ) using an adaptive subband thresholding technique is presented and applied to image compression. The technique concentrates on reducing the quantization error of the quantized vectors by "blowing out" the residual quantization errors with an LVQ scale factor. The significant coefficients of each subband are identified using an optimum adaptive thresholding scheme for each subband. A variable length coding procedure using Golomb codes is used to compress the codebook index which produces a very efficient and fast technique for entropy coding. Experimental results using the MLVQ are shown to be significantly better than JPEG 2000 and the recent VQ techniques for various test images