Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Classic Signaling Is a Novel Function of Soluble Glycoprotein 130 (sgp130), Which Is Controlled by the Ratio of Interleukin 6 and Soluble Interleukin 6 Receptor*

Background: IL-6 trans-signaling plays a critical role in chronic inflammation and cancer. Results: The trans-signaling inhibitor sgp130(Fc) also inhibits classic signaling depending on IL-6/sIL-6R ratios. Conclusion: The additional function of sgp130(Fc) suggests that in vivo only low therapeutic concentrations guarantee blockade of trans-signaling but not classic signaling. Significance: The demonstration that the trans-signaling inhibitor can also inhibit classic signaling is central for the field of IL-6 biology. IL-6 trans-signaling via the soluble IL-6 receptor (sIL-6R) plays a critical role in chronic inflammation and cancer. Soluble gp130 (sgp130) specifically inhibits IL-6 trans-signaling but was described to not interfere with classic signaling via the membrane-bound IL-6R. Physiological and most pathophysiological conditions are characterized by a molar excess of serum sIL-6R over IL-6 characterized by free IL-6 and IL-6 found in IL-6·sIL-6R complexes allowing both classic and trans-signaling. Surprisingly, under these conditions, sgp130 was able to trap all free IL-6 molecules in IL-6·sIL-6R·sgp130 complexes, resulting in inhibition of classic signaling. Because a significant fraction of IL-6 molecules did not form complexes with sIL-6R, our results demonstrate that compared with the anti-IL-6R antibody tocilizumab or the anti-trans-signaling monoclonal antibody 25F10, much lower concentrations of the dimeric sgp130Fc were sufficient to block trans-signaling. In vivo, sgp130Fc blocked IL-6 signaling in the colon but not in liver and lung, indicating that the colon is a prominent target of IL-6 trans-signaling. Our results point to a so far unanticipated role of sgp130 in the blockade of classic signaling and indicate that in vivo only low therapeutic concentrations of sgp130Fc guarantee blockade of IL-6 trans-signaling without affecting IL-6 classic signaling.
The role of the yeast plasma membrane SPS nutrient sensor in the metabolic response to extracellular amino acids

In response to discrete environmental cues, Saccharomyces cerevisiae cells adjust patterns of gene expression and protein activity to optimize metabolism. Nutrient‐sensing systems situated in the plasma membrane (PM) of yeast have only recently been discovered. Ssy1p is one of three identified components of the Ssy1p–Ptr3p–Ssy5 (SPS) sensor of extracellular amino acids. SPS sensor‐initiated signals are known to modulate the expression of a number of amino acid and peptide transporter genes (i.e. AGP1, BAP2, BAP3, DIP5, GAP1, GNP1, TAT1, TAT2 and PTR2) and arginase (CAR1). To obtain a better understanding of how cells adjust metabolism in response to extracellular amino acids in the environment and to assess the consequences of loss of amino acid sensor function, we investigated the effects of leucine addition to wild‐type and ssy1 null mutant cells using genome‐wide transcription profile analysis. Our results indicate that the previously identified genes represent only a subset of the full spectrum of Ssy1p‐dependent genes. The expression of several genes encoding enzymes in amino acid biosynthetic pathways, including the branched‐chain, lysine and arginine, and the sulphur amino acid biosynthetic pathways, are modulated by Ssy1p. Additionally, the proper transcription of several nitrogen‐regulated genes, including NIL1 and DAL80, encoding well‐studied GATA transcription factors, is dependent upon Ssy1p. Finally, several genes were identified that require Ssy1p for wild‐type expression independently of amino acid addition. These findings demonstrate that yeast cells require the SPS amino acid sensor component, Ssy1p, to adjust diverse cellular metabolic processes properly.
Effect of pre‐immunization by killed Mycobacterium bovis and vaccae on immunoglobulin E response in ovalbumin‐sensitized newborn mice

A recently advanced hypothesis suggests that decreased exposure to T‐helper (Th) 1‐inducing agents cause Th2‐biased differentiation in response to concomitant allergens. We therefore examined the effect of pre‐immunization with killed Mycobacterium bovis and killed M. vaccae which are known to be very potent inducers of Th1 immune response, on serum IgE response in ovalbumin (OVA)‐sensitized newborn mice. Eighty‐four newborn Balb/c mice were divided into four groups and were immunized intraperitoneally 24 h after birth with 50 µl of 5 × 104 colony‐forming units (c.f.u.) of killed M. bovis in group I (M. bovis group, n = 19), with 25 µl of 2.5 × 108 c.f. u. of killed M. vaccae plus 25 µl of 5 × 104 c.f. u. of killed M. bovis in group II (M. vaccae+ M. bovis group, n = 28) and with 50 µl of only phosphate‐buffered saline (PBS) in group III (no mycobacterial immunization, n = 18). No injection was applied to mice in group IV (control group, n = 19). Starting from 8 weeks of age, all mice except the control group were sensitized with 0.5 ml of 20 mg/ml OVA administered intraperitoneally 7 times every other day. Thirty days after the final injection, all animals except those in the control group were challenged with an aerosol of 2 mg/ml OVA. Forty‐eight hours later, blood was collected from all mice for determination of serum IgE levels. A statistically significant difference was observed in the serum total IgE levels between groups III and IV (p = 0.0099), indicating that the mice were successfully sensitized with OVA. Serum total IgE values of the female mice in M. bovis group were found to be significantly lower than group III (p = 0.009), while no difference was observed in males. Serum total IgE levels of the M. vaccae+M. bovis group were found to be significantly lower than group III both in male and female mice (p < 0.0001 and p = 0.0001, respectively), showing even lower values in females in comparison with controls (p = 0.0092). Pre‐immunization in the newborn period with killed M. bovis alone or in addition to M. vaccae may potentially be helpful in down‐regulating an IgE response.
Short-term dietary salt supplementation blunts telmisartan induced increases in plasma renin activity in hypertensive patients with type 2 diabetes mellitus.

Current guidelines recommend low dietary salt intake (LDS) in patients with diabetes to reduce blood pressure (BP). However, low salt intake has been associated with higher mortality rates in people with diabetes. Our aim is to examine the effect of angiotensin II receptor blocker (ARB), telmisartan, with and without dietary sodium chloride (NaCl) supplementation, on BP [mean arterial pressure (MAP)], plasma renin activity (PRA), serum aldosterone level and estimated glomerular filtration rate (eGFR) in hypertensive patients with type 2 diabetes. In a randomized, double-blind, placebo-controlled study (RCT), 28 patients with type 2 diabetes, treated with telmisartan (40 mg daily), received 2 weeks of placebo or NaCl capsules (100 mmol/24 h). Following a 6-week washout, the protocol was repeated in reverse. Twenty-four-hour urinary sodium excretion (24hUNa), ambulatory BP (ABP) monitoring and blood tests were performed before and after each study phase. The telmisartan-associated increase in PRA was blunted by approximately 50% during salt supplementation compared with placebo; median PRA was 2.3 μg/l/h with placebo compared with 1.7 μg/l/h with salt (P<0.001). A trend towards blunting of ARB induced increases in serum aldosterone was also demonstrated. Salt supplementation significantly reduced the MAP lowering effects of telmisartan (P<0.05). The present study demonstrates that salt supplementation blunts the telmisartan induced increase in PRA in patients with type 2 diabetes.
Risk factors of heart failure for patients classification with extreme learning machine

Heart failure (HF), the terminal stage of all kinds of cardiovascular disease, has a high level of morbidity and mortality. But the heavy burden of curing and managing HF can be largely reduced by early detection of it. Motivated by this problem, we study methods to determine its risk factors based on extreme learning machine (ELM). Several state-of-the-art data mining algorithms are employed to estimate the performance of various classification of the HF patients. Our data sets are extracted from reality hospital patients' data, which consist of patients' basic demographic, disease and assay information. The results show that ELM will have a better performance larger than 93% if the selected attributes have more strong correlation with the label.
The Deferral of Attacks: SP/A Theory as a Model of Terrorist Choice when Losses Are Inevitable

Abstract When a terrorist group’s aspirations far exceed the outcomes that can be expected to result from any of the available attack methods, an outcome below the terrorist group’s aspiration level is inevitable. A primary prediction of SP/A theory when applied to the study of terrorist behaviour is that when losses are inevitable the terrorist group will be risk averse and inclined to defer further action until expected outcomes improve, new attack method innovations are developed or the memory of the event that shaped aspirations has faded sufficiently that the aspiration level can be ‘reset’. This complements existing predictions of loss aversion and risk seeking behaviour over the domain of avoidable losses and provides a starting point for developing explanations for patterns of behaviour that are observed in the terrorism context, including pauses in violence, even during brutality contests, and time-lags between terrorist attacks.
Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer.

AIM To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS In 86 patients with suspected chronic pancreatitis (age: 62+/-12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endoscopic B-mode, power Doppler ultrasound and contrast-enhanced power mode (Hitachi EUB 525, SonoVue, 2.4 mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue contrast-enhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology, operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue, regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue and detection of arterial and venous vessels. RESULTS The sensitivity and specificity of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3% in 28 of 30 patients with chronic inflammatory pancreatic disease. CONCLUSION Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.
Central serous chorioretinopathy

Central serous chorioretinopathy (CSC) is a disease of the retina characterized by serous detachment of the neurosensory retina secondary to one or more focal lesions of the retinal pigment epithelium (RPE). CSC occurs most frequently in mid‐life and more often in men than in women. Major symptoms are blurred vision, usually in one eye only and perceived typically by the patient as a dark spot in the centre of the visual field with associated micropsia and metamorphopsia. Normal vision often recurs spontaneously within a few months. The condition can be precipitated by psychosocial stress and hypercortisolism. Ophthalmoscopic signs of CSC range from mono‐ or paucifocal RPE lesions with prominent elevation of the neurosensory retina by clear fluid – typical of cases of recent onset – to shallow detachments overlying large patches of irregularly depigmented RPE. The spectrum of lesions includes RPE detachments. Granular or fibrinous material may accumulate in the subretinal cavity. Serous detachment often resolves spontaneously. From first contact, counselling about the potential relation to stress and glucocorticoid medication is warranted. After 3 months without resolution of acute CSC or in chronic CSC, treatment should be considered. Resolution of detachment can usually be achieved in acute CSC by focal photocoagulation of leaking RPE lesions or, in chronic CSC, by photodynamic therapy. The effect of therapy on long‐term visual outcome is insufficiently documented. Reattachment within 4 months of onset is considered a relevant therapeutic target because prolonged detachment is associated with photoreceptor atrophy. This suggests that the value of treatment depends upon proper selection of cases that will not resolve without therapy. Chronic CSC may be difficult to differentiate from occult choroidal neovascularization secondary to CSC. Patients with chronic CSC who receive glucocorticoid treatment for systemic disease can often be managed without having to discontinue this medication.
Failure of peripheral arterial thrombolysis due to elevated plasminogen activator inhibitor type 1

To reduce the risk of intracerebral hemorrhage during thrombolytic therapy, a lower dose of tissue plasminogen activator (t-PA) or urokinase is used for acute peripheral arterial thrombi versus coronary thrombi. We hypothesized that elevated plasminogen activator inhibitor-1 (PAI-1) activity could neutralize infused t-PA or urokinase, resulting in lysis failure. Active PAI-1, active t-PA and total t-PA antigen were measured in 20 patients receiving t-PA, and active PAI-1 was measured in four patients receiving urokinase for acute peripheral arterial thrombosis. The 18 patients that successfully lysed their thrombi all had low active PAI-1 levels (10 ± 19 pmol/l) during infusion of thrombolytic therapy, while six patients that failed to lyse their thrombi had high active PAI-1 levels (1533 ± 1384 pmol/l, P = 0.00007) during infusion. Active t-PA levels during t-PA infusion were higher in the group that lysed their thrombi (536 ± 423 pmol/l versus 42 ± 45 pmol/l, P = 0.04) even though total t-PA levels were lower (1240 ± 493 pmol/l versus 1956 ± 709 pmol/l, P = 0.03). In the patients that failed to lysed their thrombi, > 95% of infused t-PA was neutralized by PAI-1. We conclude that elevated PAI-1 during acute peripheral arterial thrombolysis is associated with an increased risk of lysis failure due to reduced levels of circulating active t-PA or urokinase.
The Role of Local Communities in the Construction of the European Territory: Evidence from Romania

European integration has notable impact on the territorial organization of Europe, especially after the adoption of the Treaty of Lisbon. Therefore, it became urgent to develop guidance and best practices in the fields of territorial cohesion, urban matters and spatial planning, including with regard to local governments. Despite complicated relations in a multi-level governance setting, or because of this setting, local governments are an integral part of the construction of an European territory. The paper argues that territorial cohesion and spatial planning goals will not be achieved without a complementary focus on local communities as the engines of growth. It aims to clarify issues relating the local communities’ role in shaping and implementing European strategies and concludes with some recommendations on territorial perspectives and new goals and tools that should drive the European Union towards higher democratic integration.
Location determinant and MNE’s performance: A modeling test in the China’s automobile industry

ABSTRACT This paper argues that the location strategy is an important successful condition for multinational enterprise’s investment in China. We conduct a location–performance model for multinationals in China, which is tested using a structural equation modeling approach on a sample of 216 joint ventures of automobile multinational enterprises in China. We find that the relationship between the location determinant and multinational performance is significant and positive, and which is supported by the local partner’s performance.
Employee‐Owned Firms from a Stakeholder Perspective

This study focuses on the role of employee‐owned firms (EOFs) in value creation from a stakeholder perspective. EOFs have been defined as Social Economy enterprises in Spain following guiding principles that in our opinion should empower stakeholder governance. Therefore, the impact of employee share ownership on value creation for shareholders and stakeholders has been measured on the basis of a sample of 1006 enterprises. The results reveal that EOFs have a positive and significant influence on the distribution of value in favour of the employees but not the other stakeholders. This finding, which allows us to partially accept one of the proposed hypotheses, is consistent with previous evidence that EOFs set their objectives to maximize the value obtained by the participating employees through their financial participation in the business, and not, therefore, to maximize profits. Copyright © 2018 John Wiley & Sons, Ltd.
A CRITICAL ETHNOGRAPHY OF KOREAN CANADIAN WOMEN'S MENOPAUSE EXPERIENCE

Many Korean women living in North America interact with the health care system for a variety of reasons. Frequently, lack of understanding regarding cultural health practices results in misunderstandings and the provision of care that may be culturally inappropriate. The purpose of this critical ethnographic study is to examine how menopause is experienced by a sample of Korean-Canadian women. Data were collected through semistructured interviews with a purposive sample of 7 Korean women who have experienced menopause. Interviews were dialogic in nature and meaning was derived through collaboration with the participants. Findings revealed that the women viewed menopause as a natural process and they used facets of both Korean and Western health practices to manage menopause. Knowledge gained from this research has the potential to contribute to the provision of culturally relevant health care for Korean women during menopause.
Weight Gain in Infants Breastfed by Mothers Who Take Fluoxetine

Objective. Despite the manufacturer's recommendation that fluoxetine not be used by women while breastfeeding, many women choose to do so. There is little information available in the literature to suggest that this practice is or is not safe. The purpose of this study was to examine weight gain in infants who are breastfed by mothers who take fluoxetine, compared with weight gain in infants who are breastfed by mothers who do not take any psychotherapeutic medication. A secondary goal was to assess the frequency of reported side effects in infants who are breastfed by mothers who take fluoxetine. Methodology. A retrospective cohort study design was used. Subjects were identified from an ongoing pregnancy outcome study conducted through the California Teratogen Information Service and Clinical Research Program. A total of 64 women were interviewed who had taken fluoxetine during a pregnancy between the 1989 and 1997; 26 of these women breastfed their infants and continued to take the medication, and 38 breastfed their infants but did not take the medication. Postnatal weight gain was taken from pediatric records, and the frequency of side effects was measured by maternal response to the interview questionnaire. Results. Using linear regression analysis, the infants who were breastfed by mothers taking fluoxetine demonstrated a growth curve significantly below that of infants who were breastfed by mothers who did not take the drug. The average deficit in measurements taken between 2 weeks and 6 months of age was 392 g (95% confidence interval: −5, −780). Using a repeated measures analysis of covariance for those infants with more than one postnatal weight measurement available, the difference between the two groups was similar, ∼1.2 standard deviations (P = .005). In response to interview questions regarding side effects, no mother who breastfed her infant while taking fluoxetine reported any unusual symptoms that could be attributed to the medication. Conclusions. These data do not suggest that women who breastfeed while taking fluoxetine are likely to note unusual behavior in their infants that they consider related to use of the medication. However, although there was no excess of infants in the fluoxetine group with postnatal weight measurements >2 standard deviations below the mean, these data indicate that breastfeeding while taking fluoxetine is associated with reduced growth that may be of clinical importance in situations in which infant weight gain is already of concern.
Evolving Industrial Relations in Malta

Introduction It was in 1984 that Joseph Attard, then just retired from a long and distinguished career as a public servant in the Department of Labour, published his book Industrial Relations in Malta. He argued, correctly, that this book was the first of its kind in Malta, and in this way justified the absence of a bibliography. He was not in a position to know that his book would remain in splendid isolation for a good number of years, and has been long our of print. This volume is titled Evolving Indmtrial Relations in Malta to signal explicitly that it seeks to serve as that badly needed update to Attard's pioneering text, now sadly overtaken by events. It continues to build on the legacy of assessment and examination of labour law, traditions and practices that Attard inspired. However, it also attempts to looks gingerly ahead, interpreting the signs of the times in the light of current challenges and future prospects. Attard was shrewd to note, on the basis of his experience, that industrial relations in Malta are an amalgam of "something borrowed and something new". What has been borrowed includes the UK-bred practice oflabour-management relations, culminating in collective bargaining; more recently, it includes our first institutionalised attempts at 'social dialogue' and social partnership, this time inspired by continental Europe; and not to forget the social policy acqltis commlmalttaire of the European Union, by now fully transcribed into national legislation. Meanwhile, we have added our own special, 'new' ingredients into the industrial relations cauldron: local features include the paternalism and strong