Miracle-dz/UniFAR-FTUs huggingface dataset:
Surfactant protein-A receptor-mediated inhibition of calcium signaling in alveolar type II cells.

Receptor-mediated inhibition of cellular activating signals is not well understood. Type II alveolar cells secrete surfactant in response to such secretagogs as terbutaline, calcium (Ca) ionophores (e.g., ionomycin [Io]), and adenosine triphosphate (ATP). A cell membrane receptor for SP-A, one of the surfactant proteins, regulates secretion by negative feedback. We used quantitative fluorescence microscopy to study the effects of SP-A on alterations in cytosolic Ca2+ ([Ca2+]i) elicited by surfactant secretagogs. Freshly isolated type II cells were loaded with Fura-2, then treated with secretagog, in the presence or absence of SP-A. Io and ATP produced biphasic increases in cytosol [Ca2+]i, reflecting first Ca2+ release from intracellular stores, and then influx through the cell membrane. Thapsigargin (TG) and Io directly initiate Ca2+ release; ATP elicits Ca2+ release via receptor-mediated mechanisms. Ca2+ release causes cell membrane Ca channels to open by as yet poorly understood mechanisms. Io itself acts as an additional Ca2+ channel. SP-A blocks much of the Ca2+ release and some of the Ca2+ influx elicited by these secretagogs. Antibody against SP-A receptor restores secretagog-induced Ca2+ fluxes from inhibition by SP-A, confirming that the inhibitory activity of SP-A is mediated through its receptor. Type II cells incubated in Ca2+-free medium plus SP-A show diminished Ca2+ release responses to TG or ATP, suggesting that the action of SP-A to prevent secretagog initiated increases in [Ca2+]i may reflect its ability to block Ca2+ release from cytoplasmic Ca stores. The feedback inhibition of surfactant secretion by SP-A may, correspondingly, be a manifestation of this effect. Because recent work suggests that TGF-beta also inhibits Ca2+ fluxes, SP-A and TGF-beta could be representative of a group of physiologic regulators that act by modulating intracellular Ca signaling.
Farnesol and dodecanol effects on the Candida albicans Ras1‐cAMP signalling pathway and the regulation of morphogenesis

Candida albicans hypha formation which has been stimulated via the Ras1‐cAMP‐Efg1 signalling cascade is inhibited by farnesol, a C. albicans autoregulatory factor, and small molecules such as dodecanol. In cultures containing farnesol or dodecanol, hypha formation was restored upon addition of dibutyryl‐cAMP. The CAI4‐Ras1G13V strain, which carries a dominant‐active variant of Ras1 and forms hyphae in the absence of inducing stimuli, grew as yeast in medium with farnesol or dodecanol; the heat shock sensitivity of the CAI4‐Ras1G13V strain was also suppressed by these compounds. Neither Pde1 nor Pde2 was necessary for the repression of hyphal growth by farnesol or dodecanol. Two transcripts, CTA1 and HSP12, which are at higher levels upon mutation of Ras1 or Cdc35, were increased in abundance in cells grown with farnesol or dodecanol. Microscopic analysis of strains carrying CTA1 and HWP1 promoter fusions grown with intermediate concentrations of farnesol or dodecanol indicated a link between cells with the increased expression of cAMP‐repressed genes and cells repressed for hypha formation. Because several cAMP‐controlled outputs are affected by farnesol and dodecanol, our findings suggest that these compounds impact activity of the Ras1‐Cdc35 pathway, thus leading to an alteration of C. albicans morphology.
Virological characterization of patients treated early is able to control HIV‐1 replication after multiple cycles of structured therapy interruption

This study aimed to define clinical and virological parameters associated with spontaneous control of HIV replication in patients having initiated HAART during primary HIV infection, who underwent structured therapy interruption by two protocols with either fixed or HIV viremia‐guided scheme. At the end of the protocol all patients were changed to viremia‐guided scheme and observed for 12 months (follow‐up). Patients maintaining HIV viremia below the indications for resumption of HAART during the follow‐up, were defined controllers, those who had to resume HAART were defined non‐controllers. The following parameters were examined: pre‐interruption therapy duration, CD4+, HIV RNA, proviral DNA, evolution of viral quasispecies. No specific advantage was conferred by either interruption of structured therapy in the proportion of controllers and non‐controllers. Pre‐HAART and zenith CD4+, pre‐therapy interruption, HAART duration, but not pre‐HAART HIV RNA, were significantly higher in controllers as compared to non‐controllers. HIV RNA levels after the first interruption cycle of therapy were significantly lower in controllers than in non‐controllers. Proviral DNA levels were also lower in controllers at this time point. HIV RNA and proviral DNA levels associated with the last interruption of therapy cycle were not different from those associated with the first cycle, and, in spite of multiple waves of virus rebound, very few gag quasispecies variants emerged in each patient. The data suggest that pre‐treatment clinical parameters and virological events associated with the first viral rebound are crucial factors in determining the ability to control viral replication after multiple cycles of interruption of treatment. J. Med. Virol. 79: 1047–1054, 2007. © 2007 Wiley‐Liss, Inc.
Systemic Inflammation‐Associated Glucocorticoid Resistance and Outcome of ARDS

Abstract: Dysregulated systemic inflammation with excess activation of pro‐inflammatory transcription factor nuclear factor‐κB (NF‐κB)—activated by inflammatory signals—compared to the anti‐inflammatory transcription factor glucocorticoid receptor‐α (GRα)—activated by endogenous or exogenous glucocorticoids (GCs)—is an important pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with acute respiratory distress syndrome (ARDS). Activation of one transcription factor in excess of the binding (inhibitory) capacity of the other shifts cellular responses toward increased (dysregulated) or decreased (regulated) transcription of inflammatory mediators over time. Recent data indicate that failure to improve in ARDS (unresolving ARDS) is frequently associated with failure of the activated GRs to downregulate the transcription of inflammatory cytokines despite elevated levels of circulating cortisol, a condition defined as systemic inflammation‐associated acquired GC resistance; it is potentially reversible with prolonged GC supplementation.
Optimal Control over the Process of Innovative Product Diffusion: The Case of Sony Corporation

DOI: 10.14254/2071789X.2018/11-3/16 ABSTRACT. The article deals with the process of distribution of an innovative product using the Bass model. Numerical characteristics of the generalized Bass model are described. The function of external influence is suggested to be approximated by means of a regression equation with respect to the price function of the product under investigation, which is also a control function. The control process is based on a mathematical apparatus under the Pontryagin maximum principle. An algorithm for determining the optimal price of products in order to obtain the maximum balance profit of the corporation is given. Selected numerical results of the corporate strategy implementation for conquering the market in 2017-2020 are offered.
Rule-based learning impairment in rats with lesions to the dorsal striatum.

The present study examined the effects of lesions to the dorsal striatum (DS) in Sprague-Dawley rats, when tested on the acquisition and successive shifts in the position of a goal arm in an eight-arm radial maze. In the procedure we used, rats had to retrieve the location of one baited arm among the eight arms of the maze after it had just been presented as a sample during a forced trial. After attainment of a fixed learning criterion, rats were submitted to five successive shifts in the goal location. Results showed that DS rats were able to learn the position of the goal arm during the acquisition phase as efficiently as sham-operated rats. In contrast, when the position of the goal arm was shifted, although DS rats were able to learn its new position, they made significantly more errors and required more sessions to reach criterion than sham-operated rats. These results suggested that both groups did not solve the task using the same behavioral strategy. The analysis of responses made suggested that sham-operated rats solved the task using the pairing rule between the forced and the free run (matching-to-sample rule), while DS rats solved the task using only visuo-spatial processing. These data therefore suggest that the dorsal striatum plays an important role in rule-learning ability.
New Perspective on Myopia Control with Orthokeratology

Purpose To compare peripheral refraction along both the horizontal and vertical retinal meridians before and after orthokeratology (OK) lens wear. Methods Nineteen young adult myopic subjects (mean age, 28 ± 7 years) were fitted with OK lenses in both eyes. Central and peripheral refraction and corneal topography measurements were taken before and after 14 nights of OK. All measurements were taken with no correction or OK lens in place. Results At baseline before OK, peripheral spherical equivalent refraction (M) across the horizontal meridian did not vary significantly from center. M across the vertical meridian was more myopic than the center (p < 0.05). After OK, there was a significant hyperopic shift in M (p < 0.001); both meridians now experienced myopic peripheral refraction. At baseline, J180 across the horizontal meridian was more negative than the center, and along the vertical meridian, it was more positive than the center (all p < 0.05). At baseline, J45 was more positive than center with increased eccentricity in the temporal and inferior retina and more negative than center with increased eccentricity in the nasal and superior retina. Orthokeratology caused greater rate of change of peripheral J180 across both retinal meridians (p < 0.001). Furthermore, compared with baseline, J45 became more positive in the nasal and superior retina and more negative in the temporal and inferior retina (all p < 0.05). Conclusions Orthokeratology lenses induced significant changes in peripheral refraction along the horizontal and vertical meridians. As peripheral myopia was measured at baseline along the vertical meridian, the results of our study suggest that inducing greater degrees of myopic defocus on to the peripheral retina, more than habitually experienced, may be required for effective myopia control. Further investigation into the critical threshold of retinal area receiving myopic defocus and the impact of duration of exposure is necessary to improve the efficacy of current myopia control treatments.
Mycophenolate mofetil in renal transplantation: 3-year results from the placebo-controlled trial. European Mycophenolate Mofetil Cooperative Study Group.

BACKGROUND The European double-blind, placebo(PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acute rejection/treatment failure at 6 months. Our study presents 3-year data for patient and graft survival, and safety in the MMF-treated patients. METHODS The trial included 491 patients who were randomly assigned to receive PLA (n=166), MMF 2g (n=165), or MMF 3 g (n=160). Patients in the PLA group discontinued taking their PLA medication at 1 year posttransplantation; subsequently, they were followed-up only regarding patient and graft survival and the occurrence of malignancies. RESULTS The 3-year patient survival was 88.9, 92.7, and 91.8% in the PLA, MMF 2 g, and MMF 3 g groups, respectively. The 3-year graft survival (including death as a cause of graft loss) was 78, 84.8, and 81.2%, respectively. Acute allograft rejection was a principal cause of graft loss in all groups (PLA, 10.8%; MMF 2 g, 4.6%; MMF 3 g, 6.3%). Differences in 3-year graft loss rates (excluding death) and 95% confidence intervals for intent-to-treat comparisons of PLA versus MMF 2 g and 3 g, respectively, were 7.3% (1.1, 14.2) and 3.2% (-3.8, 10.1). This leads to a relative risk of graft loss of 0.55 in the MMF 2 g arm compared with the PLA arm. Acute allograft rejection had a major impact on graft loss at 3 years; 31.5% of patients with biopsy-proven acute rejection within 6 months of transplantation lost their graft by the end of 3 years. In contrast, only 6.6% who had no early acute rejection lost their graft by the end of the 3-year study period. Diarrhea, anemia, and leukopenia were the most common clinically relevant adverse events, occurring predominantly in the MMF 3 g group. Only one patient (MMF 3 g) developed cytomegalovirus tissue-invasive disease after the first year posttransplant. Over the 3-year posttransplant period, 12 patients developed malignancies (5 in the PLA group, 3 in the MMF 2 g group, and 4 in the MMF 3 g group). CONCLUSIONS At 3 years posttransplantation, MMF was associated with 7.6% reduction in the incidence of graft loss (excluding death). These data indicate that MMF treatment not only results in a reduction of the incidence of acute rejections but also leads to reduction of late allograft loss.
The Characteristics and Trends of Socioeconomic Metabolism in China

China has become the country with the largest resource use and has high levels of waste emissions that pose a great management challenge. To provide more details about environmental problems and to find effective solutions, this article analyzed the scale, structure, and trend of the socioeconomic metabolism in China during the period 1992–2014 based on economy‐wide material flow accounts (EW‐MFA), and predicted resource use during the period of the 13th Five‐Year Plan. The results of this study show that the scale of China's socioeconomic metabolism in China increased more than twofold, during 1992–2014. However, after 2011, with the economic slowdown, the growth rates of total material requirement (TMR), direct material input (DMI), and domestic processed output (DPO) began to decrease. China may reach an inflection point, but this point will probably not be approached before the year 2020. Material recycling (MR) has played an important role in improving resource productivity, improving it by 92.52 renminbi per tonne in 2014. Metallic minerals and fossil fuels are the main sources of hidden flow. Carbon dioxide (CO2) emissions, construction waste, and agricultural emissions have become the major sources of DPO. Because of the 13th Five‐Year Plan, China may slow the growth rate of DMI and may save 10.26 gigatonnes of resources during 2015–2020. Resource productivity is predicted to increase by 15.91%. Imports and MR may play more important roles. These suggestions are made: (1) strengthening the recycling system; (2) stronger policies, especially in metallic mineral and fossil fuels; (3) developing management systems for CO2 emissions, construction waste, and agricultural emissions; and (4) adjusting China's economic structure.
Reduced numbers of dendritic cells with a tolerogenic phenotype in the prediabetic pancreas of NOD mice

The NOD mouse is a widely used animal model of autoimmune diabetes. Prior to the onset of lymphocytic insulitis, DCs accumulate at the islet edges. Our recent work indicated that these DCs may derive from aberrantly proliferating local precursor cells. As CD8α+ DCs play a role in tolerance induction in steady‐state conditions, we hypothesized that the autoimmune phenotype might associate with deficiencies in CD8α+ DCs in the prediabetic NOD mouse pancreas. We studied CD8α+ DCs in the pancreas and pLNs of NOD and control mice, focusing on molecules associated with tolerance induction (CD103, Langerin, CLEC9A, CCR5). mRNA expression levels of tolerance‐modulating cytokines were studied in pancreatic CD8α+ DCs of NOD and control mice. In the NOD pancreas, the frequency of CD8α+CD103+Langerin+ cells was reduced significantly compared with control mice. NOD pancreatic CD8α+CD103+Langerin+ DCs expressed reduced levels of CCR5, CLEC9A, and IL‐10 as compared with control DCs. These alterations in the CD8α+CD103+Langerin+ DC population were not present in pLNs. We demonstrate local abnormalities in the CD8α+ DC population in the prediabetic NOD pancreas. These data suggest that abnormal differentiation of pancreatic DCs contributes to loss of tolerance, hallmarking the development of autoimmune diabetes.
Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance

Objectives: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. Design: A secondary analysis of prospective clinical trial data. Methods: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. Results: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. Conclusion: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.
Property Portfolio Composition and Earnings Management for Listed Property Portfolios

In this paper, we investigate how real estate portfolio composition impacts earnings management (EM) of New Zealand listed property portfolios (NZ-LPPs). We employ a panel dataset containing accounting and property data for NZ-LPPs. The findings include: (1) the office property ratio of the real estate portfolio provides the highest incentive for LPPs to engage in EM; (2) LPPs with a higher ratio of industry are less likely to use accrual EM and real EM approaches based on property transactions; and (3) LPPs with a hospital focus prefer accrual EM, while LPPs with a retail focus prefer long-term accrual EM and sales manipulation.
Import Protections in China’s Grain Markets: An Empirical Assessment

In 2016, the United States launched a trade dispute against China at the World Trade Organization over its tariff quota administration for imports of three grain commodities: maize, rice and wheat. To inform policymakers and stakeholders involved in this dispute, this article quantifies the effects of the tariff quota administration on China’s grain imports from its major trading partners. We estimate the import demand elasticities using a source differentiated model and the monthly trade data during 2013-2017, while accounting for tariff and expenditure endogeneities. We then perform counterfactual analysis and find that China’s grain imports could have been 1.2 billion dollars or 38% higher than observed in 2017. The imports from the United States, especially of wheat, would have also significantly increased. We also find that the tariff quota administration acts as an import variable levy in China’s rice and wheat markets, and it seems to be an adjunct to the domestic price support policy that aims to keep domestic prices high.
The Spread of its Message: Studying the Prominence of al-Qaida Materials in UK Terrorism Investigations

Al-Qaida emphasises its ability to communicate its core message to those who might be sympathetic towards the group and its aims. Yet we have little sense of how this relationship, between al-Qaida as messenger, and potential sympathisers as message recipients, unfolds, especially in the West. To shed light on this question, this article analyses evidential materials from police counterterrorism investigations in the UK, exploring the way and extent to which al-Qaida-related materials have featured. The analysis identifies al-Qaida as one of the more prominent groups responsible for content found in these investigations but emphasises the overall heterogeneity of the extremist Islamist media content that has been discovered. The analysis also illustrates the importance of English-language content for this particular audience and the ability of prominent ideologies, especially Anwar al-Awlaki, to retain popularity and influence beyond his grave.
Nitric Oxide Acts in Conjunction with Proinflammatory Cytokines to Promote Cell Death in Osteoblasts

Proinflammatory cytokines such as tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), and interleukin‐1β are known modulators of bone remodeling in vitro and in vivo. The same cytokines induce the production of nitric oxide (NO) in various cell types, including osteoblasts and osteoclasts, and NO has recently been implicated in the regulation of bone resorption. We investigated the relationship between NO levels and cell viability in MC3T3‐E1, a well‐characterized osteoblastic cell line. NO donors at high concentrations (≥0.5 mM) produce a significant cytotoxic effect over a 48 h period. Various combinations of the three cytokines strongly promote endogenous NO production, and high NO levels are correlated with the loss of cell viability. Although TNF‐α produces NO‐independent cytotoxicity, NO greatly enhances this cytotoxic effect. Human and mouse TNF‐α differ in their cytotoxic effects, and human TNF‐α induces lower levels of NO production. In cocultures of RAW 264.7 mouse macrophages stimulated with lipopolysaccharide and IFN‐γ, and untreated MC3T3‐E1 osteoblasts, addition of anti–TNF‐α antibody and inhibition of NO synthesis have additive, protective effects on osteoblast viability. NO cytotoxicity involves an apoptotic mechanism. Our results underline the importance of NO and TNF‐α as cytotoxic mediators in the osseous microenvironment and might explain the observed deficiency of bone formation in inflammatory sites.