Modern trends in the global economy

Gas turbine operating cycles at high temperatures often consist of load reversals mixed with hold times; the latter occurring either as cruise for aero engines or at continuous power output for land based turbines, but also at low frequency loading conditions, e.g. slow “ramp up” of engine thrust. The hold time conditions cause the crack to grow by intergranular fracture due to material damage near the crack tip, thus rapidly increasing the crack growth rate. Since the damaged zone will affect the crack propagation rate due to cyclic loadings as well, the complete load history of a component therefore has to be considered. The crack propagation model presented in this paper is based on the damaged zone concept, and considers the history effect in the form of damaged zone build up during hold times, and subsequent destruction as the crack propagates onwards by rapidly applied load reversals. By incorporating crack closure for handling different R-values, an aero engine component spectrum is evaluated for a surface crack at 550 C. The result shows a good correlation to model simulation, despite the complexity of the load spectrum

SAF-A Forms a Complex with BRG1 and Both Components Are Required for RNA Polymerase II Mediated Transcription

Background: Scaffold attachment factor A (SAF-A) participates in the regulation of gene expression by organizing chromatin into transcriptionally active domains and by interacting directly with RNA polymerase II. Methodology: Here we use co-localization, co-immunoprecipitation (co-IP) and in situ proximity ligation assay (PLA) to identify Brahma Related Gene 1 (BRG1), the ATP-driven motor of the human SWI-SNF chromatin remodeling complex, as another SAF-A interaction partner in mouse embryonic stem (mES) cells. We also employ RNA interference to investigate functional aspects of the SAF-A/BRG1 interaction. Principal Findings: We find that endogenous SAF-A protein interacts with endogenous BRG1 protein in mES cells, and that the interaction does not solely depend on the presence of mRNA. Moreover the interaction remains intact when cells are induced to differentiate. Functional analyses reveal that dual depletion of SAF-A and BRG1 abolishes global transcription by RNA polymerase II, while the nucleolar RNA polymerase I transcription machinery remains unaffected. Conclusions: We demonstrate that SAF-A interacts with BRG1 and that both components are required for RNA Polymerase I

Phosphorylated Nucleolin Interacts with Translationally Controlled Tumor Protein during Mitosis and with Oct4 during Interphase in ES Cells

BACKGROUND: Reprogramming of somatic cells for derivation of either embryonic stem (ES) cells, by somatic cell nuclear transfer (SCNT), or ES-like cells, by induced pluripotent stem (iPS) cell procedure, provides potential routes toward non-immunogenic cell replacement therapies. Nucleolar proteins serve as markers for activation of embryonic genes, whose expression is crucial for successful reprogramming. Although Nucleolin (Ncl) is one of the most abundant nucleolar proteins, its interaction partners in ES cells have remained unidentified. METHODOLOGY: Here we explored novel Ncl-interacting proteins using in situ proximity ligation assay (PLA), colocalization and immunoprecipitation (IP) in ES cells. PRINCIPAL FINDINGS: We found that phosphorylated Ncl (Ncl-P) interacted with translationally controlled tumor protein (Tpt1) in murine ES cells. The Ncl-P/Tpt1 complex peaked during mitosis and was reduced upon retinoic acid induced differentiation, signifying a role in cell proliferation. In addition, we showed that Ncl-P interacted with the transcription factor Oct4 during interphase in human as well as murine ES cells, indicating of a role in transcription. The Ncl-P/Oct4 complex peaked during early stages of spontaneous human ES cell differentiation and may thus be involved in the initial differentiation event(s) of mammalian development. CONCLUSIONS: Here we described two novel protein-protein interactions in ES cells, which give us further insight into the complex network of interacting proteins in pluripotent cells

Impact of COVID-19 pandemic on cardiovascular testing in Asia: the IAEA INCAPS-COVID study

BACKGROUND The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. OBJECTIVES This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. METHODS The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. RESULTS Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. CONCLUSIONS The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Identification of stem cell factors - Novel protein-protein interactions and their functions

Embryonic stem (ES) cells provide an unlimited source of cells potentially useful for regenerative medicine, however, prior to clinical implementation, additional basic research is needed. This thesis is focused upon different molecular aspects regarding ES cells, primarily by finding novel stem cell protein-protein interactions and their functions. As functions of a specific protein may be dependent on its interacting partner, identification of such protein-protein interactions is important. Using several different methods, for example in situ proximity ligation assay and co-immunoprecipitation, numerous novel protein-protein interactions occurring in ES cells were found. The same proteins were shown to be involved in several different protein complexes, some of them likely to be part of bigger complexes. Tpt1 and Npm1 were two such proteins found in several different interactions. Tpt1/Npm1 interacted with a prominent peak during mitosis and were proven to be involved in cell proliferation. Individual depletion of Tpt1 and Npm1 resulted in increased levels of markers of the neural and mesodermal lineages, respectively. Further, Npm1 also associated with all three core transcription factors, namely Oct4, Sox2 and Nanog, signifying the importance of Npm1 in ES cells. The Npm1/Sox2 interaction was shown to remain while cells were induced to differentiate into neural lineage, while decreasing in the other differentiation pathways, indicating of an additional role of this protein complex during differentiation to ectoderm. Phosphorylated Ncl was found to interact individually with Tpt1 and Oct4 in a cell cycle dependent manner, speculatively involved in cell proliferation and transcription. In screening for factors binding to Oct4 proximal promoter, SAF-A was found and subsequently shown to be involved in the transcriptional regulation of Oct4. The binding occurred preferentially to unmethylated Oct4 promoter and was reduced when ES cells were induced to differentiate. SAF-A was also found to interact with RNA pol II as well as STAT3, Oct4 and Sox2. In conclusion: twelve novel protein-protein interactions, involved in cell proliferation, differentiation and transcriptional regulation, are presented in this thesis

Beginning to understand stem cell creation

Even though cloning has been possible for a long time, virtually nothing is known about the molecular events that takes place during the creation of a stem cell. Here we discuss cloning and transfer of epigenetic information, which serves to maintain the gene expression pattern typical of a differentiated cell type. We find that erasure of epigenetic information can broaden the gene expression pattern of a cell type, and possibly change its fate