Miracle-dz/UniFAR-FTUs huggingface dataset:
Toll-Like Receptor 4 Is Essential in the Development of Abdominal Aortic Aneurysm

Toll-like receptor (TLR) family plays a key role in innate immunity and various inflammatory responses. TLR4, one of the well-characterized pattern-recognition receptors, can be activated by endogenous damage-associated molecular pattern molecules such as high mobility group box 1 (HMGB1) to sustain sterile inflammation. Evidence suggested that blockade of TLR4 signaling may confer protection against abdominal aortic aneurysm (AAA). Herein we aimed to obtain further insight into the mechanism by which TLR4 might promote aneurysm formation. Characterization of the CaCl2-induced AAA model in mice revealed that upregulation of TLR4 expression, localized predominantly to vascular smooth muscle cells (VSMCs), was followed by a late decline during a 28-day period of AAA development. In vitro, TLR4 expression was increased in VSMCs treated with HMGB1. Knockdown of TLR4 by siRNA attenuated HMGB1-enhanced production of proinflammatory cytokines, specifically interleukin-6 and monocyte chemoattractant protein-1 (MCP-1), and matrix-degrading matrix metalloproteinase (MMP)-2 from VSMCs. In vivo, two different strains of TLR4-deficient (C57BL/10ScNJ and C3H/HeJ) mice were resistant to CaCl2-induced AAA formation compared to their respective controls (C57BL/10ScSnJ and C3H/HeN). Knockout of TLR4 reduced interleukin-6 and MCP-1 levels and HMGB1 expression, attenuated macrophage accumulation, and eventually suppressed MMP production, elastin destruction and VSMC loss. Finally, human AAA exhibited higher TLR4 expression that was localized to VSMCs. These data suggest that TLR4 signaling contributes to AAA formation by promoting a proinflammatory status of VSMCs and by inducing proteinase release from VSMCs during aneurysm initiation and development.
Interleukin 10 suppresses experimental chronic, granulomatous inflammation induced by bacterial cell wall polymers.

BACKGROUND AND AIMS: Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions. This study examined the effect of systemically administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis, and arthritis in a rat model. METHODS: Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection, rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days. RESULTS: IL10 attenuated acute enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were more profound in the chronic granulomatous phase with decreased enterocolitis and markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes were downregulated in IL10 treated animals. CONCLUSIONS: These results indicate that exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new therapeutic approach in human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.
Numerical Analysis of the Performances of Bonded Composite Repair with Adhesive Band in Pipeline API X65

The technique of adhesively bonded composite patch repair has been successfully applied in pipeline of API X65 components repair and has recently been expanded to commercial pipeline industry. In the present paper, the crack growth behavior of cracked pipeline API X65 repaired with bonded composite patch was investigated. The ﬁnite element approach was applied in order to analyses the circumferential crack’s behavior repaired by a carbon-epoxy composite patch. The effects of the properties of the patch on the evolution of the stress intensity factor, according of angle crack tip, were discussed. The adhesive properties were optimized to increase the performance of the repair of structures by such reinforcement. Moreover, a relatively new method was developed to stop the external corrosion and the structurally reinforce steel pipes by external wrapping of damaged sections, using ﬁbre reinforced polymer (FRP) materials. The results indicated that the defect width around the circumference had little impact on the ultimate rupture pressure of the repaired vessel. On the other hand, it was found that the defect width around the circumference was affected by the stress state in the underlying pipe substrate.
Monitoring of disseminated tumor cells in bone marrow in high‐risk breast cancer patients treated with high‐dose chemotherapy

The present study aimed to investigate the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients before and after high‐dose adjuvant chemotherapy with or without progenitor stem‐cell support. One hundred and eighteen high‐risk stage II breast cancer patients entering the Scandinavian Study Group multicenter trial were randomized to 9 cycles of tailored and dose‐escalated FEC (5‐flurouracil, epirubicin, cyclophosphamide) or 3 cycles of standard FEC followed by high‐dose chemotherapy. Bone marrow (BM) samples at diagnosis and 6 months after completion of chemotherapy were assessed for the presence of cytokeratin positive (CK+) cells. Before treatment, 29% of the patients were CK+ (21% in the dose‐escalated group and 36% in the high‐dose‐group). Six months after treatment, 17% of the patients were CK+ (17 and 16% respectively). Of the 95 patients who were evaluated 6 months after treatment, 60% were consistently CK−. CK+ cells in BM was evaluated as a prognostic and predictive marker and compared to other defined prognostic factors of the primary tumor. Monitoring BM changes at the time of diagnosis and 6 months posttreatment is an independent predictive factor for breast‐cancer‐specific survival (BCS) (p = 0.001). Those who have consistent CK negative (−) BM findings constitute a group of patients with good prognosis. Our results suggest that changes in CK+ cells in BM before and after chemotherapy can be used clinically as a surrogate maker to predict outcome in breast cancer patients. © 2005 Wiley‐Liss, Inc.
Evaluating a 4‐marker signature of aggressive prostate cancer using time‐dependent AUC

We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time‐dependent measures of AUC and predictive values for discriminating lethal from non‐lethal prostate cancer.
TLR3 contributes to persistent autophagy and heart failure in mice after myocardial infarction

Toll‐like receptors (TLRs) are essential immunoreceptors involved in host defence against invading microbes. Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart. This study examined this question. The activation of TLR3 in cultured cardiomyocytes was observed to increase protein levels of autophagic components, including LC3‐II, a specific marker for autophagy induction, and p62/SQSTM1, an autophagy receptor normally degraded in the final step of autophagy. The results of transfection with a tandem mRFP‐GFP‐LC3 adenovirus and use of an autophagic flux inhibitor chloroquine both suggested that TLR3 in cardiomyocytes promotes autophagy induction without affecting autophagic flux. Gene‐knockdown experiments showed that the TRIF‐dependent pathway mediated the autophagic effect of TLR3. In the mouse model of chronic myocardial infarction, persistent autophagy was observed, concomitant with up‐regulated TLR3 expression and increased TLR3‐Trif signalling. Germline knockout (KO) of TLR3 inhibited autophagy, reduced infarct size, attenuated heart failure and improved survival. These protective effects were abolished by in vivo administration of an autophagy inducer rapamycin. Similar to the results obtained in cultured cardiomyocytes, TLR3‐KO did not prevent autophagic flux in mouse heart. Additionally, this study failed to detect the involvement of inflammation in TLR3‐KO‐derived protection, as wild‐type and TLR3‐KO hearts were comparable in inflammatory activity. It is concluded that up‐regulated TLR3 expression and signalling contributes to persistent autophagy following MI, which promotes heart failure and lethality.
Free and Total Plasma Levels of Lopinavir during Pregnancy, at Delivery and Postpartum: Implications for Dosage Adjustments in Pregnant Women

Background Physiological changes associated with pregnancy may alter antiretroviral plasma concentrations and might jeopardize prevention of mother-to-child HIV transmission. Lopinavir is one of the protease inhibitors more frequently prescribed during pregnancy in Europe. We described the free and total pharmacokinetics of lopinavir in HIV-infected pregnant and non-pregnant women, and evaluated whether significant alterations in its disposition and protein binding warrant systematic dosage adjustment. Methods Plasma samples were collected at first, second and third trimester of pregnancy, at delivery, in umbilical cord and postpartum. Lopinavir free and total plasma concentrations were measured by HPLC-MS/MS. Bayesian calculations were used to extrapolate total concentrations to trough (Cmin). Results A total of 42 HIV-positive pregnant women and 37 non-pregnant women on lopinavir/ritonavir were included in the study. Compared to postpartum and control values, total lopinavir Cmin was decreased moderately (31–39%) during pregnancy, and free Cmin minimally, showing significant alteration only at delivery (-35%). However, total and free Cmin remained in all patients above the target concentrations for wild-type virus of 1,000 ng/ml, and above the unbound IC50WT of 0.64–0.77 ng/ml of lopinavir, respectively. Lopinavir free fractions remained higher during pregnancy compared to post-partum and controls, and were influenced by α-1-acid-glycoprotein and albumin decrease. Free cord-to-mother ratio (0.43) was 2.7-fold higher than total cord-to-mother ratio (0.16), suggesting higher fetal exposure. Conclusions The moderate decrease of total lopinavir concentrations during pregnancy is not associated with proportional decrease in free concentrations. Both reach a nadir at delivery, albeit not to an extent that would put treatment-naive women at risk of insufficient exposure to the free, pharmacologically active concentrations of lopinavir. No dosage adjustment is therefore needed during pregnancy as it is unlikely to further enhance treatment efficacy but could potentially increase the risk of maternal and fetal toxicity. Nonetheless, in case of viral resistance in treatment-experienced pregnant women, loss of virological control or questionable adherence, it is justified to consider lopinavir dosage adjustment based on total plasma concentration measurement.
Investment Shocks and Business Cycles

Shocks to the marginal efficiency of investment are the most important drivers of business cycle fluctuations in U.S. output and hours. Moreover, like a textbook demand shock, these disturbances drive prices higher in expansions. We reach these conclusions by estimating a dynamic stochastic general equilibrium (DSGE) model with several shocks and frictions. We also find that neutral technology shocks are not negligible, but their share in the variance of output is only around 25 percent and even lower for hours. Labor supply shocks explain a large fraction of the variation of hours at very low frequencies, but not over the business cycle. Finally, we show that imperfect competition and, to a lesser extent, technological frictions are the key to the transmission of investment shocks in the model.
Twenty-four-hour blood pressure among Greenlanders and Danes: relationship to diet and lifestyle

Background : Greenlanders have a lower rate of cardiovascular mortality and morbidity than Danes, possibly due to lower blood pressure. However, 24-h blood pressure has never been measured in Greenlanders. The aim of this study was to compare the 24-h blood pressure of Greenlanders and Danes, and to analyse the influence of Arctic food and lifestyle on blood pressure. Methods : Four groups of healthy subjects were recruited for the study. Group I: Danes in Denmark consuming European food; group II: Greenlanders in Denmark consuming European food; group III: Greenlanders in Greenland consuming mainly European food; and group IV: Greenlanders in Greenland consuming mainly traditional Greenlandic food. All subjects underwent a physical examination, laboratory screening of blood and urine samples, and completed a questionnaire on diet, physical activity, smoking status, intake of alcohol, liquorices, vitamins and minerals. Twenty-four-hour blood pressure was measured. Results : It was found that 24-h diastolic blood pressure was lower in Greenlanders than in Danes for the whole 24-h period and during both day and night-time, whereas systolic blood pressure was the same (mean 24-h blood pressure with 95% CI: Danes 123/75 mmHg (120/73 - 127/77), Greenlanders 122/69 (119/68 - 124/70)). Among Greenlanders, blood pressure increased with age and male gender, and systolic blood pressure increased with body mass index (BMI). No association with diet was found. The difference between the two populations persisted after controlling for age, gender, BMI, outdoor temperature, and lifestyle factors. Conclusion : Greenlanders have a lower 24-h diastolic blood pressure than Danes, and it is suggested that genetic factors are mainly responsible for the lower blood pressure level among Greenlanders.
Investigation of a Class-J Power Amplifier With a Nonlinear $C_{\rm out}$  for Optimized Operation

This paper presents the operation principle of Class-J power amplifiers (PAs) with linear and nonlinear output capacitors (Couts). The efficiency of a Class-J amplifier is enhanced by the nonlinear capacitance because of the harmonic generation from the nonlinear Cout, especially the second-harmonic voltage component. This harmonic voltage allows the reduction of the phase difference between the fundamental voltage and current components from 45° to less than 45° while maintaining a half-sinusoidal shape. Therefore, a Class-J amplifier with the nonlinear Cout can deliver larger output power and higher efficiency than with a linear Cout. As a further optimized structure of the Class-J amplifier, the saturated PA, a recently-reported amplifier in our group, is presented. The phase difference of the proposed PA is zero. Like the Class-J amplifier, the PA uses a nonlinear Cout to shape the voltage waveform with a purely resistive fundamental load impedance at the current source, which enhances the output power and efficiency. The PA is favorably compared to the Class-J amplifier in terms of the waveform, load impedance, output power, and efficiency. These operations are described using both the ideal and real models of the transistor in Agilent Advanced Design System. A highly efficient amplifier based on the saturated PA is designed by using a Cree GaN HEMT CGH40010 device at 2.14 GHz. It provides a power-added efficiency of 77.3% at a saturated power of 40.6 dBm (11.5 W).
Clinical characteristics and outcomes of acute coronary syndrome patients with intra-aortic balloon pump inserted in intensive cardiac care unit of a tertiary clinic.

OBJECTIVE An intra-aortic balloon pump (IABP) is a mechanical support device that is used in addition to pharmacological treatment of the failing heart in intensive cardiac care unit (ICCU) patients. In the literature, there are limited data regarding the clinical characteristics and in-hospital outcomes of acute coronary syndrome patients in Turkey who had an IABP inserted during their ICCU stay. This study is an analysis of the clinical characteristics and outcomes of these acute coronary syndrome patients. METHODS The data of patients who were admitted to the ICCU between September 2014 and March 2017 were analyzed retrospectively. The data were retrieved from the ICCU electronic database of the clinic. A total of 142 patients treated with IABP were evaluated in the study. All of the patients were in cardiogenic shock following percutaneous coronary intervention, at the time of IABP insertion. RESULTS The mean age of the patients was 63.0±9.7 years and 66.2% were male. In-hospital mortality rate of the study population was 54.9%. The patients were divided into 2 groups, consisting of survivors and non-survivors of their hospitalization period. Multivariate analysis after adjustment for the parameters in univariate analysis revealed that ejection fraction, Thrombolysis in Myocardial Infarction flow score of ≤2 after the intervention, chronic renal failure, and serum lactate and glucose levels were independent predictors of in-hospital mortality. CONCLUSION The mortality rate remains high despite IABP support in patients with acute coronary syndrome. Patients who are identified as having a greater risk of mortality according to admission parameters should be further treated with other mechanical circulatory support devices.
A Time-Triggered Network-on-Chip

In this paper we propose a time-triggered network-on-chip (NoC) for on-chip real-time systems. The NoC provides time predictable on-and off-chip communication, a mandatory feature for dependable real-time systems. A regular structured NoC with a pseudo-static communication schedule allows for a high bandwidth. In this paper we argue for a simple, time-triggered NoC structure to achieve maximum bandwidth. We have implemented the proposed TT-NoC in a low-cost FPGA. The base bandwidth is 29 Gbit/s and the peak bandwidth 230 Gbit/s for eight nodes. The idea is in line with current on-chip multiprocessor designs, such as the cell processor. The simple design of the network and the network interlace easiest certification of the proposed NoC for safety critical applications.
Anti-CD48 Monoclonal Antibody Attenuates Experimental Autoimmune Encephalomyelitis by Limiting the Number of Pathogenic CD4+ T Cells

CD48 (SLAMF2) is an adhesion and costimulatory molecule constitutively expressed on hematopoietic cells. Polymorphisms in CD48 have been linked to susceptibility to multiple sclerosis (MS), and altered expression of the structurally related protein CD58 (LFA-3) is associated with disease remission in MS. We examined CD48 expression and function in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that a subpopulation of CD4+ T cells highly upregulated CD48 expression during EAE and were enriched for pathogenic CD4+ T cells. These CD48++CD4+ T cells were predominantly CD44+ and Ki67+, included producers of IL-17A, GM-CSF, and IFN-γ, and were most of the CD4+ T cells in the CNS. Administration of anti-CD48 mAb during EAE attenuated clinical disease, limited accumulation of lymphocytes in the CNS, and reduced the number of pathogenic cytokine-secreting CD4+ T cells in the spleen at early time points. These therapeutic effects required CD48 expression on CD4+ T cells but not on APCs. Additionally, the effects of anti-CD48 were partially dependent on FcγRs, as anti-CD48 did not ameliorate EAE or reduce the number of cytokine-producing effector CD4+ T cells in Fcεr1γ−/− mice or in wild-type mice receiving anti-CD16/CD32 mAb. Our data suggest that anti-CD48 mAb exerts its therapeutic effects by both limiting CD4+ T cell proliferation and preferentially eliminating pathogenic CD48++CD4+ T cells during EAE. Our findings indicate that high CD48 expression is a feature of pathogenic CD4+ T cells during EAE and point to CD48 as a potential target for immunotherapy.
Recent Advances in Understanding the Effects of Climate Change on Coral Reefs

Climate change is one of the greatest threats to the persistence of coral reefs. Sustained and ongoing increases in ocean temperatures and acidification are altering the structure and function of reefs globally. Here, we summarise recent advances in our understanding of the effects of climate change on scleractinian corals and reef fish. Although there is considerable among-species variability in responses to increasing temperature and seawater chemistry, changing temperature regimes are likely to have the greatest influence on the structure of coral and fish assemblages, at least over short–medium timeframes. Recent evidence of increases in coral bleaching thresholds, local genetic adaptation and inheritance of heat tolerance suggest that coral populations may have some capacity to respond to warming, although the extent to which these changes can keep pace with changing environmental conditions is unknown. For coral reef fishes, current evidence indicates increasing seawater temperature will be a major determinant of future assemblages, through both habitat degradation and direct effects on physiology and behaviour. The effects of climate change are, however, being compounded by a range of anthropogenic disturbances, which may undermine the capacity of coral reef organisms to acclimate and/or adapt to specific changes in environmental conditions.
Trusting Humans and Avatars: Behavioral and Neural Evidence

Over the past decade, information technology has dramatically changed the context in which economic transactions take place. Increasingly, transactions are computer-mediated, so that, relative to human- human interactions, human-computer interactions are gaining in relevance. Computer-mediated transactions, and in particular those related to the Internet, increase perceptions of uncertainty. Therefore, trust becomes a crucial factor in the reduction of these perceptions. To investigate this important construct, we studied individual trust behavior and the underlying brain mechanisms through a multi-round trust game. Participants acted in the role of an investor, playing against both humans and avatars. The behavioral results show that participants trusted avatars to a similar degree as they trusted humans. Participants also revealed similarity in learning an interaction partner's trustworthiness, independent of whether the partner was human or avatar. However, the neuroimaging findings revealed differential responses within the brain network that is associated with theory of mind (mentalizing) depending on the interaction partner. Based on these results, the major conclusion of our study is that, in a situation of a computer with human-like characteristics (avatar), trust behavior in human-computer interaction resembles that of human-human interaction. On a deeper neurobiological level, our study reveals that thinking about an interaction partner's trustworthiness activates the mentalizing network more strongly if the trustee is a human rather than an avatar. We discuss implications of these findings for future research.
Proteomics : Opportunities and Challenges

‘‘Proteomics’’, is the emerging technology leading to high-throughput identification and understanding of proteins. Proteomics is the protein equivalent of genomics and has captured the imagination of biomolecular scientists, worldwide. Because proteome reveals more accurately the dynamic state of a cell, tissue, or organism, much is expected from proteomics to indicate better disease markers for diagnosis and therapy monitoring. Proteomics is expected to play a major role in biomedical research, and it will have a significant impact on the development of diagnostics and therapeutics for cancer, heart ailments and infectious diseases, in future. Proteomics research leads to the identification of new protein markers for diagnostic purposes and novel molecular targets for drug