Editorial: Cancer Nanotheranostics: What Have We Learned So Far?

According to the National Cancer Institute, in 2015 an estimated of 1.7 million new cases of cancer will be diagnosed only in the United States and around 600, 000 people will die from the disease. The most common type of cancer is breast cancer, with more than 234, 000 new cases expected in the United States in 2015. The next most common cancers are prostate cancer and lung cancer.After a quarter of century of rapid technological advances, research has revealed the complexity of cancer, a disease intimately related to the dynamic transformation of the genome. These transformations trigger a range of modification to cell processes and molecular events that initiate and promote tumor genesis and progression, then local invasion and metastasis, i.e., the hallmarks of cancer development. These alterations may cause a wide scope of “diseases” that share similar molecular patterns that cause transformation and malignancy. Each of this stepwise evolution of the initial molecular event drives abnormal growth and loss of differentiation that ultimately causes tissue and organ failure. The initial molecular event may lay within the erroneous expression of a given gene, epigenetic modification and/or sporadic mutations occurring on genomic DNA during the life span of organisms. Each and every one of these molecular events may be evaluated and used as diagnostics biomarker and therapeutic target. For example, therapy action may target a mutated gene and silence its expression so as to avoid erroneous protein expression that mutates cell function. However, the full understanding of the molecular onset of this disease is still far from achieved and the search for mechanisms of treatment will follow closely..

MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease

Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2

Influenza A virus’s (IAV’s) frequent genetic changes challenge vaccine strategies and engender resistance to current drugs. We sought to identify conserved and essential RNA secondary structures within IAV’s genome that are predicted to have greater constraints on mutation in response to therapeutic targeting. We identified and genetically validated an RNA structure (packaging stem–loop 2 (PSL2)) that mediates in vitro packaging and in vivo disease and is conserved across all known IAV isolates. A PSL2-targeting locked nucleic acid (LNA), administered 3 d after, or 14 d before, a lethal IAV inoculum provided 100% survival in mice, led to the development of strong immunity to rechallenge with a tenfold lethal inoculum, evaded attempts to select for resistance and retained full potency against neuraminidase inhibitor-resistant virus. Use of an analogous approach to target SARS-CoV-2, prophylactic administration of LNAs specific for highly conserved RNA structures in the viral genome, protected hamsters from efficient transmission of the SARS-CoV-2 USA_WA1/2020 variant. These findings highlight the potential applicability of this approach to any virus of interest via a process we term ‘programmable antivirals’, with implications for antiviral prophylaxis and post-exposure therapy

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Entropic force approach to noncommutative Schwarzschild black holes signals a failure of current physical ideas

Recently, a new perspective of gravitational-thermodynamic duality as an entropic force arising from alterations in the information connected to the positions of material bodies is found. In this paper, we generalize some aspects of this model in the presence of noncommutative Schwarzschild black hole by applying the method of coordinate coherent states describing smeared structures. We implement two different distributions: (a) Gaussian and (b) Lorentzian. Both mass distributions prepare the similar quantitative aspects for the entropic force. Our study shows, the entropic force on the smallest fundamental unit of a holographic screen with radius $r_0$ vanishes. As a result, black hole remnants are unconditionally inert even gravitational interactions do not exist therein. So, a distinction between gravitational and inertial mass in the size of black hole remnant is observed, i.e. the failure of the principle of equivalence. In addition, if one considers the screen radius to be less than the radius of the smallest holographic surface at the Planckian regime, then one encounters some unusual dynamical features leading to gravitational repulsive force and negative energy. On the other hand, the significant distinction between the two distributions is conceived to occur around $r_0$, and that is worth of mentioning: at this regime either our analysis is not the proper one, or non-extensive statistics should be employed.Comment: 15 pages, 2 figures, new references added, minor revision, Title changed, to appear in EPJ Plu

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Search for high-mass diphoton resonances in pp collisions at √s = 8 TeV with the ATLAS detector

This article describes a search for high-mass resonances decaying to a pair of photons using a sample of 20.3  fb−¹ of pp collisions at √s = 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. The data are found to be in agreement with the Standard Model prediction, and limits are reported in the framework of the Randall-Sundrum model. This theory leads to the prediction of graviton states, the lightest of which could be observed at the Large Hadron Collider. A lower limit of 2.66 (1.41) TeV at 95% confidence level is set on the mass of the lightest graviton for couplings of k/M̄Pl=0.1(0.01)

Measurement of the production cross-section of a single top quark in association with a W boson at 8 TeV with the ATLAS experiment

The cross-section for the production of a single top quark in association with a W boson in proton-proton collisions at s√=8TeV is measured. The dataset corresponds to an integrated luminosity of 20.3 fb−1, collected by the ATLAS detector in 2012 at the Large Hadron Collider at CERN. Events containing two leptons and one central b-jet are selected. The W t signal is separated from the backgrounds using boosted decision trees, each of which combines a number of discriminating variables into one classifier. Production of W t events is observed with a significance of 7.7σ. The cross-section is extracted in a profile likelihood fit to the classifier output distributions. The W t cross-section, inclusive of decay modes, is measured to be 23.0 ± 1.3(stat.)− 3.5+ 3.2(syst.)±1.1(lumi.) pb. The measured cross-section is used to extract a value for the CKM matrix element |Vtb| of 1.01 ± 0.10 and a lower limit of 0.80 at the 95% confidence level. The cross-section for the production of a top quark and a W boson is also measured in a fiducial acceptance requiring two leptons with pT> 25 GeV and |η| 20 GeV and |η|  20 GeV, including both W t and top-quark pair events as signal. The measured value of the fiducial cross-section is 0.85 ± 0.01(stat.)− 0.07+ 0.07(syst.)±0.03(lumi.) pb

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362