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The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
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Pre-pedestal generation is observed in a 0.35-PW laser front end coming from a post-pedestal via instantaneous gain and pump depletion in an optical parametric amplifier during chirped-pulse amplification. Generalized simulations show how this effect arises from gain nonlinearity and applies to all optical parametric chirped-pulse-amplification systems with a post-pedestal. An experiment minimizing the effect of B-integral is used to isolate and study the newly observed conversion of a continuous post-pedestal into a continuous pre-pedestal. Matching numerical simulations confirm experimental results and additionally reveal how third-order dispersion largely controls the slope of the generated pre-pedestal.
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We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.
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The ten key characteristics (KCs) of carcinogens are based on characteristics of known human carcinogens and encompass many types of endpoints. We propose that an objective review of the large amount of cancer mechanistic evidence for the chemical bisphenol A (BPA) can be achieved through use of these KCs. A search on metabolic and mechanistic data relevant to the carcinogenicity of BPA was conducted and web-based software tools were used to screen and organize the results. We applied the KCs to systematically identify, organize, and summarize mechanistic information for BPA, and to bring relevant carcinogenic mechanisms into focus. For some KCs with very large data sets, we utilized reviews focused on specific endpoints. Over 3000 studies for BPA from various data streams (exposed humans, animals, in vitro and cell-free systems) were identified. Mechanistic data relevant to each of the ten KCs were identified, with receptor-mediated effects, epigenetic alterations, oxidative stress, and cell proliferation being especially data rich. Reactive and bioactive metabolites are also associated with a number of KCs. This review demonstrates how the KCs can be applied to evaluate mechanistic data, especially for data-rich chemicals. While individual entities may have different approaches for the incorporation of mechanistic data in cancer hazard identification, the KCs provide a practical framework for conducting an objective examination of the available mechanistic data without a priori assumptions on mode of action. This analysis of the mechanistic data available for BPA suggests multiple and inter-connected mechanisms through which this chemical can act.
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Compuestos de Bencidrilo , Carcinógenos , Fenoles , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Humanos , Animales , Carcinógenos/toxicidad , Neoplasias/inducido químicamenteRESUMEN
Objective: To analyze the correlative factors of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and to construct and verify the online nomographic prediction model. Methods: A case control study. The clinical data of 213 diabetic patients with Klebsiella pneumoniae liver abscess admitted to the Third Affiliated Hospital of Soochow University from January 1, 2015 to December 31, 2021 were retrospectively analyzed. The patients were divided into the training set (149 cases) and the test set (64 cases) by stratified random sampling method at a ratio of 7â¶3. Synthetic minority over-sampling technique(SMOTE) was used to process the imbalanced data, then Lasso regression was used to screen out the optimal feature variables in the training set and multivariate logistic regression model was used to construct the prediction model of invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess, and verify it in the training set and test set. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the prediction efficiency of the model, and the simple and online interactive dynamic web page column graph was constructed. Results: Among the 213 patients, 60 were males and 153 were females, aged of (61.4±12.0) years. A total of 25(11.74%) diabetic patients with Klebsiella pneumoniae liver abscess developed invasion syndrome, which were included in divided into invasive K.pneumoniae liver abscesses syndrome (IKPLAS) group, and the other 188 cases were in without invasive K.pneumoniae liver abscesses syndrome (NIKPLAS) group. SMOTE algorithm was used for oversampling processing, so that the ratio of positive and negative samples was 1â¶1. In the oversampling training set, 5 main risk factors were screened based on Lasso regression, namely fasting blood glucose (λ=0.063), hemoglobin (λ=-0.042), blood urea nitrogen (λ=-0.050), abscess size (λ=-0.025) and sequential organ failure assessment (SOFA) score (λ=0.450), respectively. Multivariate logistic regression model showed that fasting blood glucose (OR=1.20, 95%CI: 0.98-1.48, P=0.006), hemoglobin (OR=0.90, 95%CI: 0.86-0.95, P<0.001), blood urea nitrogen (OR=1.22, 95%CI: 1.03-1.43, P=0.017), abscess diameter (OR=0.76, 95%CI: 0.61-0.94, P=0.010), SOFA score (OR=3.08, 95%CI: 2.18-4.36, P<0.001) were associated with invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The area under the curve of ROC in the training set was 0.966 (95%CI: 0.943-0.989), the sensitivity was 90.5%, and the specificity was 91.3%. The area under the curve of the validation set ROC was 0.946 (95%CI: 0.902-0.991), with a sensitivity of 79.6% and a specificity of 88.9%. The calibration curves drawn in the training set and the test set fit well with the ideal curve. DCA showed that the neomorph prediction model had a good clinical net benefit when predicting the risk of IKPLAS in patients with diabetes complicated with Klebsiella pneumoniae liver abscess was 0.10-0.40. Conclusions: Fasting blood glucose, hemoglobin, urea nitrogen, abscess size and SOFA score are the related factors for invasion syndrome in patients with diabetes complicated with Klebsiella pneumoniae liver abscess. The constructed column graph can effectively predict the risk of invasion syndrome in patients with diabetes complicated with Klebsiae pneumoniae liver abscess.
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Diabetes Mellitus , Infecciones por Klebsiella , Absceso Hepático , Masculino , Femenino , Humanos , Anciano , Klebsiella pneumoniae , Estudios de Casos y Controles , Estudios Retrospectivos , Glucemia , Infecciones por Klebsiella/complicaciones , Absceso Hepático/complicaciones , Síndrome , HemoglobinasRESUMEN
BACKGROUND: Compared to photon beam, carbon-ion radiotherapy (CIRT) has both physical and biological advantages. AIM: To examine whether two-dimensional (2D) CIRT is dosimetrically superior to photon beam volume-modulated arc therapy (VMAT) in protecting the normal tissues for stage III non-small-cell lung cancer (NSCLC). SUBJECTS AND METHODS: A retrospective study was conducted. Thirteen patients with stage III NSCLC treated in our center with curative CIRT and a sham photon beam VMAT treatment planning with the same normal tissue dose constraints were included for analysis. Target dose distributions and the homogeneity index (HI) within the planning target volumes were compared. RESULTS: Both CIRT and VMAT plans have good tumor coverage with no significant differences in D98, D95, and D50 of Planning target volume 1 (PTV1) between the two plans. The HIs between the two plans are similar. The HI of PTV2 is superior in the CIRT plan (CIRT vs. VMAT: 0.08 vs. 0.16, P < 0.05). In general, CIRT results in a lower dose of the organ-at-risk (OAR) than the photon plans. The V5, V10, V20, V30, V40, and Dmean of the contralateral lung in the CIRT plan are significantly lower than that of the photon VMAT. For the ipsilateral lung, the V5 of CIRT is significantly lower. The CIRT also had significantly lower spinal cord Dmax, esophageal Dmean and V50, V10 and V30 of bone, and V50 of the trachea and bronchial tree. CONCLUSIONS: Compared with photon VMAT, 2D-CIRT using the passive beam scanning technique significantly reduces the radiation dose to the OARs in curative radiotherapy of stage III NSCLC, suggesting a better protection of the normal tissues.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Radioterapia de Intensidad Modulada , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Radioterapia de Intensidad Modulada/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/radioterapia , Rayos X , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , CarbonoRESUMEN
Optical parametric chirped-pulse-amplification produces two broadband pulses, a signal and an idler, that can both provide peak powers >100 GW. In most cases the signal is used, but compressing the longer-wavelength idler opens up opportunities for experiments where the driving laser wavelength is a key parameter. This paper will describe several subsystems that were added to a petawatt class, Multi-Terawatt optical parametric amplifier line (MTW-OPAL) at the Laboratory for Laser Energetics to address two long-standing issues introduced by the use of the idler, angular dispersion, and spectral phase reversal. To the best of our knowledge, this is the first time that compensation of angular dispersion and phase reversal has been achieved in a single system and results in a 100 GW, 120-fs duration, pulse at 1170 nm.
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Optical parametric chirped-pulse amplification (OPCPA) using high-energy Nd:glass lasers has the potential to produce ultra-intense pulses (>1023 W/cm2). We report on the performance of the final high-efficiency amplifier in an OPCPA system based on large-aperture (63 × 63-mm2) partially deuterated potassium dihydrogen phosphate (DKDP) crystals. The seed beam (180-nm bandwidth, 110 mJ) was provided by the preceding OPCPA stages. A maximum pump-to-signal conversion efficiency of 41% and signal energy up to 13 J were achieved with a 52-mm-long DKDP crystal due to the flattop super-Gaussian pump beam profile and flat-in-time pulse shape.
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The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°
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We experimentally demonstrate how divided-pulse nonlinear compression can be used to improve the temporal contrast of a laser pulse train while simultaneously temporally compressing the pulses. We measure a contrast improvement of almost four orders of magnitude on a nanosecond time scale and temporally compress the pulses from 1.2 ps to 187 fs. The efficiency of our method is also competitive with other contrast improvement methods, with 72% efficiency measured for the main pulse. We expect the method will be useful in the continuing development of high-power, Yb regenerative amplifiers, which suffer from both significant prepulses and relatively long pulse durations.
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We present a theoretical and experimental analysis of the signal phase introduced by the pump-beam wavefront and spatial profile during optical parametric amplification (OPA) process. The theory predicts the appearance of an additional wavefront in the amplified signal beam that is proportional to the spatial derivative of the pump-beam wavefront. The effect of the pump-beam profile on the signal-beam wavefront is also investigated. Our experiments tested these theoretical predictions by comparing the wavefront of the signal beam before and after amplification in a multi-joule broadband OPA. The measured signal wavefront was shown to have the expected dependence on the pump-beam profile and wavefront. These results can be considered when designing petawatt-scale ultrabroadband optical parametric chirped-pulse-amplification systems.
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We demonstrate how pulse energy in hollow-core fiber can be scaled beyond gas-ionization limitations using divided-pulse nonlinear compression. With one pulse, ionization limits our fiber's output pulse energy to 2.7 mJ at an input of 4 mJ. By dividing the pulse to four low-energy pulses before the fiber, we eliminated the ionization and scaled the pulse energy 2.5× to 6.6 mJ at an input energy of 10 mJ. Larger energy scaling is possible, as our maximum pulse energy has not reached the new gas ionization threshold. Our results motivate applying the method to state-of-the-art systems for large pulse energy scaling without prohibitive system size increases.
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Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.
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The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.
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The human microbiome plays an important role in our health and identifying factors associated with microbiome composition provides insights into inherent disease mechanisms. By amplifying and sequencing the marker genes in high-throughput sequencing, with highly similar sequences binned together, we obtain operational taxonomic units (OTUs) profiles for each subject. Due to the high-dimensionality and nonnormality features of the OTUs, the measure of diversity is introduced as a summarization at the microbial community level, including the distance-based beta-diversity between individuals. Analyses of such between-subject attributes are not amenable to the predominant within-subject-based statistical paradigm, such as t-tests and linear regression. In this paper, we propose a new approach to model beta-diversity as a response within a regression setting by utilizing the functional response models (FRMs), a class of semiparametric models for between- as well as within-subject attributes. The new approach not only addresses limitations of current methods for beta-diversity with cross-sectional data, but also provides a premise for extending the approach to longitudinal and other clustered data in the future. The proposed approach is illustrated with both real and simulated data.
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Microbiota , Estudios Transversales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Microbiota/genéticaRESUMEN
Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.
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Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , China/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina , Humanos , Masculino , Aceptación de la Atención de Salud , Conducta SexualRESUMEN
In optical parametric chirped-pulse amplification (OPCPA), pump temporal intensity modulation is transferred to the chirped-signal spectrum via instantaneous parametric gain and results in contrast degradation of the recompressed signal. We investigate, for the first time to our knowledge, the pump-to-signal noise transfer in a two-stage ultra-broadband OPCPA pumped by a single laser and show the dependence of pump-induced signal noise, characterized both before and after pulse compression, on the difference in pump-seed delay in the two stages. We demonstrate an up-to-15-dB reduction of the pump-induced contrast degradation via pump-seed delay optimization. Experiments and simulations show that, even when parametric amplifiers are operated in saturation, the pump-seed delay can be used to minimize the pump-induced contrast degradation that is attributed largely to the noises from the unsaturated edges of the pulse and that of the beam.
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A Watt-level continuous and single frequency blue laser at 461 nm is obtained by frequency-doubling an amplified diode laser operating at 922 nm via a LBO crystal in a resonant Fabry-Pérot cavity. We achieved a best optical conversion efficiency equal to 87% with more than 1 W output power in the blue, and limited by the available input power. The frequency-converted beam is characterized in terms of long term power stability, residual intensity noise, and geometrical shape. The blue beam has a linewidth of the order of 1 MHz, and we used it to magneto-optically trap 88Sr atoms on the 5s2â 1S0 - 5s5pâ 1P1 transition. The low-finesse, linear-cavity doubling system is very robust, maintains the lock for several days, and is compatible with a tenfold increase of the power levels which could be obtained with fully-fibered amplifiers and large mode area fibers.
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We propose a method to exploit high-finesse optical resonators for light-assisted coherent manipulation of atomic ensembles, overcoming the limit imposed by the finite response time of the cavity. The key element of our scheme is to rapidly switch the interaction between the atoms and the cavity field with an auxiliary control process as, for example, the light shift induced by an optical beam. The scheme is applicable to other atomic species, both in trapped and free fall configurations, and can be adopted to control the internal and/or external atomic degrees of freedom. Our method will open new possibilities in cavity-aided atom interferometry and in the preparation of highly nonclassical atomic states.
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We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.