Accelerated Aging Experiments for Prognostics of Damage Growth in Composite Materials

Composite structures are gaining importance for use in the aerospace industry. Compared to metallic structures their behavior is less well understood. This lack of understanding may pose constraints on their use. One possible way to deal with some of the risks associated with potential failure is to perform in-situ monitoring to detect precursors of failures. Prognostic algorithms can be used to predict impending failures. They require large amounts of training data to build and tune damage model for making useful predictions. One of the key aspects is to get confirmatory feedback from data as damage progresses. These kinds of data are rarely available from actual systems. The next possible resource to collect such data is an accelerated aging platform. To that end this paper describes a fatigue cycling experiment with the goal to stress carbon-carbon composite coupons with various layups. Piezoelectric disc sensors were used to periodically interrogate the system. Analysis showed distinct differences in the signatures of growing failures between data collected at conditions. Periodic X-radiographs were taken to assess the damage ground truth. Results after signal processing showed clear trends of damage growth that were correlated to damage assessed from the X-ray images

Hydrogen sulfide-linked persulfidation of ABI4 controls ABA responses through the transactivation of MAPKKK18 in Arabidopsis

Hydrogen sulfide (H2S) is a signaling molecule that regulates plant hormone and stress responses. The phytohormone abscisic acid (ABA) plays an important role in plant adaptation to unfavorable environmental conditions and induces the persulfidation of L-CYSTEINE DESULFHYDRASE1 (DES1) and the production of H2S in guard cells. However, it remains largely unclear how H2S and protein persulfidation participate in the relay of ABA signals. In this study, we discovered that ABSCISIC ACID INSENSITIVE 4 (ABI4) acts downstream of DES1 in the control of ABA responses in Arabidopsis. ABI4 undergoes persulfidation at Cys250 that is triggered in a time-dependent manner by ABA, and loss of DES1 function impairs this process. Cys250 and its persulfidation are essential for ABI4 function in the regulation of plant responses to ABA and the H2S donor NaHS during germination, seedling establishment, and stomatal closure, which are abolished in the ABI4Cys250Ala mutated variant. Introduction of the ABI4Cys250Ala variant into the abi4 des1 mutant did not rescue its hyposensitivity to ABA. Cys250 is critical for the binding of ABI4 to its cognate motif in the promoter of Mitogen-Activated Protein Kinase Kinase Kinase 18 (MAPKKK18), which propagates the MAPK signaling cascade induced by ABA. Furthermore, the DES1-mediated persulfidation of ABI4 enhances the transactivation activity of ABI4 toward MAPKKK18, and ABI4 can bind the DES1 promoter, forming a regulatory loop. Taken together, these findings advance our understanding of a post-translational regulatory mechanism and suggest that ABI4 functions as an integrator of ABA and MAPK signals through a process in which DES1-produced H2S persulfidates ABI4 at Cys250

Clinical trial recruitment of people who speak languages other than English: a Childrens Oncology Group report.

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Childrens Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials

Japanese Encephalitis Viruses from Bats in Yunnan, China

Genome sequencing and virulence studies of 2 Japanese encephalitis viruses (JEVs) from bats in Yunnan, China, showed a close relationship with JEVs isolated from mosquitoes and humans in the same region over 2 decades. These results indicate that bats may play a role in human Japanese encephalitis outbreaks in this region

Cluster and MMS simultaneous observations of magnetosheath high speed jets and their impact on the magnetopause

When the supersonic solar wind encounters the Earth's magnetosphere a shock, called bow shock, is formed and the plasma is decelerated and thermalized in the magnetosheath downstream from the shock. Sometimes, however, due to discontinuities in the solar wind, bow shock ripples or ionized dust clouds carried by the solar wind, high speed jets (HSJs) are observed in the magnetosheath. These HSJs have typically a Vx component larger than 200 km s−1 and their dynamic pressure can be a few times the solar wind dynamic pressure. They are typically observed downstream from the quasi-parallel bow shock and have a typical size around one Earth radius (RE) in XGSE. We use a conjunction of Cluster and MMS, crossing simultaneously the magnetopause, to study the characteristics of these HSJs and their impact on the magnetopause. Over 1 h 15 min interval in the magnetosheath, Cluster observed 21 HSJs. During the same period, MMS observed 12 HSJs and entered the magnetosphere several times. A jet was observed simultaneously by both MMS and Cluster and it is very likely that they were two distinct HSJs. This shows that HSJs are not localized into small regions but could span a region larger than 10 RE, especially when the quasi-parallel shock is covering the entire dayside magnetosphere under radial IMF. During this period, two and six magnetopause crossings were observed, respectively, on Cluster and MMS with a significant angle between the observation and the expected normal deduced from models. The angles observed range between from 11° up to 114°. One inbound magnetopause crossing observed by Cluster (magnetopause moving out at 142 km s−1) was observed simultaneous to an outbound magnetopause crossing observed by MMS (magnetopause moving in at −83 km s−1), showing that the magnetopause can have multiple local indentation places, most likely independent from each other. Under the continuous impacts of HSJs, the magnetopause is deformed significantly and can even move in opposite directions at different places. It can therefore not be considered as a smooth surface anymore but more as surface full of local indents. Four dust impacts were observed on MMS, although not at the time when HSJs are observed, showing that dust clouds would have been present during the observations. No dust cloud in the form of Interplanetary Field Enhancements was however observed in the solar wind which may exclude large clouds of dust as a cause of HSJs. Radial IMF and Alfvén Mach number above 10 would fulfill the criteria for the creation of bow shock ripples and the subsequent crossing of HSJs in the magnetosheath.publishedVersio

RAGE Mediates a Novel Proinflammatory Axis A Central Cell Surface Receptor for S100/Calgranulin Polypeptides

AbstractS100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (e xtracellular n ewly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury

A systematic review of the effectiveness of qigong exercise in supportive cancer care

PURPOSE: Qigong as a complementary and alternative modality of traditional Chinese medicine is often used by cancer patients to manage their symptoms. The aim of this systematic review is to critically evaluate the effectiveness of qigong exercise in cancer care. METHODS: Thirteen databases were searched from their inceptions through November 2010. All controlled clinical trials of qigong exercise among cancer patients were included. The strength of the evidence was evaluated for all included studies using the Oxford Centre for Evidence-based Medicine Levels of Evidence. The validity of randomized controlled trials (RCTs) was also evaluated using the Jadad Scale. RESULTS: Twenty-three studies including eight RCTs and fifteen non-randomized controlled clinical trials (CCTs) were identified. The effects of qigong on physical and psychosocial outcomes were examined in 14 studies and the effects on biomedical outcomes were examined in 15 studies. For physical and psychosocial outcomes, it is difficult to draw a conclusion due to heterogeneity of outcome measures and variability of the results in the included studies. Among reviewed studies on biomedical outcomes, a consistent tendency appears to emerge which suggests that the patients treated with qigong exercise in combination with conventional methods had significant improvement in immune function than the patients treated with conventional methods alone. CONCLUSIONS: Due to high risk of bias and methodological problems in the majority of included studies, it is still too early to draw conclusive statements. Further vigorously designed large-scale RCTs with validated outcome measures are needed.published_or_final_versio

Tamoxifen resistance in breast cancer is regulated by the EZH2–ERa–GREB1 transcriptional axis

Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor a (ERa) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERa cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERa coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program. Significance: This study suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program defined within.Fil: Wu, Yanming. University of Texas at San Antonio; Estados UnidosFil: Zhang, Zhao. University of Texas at San Antonio; Estados UnidosFil: Cenciarini, Mauro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Proietti Anastasi, Cecilia Jazmín. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Amasino, Matías Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Hong, Tao. University of Texas at San Antonio; Estados Unidos. Central South University; ChinaFil: Yang, Mei. University of Texas at San Antonio; Estados UnidosFil: Liao, Yiji. University of Texas at San Antonio; Estados UnidosFil: Chiang, Huai-Chin. University of Texas at San Antonio; Estados Unidos. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Kaklamani, Virginia G.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Jeselsohn, Rinath. Dana-farber Cancer Institute; Estados UnidosFil: Vadlamudi, Ratna K.. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Huang, Tim Hui Ming. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: Li, Rong. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio;Fil: De Angelis, Carmine. Baylor College Of Medicine; Estados UnidosFil: Fu, Xiaoyong. Baylor College Of Medicine; Estados UnidosFil: Elizalde, Patricia Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Schiff, Rachel. Baylor College Of Medicine; Estados UnidosFil: Brown, Myles. Dana farber Cancer Institute; Estados UnidosFil: Xu, Kexin. University Of Texas Health Science Center At San Antonio (ut Health San Antonio) ; University Of Texas At San Antonio

SUNRISE: The rich molecular inventory of high-redshift dusty galaxies revealed by broadband spectral line surveys

Understanding the nature of high-$z$ dusty galaxies requires a comprehensive view of their ISM and molecular complexity. However, the molecular ISM at high redshifts is commonly studied using only a few species beyond CO, limiting our understanding of the ISM in these objects. In this paper, we present the results of deep 3 mm spectral line surveys using the NOEMA targeting two lensed dusty galaxies: APM 08279+5255 (APM), a quasar at redshift $z=3.911$, and NCv1.143 (NC), a $z=3.565$ starburst galaxy. The spectral line surveys cover rest-frame frequencies from about 330-550 GHz. We report the detection of 38 and 25 emission lines in APM and NC, respectively. The spectra reveal the chemical richness and the complexity of the physical properties of the ISM. By comparing the spectra of the two sources and combining the gas excitation analysis, we find that the physical properties and the chemical imprints of the ISM are different between them: the molecular gas is more excited in APM, exhibiting higher molecular-gas temperatures and densities compared to NC; the chemical abundances in APM are akin to the values of local AGN, showing boosted relative abundances of the dense gas tracers that might be related to high-temperature chemistry and/or XDRs, while NC more closely resembles local starburst galaxies. The most significant differences are found in H2O, where the 448 GHz H2O line is significantly brighter in APM, likely linked to the intense far-infrared radiation from the dust powered by AGN. Our astrochemical model suggests that, at such high column densities, UV radiation is less important in regulating the ISM, while CRs (and/or X-rays and shocks) are the key players in shaping the abundance of the molecules. Such deep spectral line surveys open a new window to study the physical and chemical properties of the ISM and the radiation field of galaxies in the early Universe. (abridged)Comment: Submitted to A&A; under review. Abstract abridged. Comments are welcome