Kaikki aineistot
Lisää
Abstract This paper presents simultaneous detached proton auroras that appeared in both hemispheres at 11:06 UT, 08 March 2012, just 2 min after a sudden solar wind pressure enhancement (~11:04 UT) hit the Earth. They were observed under northward interplanetary magnetic field Bz condition and during the recovery phase of a moderate geomagnetic storm. In the Northern Hemisphere, Defense Meteorological Satellite Program/Special Sensor Ultraviolet Spectrographic Imager observed that the detached arc occurred within 60°–65° magnetic latitude and covered a few magnetic local time (MLT) hours ranging from 0530 to 0830 MLT with a possible extension toward noon. At the same time (11:06 UT), Polar Orbiting Environment Satellites 19 detected a detached proton aurora around 1300 MLT in the Southern Hemisphere, centering ~62° magnetic latitude, which was at the same latitudes as the northern detached arc. This southern aurora was most probably a part of a dayside detached arc that was conjugate to the northern one. In situ particle observations indicated that the detached auroras were dominated by protons/ions with energies ranging from around 20 keV to several hundreds of keV, without obvious electron precipitations. These detached arcs persisted for less than 6 min, consistent with the impact from pressure enhancement and the observed electromagnetic ion cyclotron (EMIC) waves. It is suggested that the increasing solar wind pressure pushed the hot ions in the ring current closer to Earth where the steep gradient of cold plasma favored EMIC wave growth. By losing energy to EMIC waves the energetic protons (>20 keV) were scattered into the loss cone and produced the observed detached proton auroras.
Abstract The field of structural engineering is vast, spanning areas from the design of new infrastructure to the assessment of existing infrastructure. From the onset, traditional entry-level university courses teach students to analyse structural responses given data including external forces, geometry, member sizes, restraint, etc.—characterizing a forward problem (structural causalities → structural response). Shortly thereafter, junior engineers are introduced to structural design where they aim to, for example, select an appropriate structural form for members based on design criteria, which is the inverse of what they previously learned. Similar inverse realizations also hold true in structural health monitoring and a number of structural engineering sub-fields (response → structural causalities). In this light, we aim to demonstrate that many structural engineering sub-fields may be fundamentally or partially viewed as inverse problems and thus benefit via the rich and established methodologies from the inverse problems community. To this end, we conclude that the future of inverse problems in structural engineering is inexorably linked to engineering education and machine learning developments.
The interfacial energetics are known to play a crucial role in organic diodes, transistors, and sensors. Designing the metal-organic interface has been a tool to optimize the performance of organic (opto)electronic devices, but this is not reported for organic thermoelectrics. In this work, it is demonstrated that the electrical power of organic thermoelectric generators (OTEGs) is also strongly dependent on the metal-organic interfacial energetics. Without changing the thermoelectric figure of merit (ZT) of polythiophene-based conducting polymers, the generated power of an OTEG can vary by three orders of magnitude simply by tuning the work function of the metal contact to reach above 1000 µW cm−2. The effective Seebeck coefficient (Seff) of a metal/polymer/metal single leg OTEG includes an interfacial contribution (Vinter/ΔT) in addition to the intrinsic bulk Seebeck coefficient of the polythiophenes, such that Seff = S + Vinter/ΔT varies from 22.7 µV K−1 [9.4 µV K−1] with Al to 50.5 µV K−1 [26.3 µV K−1] with Pt for poly(3,4-ethylenedioxythiophene):p-toluenesulfonate [poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate)]. Spectroscopic techniques are used to reveal a redox interfacial reaction affecting locally the doping level of the polymer at the vicinity of the metal-organic interface and conclude that the energetics at the metal-polymer interface provides a new strategy to enhance the performance of OTEGs.
Introduction: Emotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese school-based program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland. Methods: The cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named “Let’s learn about emotions” and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers’ manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability. Discussion: The originality of this study underlies in the East–West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems. Ethics: The ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study.
Abstract Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cyclic adenosine monophosphate (cAMP)-dependent signaling pathway and downstream mediators. To investigate protein–protein interaction partners of FSHR at resting state and upon FSH stimulation, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. Interestingly, while only WT FSHR interacted with FSH, insulin-like growth factor 1 receptor (IGF1R), for example, interacted with both WT and A189V FSHR upon FSH stimulation. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.
Abstract Context: Radio continuum surveys of the Galactic plane are an excellent way to identify different source populations such as planetary nebulae, H II regions, and radio stars and characterize their statistical properties. The Global View of Star Formation in the Milky Way (GLOSTAR) survey will study the star formation in the Galactic plane between −2° < l < 85° and |b| < 1° with unprecedented sensitivity in both flux density (∼40 μJy beam−1) and range ofangular scales (∼1′′.5 to the largest radio structures in the Galaxy). Aims: In this paper we present the first results obtained from a radio continuum map of a 16-square-degree-sized region of the Galactic plane centered on l = 32° and b = 0° (28° < l < 36° and |b| <1°). This map has a resolution of 18′′ and a sensitivity of ∼60−150 μJy beam−1. Methods: We present data acquired in 40 h of observations with the VLA in D-configuration. Two 1 GHz wide sub-bands were observed simultaneously and they were centered at 4.7 and 6.9 GHz. These data were calibrated and imaged using the Obit software package. The source extraction was performed using the BLOBCAT software package and verified through a combination of visual inspection and cross-matching with other radio and mid-infrared surveys. Results: The final catalog consists of 1575 discrete radio sources and 27 large scale structures (including W43 and W44). By cross-matching with other catalogs and calculating the spectral indices (S(ν) ∝ να), we have classified 231 continuum sources as H II regions, 37 as ionization fronts, and 46 as planetary nebulae. The longitude and latitude distribution and negative spectral indices are all consistent with the vast majority of the unclassified sources being extragalactic background sources. Conclusions: We present a catalog of 1575 radio continuum sources and discuss their physical properties, emission nature, and relation to previously reported data. These first GLOSTAR results have increased the number of reliable H II regions in this part of the Galaxy by a factor of four.
In Wendelstein 7-X (W7-X), a new ion cyclotron resonance heating (ICRH) antenna will be commissioned during the operational campaign OP2.1. The antenna will have to sustain power loads not only from thermal plasma and radiation but also fast ions. Predictive simulations of fast-ion power loads to the antenna components are therefore important to establish safe operational limits. In this work, the fast-ion power loads from the W7-X neutral beam injection (NBI) system to the ICRH antenna was simulated using the ASCOT suite of codes. Five reference magnetic configurations and five antenna positions were considered to provide an overview of power load behavior under various operating conditions. The NBI power load was found to have an exponential dependence on the antenna insertion depth. Differences between magnetic configurations were significant, with the antenna limiter power load varying between 380 W and 100 kW depending on the configuration. Qualitative differences in power load patterns between configurations were also observed, with the low mirror and low iota configurations exhibiting higher loads to the sensitive antenna straps. The local fast-ion power flux to the antenna limiter was also considered and found to exceed the 2.0 MW m−2 steady-state safety limit only in specific cases. The NBI system might thus pose a safety concern to the ICRH antenna during concurrent NBI-ICRH operation, but additional heat propagation simulations of antenna components are needed to establish more realistic operational time limits.
Abstract With their high mobility, unmanned aerial vehicles (UAVs) become appealing data collectors in hard-to-reach wide-area distributed sensor networks. Different from existing works focusing on the perspective of UAVs for service order optimization and UAV utility maximization, we consider the utilities of both sensors and UAVs, and innovatively model the competition among sensors (buyers) for the service of UAVs (sellers) as an auction game. A “unity makes strength” strategy is exploited. That is, to strengthen the bidding competitiveness, a group-buying coalition auction method that encourages sensors to form coalitions to bid for UAV service is proposed. Besides, we propose a parallel variable neighborhood ascent search algorithm, we can quickly determine the approximately optimal group-buying coalition structure. Numerical results show that the proposed method outperforms the joint trajectory design-task scheduling (TDTS) UAV-to-community method and the single coalition formation game (CFG) method.
Summary Background: Cardiovascular diseases may originate in childhood. Biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimise prevention strategies. Methods: In this prospective study, by applying a machine learning to high throughput NMR-based metabolomics data, we identified circulating childhood metabolic predictors of adult cardiovascular disease risk (MetS score) in a cohort of 396 females, followed from childhood (mean age 11·2 years) to early adulthood (mean age 18·1 years). The results obtained from the discovery cohort were validated in a large longitudinal birth cohort of females and males followed from puberty to adulthood (n = 2664) and in four cross-sectional data sets (n = 6341). Findings: The identified childhood metabolic signature included three circulating biomarkers, glycoprotein acetyls (GlycA), large high-density lipoprotein phospholipids (L-HDL-PL), and the ratio of apolipoprotein B to apolipoprotein A-1 (ApoB/ApoA) that were associated with increased cardio-metabolic risk in early adulthood (AUC = 0·641‒0·802, all p<0·01). These associations were confirmed in all validation cohorts with similar effect estimates both in females (AUC = 0·667‒0·905, all p<0·01) and males (AUC = 0·734‒0·889, all p<0·01) as well as in elderly patients with and without type 2 diabetes (AUC = 0·517‒0·700, all p<0·01). We subsequently applied random intercept cross-lagged panel model analysis, which suggested bidirectional causal relationship between metabolic biomarkers and cardio-metabolic risk score from childhood to early adulthood. Interpretation: These results provide evidence for the utility of a circulating metabolomics panel to identify children and adolescents at risk for future cardiovascular disease, to whom preventive measures and follow-up could be indicated.
Abstract Compared to the intermediate deliverable D1.2.1, additional results regarding the achievable rate region and performance limit analyses for different toy scenarios (TSs) have been achieved, which are provided in this deliverable. For TS1, we investigate the impact of the line-of-sight component on outage probability with lossy forwarding strategy. Moreover, an improved selective decode-and-forward scheme with least square based symbol level filtering is proposed in order to improve the bit error rate performance of the relaying system. Regarding TS2, the lower bound of the Hamming distortion in the binary chief executive officer (CEO) problem is derived by minimizing the distortion function subject to the inequalities between the obtained tighter outer bound and the channel capacities. An extension to an arbitrary number of sources in the CEO problem is also studied. TS3 is modeled by Slepian-Wolf coding, and we achieve the upper bound of the outage probability by reducing and relaxing the rate constraints. Regarding TS4, we extend the orthogonal transmission to its non-orthogonal counterpart and analyze the outage probability relying on the theorem of multiple access channel with a helper.
Abstract Air pollution introduces a major challenge for societies, where it leads to the premature deaths of millions of people each year globally. Massive deployment of air quality sensing devices and data analysis for the resultant data will pave the way for the development of real-time intelligent applications and services, e.g., minimization of exposure to poor air quality either on an individual or city scale. 5G and edge computing supports dense deployments of sensors at high resolution with ubiquitous connectivity, high bandwidth, high-speed gigabit connections, and ultralow latency analysis. This article conceptualizes AI-powered scalable air quality monitoring and presents two systems of calibrating low-cost air quality sensors and the image processing of pictures captured by hyperspectral cameras to better detect air quality. We develop and deploy different AI algorithms in these two systems on a 5G edge testbed and perform a detailed analytics regarding to 1) the performance of AI algorithms and 2) the required communication and computation resources.
Abstract Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions. Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up. Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.
Abstract This deliverable provides comprehensive analytical and simulation results of the coding/decoding algorithms used in RESCUE. The algorithms are applied to various frameworks and investigated the applicability in selected cases. We also address the impact of lossy forwarding (LF) relaying in fading channels and specifically consider the evaluation of frame error rates (FERs) in comparison with lossless decode-andforward (DF). Moreover, the deliverable proposes an algorithm for opportunistic relay selection in LF-based networks where the best relay can be found using a machine learning method. Remarkable performance gains are observed in a case where LF concept is applied in multi-antenna scenario, in which relays can transmit and receive at the same time by using multiple antennas for interference cancelation. Furthermore, we apply joint decoding (JD) into IEEE 802.11WiFi standard. In addition, we present an error rate model for RESCUE physical layer to be used when designing higher layer protocols. After analyzing the results presented in this deliverable, we conclude that RESCUE concept is especially suitable for the cases where the retransmissions are not preferable or not even possible.
Abstract Rotational structures have been measured using the Jurogam II and GAMMASPHERE arrays at low spin following the 155Gd(α,2n)157Dy and 148Nd(12C,5n)155Dy reactions at 25 and 65 MeV, respectively. We report high-K bands, which are conjectured to be the first candidates of a Kπ=2+γ vibrational band, built on the [505]11/2− neutron orbital, in both odd-A155,157Dy isotopes. The coupling of the first excited K=0+ states or the so-called β vibrational bands at 661 and 676 keV in 154Dy and 156Dy to the [505]11/2− orbital, to produce a Kπ=11/2− band, was not observed in both 155Dy and 157Dy, respectively. The implication of these findings on the interpretation of the first excited 0+ states in the core nuclei 154Dy and 156Dy are also discussed.
Abstract Phase changes of sea salt particles alter their physical and chemical properties, which is significant for Earth’s chemistry and energy budget. In this study, a continuous flow diffusion chamber is used to investigate deliquescence, homogeneous and heterogeneous ice nucleation between 242 K and 215 K, of four salts: pure NaCl, pure MgCl2, synthetic sea water salt, and salt distilled from sampled sea water. Anhydrous particles, aqueous droplets and ice particles were discriminated using a polarisation-sensitive optical particle counter coupled with a machine learning analysis technique. The measured onset deliquescence relative humidities agree with previous studies, where sea water salts deliquescence at lower humidities than pure NaCl. Deliquesced salt droplets homogenously freeze when the relative humidity reaches a sufficiently high value at temperatures below 233 K. From 224 K and below, deposition nucleation freezing on a fraction of NaCl particles was observed at humidities lower than the deliquescence relative humidity. At these low temperatures, otherwise unactivated salt particles deliquesced at the expected deliquescence point, followed by homogeneous freezing at temperatures as low as 215 K. Thus, the observed sea salt particles exhibit a triad of temperature-dependent behaviours. First, they act as cloud condensation particles (CCNs) > 233 K, second they can be homogeneous freezing nuclei (HFNs) < 233 K and finally they act as ice nucleating particles (INPs) for heterogeneous nucleation <224 K.
Abstract Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. Design: Summary of the one-day workshop held virtually on June 22nd, 2021. Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. Conclusions: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.
Abstract Five species of mosses (Bryophyta: Oncophorus demetrii, Oncophorus integerrimus, Oxyrrhynchium speciosum, Sphagnum divinum and Sphagnum medium) and one of liverworts (Marchantiophyta: Kurzia trichoclados) are presented as new for Finland. Seligeria calcarea and Seligeria pusilla, previously thought to be regionally extinct from Finland, are reported to being found again. New records in biogeographical provinces for 74 species of mosses and 36 species of liverworts are listed. Finally, 17 occurrences in provinces are removed due to misidentifications or missing specimens.
Excited states in 56Zn were populated following one-neutron removal from a 57Zn beam impinging on a Be target at intermediate energies in an experiment conducted at the Radioactive Isotope Beam Factory at RIKEN. Three γ rays were observed and tentatively assigned to the 6+→4+→2+→0+ yrast sequence. This turns 56Zn into the heaviest Tz=−2 nucleus in which excited states are known. The excitation-energy differences between these levels and the isobaric analogue states in the Tz=+2 mirror partner, 56Fe, are compared with large-scale shell-model calculations considering the full pf valence space and various isospin-breaking contributions. This comparison, together with an analysis of the mirror energy differences in the A=58, Tz=±1 pair 58Zn and 58Ni, provides valuable information with respect to the size of the monopole radial and the isovector multipole isospin-breaking terms in the region above doubly-magic 56Ni.
Abstract Objectives: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. Design: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). Results: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57–0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52–0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. Conclusions: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.
Abstract Background: Myeloid cells represent an abundant yet heterogeneous cell population in the colorectal cancer microenvironment, and their roles remain poorly understood. Methods: We used multiplexed immunofluorescence combined with digital image analysis to identify CD14+ monocytic and CD15+ granulocytic cells and to evaluate their maturity (HLA-DR and CD33), immunosuppressive potential (ARG1) and proximity to cytokeratin (KRT)-positive tumor cells in 913 colorectal carcinomas. Using covariate data of 4465 incident colorectal cancers in two prospective cohort studies, the inverse probability weighting method was used with multivariable-adjusted Cox proportional hazards models to assess cancer-specific mortality according to ordinal quartiles (Q1–Q4) of myeloid cell densities. Immune cell–tumor cell proximity was measured with the nearest neighbor method and the G-cross function, which determines the likelihood of any tumor cell having at least one immune cell of the specified type within a certain radius. Results: Higher intraepithelial (Ptrend=0.0002; HR for Q4 (vs Q1), 0.48, 95% CI 0.31 to 0.76) and stromal (Ptrend <0.0001; HR for Q4 (vs Q1), 0.42, 95% CI 0.29 to 0.63) densities of CD14+HLA-DR+ cells were associated with lower colorectal cancer-specific mortality while, conversely, higher intraepithelial densities of CD14+HLA-DR− cells were associated with higher colorectal cancer-specific mortality (Ptrend=0.0003; HR for Q4 (vs Q1), 1.78, 95% CI 1.25 to 2.55). Spatial analyses indicated that CD15+ cells were located closer to tumor cells than CD14+ cells, and CD14+HLA-DR+ cells were closer to tumor than CD14+HLA-DR− cells (p<0.0001). The G-cross proximity measurement, evaluating the difference in the likelihood of any tumor cell being colocated with at least one CD14+HLA-DR+ cell versus CD14+HLA-DR− cell within a 20 μm radius, was associated with lower colorectal cancer-specific mortality (Ptrend <0.0001; HR for Q4 (vs Q1), 0.37, 95% CI 0.24 to 0.57). Conclusions: Myeloid cell populations occur in spatially distinct distributions and exhibit divergent, subset-specific prognostic significance in colorectal cancer, with mature CD14+HLA-DR+ and immature CD14+HLA-DR− monocytic phenotypes most notably showing opposite associations. These results highlight the prognostic utility of multimarker evaluation of myeloid cell infiltrates and reveal a previously unrecognized degree of spatial organization for myeloid cells in the immune microenvironment.
Abstract Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3−), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1−CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (Ptrend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (Ptrend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (Ptrend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3−GZMB+ NK cells and NCAM1vCD3v NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization.
Abstract Background: Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies. Methods: We examined Crohn’s-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load. Results: Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42–0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12–0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2). Conclusions: The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.
Abstract Experimental signatures of moderately enhanced octupole correlations at high spin in 136Nd are indicated for the first time. The extracted dipole moments of two negative-parity bands are only two times smaller than those of the lanthanide nuclei with N≈90 which present well-established octupole correlations. Calculations using the cranked quasiparticle random phase approximation and a model of quadrupole-octupole rotations with octupole vibrations reveal the structure of the bands and the enhanced octupole correlations at high spin in 136Nd.
Abstract Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of 3He and 4He fluxes are presented. The measurements are based on 100 million 4He nuclei in the rigidity range from 2.1 to 21 GV and 18 million 3He from 1.9 to 15 GV collected from May 2011 to November 2017. We observed that the 3He and 4He fluxes exhibit nearly identical variations with time. The relative magnitude of the variations decreases with increasing rigidity. The rigidity dependence of the 3He/4He flux ratio is measured for the first time. Below 4 GV, the 3He/4He flux ratio was found to have a significant long-term time dependence. Above 4 GV, the 3He/4He flux ratio was found to be time independent, and its rigidity dependence is well described by a single power law ∝RΔ with Δ=−0.294±0.004. Unexpectedly, this value is in agreement with the B/O and B/C spectral indices at high energies.
Abstract Background/Objectives: Tumour budding and poorly differentiated clusters (PDC) represent forms of tumour invasion. We hypothesised that T-cell densities (reflecting adaptive anti-tumour immunity) might be inversely associated with tumour budding and PDC in colorectal carcinoma. Methods: Utilising 915 colon and rectal carcinomas in two U.S.-wide prospective cohort studies, and multiplex immunofluorescence combined with machine learning algorithms, we assessed CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3 co-expression patterns in lymphocytes. Tumour budding and PDC at invasive fronts were quantified by digital pathology and image analysis using the International tumour Budding Consensus Conference criteria. Using covariate data of 4,420 incident colorectal cancer cases, inverse probability weighting (IPW) was integrated with multivariable logistic regression analysis that assessed the association of T-cell subset densities with tumour budding and PDC while adjusting for selection bias due to tissue availability and potential confounders, including microsatellite instability status. Findings: Tumour budding counts were inversely associated with density of CD3+CD8+ [lowest vs. highest: multivariable odds ratio (OR), 0.50; 95% confidence interval (CI), 0.35–0.70; Ptrend < 0.001] and CD3+CD8+CD45RO+ cells (lowest vs. highest: multivariable OR, 0.44; 95% CI, 0.31–0.63; Ptrend < 0.001) in tumour epithelial region. Tumour budding levels were associated with higher colorectal cancer-specific mortality (multivariable hazard ratio, 2.13; 95% CI, 1.57–2.89; Ptrend < 0.001) in Cox regression analysis. There were no significant associations of PDC with T-cell subsets. Interpretation: Tumour epithelial naïve and memory cytotoxic T cell densities are inversely associated with tumour budding at invasive fronts, suggesting that cytotoxic anti-tumour immunity suppresses tumour microinvasion.
Abstract Background: Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. Methods: Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses’ Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn’s-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results: The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer–specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided Pinteraction = 0.009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. Conclusions: The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.
Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
Abstract Background: The relationships between tumor stromal features (such as desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles) and immune cells in the colorectal carcinoma microenvironment have not yet been fully characterized. Methods: In 908 tumors with available tissue among 4,465 incident colorectal adenocarcinoma cases in two prospective cohort studies, we examined desmoplastic reaction, myxoid stroma, and keloid-like collagen bundles. We conducted multiplex immunofluorescence for T cells [CD3, CD4, CD8, CD45RO (PTPRC), and FOXP3] and for macrophages [CD68, CD86, IRF5, MAF, and MRC1 (CD206)]. We used the inverse probability weighting method and the 4,465 incident cancer cases to adjust for selection bias. Results: Immature desmoplastic reaction was associated with lower densities of intraepithelial CD3+CD8+CD45RO+ cells [multivariable odds ratio (OR) for the highest (vs. lowest) density category, 0.43; 95% confidence interval (CI), 0.29–0.62; Ptrend <0.0001] and stromal M1-like macrophages [the corresponding OR, 0.44; 95% CI, 0.28–0.70; Ptrend = 0.0011]. Similar relations were observed for myxoid stroma [intraepithelial CD3+CD8+CD45RO+ cells (Ptrend <0.0001) and stromal M1-like macrophages (Ptrend = 0.0007)] and for keloid-like collagen bundles (Ptrend <0.0001 for intraepithelial CD3+CD8+CD45RO+ cells). In colorectal cancer-specific survival analyses, multivariable-adjusted hazard ratios (with 95% confidence intervals) were 0.32 (0.23–0.44; Ptrend <0.0001) for mature (vs. immature) desmoplastic reaction, 0.25 (0.16–0.39; Ptrend <0.0001) for absent (vs. marked) myxoid stroma, and 0.12 (0.05–0.28; Ptrend <0.0001) for absent (vs. marked) keloid-like collagen bundles. Conclusions: Immature desmoplastic reaction and myxoid stroma were associated with lower densities of tumor intraepithelial memory cytotoxic T cells and stromal M1-like macrophages, likely reflecting interactions between tumor, immune, and stromal cells in the colorectal tumor microenvironment.
Abstract Objectives: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma. Methods: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations. Results: Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41–1.51), 0.64 (0.32–1.28) and 0.50 (0.25–0.99), respectively (Ptrend = 0.032). Conclusions: Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.
We report simultaneous observations at different energy bands in radio, optical, UV, X-rays and γ rays of the flat-spectrum radio-quasar 3C 345. We built the light curve of the source at different frequencies from 2008, the beginning of the Fermi all-sky survey, to 2016, using new data and public archives. In particular we obtained several optical spectra, to study the behavior of emission lines and the continuum in different activity states and to derive the black hole mass. 3C 345 showed two flaring episodes in 2009, which occurred simultaneously in γ ray, optical/UV and X-rays, and were later followed in radio. The source shows an inverse Compton dominated spectral energy distribution, which moved from higher to lower frequencies from the high to the low state. The reverberation of emission lines during one outburst event allowed us to constrain the location of production of γ rays very close to the broad-line region, and possibly in the jet-base. We report the observation of an increased accretion after the outburst, possibly induced by the decrease of magnetic field intensity with respect to the low state.
Abstract The Alpha Magnetic Spectrometer (AMS) is a precision particle physics detector on the International Space Station (ISS) conducting a unique, long-duration mission of fundamental physics research in space. The physics objectives include the precise studies of the origin of dark matter, antimatter, and cosmic rays as well as the exploration of new phenomena. Following a 16-year period of construction and testing, and a precursor flight on the Space Shuttle, AMS was installed on the ISS on May 19, 2011. In this report we present results based on 120 billion charged cosmic ray events up to multi-TeV energies. This includes the fluxes of positrons, electrons, antiprotons, protons, and nuclei. These results provide unexpected information, which cannot be explained by the current theoretical models. The accuracy and characteristics of the data, simultaneously from many different types of cosmic rays, provide unique input to the understanding of origins, acceleration, and propagation of cosmic rays.
Abstract We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0 x 108 electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6 sigma at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.
Rotational structures have been measured using the Jurogam II and GAMMASPHERE arrays at low spin following the 155Gd(α,2n)157Dy and 148Nd(12C,5n)155Dy reactions at 25 and 65 MeV, respectively. We report high-K bands, which are conjectured to be the first candidates of a Kπ=2+γ vibrational band, built on the [505]11/2− neutron orbital, in both odd-A155,157Dy isotopes. The coupling of the first excited K=0+ states or the so-called β vibrational bands at 661 and 676 keV in 154Dy and 156Dy to the [505]11/2− orbital, to produce a Kπ=11/2− band, was not observed in both 155Dy and 157Dy, respectively. The implication of these findings on the interpretation of the first excited 0+ states in the core nuclei 154Dy and 156Dy are also discussed.
Abstract We report the observation of new properties of primary iron (Fe) cosmic rays in the rigidity range 2.65 GV to 3.0 TV with 0.62×106 iron nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. Above 80.5 GV the rigidity dependence of the cosmic ray Fe flux is identical to the rigidity dependence of the primary cosmic ray He, C, and O fluxes, with the Fe/O flux ratio being constant at 0.155±0.006. This shows that unexpectedly Fe and He, C, and O belong to the same class of primary cosmic rays which is different from the primary cosmic rays Ne, Mg, and Si class.
Abstract We report the observation of new properties of primary cosmic rays, neon (Ne), magnesium (Mg), and silicon (Si), measured in the rigidity range 2.15 GV to 3.0 TV with 1.8×106 Ne, 2.2×106 Mg, and 1.6×106 Si nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The Ne and Mg spectra have identical rigidity dependence above 3.65 GV. The three spectra have identical rigidity dependence above 86.5 GV, deviate from a single power law above 200 GV, and harden in an identical way. Unexpectedly, above 86.5 GV the rigidity dependence of primary cosmic rays Ne, Mg, and Si spectra is different from the rigidity dependence of primary cosmic rays He, C, and O. This shows that the Ne, Mg, and Si and He, C, and O are two different classes of primary cosmic rays.
Abstract Background: Aberrant somatic genomic alteration including copy number amplification is a hallmark of cancer genomes. We previously profiled genomic landscapes of prostate cancer (PCa), yet the underlying causal genes with prognostic potential has not been defined. It remains unclear how a somatic genomic event cooperates with inherited germline variants contribute to cancer predisposition and progression. Methods: We applied integrated genomic and clinical data, experimental models and bioinformatic analysis to identify GATA2 as a highly prevalent metastasis-associated genomic amplification in PCa. Biological roles of GATA2 in PCa metastasis was determined in vitro and in vivo. Global chromatin co-occupancy and co-regulation of GATA2 and SMAD4 was investigated by coimmunoprecipitation, ChIP-seq and RNA-seq assays. Tumor cellular assays, qRT-PCR, western blot, ChIP, luciferase assays and CRISPR-Cas9 editing methods were performed to mechanistically understand the cooperation of GATA2 with SMAD4 in promoting TGFβ1 and AR signaling and mediating inherited PCa risk and progression. Results: In this study, by integrated genomics and experimental analysis, we identified GATA2 as a prevalent metastasis-associated genomic amplification to transcriptionally augment its own expression in PCa. Functional experiments demonstrated that GATA2 physically interacted and cooperated with SMAD4 for genome-wide chromatin co-occupancy and co-regulation of PCa genes and metastasis pathways like TGFβ signaling. Mechanistically, GATA2 was cooperative with SMAD4 to enhance TGFβ and AR signaling pathways, and activated the expression of TGFβ1 via directly binding to a distal enhancer of TGFβ1. Strinkingly, GATA2 and SMAD4 globally mediated inherited PCa risk and formed a transcriptional complex with HOXB13 at the PCa risk-associated rs339331/6q22 enhancer, leading to increased expression of the PCa susceptibility gene RFX6. Conclusions: Our study prioritizes causal genomic amplification genes with prognostic values in PCa and reveals the pivotal roles of GATA2 in transcriptionally activating the expression of its own and TGFβ1, thereby co-opting to TGFβ1/SMAD4 signaling and RFX6 at 6q22 to modulate PCa predisposition and progression.
Abstract Precise knowledge of the charge and rigidity dependence of the secondary cosmic ray fluxes and the secondary-to-primary flux ratios is essential in the understanding of cosmic ray propagation. We report the properties of heavy secondary cosmic ray fluorine F in the rigidity \(R\) range 2.15 GV to 2.9 TV based on 0.29 million events collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. The fluorine spectrum deviates from a single power law above 200 GV. The heavier secondary-to-primary F/Si flux ratio rigidity dependence is distinctly different from the lighter B/O (or B/C) rigidity dependence. In particular, above 10 GV, the \(\frac{F/Si}{B/O}\) ratio can be described by a power law \(R^{δ}\) with \(δ\)=0.052±0.007. This shows that the propagation properties of heavy cosmic rays, from F to Si, are different from those of light cosmic rays, from He to O, and that the secondary cosmic rays have two classes.
Excited states in the Tz = 0, −1 nuclei 62Ga and 62Ge were populated in direct reactions of relativistic radioactive ion beams at the RIBF. Coincident γ rays were measured with the DALI2+ array and uniquely assigned to the A = 62 isobars. In addition, 62Ge was also studied independently at JYFL-ACCLAB using the 24Mg(40Ca,2n) 62Ge fusion-evaporation reaction. The first excited T = 1, Jπ = 2+ states in 62Ga and 62Ge were identified at 979(1) and 965(1) keV, respectively, resolving discrepant interpretations in the literature. States beyond the first 2 + state in 62Ge were also identified for the first time in the present work. The results are compared with shell-model calculations in the f p model space. Mirror and triplet energy differences are analyzed in terms of individual charge-symmetry and charge-independence breaking contributions. The MED results confirm the shrinkage of the p-orbits’ radii when they are occupied by at least one nucleon on average.
Abstract We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38 x 106 sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167 ± 0.006, for Ne/Si is 0.833 ± 0.025, for Mg/Si is 0.994 ± 0.029, and for C/O is 0.836 ± 0.025. These values are determined independent of cosmic-ray propagation.
Abstract Evidence indicates the pathogenic role of epigenetic alterations in early-onset colorectal cancers diagnosed before age 50. However, features of colorectal cancers diagnosed at age 50–54 (hereafter referred to as “intermediate-onset”) remain less known. We hypothesized that tumor long interspersed nucleotide element-1 (LINE-1) hypomethylation might be increasingly more common with decreasing age of colorectal cancer diagnosis. In 1356 colorectal cancers, including 28 early-onset and 66 intermediate-onset cases, the tumor LINE-1 methylation level measured by bisulfite-PCR-pyrosequencing (scaled 0 to 100) showed a mean of 63.6 (standard deviation (SD) 10.1). The mean tumor LINE-1 methylation level decreased with decreasing age (mean 64.7 (SD 10.4) in age ≥70, 62.8 (SD 9.4) in age 55–69, 61.0 (SD 10.2) in age 50–54, and 58.9 (SD 12.0) in age <50; p < 0.0001). In linear regression analysis, the multivariable-adjusted β coefficient (95% confidence interval (CI)) (vs. age ≥70) was −1.38 (−2.47 to −0.30) for age 55–69, −2.82 (−5.29 to −0.34) for age 50–54, and −4.54 (−8.24 to −0.85) for age <50 (Ptrend = 0.0003). Multivariable-adjusted hazard ratios (95% CI) for LINE-1 methylation levels of ≤45, 45–55, and 55–65 (vs. >65) were 2.33 (1.49–3.64), 1.39 (1.05–1.85), and 1.29 (1.02–1.63), respectively (Ptrend = 0.0005). In conclusion, tumor LINE-1 hypomethylation is increasingly more common with decreasing age of colorectal cancer diagnosis, suggesting a role of global DNA hypomethylation in colorectal cancer arising in younger adults.
Abstract We report the properties of sodium (Na) and aluminum (Al) cosmic rays in the rigidity range 2.15 GV to 3.0 TV based on 0.46 million sodium and 0.51 million aluminum nuclei collected by the Alpha Magnetic Spectrometer experiment on the International Space Station. We found that Na and Al, together with nitrogen (N), belong to a distinct cosmic ray group. In this group, we observe that, similar to the N flux, both the Na flux and Al flux are well described by the sums of a primary cosmic ray component (proportional to the silicon flux) and a secondary cosmic ray component (proportional to the fluorine flux). The fraction of the primary component increases with rigidity for the N, Na, and Al fluxes and becomes dominant at the highest rigidities. The Na/Si and Al/Si abundance ratios at the source, 0.036 +/- 0.003 for Na/Si and 0.103 +/- 0.004 for Al/Si, are determined independent of cosmic ray propagation.
Abstract We present the precision measurement of the daily proton fluxes in cosmic rays from May 20, 2011 to October 29, 2019 (a total of 2824 days or 114 Bartels rotations) in the rigidity interval from 1 to 100 GV based on 5.5 x 109 protons collected with the Alpha Magnetic Spectrometer aboard the International Space Station. The proton fluxes exhibit variations on multiple timescales. From 2014 to 2018, we observed recurrent flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. The rigidity dependence of the 27-day periodicity is different from the rigidity dependences of 9-day and 13.5-day periods. Unexpectedly, the strength of 9-day and 13.5-day periodicities increases with increasing rigidities up to similar to 10 GV and similar to 20 GV, respectively. Then the strength of the periodicities decreases with increasing rigidity up to 100 GV.
Excited states of the rubidium isotopes 3787, 89, 91Rb have been studied at the INFN Legnaro National Laboratory. Measurements of the γγ-ray decay of fragments produced in binary grazing reactions resulting from the interaction of a beam of 530 MeV 96Zr ions with a 124Sn target have been complemented by studies of the γγ-ray decay of fission fragments produced in the interaction of a beam of 230 MeV 36S ions with a thick 176Yb target. The structure of the yrast states of 3787, 89, 91Rb has been discussed within the context of spherical shell-model and cranked Nilsson-Strutinsky calculations.
Abstract We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range allows us to study and disentangle shake processes and intramolecular inelastic scattering effects. In this gas-phase study, relative intensities of the carbon 1s photoelectron lines from chemically inequivalent carbon atoms in the same molecule have been measured as a function of the incident photon energy in the range of 300–6000 eV. We present relative cross sections for the chemically shifted carbon 1s lines in the photoelectron spectra of ethyl trifluoroacetate (the “ESCA” molecule). The results are compared with those of methyl trifluoroacetate and S-ethyl trifluorothioacetate as well as a series of chloro-substituted ethanes and 2-butyne. In the soft X-ray energy range, the cross sections show an extended X-ray absorption fine structure type of wiggles, as was previously observed for a series of chloroethanes. The oscillations are damped in the hard X-ray energy range, but deviations of cross-section ratios from stoichiometry persist, even at high energies. The current findings are supported by theoretical calculations based on a multiple scattering model. The use of soft and tender X-rays provides a more complete picture of the dominant processes accompanying photoionization. Such processes reduce the main photoelectron line intensities by 20–60%. Using both energy ranges enabled us to discern the process of intramolecular inelastic scattering of the outgoing electron, whose significance is otherwise difficult to assess for isolated molecules. This effect relates to the notion of the inelastic mean free path commonly used in photoemission studies of clusters and condensed matter.
Abstract Background: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. Methods: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. Results: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). Conclusions: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery.
Abstract Purpose: While evidence indicates that Fusobacterium nucleatum (F. nucleatum) may promote colorectal carcinogenesis through its suppressive effect on T-cell–mediated antitumor immunity, the specific T-cell subsets involved remain uncertain. Experimental Design: We measured F. nucleatum DNA within tumor tissue by quantitative PCR on 933 cases (including 128 F. nucleatum–positive cases) among 4,465 incident colorectal carcinoma cases in two prospective cohorts. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms for CD3, CD4, CD8, CD45RO (PTPRC isoform), and FOXP3 measured various T-cell subsets. We leveraged data on Bifidobacterium, microsatellite instability (MSI), tumor whole-exome sequencing, and M1/M2-type tumor-associated macrophages [TAM; by CD68, CD86, IRF5, MAF, and MRC1 (CD206) multimarker assay]. Using the 4,465 cancer cases and inverse probability weighting method to control for selection bias due to tissue availability, multivariable-adjusted logistic regression analysis assessed the association between F. nucleatum and T-cell subsets. Results: The amount of F. nucleatum was inversely associated with tumor stromal CD3+ lymphocytes [multivariable OR, 0.47; 95% confidence interval (CI), 0.28–0.79, for F. nucleatum–high vs. -negative category; Ptrend = 0.0004] and specifically stromal CD3+CD4+CD45RO+ cells (corresponding multivariable OR, 0.52; 95% CI, 0.32–0.85; Ptrend = 0.003). These relationships did not substantially differ by MSI status, neoantigen load, or exome-wide tumor mutational burden. F. nucleatum was not significantly associated with tumor intraepithelial T cells or with M1 or M2 TAMs. Conclusions: The amount of tissue F. nucleatum is associated with lower density of stromal memory helper T cells. Our findings provide evidence for the interactive pathogenic roles of microbiota and specific immune cells.
Abstract Background: Safe, effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in children younger than 12 years of age. Methods: A phase 1, dose-finding study and an ongoing phase 2–3 randomized trial are being conducted to investigate the safety, immunogenicity, and efficacy of two doses of the BNT162b2 vaccine administered 21 days apart in children 6 months to 11 years of age. We present results for 5-to-11-year-old children. In the phase 2–3 trial, participants were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at the dose level identified during the open-label phase 1 study or placebo. Immune responses 1 month after the second dose of BNT162b2 were immunologically bridged to those in 16-to-25-year-olds from the pivotal trial of two 30-μg doses of BNT162b2. Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed. Results: During the phase 1 study, a total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level). On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study. In the phase 2–3 trial, a total of 2268 children were randomly assigned to receive the BNT162b2 vaccine (1517 children) or placebo (751 children). At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, ≥0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3). Conclusions: A Covid-19 vaccination regimen consisting of two 10-μg doses of BNT162b2 administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age.
Abstract The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition.