Detection of the IceCube-170922A neutrino coincident with the flaring blazar TXS 0506+056, the first and only ∼3 high-energy neutrino source association to date, offers a potential breakthrough in ...our understanding of high-energy cosmic particles and blazar physics. We present a comprehensive analysis of TXS 0506+056 during its flaring state, using newly collected Swift, NuSTAR, and X-shooter data with Fermi observations and numerical models to constrain the blazar's particle acceleration processes and multimessenger (electromagnetic (EM) and high-energy neutrino) emissions. Accounting properly for EM cascades in the emission region, we find a physically consistent picture only within a hybrid leptonic scenario, with γ-rays produced by external inverse-Compton processes and high-energy neutrinos via a radiatively subdominant hadronic component. We derive robust constraints on the blazar's neutrino and cosmic-ray emissions and demonstrate that, because of cascade effects, the 0.1-100 keV emissions of TXS 0506+056 serve as a better probe of its hadronic acceleration and high-energy neutrino production processes than its GeV-TeV emissions. If the IceCube neutrino association holds, physical conditions in the TXS 0506+056 jet must be close to optimal for high-energy neutrino production, and are not favorable for ultrahigh-energy cosmic-ray acceleration. Alternatively, the challenges we identify in generating a significant rate of IceCube neutrino detections from TXS 0506+056 may disfavor single-zone models, in which γ-rays and high-energy neutrinos are produced in a single emission region. In concert with continued operations of the high-energy neutrino observatories, we advocate regular X-ray monitoring of TXS 0506+056 and other blazars in order to test single-zone blazar emission models, clarify the nature and extent of their hadronic acceleration processes, and carry out the most sensitive possible search for additional multimessenger sources.
The primary cilium is a microtubule-based organelle that senses extracellular signals as a cellular antenna 1. Primary cilia are found on many types of cells in our body and play important roles in ...development and physiology. Defects of primary cilia cause a broad class of human genetic diseases called ciliopathies. To gain new insights into ciliary functions and better understand the molecular mechanisms underlying ciliopathies, it is of high importance to generate a catalog of primary cilia proteins. In this study, we isolated primary cilia from mouse kidney cells by using a calcium-shock method and identified 195 candidate primary cilia proteins by MudPIT (multidimensional protein identification technology), protein correlation profiling, and subtractive proteomic analysis. Based on comparisons with other proteomic studies of cilia, around 75% of our candidate primary cilia proteins are shared components with motile or specialized sensory cilia. The remaining 25% of the candidate proteins are possible primary cilia-specific proteins. These possible primary cilia-specific proteins include EVC2, INPP5E, and inversin, several of which have been linked to known ciliopathies. We have performed the first reported proteomic analysis of primary cilia from mammalian cells. These results provide new insights into primary cilia structure and function.
► This is the first reported proteomic analysis of generic mammalian primary cilia ► 195 proteins were identified as components of generic mammalian primary cilia ► 75% of generic primary cilia proteins are also found in motile or sensory cilia ► Most IFT proteins are conserved in generic primary, sensory, and motile cilia
To provide guidance on exercise, diet, and weight management during active cancer treatment in adults.
A systematic review of the literature identified systematic reviews and randomized controlled ...trials evaluating the impact of aerobic and resistance exercise, specific diets and foods, and intentional weight loss and avoidance of weight gain in adults during cancer treatment, on quality of life, treatment toxicity, and cancer control. PubMed and the Cochrane Library were searched from January 2000 to May 2021. ASCO convened an Expert Panel to review the evidence and formulate recommendations.
The evidence base consisted of 52 systematic reviews (42 for exercise, nine for diet, and one for weight management), and an additional 23 randomized controlled trials. The most commonly studied types of cancer were breast, prostate, lung, and colorectal. Exercise during cancer treatment led to improvements in cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes. Preoperative exercise in patients with lung cancer led to a reduction in postoperative length of hospital stay and complications. Neutropenic diets did not decrease risk of infection during cancer treatment.
Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. Evidence for other dietary and weight loss interventions during cancer treatment was very limited. The guideline discusses special considerations, such as exercise in individuals with advanced cancer, and highlights the critical need for more research in this area, particularly regarding diet and weight loss interventions during cancer treatment.Additional information is available at www.asco.org/supportive-care-guidelines.
Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role ...as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.
An important aspect in designing interactive, action-based interfaces is reliably recognizing actions with minimal latency. High latency causes the system’s feedback to lag behind user actions and ...thus significantly degrades the interactivity of the user experience. This paper presents algorithms for reducing latency when recognizing actions. We use a latency-aware learning formulation to train a logistic regression-based classifier that automatically determines distinctive canonical poses from data and uses these to robustly recognize actions in the presence of ambiguous poses. We introduce a novel (publicly released) dataset for the purpose of our experiments. Comparisons of our method against both a Bag of Words and a Conditional Random Field (CRF) classifier show improved recognition performance for both pre-segmented and online classification tasks. Additionally, we employ GentleBoost to reduce our feature set and further improve our results. We then present experiments that explore the accuracy/latency trade-off over a varying number of actions. Finally, we evaluate our algorithm on two existing datasets.
In addition to the popular method of fluorescent protein fusion, live cell protein imaging has now seen more and more application of epitope tags. The small size of these tags may reduce functional ...perturbation and enable signal amplification. To address their background issue, we adapt self-complementing split fluorescent proteins as epitope tags for live cell protein labelling. The two tags, GFP11 and sfCherry11 are derived from the eleventh β-strand of super-folder GFP and sfCherry, respectively. The small size of FP11-tags enables a cost-effective and scalable way to insert them into endogenous genomic loci via CRISPR-mediated homology-directed repair. Tandem arrangement FP11-tags allows proportional enhancement of fluorescence signal in tracking intraflagellar transport particles, or reduction of photobleaching for live microtubule imaging. Finally, we show the utility of tandem GFP11-tag in scaffolding protein oligomerization. These experiments illustrate the versatility of FP11-tag as a labelling tool as well as a multimerization-control tool for both imaging and non-imaging applications.
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