Predicting Neutron Production from Cosmic-ray Muons

Fast neutrons from cosmic-ray muons are an important background to underground low energy experiments. The estimate of such background is often hampered by the difficulty of measuring and calculating neutron production with sufficient accuracy. Indeed substantial disagreement exists between the different analytical calculations performed so far, while data reported by different experiments is not always consistent. We discuss a new unified approach to estimate the neutron yield, the energy spectrum, the multiplicity and the angular distribution from cosmic muons using the Monte Carlo simulation package FLUKA and show that it gives a good description of most of the existing measurements once the appropriate corrections have been applied.Comment: 8 pages, 7 figure

Muon-Induced Background Study for Underground Laboratories

We provide a comprehensive study of the cosmic-ray muon flux and induced activity as a function of overburden along with a convenient parameterization of the salient fluxes and differential distributions for a suite of underground laboratories ranging in depth from $\sim$1 to 8 km.w.e.. Particular attention is given to the muon-induced fast neutron activity for the underground sites and we develop a Depth-Sensitivity-Relation to characterize the effect of such background in experiments searching for WIMP dark matter and neutrinoless double beta decay.Comment: 18 pages, 28 figure

Influence of hadronic interaction models and the cosmic ray spectrum on the high energy atmospheric muon and neutrino flux

The recent observations of muon charge ratio up to about 10 TeV and of atmospheric neutrinos up to energies of about 400 TeV has triggered a renewed interest into the high-energy interaction models and cosmic ray primary composition. A reviewed calculation of lepton spectra produced in cosmic-ray induced extensive air showers is carried out with a primary cosmic-ray spectrum that fits the latest direct measurements below the knee. In order to achieve this, we used a full Monte Carlo method to derive the inclusive differential spectra (yields) of muons, muon neutrinos and electron neutrinos at the surface for energies between 80 GeV and hundreds of PeV. The air shower simulator {\sc corsika} 6.990 was used for showering and propagation of the secondary particles through the atmosphere, employing the established high-energy hadronic interaction models {\sc sibyll} 2.1, {\sc qgsjet-01} and {\sc qgsjet-ii 03}. We show that the performance of the interaction models allows makes it possible to predict the spectra within experimental uncertainties, while {\sc sibyll} generally yields a higher flux at the surface than the qgsjet models. The calculation of the flavor and charge ratios has lead to inconsistent results, mainly influenced by the different representations of the K/$\pi$ ratio within the models. Furthermore, we could quantify systematic uncertainties of atmospheric muon- and neutrino fluxes, associated to the models of the primary cosmic-ray spectrum and the interaction models. For most recent parametrizations of the cosmic-ray primary spectrum, atmospheric muons can be determined with an uncertainty smaller than $^{+15}_{-13}$% of the average flux. Uncertainties of the muon- and electron neutrino fluxes can be calculated within an average error of $^{+32}_{-22}$% and $^{+25}_{-19}$%, respectively.Comment: 16 pages, 10 figures, version 2 includes analytic approximatio

Neutron production by cosmic-ray muons at shallow depth

The yield of neutrons produced by cosmic ray muons at a shallow depth of 32 meters of water equivalent has been measured. The Palo Verde neutrino detector, containing 11.3 tons of Gd loaded liquid scintillator and 3.5 tons of acrylic served as a target. The rate of one and two neutron captures was determined. Modeling the neutron capture efficiency allowed us to deduce the total yield of neutrons $Y_{tot} = (3.60 \pm 0.09 \pm 0.31) \times 10^{-5}$ neutrons per muon and g/cm$^2$. This yield is consistent with previous measurements at similar depths.Comment: 12 pages, 3 figure

Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

PURPOSE The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 – gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two – next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response

Muon `Depth -- Intensity' Relation Measured by LVD Underground Experiment and Cosmic-Ray Muon Spectrum at Sea Level

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured angular distribution of muon intensity has been converted to the `depth -- vertical intensity' relation in the depth range from 3 to 12 km w.e.. The analysis of this relation allowed to derive the power index, $\gamma$, of the primary all-nucleon spectrum: $\gamma=2.78 \pm 0.05$. The `depth -- vertical intensity' relation has been converted to standard rock and the comparison with the data of other experiments has been done. We present also the derived vertical muon spectrum at sea level.Comment: 7 pages, 3 figures, to be published on Phys. Rev.

Study of single muons with the Large Volume Detector at Gran Sasso Laboratory

The present study is based on the sample of about 3 mln single muons observed by LVD at underground Gran Sasso Laboratory during 36500 live hours from June 1992 to February 1998. We have measured the muon intensity at slant depths from 3 km w.e. to 20 km w.e. Most events are high energy downward muons produced by meson decay in the atmosphere. The analysis of these muons has revealed the power index of pion and kaon spectrum: 2.76 \pm 0.05. The reminders are horizontal muons produced by the neutrino interactions in the rock surrounding LVD. The value of this flux is obtained. The results are compared with Monte Carlo simulations and the world data.Comment: 13 pages, 2 figures, accepted for publication in "Physics of Atomic Nuclei

Применение таргетной терапии в лечении пациентов с нейроэндокринными опухолями желудочнокишечного тракта и поджелудочной железы

Extensive investigation of neuroendocrine tumors (NETs) has only started in recent years. The increased attention to this issue is due to the more frequent detection of NETs as a result of diagnostic methods improvement.The limited effectiveness of chemotherapy for well-differentiated advanced metastatic NETs of gastrointestinal tract (GIT) and pancreas demonstrates the need for development of the new and more effective treatment options.Recent studies on specific biological features of NETs have led to the development of the new targeted therapies which take into account high vascularization and overexpression of specific growth factors and related tyrosine kinase receptors. Thus, studying the mTOR TSC2, PTEN and PIK3CA signaling pathways opens up the new opportunities in the treatment of gastrointestinal or pancreatic NETs, especially in case of inoperable or metastatic tumors. Targeted therapy, which specifically inhibits growth factor receptors and related signaling pathways, is a promising approach to drug therapy for patients with gastrointestinal or pancreatic NETs.This review summarizes the state of the art and prospects for using targeted therapy, and describes clinical studies in the treatment of gastrointestinal and pancreatic NETs.Проблема нейроэндокринных опухолей (НЭО) стала углубленно изучаться только в последние годы. Возросшее внимание к ней обусловлено увеличением частоты обнаружения НЭО в связи с совершенствованием методов диагностики.Ограниченная эффективность химиотерапии у высокодифференцированных распространенных метастатических НЭО желудочно-кишечного тракта (ЖКТ) и поджелудочной железы (ПЖ) подчеркивает необходимость поиска новых и более эффективных вариантов лекарственного лечения.Недавние исследования специфических биологических особенностей НЭО привели к разработке новых целевых методов лечения, которые учитывают высокую васкуляризацию и гиперэкспрессию специфических факторов роста и родственных рецепторов тирозинкиназы. Таким образом, с изучением сигнальных путей mTOR TSC2, PTEN и PIK3CA открываются новые возможности в лечении пациентов с НЭО ЖКТ и ПЖ, особенно неоперабельных и метастатических форм. Таргетная терапия, которая специфически ингибирует рецепторы факторов роста и связанные с ними сигнальные пути, является многообещающим подходом лекарственного лечения НЭО ЖКТ и ПЖ.В этом обзоре кратко изложено состояние и перспективы использования таргетной терапии, описаны клинические исследования в лечении НЭО ЖКТ и ПЖ

Upper Limit on the Prompt Muon Flux Derived from the LVD Underground Experiment

We present the analysis of the muon events with all muon multiplicities collected during 21804 hours of operation of the first LVD tower. The measured depth-angular distribution of muon intensities has been used to obtain the normalization factor, A, the power index, gamma, of the primary all-nucleon spectrum and the ratio, R_c, of prompt muon flux to that of pi-mesons - the main parameters which determine the spectrum of cosmic ray muons at the sea level. The value of gamma = 2.77 +/- 0.05 (68% C.L.) and R_c < 2.0 x 10^-3 (95% C.L.) have been obtained. The upper limit to the prompt muon flux favours the models of charm production based on QGSM and the dual parton model.Comment: 10 pages, 4 figures, RevTex. To appear in Phys. Rev.