Miracle-dz/UniFAR-FTUs huggingface dataset:
The Adapter Protein LAT Enhances Fcγ Receptor-mediated Signal Transduction in Myeloid Cells*

FcγR clustering in monocytes initiates a cascade of signaling events that culminate in biological responses such as phagocytosis, production of inflammatory cytokines, and generation of reactive oxygen species. We have identified and determined the function of the adapter protein linker of activation of T cell (LAT) in FcγR-mediated signaling and function. Clustering of FcγRs on the human monocytic cell line, THP-1, induces phosphorylation of a major 36-kDa protein which immunoreacts with anti-LAT antisera. Our data indicate that although both the 36-kDa and 38-kDa isoforms of LAT are expressed in THP-1 and U937 human monocytic cells, FcγR clustering induces phosphorylation of the 36-kDa isoform only. Co-immunoprecipitation experiments revealed a constitutive association of p36 LAT with both FcγRI and FcγRIIa immunoprecipitates, and an activation-induced association of LAT with PLCγ1, Grb2, and the p85 subunit of phosphatidylinositol 3-kinase. Transient transfection experiments in COS-7 cells indicated that overexpression of a wild type but not a dominant-negative LAT, that is incapable of binding to p85, enhances phagocytosis by FcγRI. Furthermore, bone marrow-derived macrophages from LAT-deficient mice displayed reduced phagocytic efficiency in comparison to the macrophages from wild-type mice. Thus, we conclude that p36 LAT serves to enhance FcγR-induced signal transduction in myeloid cells.
The Additive Effects of Ischemic Postconditioning and Cyclosporine-A on Nitric Oxide Activity and Functions of Diabetic Myocardium Injured by Ischemia/Reperfusion

Background: The interaction of diabetes with cardioprotection by postconditioning in ischemia/reperfusion injury remains unclear. The aim of this study was to investigate the concomitant effects of ischemic postconditioning (IPostC) and cyclosporine-A (CsA) on nitric oxide (NO) content and parameters of cardiac function of the diabetic myocardium injured by ischemia/reperfusion. Methods: Diabetes was induced by single injection of streptozotocin (50 mg/kg; intraperitoneally [ip]) in Wistar rats (250-320 g) and the diabetic period was 8 weeks. The hearts (n = 96) were removed quickly, mounted on Langendorff apparatus, and then subjected to 30-minute regional ischemia followed by 45-minute reperfusion. Ischemic postconditioning was induced by 3 cycles of 30-second reperfusion/ischemia at the onset of reperfusion. Myocardial function was measured throughout the experiment, and infarct size (IS) was identified by triphenyltetrazolium chloride (TTC) staining. Total amounts of NO metabolites were determined using Griess method and enzyme-linked immunosorbent assay (ELISA) reader. Results: Administration of either IPostC or CsA alone in nondiabetic animals significantly improved myocardial function and reduced the ISs (28% ± 1.9% or 23% ± 2.0% vs 41% ± 2.9% of the risk zone [RZ], respectively; P < .01), but they had no effect on diabetic hearts (35% ± 1.8% or 32% ± 2.1% vs 39% ± 3.1%, respectively). In addition, myocardial NO level was significantly increased by IPostC only in nondiabetic animals (P < .01). However, after administration of CsA (5 minutes before and 10 minutes after the onset of reperfusion) in postconditioned animals, the cardioprotective and NO-enhancing effects of IPostC were restored in diabetic rats (IS: 21% ± 1.1% vs 39% ± 3.1%), similar to those in nondiabetic controls (19% ± 1.3% vs 41% ± 2.9%; P < .01). Conclusion: The present study indicated that IPostC or CsA failed to affect NO levels and failed to protect the diabetic myocardium against ischemia/reperfusion injury. Moreover, concomitant administration of CsA and IPostC at reperfusion can increase NO content and protect the diabetic myocardium.
Pulmonary vascular–bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

BACKGROUND Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics. OBJECTIVE To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause–effect relation of pulmonary vascular–bronchial interactions. DESIGN Prospective, cross sectional study. SETTING Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation. INTERVENTIONS Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis. MAIN OUTCOME MEASURES Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs). RESULTS 28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H2O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H2O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H2O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold. CONCLUSIONS Acute changes in pulmonary blood flow are associated with simultaneous changes in lung mechanics. While these changes are small they may represent a valid model to explain the pathophysiological impact of spontaneous changes in pulmonary blood flow in clinically more critical situations in children with congenital heart disease.
Fundamental clusters in spatial 2×2 games

The notion of fundamental clusters is introduced, serving as a rule of thumb to characterize the statistical properties of the complex behaviour of cellular automata such as spatial 2×2 games. They represent the smallest cluster size determining the fate of the entire system. Checking simple growth criteria allows us to decide whether the cluster–individuals, e.g. some mutant family, are capable of surviving and invading a resident population. In biology, spatial 2×2 games have a broad spectrum of applications ranging from the evolution of cooperation and intraspecies competition to disease spread. This methodological study allows simple classifications and long–term predictions in various biological and social models to be made. For minimal neighbourhood types, we show that the intuitive candidate, a 3×3 cluster, turns out to be fundamental with certain weak limitations for the Moore neighbourhood but not for the Von Neumann neighbourhood. However, in the latter case, 2×2 clusters generally serve as reliable indicators to whether a strategy survives. Stochasticity is added to investigate the effects of varying fractions of one strategy present at initialization time and to discuss the rich dynamic properties in greater detail. Finally, we derive Liapunov exponents for the system and show that chaos reigns in a small region where the two strategies coexist in dynamical equilibrium.
An experiment in using IMUNES and Conpot to emulate honeypot control networks

Honeypots are used as a security measure both to divert the attention of a potential attackers intentions and to reveal the attacker since the only reason someone would interact with honeypots is if they are looking for a vulnerable target. Honeypots emulate only a part of the machine they are supposed to represent and contain no valuable data. ICS (Industrial Control System) is a term that is used for a system that monitors industrial plants, distributed control systems or other systems that mostly contain PLCs (Programmable Logic Controllers). Conpot is an open source honeypot that emulates PLC devices so it can be used in ICSs. However, Conpot can not emulate complex honeypot networks. The aim of this project is to make a tool that can be used to design a honeypot network which emulates an ICS. A network designed with that tool will be simulated as a part of this project and the data collected during the simulation will be analyzed.
Prospect Theory and sentiment-driven fluctuations

Abstract In this paper we aim to present a novel channel through which the volatility of the monetary/financial sector affects the instability of the real macroeconomic variables originated by self-fulfilling market sentiments. To this aim, we insert some elements of Prospect Theory in the preferences of agents living in an overlapping generations economy where consumers’ heterogeneity and firms’ imperfect information on the level of aggregate demand allow market sentiments to affect the equilibrium path of the economy under rational expectations. In this environment, greater heterogeneity in the household’s narrow framing parameter and in the degree of competition in goods markets favor the emergence of self-fulfilling equilibria by exacerbating the coordination problem generated by a pair-wise matching process taking place in the labor market. Furthermore, the more dispersed are agents’ deviations from standard rationality the higher is the volatility of the economy due to sentiment fluctuations. Finally, a higher volatility of the money/financial market, by increasing the effect of Prospect Theory on households’ choices under risk, increases the noise of the signal upon which firms make their hiring decisions; this, in its turn, generates greater variability in market sentiments and hence in real economic activity.
Genetic inactivation of RelA/p65 sensitizes adult mouse hepatocytes to TNF-induced apoptosis in vivo and in vitro.

BACKGROUND & AIMS The transcription factor nuclear factor (NF)-kappaB plays a critical role in mediating survival of hepatocytes in response to tumor necrosis factor (TNF)-alpha during development because mice deficient for the NF-kappaB subunit RelA/p65 die in utero because of TNF-induced liver apoptosis. For the adult liver, conflicting concepts exist as to whether soluble TNF can trigger apoptosis when NF-kappaB activation is impaired. By creating a mouse model in which the transactivating NF-kappaB subunit RelA/p65 can be genetically inactivated in hepatocytes using the Cre/lox system, we sought to clarify the role of NF-kappaB in TNF-mediated hepatocyte apoptosis. METHODS Deletion of RelA/p65 in the liver was achieved using an inducible conditional knockout system (rela(F/F)MxCre mice) or, hepatocyte-specifically, using a developmental conditional knockout system (rela(F/F)AlbCre mice). RESULTS Disruption of RelA/p65 rendered mice sensitive to lethal liver injury upon TNF administration. Primary RelA/p65-deficient hepatocytes showed no NF-kappaB activation and undergo rapid apoptosis after TNF treatment. In contrast, hepatocytes deficient for I kappa B-kinase beta (IKK beta), displayed residual NF-kappaB activity and consecutively only mild apoptosis in response to TNF. TNF-induced apoptosis in RelA/p65-deficient hepatocytes was accompanied by prolonged activation of c-jun activating kinase (JNK) and rapid, largely proteasome-independent elimination of the long splice form of the antiapoptotic cellular FLICE inhibitor protein (c-FLIP(L)). Gene silencing of caspase-8, caspase-inhibitors, inhibition of JNK, or administration of antioxidants inhibited apoptosis and elimination of c-FLIP(L). CONCLUSIONS RelA/p65 is essential for TNF-induced NF-kappaB activation in adult hepatocytes. Genetic deletion of a functional RelA/p65 sensitizes these cells to apoptosis in response to soluble TNF in vivo and in vitro.
Occupational rhinosinusitis due to etoposide, an antineoplastic agent.

OBJECTIVE This paper reports a rare case of an occupational hypersensitivity reaction to an antineoplastic agent. METHODS This is a clinical case report of a 45-year-old nurse who developed throat irritation and chronic nasal congestion followed by sinusitis shortly after beginning work at an oncological out-patient clinic. The symptoms disappeared upon leaving the clinic two years later, but they returned when she resumed work at the oncology unit at Hillerød Hospital, Denmark, handling chemotherapy on a daily basis. We performed in vitro histamine release tests against nine suspected antineoplastic agents. RESULTS The patient's histamine release test against the antineoplastic agent etoposide was positive; the other test results were negative. The histamine release test against etoposide using passive sensitization was also negative. Upon leaving the oncology department, the symptoms of the nurse disappeared once again. She was given a diagnosis of rhinosinusitis. CONCLUSION This case of a hypersensitivity reaction to etoposide was judged to be of occupational origin. It was not clear whether it was immunoglobulin E (IgE) or non-IgE mediated.
Selective increase in monocyte p38 mitogen-activated protein kinase activity in metabolic syndrome

Objective: Metabolic syndrome is a common disorder that predisposes to both cardiovascular disease and diabetes. There is paucity of data on cellular signal transduction pathways in metabolic syndrome. This study determined monocyte mitogen-activated protein kinase activity in patients with metabolic syndrome. Research design and methods: The p38, extracellular signal-regulated kinase-1/2 and Jun N-terminal kinase–mitogen-activated protein kinase activities were assayed in isolated monocytes from patients with metabolic syndrome and controls (n = 36 per group) and correlated with features of metabolic syndrome, inflammation and oxidative stress biomarkers. Results: A significant increase in p38 mitogen-activated protein kinase activity was observed in metabolic syndrome even following adjustment for adiposity. There were no significant differences in extracellular signal-regulated kinase-1/2 and Jun N-terminal kinase activities. P38 mitogen-activated protein kinase activity correlated significantly with homeostasis model assessment–estimated insulin resistance and biomarkers of inflammation and oxidative stress. Conclusions: We are first to observe a selective increase in monocyte p38 mitogen-activated protein kinase activity in metabolic syndrome and suggest it as a pivotal molecular target for ameliorating insulin resistance and inflammation.
The Romanian Family Businesses Philosophy for Performance and Sustainability

Family businesses represent a large segment of private companies and contribute greatly to economic growth. In this context, the objectives of this paper are to identify the characteristics of Romanian family businesses, starting from their involvement and governance mechanisms, and also to investigate if these specific items allow them to act towards creating sustainable businesses. In order to achieve these objectives, we have used qualitative and quantitative research, consisting of two phases: (a) we have analyzed the reports regarding the Romanian family businesses, in order to identify their characteristics; and (b) we have empirically tested if the characteristics are correlated with company financial performance and social responsibility. The results show that Romanian family businesses are aware of the changes that may appear and that they have started to implement internal processes oriented towards sustainability. Also, the main family involvements in business were ownership, governance, management and succession, which have a correlation with the performance of their company.
Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice

Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice.
Genomic Diversification among Archival Strains of Salmonella enterica Serovar Typhimurium LT7

ABSTRACT To document genomic changes during long periods of storage, we analyzed Salmonella enterica serovar Typhimurium LT7, a mutator strain that was previously reported to have higher rates of mutations compared to other serovar Typhimurium strains such as LT2. Upon plating directly from sealed agar stabs that had been stocked at room temperature for up to four decades, many auxotrophic mutants derived from LT7 gave rise to colonies of different sizes. Restreaking from single colonies consistently yielded colonies of diverse sizes even when we repeated single-colony isolation nine times. Colonies from the first plating had diverse genomic changes among and even within individual vials, including translocations, inversions, duplications, and point mutations, which were detected by rare-cutting endonuclease analysis with pulsed-field gel electrophoresis. Interestingly, even though the colony size kept diversifying, all descendents of the same single colonies from the first plating had the same sets of detected genomic changes. We did not detect any colony size or genome structure diversification in serovar Typhimurium LT7 stocked at −70°C or in serovar Typhimurium LT2 stocked either at −70°C or at room temperature. These results suggest that, although colony size diversification occurred during rapid growth, all detected genomic changes took place during the storage at room temperature and were carried over to their descendents without further changes during rapid growth in rich medium. We constructed a genomic cleavage map on the LT7 strain that had been stocked at −70°C and located all of the detected genomic changes on the map. We speculated on the significance of mutators for survival and evolution under environmentally stressed conditions.
A Primer on Neo-Fisherian Economics

Conventional models imply that central banks aiming to raise inflation should lower nominal rates and thus stimulate aggregate demand. However, several economists have recently challenged this conventional wisdom in favour of an alternative “neo-Fisherian’’ view under which higher nominal rates might in fact lead to higher inflation. In this note, we show that a simple New Keynesian model can indeed deliver a neo-Fisherian link from higher nominal rates to higher inflation. However, the conditions under which this link emerges include a configuration of fiscal and monetary policy, which departs substantially from the configuration normally assumed in the New Keynesian literature. In particular, this configuration involves a commitment that the central bank will not respond too aggressively if inflation is off target, in the sense that policy will be set in a manner inconsistent with the Taylor principle. Active use of inflation to manage real government debt would also be needed. We identify significant challenges associated with both these conditions and argue that they militate against policies that aim to exploit the neo-Fisherian mechanism.
High‐risk HPV presence in cervical specimens after a large loop excision of the cervical transformation zone: Significance of newly detected hr‐HPV genotypes

Large loop excision of the cervical transformation zone (LLETZ) is a well‐established treatment for high‐grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high‐risk (hr‐) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr‐HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr‐HPV in 85 high‐grade squamous cervical LLETZ biopsies and in the first follow‐up smear was determined. In 80 (94%) of the LLETZ biopsies hr‐HPV was detected in contrast to 30 (35%) hr‐HPV positive follow‐up scrapes. Twenty of the 80 hr‐HPV positive women (25%) had the same hr‐HPV genotypes in their follow‐up cervical smears as was found in the corresponding biopsies. In the follow‐up smear of 13 women a new hr‐HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re‐activation of this virus from proximal layers of the cervical canal incised during surgery. J. Med. Virol. 79:314–319, 2007. © 2007 Wiley‐Liss, Inc.
Gender Differentiated Impacts of Commodity Price Shocks on Households’ Consumption Behavior: A Natural Experiment

Using information collected from more than 29,000 households by the Bangladesh Bureau of Statistics, the present study examines the gender-differentiated impacts of the commodity price hikes in 2008-09 on food and non-food consumption behavior based on the sex of the household head. Applying the difference-indifference estimation procedure in a natural experiment setting, this study demonstrates that, in general, commodity price hikes more adversely affected the female-headed households. In 2010, they were forced to reduce expenditures on food and non-food items, and particularly cereal, non-cereal, health and education expenditures, more than the male-headed households. However, this study clearly shows that the impacts of commodity price hikes were lower on the female-headed households headed by educated females and those who owned larger pieces of land, received remittances, and allocated labor to non-farm sectors. These sub-sets were not affected by the commodity price shocks in 2010 compared to 2000. The findings strongly suggest that the provision of both human and physical capital is instrumental in developing countries to empower female headed-households to withstand economic shocks.