Consistent analysis of one-nucleon spectroscopic factors involving weakly- and strongly-bound nucleons
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Ribosome assembly is a complex process that requires hundreds of essential assembly factors, including Rix7 (NVL2 in mammals) and Nsa1 (WDR74 in mammals). Rix7 is a type II double ring, AAA-ATPase, which is closely related to the well-known Cdc48/p97. Previous studies in Saccharomyces cerevisiae suggest that Rix7 mediates the release of Nsa1 from nucleolar pre-60S particles; however, the underlying mechanisms of this release are unknown. Through multiple structural analyses we show that S. cerevisiae Nsa1 is composed of an N-terminal seven-bladed WD40 domain followed by a lysine-rich C terminus that extends away from the WD40 domain and is required for nucleolar localization. Additional co-immunoprecipitation assays with the mammalian homologs identified a well-conserved interface within WDR74 that is important for its association with NVL2. We further show that WDR74 associates with the D1 AAA domain of NVL2, which represents a novel mode of binding of a substrate with a type II AAA-ATPase.
Theoretical estimates for the astrophysical S-factor and the rate of the reaction d(α, γ){sup 6}Li were obtained on the basis of the two-body model involving an α−d potential that has a simple Gaussian form and which describes correctly S-, P-, and D-wave phase shifts, the binding energy, and the asymptotic normalization coefficient for the S-wave bound state. The wave functions for the bound and continuum channels were calculated with the aid of the highly precise Numerov algorithm. The results for the contributions of the E1 and E2 transition components reveal a good convergence as the upper limit in the effective integrals increases up to 40 fm. The results obtained for the astrophysical S-factor and the rate of the reaction d(α, γ){sup 6}Li in the temperature range of 10{sup 6}K ≤ T ≤ 10{sup 10} K agree well with the results of the calculations performed by A.M. Mukhamedzhanov and his coauthors [Phys. Rev. C 83, 055805 (2011)] by using the known asymptotic form of the wave function at low energies and a complicated two-body potential at higher energies.
Background: The nuclear protein Src-associated protein of 68 kDa in mitosis (Sam68) is known to bind RNA and be involved in cellular processes triggered in response to environmental stresses, including virus infection. Interestingly, Sam68 is a multi-functional protein implicated in the life cycle of retroviruses and picornaviruses and is also considered a marker of virus-induced stress granules (SGs). Recently, we demonstrated the partial redistribution of Sam68 to the cytoplasm in FMDV infected cells, its interaction with viral protease 3C pro , and found a significant reduction in viral titers as consequence of Sam68-specific siRNA knockdowns. Despite of that, details of how it benefits FMDV remains to be elucidated. Methods: Sam68 cytoplasmic localization was examined by immunofluorescent microscopy, counterstaining with antibodies against Sam68, a viral capsid protein and markers of SGs. The relevance of RAAA motifs in the IRES was investigated using electromobility shift assays with Sam68 protein and parental and mutant FMDV RNAs. In addition, full genome WT and mutant or G-luc replicon RNAs were tested following transfection in mammalian cells. The impact of Sam68 depletion to virus protein and RNA synthesis was investigated in a cell-free system. Lastly, through co-immunoprecipitation, structural modeling, and subcellular fractionation, viral protein interactions with Sam68 were explored. Results: FMDV-induced cytoplasmic redistribution of Sam68 resulted in it temporarily co-localizing with SG marker: TIA-1. Mutations that disrupted FMDV IRES RAAA motifs, with putative affinity to Sam68 in domain 3 and 4 cause a reduction on the formation of ribonucleoprotein complexes with this protein and resulted in non-viable progeny viruses and replication-impaired replicons. Furthermore, depletion of Sam68 in cell-free extracts greatly diminished FMDV RNA replication, which was restored by addition of recombinant Sam68. The results here demonstrated that Sam68 specifically co-precipitates with both FMDV 3D pol and 3C pro consistent with early observations of FMDV 3C pro -induced cleavage of Sam68. Conclusion: We have found that Sam68 is a specific binding partner for FMDV non-structural proteins 3C pro and 3D pol and showed that mutations at RAAA motifs in IRES domains 3 and 4 cause a decrease in Sam68 affinity to these RNA elements and rendered the mutant RNA non-viable. Interestingly, in FMDV infected cells re-localized Sam68 was transiently detected along with SG markers in the cytoplasm. These results support the importance of Sam68 as a host factor co-opted by FMDV during infection and demonstrate that Sam68 interact with both, FMDV RNA motifs in the IRES and viral non-structural proteins 3C pro and 3D pol .
A technique for information retrieval includes parsing a corpus to identify a number of wordform instances within each document of the corpus. A weighted morpheme-by-document matrix is generated based at least in part on the number of wordform instances within each document of the corpus and based at least in part on a weighting function. The weighted morpheme-by-document matrix separately enumerates instances of stems and affixes. Additionally or alternatively, a term-by-term alignment matrix may be generated based at least in part on the number of wordform instances within each document of the corpus. At least one lower rank approximation matrix is generated by factorizing the weighted morpheme-by-document matrix and/or the term-by-term alignment matrix.
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Purpose: The purpose of this study was to evaluate altered pulmonary function retrospectively after RFA. Methods: This retrospective study comprised 41 ablation sessions for 39 patients (22 men and 17 women; mean age, 64.8 years). Vital capacity (VC) and forced expiratory volume in 1 s (FEV{sub 1}) at 1 and 3 months after RFA were compared with the baseline (i.e., values before RFA). To evaluate the factors that influenced impaired pulmonary function, univariate analysis was performed by using multiple variables. If two or more variables were indicated as statistically significant by univariate analysis, these variables were subjected to multivariate analysis to identify independent factors. Results: The mean VC and FEV{sub 1} before RFA and 1 and 3 months after RFA were 3.04 and 2.24 l, 2.79 and 2.11 l, and 2.85 and 2.13 l, respectively. The values at 1 and 3 months were significantly lower than the baseline. Severe pleuritis after RFA was identified as the independent factor influencing impaired VC at 1 month (P = 0.003). For impaired FEV{sub 1} at 1 month, only severe pleuritis (P = 0.01) was statistically significant by univariate analysis. At 3 months, severe pleuritis (VC, P = 0.019; FEV{sub 1}, P = 0.003) and an ablated parenchymal volume {>=}20 cm{sup 3} (VC, P = 0.047; FEV{sub 1}, P = 0.038) were independent factors for impaired VC and FEV{sub 1}. Conclusions: Pulmonary function decreased after RFA. RFA-induced severe pleuritis and ablation of a large volume of marginal parenchyma were associated with impaired pulmonary function.
We extend the QCD Parton Model analysis using a factorized nuclear structure model incorporating individual nucleons and pairs of correlated nucleons. Our analysis of high-energy data from lepton deep-inelastic scattering, Drell-Yan, and W and Z boson production simultaneously extracts the universal effective distribution of quarks and gluons inside correlated nucleon pairs, and their nucleus-specific fractions. Such successful extraction of these universal distributions marks a significant advance in our understanding of nuclear structure properties connecting nucleon- and parton-level quantities. Published by the American Physical Society 2024
Purpose: Concurrent chemoradiation therapy (CCRT) improves survival compared with sequential treatment for locally advanced non-small cell lung cancer, but it increases toxicity, particularly radiation esophagitis (RE). Validated predictors of RE for clinical use are lacking. We performed an individual-patient-data meta-analysis to determine factors predictive of clinically significant RE. Methods and Materials: After a systematic review of the literature, data were obtained on 1082 patients who underwent CCRT, including patients from Europe, North America, Asia, and Australia. Patients were randomly divided into training and validation sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade ≥2 and grade ≥3) were assessed using logistic modeling, with the concordance statistic (c statistic) used to evaluate the performance of each model. Results: The median radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1 years. Most patients (91%) received platinum-containing CCRT regimens. The development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3 in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On univariable analysis using the training set, several baseline factors were statistically predictive of RE (P<.05), but only dosimetric factors had good discrimination scores (c > .60). On multivariable analysis, the esophageal volume receiving ≥60 Gy (V60) alone emerged as the best predictor of grade ≥2 and grade ≥3 RE, with good calibration and discrimination. Recursive partitioning identified 3 risk groups: low (V60 <0.07%), intermediate (V60 0.07% to 16.99%), and high (V60 ≥17%). With use of the validation set, the predictive model performed inferiorly for the grade ≥2 endpoint (c = .58) but performed well for the grade ≥3 endpoint (c = .66). Conclusions: Clinically significant RE is common, but life-threatening complications occur in <1% of patients. Although several factors are statistically predictive of RE, the V60 alone provides the best predictive ability. Efforts to reduce the V60 should be prioritized, with further research needed to identify and validate new predictive factors.
Purpose: The new 7th edition of the American Joint Committee on Cancer TNM staging system is based on pathologic data from esophageal cancers treated by surgery alone. There is no information available on evaluation of the new staging system with regard to prognosis of patients treated with chemoradiotherapy (CRT). The objective of this study was to evaluate the prognostic impact of the new staging system on esophageal cancer patients treated with CRT. Methods and Materials: A retrospective review was performed on 301 consecutive esophageal squamous cell carcinoma patients treated with CRT. Comparisons were made of the prognostic impacts of the 6th and 7th staging systems and the prognostic impacts of stage and prognostic groups, which were newly defined in the 7th edition. Results: There were significant differences between Stages I and III (p < 0.01) according to both editions. However, the 7th edition poorly distinguishes the prognoses of Stages III and IV (p = 0.36 by multivariate analysis) in comparison to the 6th edition (p = 0.08 by multivariate analysis), although these differences were not significant. For all patients, T, M, and gender were independent prognostic factors by multivariate analysis (p < 0.05). For the Stage I and II prognostic groups, survival curves showed a stepwise decrease with increase in stage, except for Stage IIA. However, there were no significant differences seen between each prognostic stage. Conclusions: Our study indicates there are several problems with the 7th TNM staging system regarding prognostic factors in patients undergoing CRT.
Purpose: To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). Methods and Materials: This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. Results: Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. Conclusion: Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.
Purpose: To evaluate prognostic factors for survival after stereotactic radiosurgery (SRS) for new, progressive, or recurrent brain metastases (BM) after prior whole brain radiotherapy (WBRT). Methods and Materials: Patients treated between 1991 and 2007 with Gamma Knife SRS for BM after prior WBRT were retrospectively reviewed. Potential prognostic factors were analyzed overall and by primary site using univariate and stepwise multivariate analyses and recursive partitioning analysis, including age, Karnofsky performance status (KPS), primary tumor control, extracranial metastases, number of BM treated, total SRS target volume, and interval from WBRT to SRS. Results: A total of 310 patients were analyzed, including 90 breast, 113 non-small-cell lung, 31 small-cell lung, 42 melanoma, and 34 miscellaneous patients. The median age was 56, KPS 80, number of BM treated 3, and interval from WBRT to SRS 8.1 months; 76% had controlled primary tumor and 60% had extracranial metastases. The median survival was 8.4 months overall and 12.0 vs. 7.9 months for single vs. multiple BM treated (p = 0.001). There was no relationship between number of BM and survival after excluding single-BM patients. On multivariate analysis, favorable prognostic factors included age <50, smaller total target volume, and longer interval from WBRT to SRS in breast cancer patients; smaller number of BM, KPS >60, and controlled primary in non-small-cell lung cancer patients; and smaller total target volume in melanoma patients. Conclusions: Among patients treated with salvage SRS for BM after prior WBRT, prognostic factors appeared to vary by primary site. Although survival time was significantly longer for patients with a single BM, the median survival time of 7.9 months for patients with multiple BM seems sufficiently long for salvage SRS to appear to be worthwhile, and no evidence was found to support the use of a cutoff for number of BM appropriate for salvage SRS.
Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.
Hotel facilities present abundant opportunities for energy savings. In the United States, there are around 25,000 hotels that spend on an average of $2,196 on energy costs per room each year. This amounts to about 6% of the total annual hotel operating cost. However, unlike offices, there are limited studies on establishing appropriate baselines and quantifying hotel energy savings given the variety of services and amenities, unpredictable customer behaviors, and the around-the-clock operation hours. In this study, we investigate behavior driven energy savings for three medium-size (around 90,000 sf2) hotels that offer similar services in different climate zones. We first used Department of Energy Asset Scoring Tool to establish baseline models. We then conducted energy saving analysis in EnergyPlus based on a behavior model that defines the upper bound and lower bound of customer and hotel staff behavior. Lastly, we presented a probabilistic energy savings outlook for each hotel. The analysis shows behavior driven energy savings up to 25%. We believe this is the first study to incorporate behavioral factors into energy analysis for hotels. It also demonstrates a procedure to quickly create tailored baselines and identify improvement opportunities for hotels.
We hereby offer a comprehensive analysis of various factors that could potentially enable terahertz quantum cascade lasers (THz QCLs) to achieve room temperature performance. We thoroughly examine and integrate the latest findings from recent studies in the field. Our work goes beyond a mere analysis; it represents a nuanced and comprehensive exploration of the intricate factors influencing the performance of THz QCLs. Through a comprehensive and holistic approach, we propose novel insights that significantly contribute to advancing strategies for improving the temperature performance of THz QCLs. This all-encompassing perspective allows us not only to present a synthesis of existing knowledge but also to offer a fresh and nuanced strategy to improve the temperature performance of THz QCLs. We draw new conclusions from prior works, demonstrating that the key to enhancing THz QCL temperature performance involves not only optimizing interface quality but also strategically managing doping density, its spatial distribution, and profile. This is based on our results from different structures, such as two experimentally demonstrated devices: the spit-well resonant-phonon and the two-well injector direct-phonon schemes for THz QCLs, which allow efficient isolation of the laser levels from excited and continuum states. In these schemes, the doping profile has a setback that lessens the overlap of the doped region with the active laser states. Our work stands as a valuable resource for researchers seeking to gain a deeper understanding of the evolving landscape of THz technology. Furthermore, we present a novel strategy for future endeavors, providing an enhanced framework for continued exploration in this dynamic field. This strategy should pave the way to potentially reach higher temperatures than the latest records reached for T max of THz QCLs.
The study of d+d reactions is of major interest since their reaction rates affect the predicted abundances of D, 3 He, and 7 Li. In particular, recent measurements of primordial D/H ratios call for reduced uncertainties in the theoretical abundances predicted by Big Bang nucleosynthesis (BBN). Different authors have studied reactions involved in BBN by incorporating new experimental data and a careful treatment of systematic and probabilistic uncertainties. To analyze the experimental data, Coc et al. used results of ab initio models for the theoretical calculation of the energy dependence of S -factors in conjunction with traditional statistical methods based on χ 2 minimization. Bayesian methods have now spread to many scientific fields and provide numerous advantages in data analysis. Astrophysical S -factors and reaction rates using Bayesian statistics were calculated by Iliadis et al. In this paper we present a similar analysis for two d+d reactions, d(d, n) 3 He and d(d, p) 3 H, that has been translated into a total decrease of the predicted D/H value by 0.16%.
This data package summarizes the exposure assumptions, equations, and methods used to calculate radionuclide-specific unit dose factors and the radiological doses for both groundwater and atmospheric pathways as a part of the revised Hanford Site Composite Analysis. An All-Pathways Representative Person exposure scenario is considered to evaluate exposure via both groundwater and atmospheric transport pathways. The radiological dose assessments for both groundwater and atmospheric pathways are included in the performance assessments for various Waste Management Areas at the Hanford Site. This data package calculates exposure route-specific and total unit dose factors for composite-analysis-specific radionuclides of concern based on the exposure assumptions used in the composite analysis and performance assessments. This data package presents the results and comparison of the radionuclide-specific unit dose factors based on the exposure assumptions used in the revised composite analysis and various performance assessments.