Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased tenascin C and Toll-like receptor 4 levels in visceral adipose tissue as a link between inflammation and extracellular matrix remodeling in obesity.

CONTEXT Obesity is associated with an altered inflammatory and extracellular matrix (ECM) profile. Tenascin C (TNC) is an ECM glycoprotein with proinflammatory effects. OBJECTIVE We aimed to explore the expression levels of TNC in adipose tissue analyzing the contribution of adipocytes and stromovascular fraction cells (SVFC) as well as its impact on inflammation and ECM regulation. We also analyzed the effect of the stimulation with TNF-α and lipopolysaccharide (LPS) on both SVFC and adipocytes. PATIENTS AND METHODS Samples obtained from 75 subjects were used in the study. Expression levels of TNC, TLR4, MMP2, and MMP9 were analyzed in visceral adipose tissue (VAT) as well as in both adipocytes and SVFC. In addition, Tnc expression was measured in two mice models of obesity. RESULTS We show, for the first time, that VAT expression levels of TNC are increased in normoglycemic and type 2 diabetic obese patients (P<0.01) as well as in obese patients with nonalcoholic steatohepatitis (P<0.01). Furthermore, expression levels of Tnc in epididymal adipose tissue from two different mice models of obesity were significantly increased (P<0.01). TNC and TLR4 were mainly expressed by SVFC, and its expression was significantly enhanced (P<0.01) by TNF-α treatment. LPS treatment also increased mRNA levels of TNC. Moreover, the addition of exogenous TNC induced (P<0.05) TLR4 and CCL2 mRNA expression in human adipocyte cultures. CONCLUSIONS These findings indicate that TNC is involved in the etiopathology of obesity via visceral adipose tissue inflammation representing a link with ECM remodeling.
Origins of the Chinese Yak: Evidence from Maternal and Paternal Inheritance

It is well understood that the yak originates from China, but facts regarding origin time and evolutionary relationship with other species of Bovini, are largely disputed. Here, we have analyzed the phylogenetic relationship of eight representative species of Bovini, based on the Cytochrome b gene of mitochondrial DNA and TSPY gene of chromosome Y. We also estimated the divergence times of these different species. Results showed that the divergence time of domestic yak (Poephagus grunniens) and wild yak (Poephagus mutus) was 0.28 MYA. Considering archaeology evidence and historical records, we suggest that the domestic yak and today's wild yak shared one common ancestor, the primitive yak, 0.28 MYA. For the yak and American bison, the sequence divergence is the lowest (3.80, 0.50) and the divergence time is the latest (0.85 - 1.19 MYA), less than that between yak and cattle/zebu (8.30, 0.75 and 1.70 - 2.15 MYA). Phylogenetic analysis indicates that the yak and American bison were clustered together. Investigation of maternal inheritance (Cytochrome b) and paternal inheritance (TSPY) also proved that the genetic relationship between the yak and American bison was the closest, they evolved from one common ancestor, and their divergence time was later, during the metaphase of Pleistocene.
Role of mitochondria in non‐alcoholic fatty liver disease

Mitochondrial dysfunction is involved in the three stages of the transition from lack of exercise and excessive food intake to insulin resistance, diabetes and non‐alcoholic steatohepatitis (NASH). In muscle, lack of exercise, a fat‐rich diet, a polymorphism in peroxisome proliferator‐activated receptor γ coactivator‐1 (PGC‐1), and possibly age‐related mitochondrial DNA (mtDNA) mutations may variously combine their effects to decrease PGC‐1 expression, mitochondrial biogenesis and fat oxidation. Together with excessive food intake, insufficient fat oxidation causes fat accumulation and cellular stress in myocytes. The activation of Jun N‐terminal kinase and protein kinase C‐θ triggers the serine phosphorylation and inactivation of the insulin receptor substrate, and hampers the insulin‐mediated translocation of glucose transporter‐4 to the plasma membrane. Initially, the trend for increased blood glucose increases insulin secretion by pancreatic β‐cells. High plasma insulin levels compensate for insulin resistance in muscle and maintain normal blood glucose levels. Eventually, however, increased uncoupling protein‐2 expression and possibly acquired mtDNA mutations in pancreatic β‐cells can blunt glucose‐mediated adenosine triphosphate (ATP) formation and insulin secretion, to cause diabetes in some patients. High plasma glucose and/or insulin levels induce hepatic lipogenesis and cause hepatic steatosis. In fat‐engorged hepatocytes, several vicious cycles involving tumor necrosis factor‐α, reactive oxygen species (ROS), peroxynitrite, and lipid peroxidation products alter respiratory chain polypeptides and mtDNA, thus partially blocking the flow of electrons in the respiratory chain. The overreduction of upstream respiratory chain complexes increases mitochondrial ROS and peroxynitrite formation. Oxidative stress increases the release of lipid peroxidation products and cytokines, which together trigger the liver lesions of NASH.
POPX2 phosphatase regulates cell polarity and centrosome placement

Proper centrosome positioning is critical for many cellular functions, such as cell migration and maintenance of polarity. During wound healing, fibroblasts orient their centrosomes such that they face the wound edge. The centrosome orientation determines the direction of cells’ migration so that they can close the wound effectively. In this study, we investigated the regulation of centrosome polarization and have identified the phosphatase POPX2 as an important regulator of centrosome orientation. We found that POPX2 inhibits centrosome centration, but not rearward nuclear movement, by regulating multiple proteins that function in centrosome positioning. High POPX2 levels result in reduced motility of the kinesin-2 motor, which, in turn, inhibits the transport of N-cadherin to the cell periphery and cell junctions. Loss of N-cadherin localization to the cell membrane affects the localization of focal adhesions and perturbs CDC42-Par6/PKCζ signaling. In addition, overexpression of POPX2 also results in a loss of Par3 localization to the cell periphery and reduced levels of LIC2 (dynein light intermediate chain 2), leading to defects in microtubule tethering and dynamics at cell-cell contacts. Therefore, POPX2 functions as a regulator of signaling pathways to modulate the positioning of centrosome in fibroblast during wound healing.
Selective approach for transperitoneal and extraperitoneal endoscopic nephrectomy in children.

PURPOSE From the experience of a large combined series of transperitoneal (TP) and retroperitoneal (RP) endoscopic complete and partial nephroureterectomies in children, we present a logical selective endoscopic approach to benign renal pathology. MATERIALS AND METHODS During a 5-year period 122 complete nephrectomies and nephroureterectomies (bilateral 2, invisible ectopic 8) and 63 partial nephroureterectomies for duplex (52 upper, 8 lower) or singleton polar disease (xanthogranulomatous pyelonephritis 1, cyst 2) were performed. Of the partial nephrectomies, ureterectomy, bladder repair and lower moiety reimplantation were performed in 8. Patient age ranged from 2.7 months to 14 years (mean 2.9 years). Preoperative weight ranged from 2.7 to 98 kg (mean 12.3). The position of the renal remnant, the presence or absence of a refluxing ureter and the need for ureterectomy were the major determining factors affecting choice of endoscopic approach. RESULTS A total of 179 (96.7%) procedures were successfully completed endoscopically. The 6 open conversions (3.2%) occurred early in our experience. The operating time reflected the complexity of the excision and lower urinary reconstruction (lateral and posterior RP 25 to 145 minutes [mean 92]) TP with ureterocelectomy and bladder neck repair 105 to 355 minutes [mean 153]. Hospital stay for RP and simple TP was 1.5 days (mean 1 to 4) and for complicated TP 2 to 8 days (mean 3.5). CONCLUSIONS We suggest a posterior retroperitoneal approach with isolated renal excision without extended ureterectomy. The lateral retroperitoneal approach allows complete ureterectomy as well as better exposure to horseshoe and pelvic kidneys and, therefore, avoids exposure to intraperitoneal structures. Finally, the transperitoneal approach is recommended when complete moiety excision with lower urinary reconstruction is anticipated.
Are Investors Concerned by Annual Corporate Governance Reports? Some Evidence from the Spanish Stock Market

While prior research has generally shown a positive price reaction to voluntary declarations of compliance with codes of corporate governance, this is the first paper to examine how investors react to the release of mandatory corporate governance reports. Positive reactions to declarations of compliance are generally interpreted in terms of signalling effects for those companies more committed with transparency. However, once corporate governance reports are mandatory, such signalling effects make no sense anymore. In the current context, the market would react according to the relevance of the information conveyed by the report. While prior related research has examined market reactions only through the behaviour of returns, we use three indicators: returns, price volatility and trading volumes. Our main result would be the lack of a significant market reaction to the release of corporate governance reports. This finding is robust as it is reported for each indicator of market reaction. However, for some subsamples of firms we show some weak reactions in the lines suggested by the agency theory. Our results might have some implications for regulators and policy makers when designing corporate governance regulations.
Topical FK‐506 Prevents Experimental Corneal Allograft Rejection

We evaluated the efficacy of topical cyclodextrin-encapsulated FK-506 in the prevention of experimental corneal allograft rejection. Two weeks after inducing corneal inflammation and neovascularization with 8–0 silk sutures, 23 albino rabbits received a unilateral 8-mm diameter central penetrating corneal allograft from pigmented donors. Rabbits were randomly assigned to no treatment (eight eyes), topical cyclodextrin four times daily for 28 days (seven eyes), or topical FK-506 0.3 mg/ml in a cyclodextrin suspension (eight eyes) four times daily for 28 days. Grafts were examined daily for degree of inflammation, neovascularization, edema, and signs of rejection for up to 100 days. Seven of eight (88%) untreated grafts and five of seven (71%) cyclodextrin-treated grafts rejected at a median of 3 weeks after transplantation, whereas only two (25%) of eight FK-506–treated grafts rejected and did so at a significantly longer interval (p < 0.005). Topical FK-506 prevents or delays corneal allograft rejection after experimental corneal transplantation.
CAUSAL RELATIONSHIP BETWEEN MACROECONOMIC VARIABLES AND STOCK PRICES IN PAKISTAN

ABSTRACT The intention of this research is to provide empirical evidence regarding causality among interest rate, inflation rate and exchange rate with stock prices in Pakistan for the period from 1990 to 2015. The findings from cointegration test indicated that there was a negative relationship of interest rate, inflation rate and exchange rate with stock prices. Granger causality test result shows unidirectional causality running from interest rate to stock prices and no causality was observed for inflation rate and exchange rate. The overall evidence proposed that equity market of Pakistan does not incorporate substantial information of interest rate, inflation rate and exchange rate in its stock prices and do not reflect the macroeconomic condition of the country.
Corporate tax reforms and tax-motivated profit shifting: evidence from the EU

This paper examines whether the profit-shifting trend in Europe during 2003–2013 can be explained by tax policy changes. Consistent with prior literature, we find that affiliates’ profits are sensitive to tax rate changes. However, we document that tax base–broadening reforms have mitigated the incentives for both inward and outward profit shifting. In particular, we find that anti-avoidance rules prevent multinational companies from shifting profits out of their foreign affiliates, whereas other tax base–broadening rules, such as restrictions on the deductibility of tax losses or on group tax relief, reduce the incentives for multinational companies to shift profits into foreign affiliates. Furthermore, we find evidence of a downward trend in profit shifting across European countries, especially when the tax enforcement is stricter. Overall, these results suggest that broader tax bases and stricter tax enforcement have successfully curbed this particular tax strategy.
Killer Debt: The Impact of Debt on Mortality

This study analyzes the effect of individual finances (specifically creditworthiness and severely delinquent debt) on mortality risk. A large (approximately 170,000 individuals) subsample of a quarterly panel data set of individual credit reports is utilized in an instrumental variables design. The possibility of the reverse causality of bad health causing debt and death is removed by instrumenting for individual finances post 2011 using the exposure to the housing crisis based on their 2005 residence. Worsening creditworthiness and increases in severely delinquent debt are found to lead to increases in individual mortality risk. This result has implications for the benefit of policies such as the social safety net, which aims to protect individual finances, by adding reduced mortality to the benefit of any intervention.
Modeling Fiscal Stress and Contracting Out in Local Government: The Influence of Time, Financial Condition, and the Great Recession

Various studies have analyzed the relationship between fiscal stress and contracting out, but have failed to achieve conclusive results. In this article, we take a broad view of fiscal stress, addressed in terms of financial condition and studied over a lengthy period (2000-2010). The relationship between fiscal stress and contracting out is studied using a dynamic model, based on survival analysis, a methodology that enables us to take into account the effect of time on this relationship. As this study period includes the years of the Great Recession (2008-2010), we also highlight the impact of this event on the fiscal stress–contracting out relation. The results obtained suggest that taking into account the passage of time and conducting a long-term assessment of financial condition enable a more precise understanding of this relation. We also find that the Great Recession reduced the probability of local governments’ contracting out public services.
Matrix metalloproteinase inhibition prevents colon cancer peritoneal carcinomatosis development and prolongs survival in rats.

Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation which play a role in cancer progression and metastatic spreading. We investigated the effects of the MMP inhibitor, batimastat, in vitro on the proliferation and invasiveness of the rat colon cancer cell line DHD/K12, and in vivo on the growth of an aggressive model of peritoneal carcinomatosis producing haemorrhagic ascites and metastases, obtained in the rat by i.p. injection of DHD/K12 cells. MMP production was studied in conditioned culture media, solid tumors and ascitic fluid. In vivo, after injection of tumor cells on day 0, rats received i.p. daily either batimastat (30 mg/kg) or equal volume of vehicle from day 2 until killing on day 43 (series I) or from day 13 until death (series II). The grade of peritoneal carcinomatosis, ascite volume, number and size of liver metastases were evaluated in both series, and survival in series II. MMPs-1, -2 and -9 were identified in culture media, tumors and ascites. In vitro, batimastat did not modify DHD/K12 cell proliferation and slightly reduced cell invasion. In vivo, in series I, batimastat treatment totally prevented peritoneal carcinomatosis and liver metastasis development. In series II, it significantly prolonged survival (P < 0.0002) and reduced peritoneal carcinomatosis (P < 0.001) and hepatic metastases number as compared with controls. However, batimastat-treated rats of the two series had peritoneal inflammation with marked ascites. Nevertheless, inhibition of MMP is a new therapeutic approach which may be promising in treatment of microtumors as in more advanced cancer stages.
Evaluation of mannitol salt agar with oxacillin as a screening medium for methicillin-resistant Staphylococcus aureus

We evaluated the use of mannitol salt agar with oxacillin for use as a primary screening medium for the simultaneous detection and identification of methicillin-resistant Staphylococcus aureus in clinical surveillance specimens. Oxacillin agar dilution susceptibility tests with mannitol salt agar and Mueller-Hinton agar were performed in parallel with disk-agar diffusion testing on 95 oxacillin-susceptible and 105 oxacillin-resistant S. aureus stock isolates. MICs were found to be comparable, showing distinct separation of susceptible and resistant isolates into two groups with MICs of less than or equal to 2 and greater than or equal to 32 micrograms/ml, respectively. In accord with these findings, 4 micrograms of oxacillin per ml was selected for use in the screening medium. For performance evaluation, mannitol salt agar with 4 micrograms of oxacillin per ml was compared with mannitol salt agar without oxacillin by performing parallel screening tests on 153 clinical surveillance specimens. For detection of methicillin-resistant S. aureus, mannitol salt agar with 4 micrograms of oxacillin per ml was as sensitive as mannitol salt agar without oxacillin and required significantly fewer confirmatory tests. For primary identification of methicillin-resistant S. aureus, mannitol salt agar with 4 micrograms of oxacillin per ml was 6.4% false-positive and 1.1% false-negative, with a 93.6% positive predictive value. These findings indicate that mannitol salt agar with 4 micrograms of oxacillin per ml can be used as a reliable and cost-effective screening medium for the simultaneous detection and identification of methicillin-resistant S. aureus in clinical surveillance specimens.
Fair prices & fair wages : implications for macroeconomic dynamics in closed & open economies

In this dissertation, I present five dynamic general equilibrium models. The distinguishing feature of these models is that they incorporate reciprocal altruistic behavior into an otherwise standard New Keynesian framework. In particular, I extend the New Keynesian model such that the assumed price and wage formation is line with the facts that recent empirical research assessed for price and wage setting behavior of firms and workers. In Chapter 2, I study an economy where a contractionary (expansionary) monetary policy shock gives rise to a more (less) frequent price adjustment. In Chapter 3, I analyze the comovements of employment, wages, and inflation with output, paying particular attention to the lead-lag relation between inflation and output. In Chapters 4 and 5, I analyze the impact of an increase in international trade in financial assets on labor market volatility and on the effectiveness of fiscal policy, respectively. In Chapter 6, I analyze the dynamic effects of monetary policy and technology shocks, with a focus on real exchange rate movements, under different assumptions for market imperfections and completeness.
The Absurdity of Economists’ Sacrifice-free Solutions to Climate Change

Abstract John Broome and Duncan Foley have argued that it is a ‘misperception’ that the ‘control of global warming is costly’ and that we can make ‘sacrifices unnecessary’. There are a number of assumptions that are essential for this idea to work. These assumptions can be challenged. Furthermore, my claim is not merely that the Broome/Foley argument is flawed, and therefore unlikely to be successful. I will argue that it is potentially harmful, leading to harms for the present generation and for future generations.
Development of pseudo‐linear gradient elution for high‐throughput resin selectivity screening in RoboColumn® Format

Rapid development of chromatographic processes relies on effective high‐throughput screening (HTS) methods. This article describes the development of pseudo‐linear gradient elution for resin selectivity screening using RoboColumns®. It gives guidelines for the implementation of this HTS method on a Tecan Freedom EVO® robotic platform, addressing fundamental aspects of scale down and liquid handling. The creation of a flexible script for buffer preparation and column operation plus efficient data processing provided the basis for this work. Based on the concept of discretization, linear gradient elution was transformed into multistep gradients. The impact of column size, flow rate, multistep gradient design, and fractionation scheme on separation efficiency was systematically investigated, using a ternary model protein mixture. We identified key parameters and defined optimal settings for effective column performance. For proof of concept, we examined the selectivity of several cation exchange resins using various buffer conditions. The final protocol enabled a clear differentiation of resin selectivity on miniature chromatography column (MCC) scale. Distinct differences in separation behavior of individual resins and the influence of buffer conditions could be demonstrated. Results obtained with the robotic platform were representative and consistent with data generated on a conventional chromatography system. A study on antibody monomer/high molecular weight separation comparing MCC and lab scale under higher loading conditions provided evidence of the applicability of the miniaturized approach to practically relevant feedstocks with challenging separation tasks as well as of the predictive quality for larger scale. A comparison of varying degrees of robotic method complexity with corresponding effort (analysis time and labware consumption) and output quality highlights tradeoffs to select a method appropriate for a given separation challenge or analytical constraints. © 2016 American Institute of Chemical Engineers Biotechnol. Prog. , 32:1503–1519, 2016
Locus of control as moderator: an explanation for additive versus interactive findings in the demand-discretion model of work stress?

Research based on Karasek's (1979) model of work stress has produced conflicting results; although some evidence of the demand X discretion interactions predicted by the model has been reported, most studies have failed to demonstrate interactive effects in relation to mental health outcomes. The present article investigates locus of control (LOC) as a potential moderator of demand/discretion effects. In a sample of civil servants (N = 590), regression analyses demonstrated a three-way LOC X demand X discretion interaction (p less than .01) for affective distress, but not for absence frequency. In longitudinal data from student teachers (N = 147), a similar three-way interaction was observed (p less than .05). In this case, the result applied specifically to anxiety as an outcome, and not to social dysfunction. In each study, the form of the three-way interaction was such that demand and discretion combined interactively to predict outcome for externals (-1SD LOC), in a manner consistent with Karasek's predictions, whereas for internals (+1SD LOC) additive findings were obtained. The implications of these results are discussed with reference to the demand-discretion model, and to the issues of stressor-outcome specificity raised by Broadbent (1985).