Miracle-dz/UniFAR-FTUs huggingface dataset:
The major immediate-early proteins IE1 and IE2 of human cytomegalovirus colocalize with and disrupt PML-associated nuclear bodies at very early times in infected permissive cells

The major immediate-early (MIE) gene products of human cytomegalovirus (HCMV) are nuclear phosphoproteins that are thought to play key roles in initiating lytic cycle gene regulation pathways. We have examined the intranuclear localization pattern of both the IE1 and IE2 proteins in virus-infected and DNA-transfected cells. When HCMV-infected human diploid fibroblast (HF) cells were stained with specific monoclonal antibodies, IE1 localized as a mixture of nuclear diffuse and punctate patterns at very early times (2 h) but changed to an exclusively nuclear diffuse pattern at later times. In contrast, IE2 was distributed predominantly in nuclear punctate structures continuously from 2 to at least 12 h after infection. These punctate structures resembled the preexisting PML-associated nuclear bodies (ND10 or PML oncogenic domains [PODs]) that are disrupted and dispersed by the IE110 protein as a very early event in herpes simplex virus (HSV) infection. However, HCMV differed from HSV by leading instead to a change in both the PML and SP100 protein distribution from punctate bodies to uniform diffuse patterns, a process that was complete in 50% of the cells at 2 h and in 90% of the cells by 4 h after infection. Confocal double-label indirect immunofluorescence assay analysis confirmed that both IE1 and IE2 colocalized transiently with PML in punctate bodies at very early times after infection. In transient expression assays, introduction of IE1-encoding plasmid DNA alone into Vero or HF cells produced the typical total redistribution of PML into a uniform nuclear diffuse pattern together with the IE1 protein, whereas introduction of IE2-encoding plasmid DNA alone resulted in stable colocalization of the IE2 protein with PML in the PODs. A truncated mutant form of IE1 gave large nuclear aggregates and failed to redistribute PML, and similarly a deleted mutant form of IE2 failed to colocalize with the punctate PML bodies, confirming the specificity of these effects. Furthermore, both Vero and U373 cell lines constitutively expressing IE1 also showed total PML relocalization together with the IE1 protein into a nuclear diffuse pattern, although a very small percentage of the cells which failed to express IE1 reverted to a punctate PML pattern. Finally, the PML redistribution activity of IE1 and the direct association of IE2 with PML punctate bodies were both confirmed by infection with E1A-negative recombinant adenovirus vectors expressing either IE1 or IE2 alone. These results confirm that transient colocalization with and disruption of PML-associated nuclear bodies by IE1 and continuous targeting to PML-associated nuclear bodies by IE2 are intrinsic properties of these two MIE regulatory proteins, which we suggest may represent critical initial events for efficient lytic cycle infection by HCMV.
The ability of an electrocardiogram to predict fatal and non-fatal cardiac events in asymptomatic middle-aged subjects

Abstract Introduction: The long-term prognostic value of a standard 12-lead electrocardiogram (ECG) for predicting cardiac events in apparently healthy middle-aged subjects is not well defined. Materials and methods: A total of 9511 middle-aged subjects (mean age 43 ± 8.2 years, 52% males) without a known cardiac disease and with a follow-up 40 years were included in the study. Fatal and non-fatal cardiac events were collected from the national registries. The predictive value of ECG was separately analyzed for 10 and 30 years. Major ECG abnormalities were classified according to the Minnesota code. Results: Subjects with major ECG abnormalities (N = 1131) had an increased risk of cardiac death after 10-years (adjusted hazard ratio [HR] 1.7; 95% confidence interval [95% CI], 1.1–2.5, p = 0.009) and 30-years of follow-up (HR 1.3, 95% CI, 1.1–1.5, p < 0.001). Model discrimination measured with the C-index showed only a minor improvement with the inclusion of ECG abnormalities: 0.851 versus 0.853 and 0.742 versus 0.743 for 10- and 30-year follow-up, respectively. ECG did not predict non-fatal cardiac events after 10-years or 30-years of follow-up. Discussion: Major ECG abnormalities are associated with an increased risk of short and long-term cardiac mortality in middle-aged subjects. However, the improvement in discrimination between subjects with and without fatal cardiac events was marginal with abnormal ECG. KEY MESSAGES: Abnormalities observed on 12-lead electrocardiogram are shown to have prognostic significance for cardiac events in elderly subjects without known cardiac disease. Our results suggest that ECG abnormalities increase the risk of fatal cardiac events also in middle-aged healthy subjects.
Magnetic Stimulation of the Brain in Animal Depression Models Responsive to ECS

Studies in humans show antidepressant potential for transcranial magnetic stimulation (TMS). We therefore studied TMS in animal models of depression and compared its effects with those of ECS. ECS in rats has several robust behavioral effects, including enhancement of apomorphine-induced stereotypy, reduction of immobility time in the Porsolt swim test, and increases in seizure threshold for subsequent stimulation. Seven or 10 days of daily TMS consistently enhanced apomorphineinduced stereotypy, whereas a single session of TMS did not. Two TMS treatments markedly reduced immobility in the Porsolt swim test, as does ECS. A single TMS treatment markedly reduces the percentage of rats seizing in response to a ECS-like electrical stimulus to the brain 10 s later, as does an ECS treatment itself but not a sub-convulsive electrical stimulus to the brain. Long-term administration of ECS as well as other antidepressant treatments downregulates β-adrenergic receptors. We found that TMS significantly reduced the density of [3H]CGP-12177 (a radioligand with β-adrenergic affinity) binding sites in cortical (p < 0.05) but not hippocampal membranes. The role of monoamines in the mechanism of action of antidepressant treatments was investigated in numerous studies. Region-specific changes in the brain steady-state levels, and turnover rates of monoamines were detected 10 s after administration of a single repetitive TMS (rTMS) session. In the striatum and hippocampus, dopamine levels were increased by 25 ± 1.5% and 18 ± 0.8%, respectively, but were reduced in frontal cortex and decreased in the striatum and hippocampus in the TMS-treated rats with no change to the midbrain. TMS caused an increase in serotonin and 5-HIAA levels in the hippocampus but not in other brain regions examined in this study. The ability of TMS to induce behavioral and biochemical alterations similar to those of ECS may further support the potential role of TMS as an antidepressant treatment and bring us closer to the understanding of the mechanism of action of TMS.
Factors Related to Patients' Adherence to Medication and Lifestyle Change Recommendations: Data from Canada

The purpose of this study was to investigate factors related to patients' adherence to prescribed medications and recommended lifestyle changes. Two hundred and ninety-eight adults from a northern Canadian community filled out a questionnaire. Several intriguing findings emerged: (a) Adherence to lifestyle changes and participants' age presented a U-shape relationship; (b) Those who perceived themselves to be in poor health were less likely than those in good health to adhere to lifestyle changes; (c) Barriers such as the severe winter weather, lack of transportation, and cost of medications contributed negatively to adherence; and (d) If doctors provided sufficient information on the benefits and use of the prescribed medications and the proposed lifestyle changes and if patients reported trusting their doctors, they tended to adhere more. Physicians can play an important role in promoting adherence among patients. Community health workers should make efforts in reducing barriers that interfere with patient adherence.
Using of Fish Pathological Alterations to Assess Aquatic Pollution : A Review

Using of fish pathology is well established as an essential section of the set of ‘biomarkers’ applied in biological effects of variety pollutants monitoring programs in Europe such as International Council for the Exploration of the Sea (ICES). Use of histopathological techniques allows investigators to examine specific target organs and cells as they are affected by exposure to environmental chemicals. Moreover, it offers a means of detecting acute and chronic harmful effects of exposure in the tissues and organs of individual animals. This review provides a general evaluation of the main pathological alterations reported in fish exposed to contaminants.
The Restructuring of the Financial System in the 21st century

The financial system on the first decades of the 21st century followed the trend of the last decades of the 20th century with corporate restructuring and international financial markets integration and delocalization being oriented by profits and mergers and acquisitions. The global economy and financial structure changes, in the current century, derived from financial innovations, market deregulation, globalization, technology, market structure changes, regulatory reforms, and (re)formulation of central banks' monetary policy. Currently, the financial system is interconnected, interactive, interdependent, and became over-leveraged. The present chapter focuses on the analysis of the evolution of the financial system and the main determinants of global financial markets restructuring on last decades to explain the relevant changes verified in the financial system in the 21st century. After a literature review, an evaluative and descriptive macro analysis of the financial system is presented to study the process of restructuring of the financial system in the main developed economies.
ABBYY: the digitization of language and text

Subject area Entrepreneurship, Innovation Management, Bringing Technology to Market, International Growth Strategy from Emerging Markets, Russia, B2B Marketing. Study level/applicability MBA and executive education programs, technology management programs and electives. Case overview The case investigates the 20-years growth story of ABBYY, one of the most successful Russian technological companies in a global market. It covers the company’s roots, development of unique technology, evolution of products, market development and globalization and discusses a strategic threat from Google Translate to the company’s sustainable position and its business model. Expected learning outcomes The expected learning outcome is to discuss the key issues associated with establishing, growing and globalizing technology-driven business in an emerging market: bringing technology to market, defining customer value proposition, entering overseas markets from Russia, building partnerships, developing organizational structure to fit growth, financing rapid growth and solving “Innovator’s Dilemma”. Supplementary materials Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes. Subject code CSS 3: Entrepreneurship.
Improved reliability of HfO/sub 2//SiON gate stack by fluorine incorporation

Effects of fluorine (F) incorporation on the reliabilities of pMOSFETs with HfO/sub 2//SiON gate stacks have been studied. In this letter, fluorine was incorporated during the source/drain implant step and was diffused into the gate stacks during subsequent dopant activation. The authors found that F introduction only negligibly affects the fundamental electrical properties of the transistors, such as threshold voltage V/sub th/, subthreshold swing, gate leakage current, and equivalent oxide thickness. In contrast, reduced generation rates in interface states and charge trapping under constant voltage stress and bias temperature stress were observed for the fluorine-incorporated split. Moreover, the authors demonstrated for the first time that F incorporation could strengthen the immunity against plasma charging damage.
Understanding preferences of German flower consumers: the desire for sustained beauty

Purpose The purpose of this paper is to provide insights for flower retailers, horticultural practitioners and marketing managers into the prioritisation of cut flower attributes by German residents. Design/methodology/approach Applying a best–worst scaling approach, this analysis identified the relative ranking of importance amongst product attributes relevant to German consumers when buying fresh cut flowers. A latent class analysis determined four flower consumer segments for further study. The study builds on a sample of 978 consumers and is consistent with the most recent German census in terms of age, gender, income and federal state. Findings The best-worst analysis showed that intrinsic flower attributes, in particular appearance, freshness and scent were found to be more important to German consumers than the extrinsic attributes studied, namely, price, country of origin and a certification indicating fair trade. The latent class analysis determined four consumer segments that desire either budget, luxury or ethical flowers or more information about flowers. For all identified consumer segments, appearance was the attribute of greatest importance. The segments that desired luxury or ethical flowers, as well as the segment that desires more information were interested in appearance, but also had relatively large shares of preferences dedicated to flower freshness guarantees. The preference for freshness guarantees in addition to appearance may be interpreted jointly as a desire for not only beautiful and aesthetically pleasing flowers, but for sustained beauty. Originality/value Internationally, the study fills a research gap by exploring consumer’s relative preference for cut flower attributes. In contrast to existing studies on consumer preferences for flowers in Germany, the present study builds on a sample that was targeted in terms of age, gender, net household income and federal state to the most recent German census.
A new 3X interleaved bidirectional switched capacitor converter

An interleaved bidirectional switched capacitor converter with regulation capability is proposed in this paper. This converter is able to step up the voltage to near three times and regulate the output, while maintaining continuous input current as well as small output voltage ripple. Due to its natural interleaved structure, fewer components are required compared with traditional interleaved switched-capacitor converter with similar functionality. The proposed topology can also be modified as unidirectional converter with reduced number of switches. A PWM technique is proposed to regulate the output voltage. A modeling method is presented which provides the voltage gain formula. Criterion for high efficiency switched capacitor converter design is obtained. A 10W 5V to 14V prototype of proposed SC converter with efficiency higher than 90% was realized. The experimental results demonstrate the feasibility of proposed topology and regulation technique.
Emergency contraceptive pills: a simple proposal to reduce unintended pregnancies.

A new form of postcoital contraceptive therapy is described as more effective because of reduced incidence of nausea, vomiting, and breast tenderness. Other forms of emergency contraceptive pills (ECPs) are the "Yuzpe" method or high-dose contraceptives. The new method calls for administration of 3 200-mg tablets of danocrine (Danazol) within 72 hours of unprotected intercourse and a second dose 12 hours later. There are mixed reviews of the efficacy of danocrine and ECPs. In one comparative study of ECP and danocrine use, efficacy of danocrine was greater but not significantly so. Another study found danocrine so ineffective that the study was halted. ECP use would not end unintended pregnancies caused by method failure unless it was condom failure. Estimates of ECP use involve 75% of the 1.7 million women with user or method failure, all 1.9 million women with unintended pregnancies from nonuse of contraceptives, and some of the 1.6 million abortion users. An obstacle to ECP use is lack of knowledge due to lack of Food and Drug Administration approval of Ovral and Danazol and physician concern for legal liability. Another obstacle consists in the logistics of obtaining ECPs and the fear of side effects. Provision of ECP kits with 3-5 regimens in clinic or physician offices is proposed for women without contraindications. Anticipated objections are reported to be encouragement of contraceptive risk taking, the health risks of repeated use, restrictions in Title X programs, and the drug effect on fertilization. Another proposal is to sell ECPs as over the counter drugs or in vending machines and changing US contraceptive prescription laws. Objections to elimination of the physician prescription requirement might be an increase in use among women with contraindications and a decrease in regular checkups and Pap tests. The objections could be overcome with proper package labeling. Paternalism is not a sufficient justification for requiring prescription of contraceptives and medical visits. ECPs, in fact, are already available as low dose contraceptives such as Lo/Ovral, Nordette, Levlen, Triphasil, and Tri-Levlen when 4 pills are used. Instructions for ECP use are given.
Electric Fields Contribute to Directed Migration of Human Retinal Pigment Epithelial Cells via Interaction between F-Actin and β1 Integrin

Purpose: To observe the effects of electric fields (EFs) on the migration of human retinal pigment epithelial (RPE) cells and to explore possible related mechanisms. Methods: Cultured human RPE cells were exposed to EFs, and images of the cells were obtained at regular intervals to evaluate the cell migration and viability. Distribution of F-actin and β 1 integrin was measured by immunohistochemistry. Expression of β 1 integrin was determined by PCR and Western blotting. Results: Exposure to EFs resulted in a cathodal-directed migration of RPE cells and a cathodal accumulation of F-actin and β 1 integrin in the cells. EF stimulation increased expression of β 1 integrin both in mRNA and protein levels. These effects could be inhibited by cytochalasin B. Conclusion: EFs induce directed migration of RPE cells, and this effect is, to some extent, regulated by the interaction between cytoskeleton and integrins.
Coronary Angiography with Magnetization‐Prepared T2 Contrast

A magnetization‐prepared, T2‐weighted sequence (T2 Prep) is used to suppress muscle and venous structures. When combined with lipid suppression, this technique improves the visualization of the coronary arteries. T2 Prep was designed to be robust in the presence of flow as well as B0 and B1 inho‐mogeneities and may be combined with virtually any imaging technique. Here, it is implemented with both a single‐slice spiral acquisition and a multi‐slice spiral method that acquires up to 15 slices in a single breath‐holding interval.
A Guide to the Natural History of Freshwater Lake Bacteria

SUMMARY Freshwater bacteria are at the hub of biogeochemical cycles and control water quality in lakes. Despite this, little is known about the identity and ecology of functionally significant lake bacteria. Molecular studies have identified many abundant lake bacteria, but there is a large variation in the taxonomic or phylogenetic breadths among the methods used for this exploration. Because of this, an inconsistent and overlapping naming structure has developed for freshwater bacteria, creating a significant obstacle to identifying coherent ecological traits among these groups. A discourse that unites the field is sorely needed. Here we present a new freshwater lake phylogeny constructed from all published 16S rRNA gene sequences from lake epilimnia and propose a unifying vocabulary to discuss freshwater taxa. With this new vocabulary in place, we review the current information on the ecology, ecophysiology, and distribution of lake bacteria and highlight newly identified phylotypes. In the second part of our review, we conduct meta-analyses on the compiled data, identifying distribution patterns for bacterial phylotypes among biomes and across environmental gradients in lakes. We conclude by emphasizing the role that this review can play in providing a coherent framework for future studies.
Diameter and photospheric structures of Canopus from AMBER/VLTI interferometry ,

Context. Direct measurements of fundamental parameters and photospheric structures of post-main-sequence intermediate-mass stars are required for a deeper understanding of their evolution. Aims. Based on near-IR long-baseline interferometry we aim to resolve the stellar surface of the F0 supergiant star Canopus, and to precisely measure its angular diameter and related physical parameters. Methods. We used the AMBER/VLTI instrument to record interferometric data on Canopus: visibilities and closure phases in the H and K bands with a spectral resolution of 35. The available baselines (’ 60 110 m) and the high quality of the AMBER/VLTI observations allowed us to measure fringe visibilities as far as in the third visibility lobe. Results. We determined an angular diameter of = = 6:93 0:15 mas by adopting a linearly limb-darkened disk model. From this angular diameter and Hipparcos distance we derived a stellar radius R = 71:4 4:0R . Depending on bolometric fluxes existing in the literature, the measured = provides two estimates of the e ective temperature: Te = 7284 107 K and Te = 7582 252 K. Conclusions. In addition to providing the most precise angular diameter obtained to date, the AMBER interferometric data point towards additional photospheric structures on Canopus beyond the limb-darkened model alone. A promising explanation for such surface structures is the presence of convection cells. We checked such a hypothesis using first order star-cell models and concluded that the AMBER observations are compatible with the presence of surface convective structures. This direct detection of convective cells on Canopus from interferometry can provide strong constraints to radiation-hydrodynamics models of photospheres of F-type supergiants.
Extended-dosage-interval regimens of erythropoietic agents in chemotherapy-induced anemia.

PURPOSE The safety and efficacy of extended-dosage-interval regimens of erythropoiesis-stimulating agents (ESAs) for managing chemotherapy-induced anemia (CIA) are reviewed. SUMMARY Anemia is a frequent complication of chemotherapy. The ESAs epoetin alfa and darbepoetin alfa have been shown to safely and effectively manage CIA; comparable outcomes have been demonstrated between epoetin alfa 40,000 units once weekly and darbepoetin alfa 200 microg every two weeks. These commonly prescribed regimens necessitate extra clinic visits by cancer patients receiving cyclic chemotherapy. ESA administration can now often be synchronized with a three-week chemotherapy cycle because of the recent approval of darbepoetin alfa 500 microg every three weeks for CIA. However, in the Phase III trial providing the basis for this new dosage recommendation, more than 70% of patients required a 40% reduction in the dosage, resulting in an average dose of 375 microg every three weeks. The extended-dosage-interval regimens have not been associated with an increase in cardiovascular or thrombotic adverse events. Extended-dosage-interval regimens of epoetin alfa are under investigation and may provide additional alternatives. Synchronizing ESA therapy with scheduled chemotherapy visits would help minimize disruptions for patients and caregivers and improve the use of health care resources. CONCLUSION Administration of darbepoetin alfa every three weeks offers the convenience of synchronization of treatment with 21-day-cycle chemotherapy in many patients with CIA. Extended-dosage-interval regimens for epoetin alfa are being investigated and show promise.