Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt-signaling pathway in cholangiocarcinoma cells.

BACKGROUND & AIMS Cholangiocarcinomas often arise within a background of chronic inflammation suggesting that inflammation imparts survival signals to this cancer. Previous studies have also shown that the inflammatory cytokine interleukin (interleukin [IL]-6) contributes to survival signals in an autocrine fashion and that myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the B-cell leukemia-2 family, is an important participant in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in this neoplasm. The present study evaluated the possibility that IL-6 signaling contributes to Mcl-1 up-regulation in cholangiocarcinoma. METHODS Protein kinase B (Akt) and Mcl-1 expression in human tissue was assessed by immunohistochemistry. The relationship between IL-6 signaling, Akt activity, and Mcl-1 expression was examined in cell lines. RESULTS Immunohistochemistry showed that the serine/threonine kinase Akt and Mcl-1 are strongly expressed in the preneoplastic bile duct inflammatory disease primary sclerosing cholangitis and in human cholangiocarcinoma specimens. Immunoblotting showed that Akt is expressed and constitutively phosphorylated in 3 human cholangiocarcinoma lines. Further analysis showed that treatment with anti-IL-6-neutralizing antiserum led to reduced Akt phosphorylation, diminished Mcl-1 expression, and enhanced TRAIL sensitivity. Likewise, the Akt inhibitor A443654.3 led to diminished signaling through the Akt pathway, decreased Mcl-1 expression, and enhanced TRAIL-mediated apoptosis. CONCLUSIONS These findings not only show that an autocrine IL-6/Akt signaling pathway enhances Mcl-1 expression in cholangiocarcinoma but also suggest a strategy for overcoming the resulting apoptosis resistance.
The challenges and utilization of e-commerce : use of Internet by small to medium-sized enterprises in the United Kingdom

The Internet is portrayed by the media, academia and IT professionals as a new frontier that will transform and revolutionise the way business is conducted globally. The contribution of small to medium-sized enterprises (SMEs) is extremely important to the economy of many countries and their contribution cannot be over-emphasised. SMEs account for more than 50% of private-sector employment in the UK and currently are contributing most of the private sector employment growth. Information technology, particularly the Internet, has the potential to radically change the way business is conducted, offering a competitive edge and a gateway to the global marketplace. Although much has been claimed about the potential benefits of the use of the Internetin businesses, there appears to be little evidence at present to indicate the actual level of usage in SMEs. In order to address this, this paper presents the results from a survey of UK SMEs between March and June 1999. The survey gives a current picture of how SMEs are using the Internet and its technology, including the benefits, the issues and the impact of use on business activities.
The maintenance of a sustained thrombolytic state in man. I. Induction and effects.

coccal metabolism, is a highly effective activator of human plasminogen. Plasmin, the enzyme formed following plasminogen activation, exerts powerful proteolytic and fibrinolytic effects at neutral hydrogen ion concentrations, which in vivo mediate the mechanisms of physiological fibrinolysis. Consequently, hopes have been entertained that the intravenous injection of streptokinase, or of streptokinase-activated plasmin, might prove to be of benefit in the therapy of human thromboembolic disease. Animal experiment, despite the lessened effectiveness of streptokinase as an activator of animal plasminogen and the difficulties of species variability, has yielded striking findings. The intravenous injection of very large doses of streptokinase has been shown to produce lysis of artificially produced thrombi in the arteries of dogs (1) and in the veins of rabbits (2), to cause the clearance of peritoneal exudate evoked by trauma (3) and more recently to prevent or remove fibrinoid lesions secondary to the generalized Shwartzman response (4). These findings appear to be of unequivocal significance but the precise mechanism of their production has been uncertain.
A rise in the intracellular Ca2+ concentration of isolated rat supraoptic cells in response to oxytocin.

1. Intracellular Ca2+ concentration ([Ca2+]i) was monitored in single cells isolated from adult rat supraoptic (SO) nuclei. The great majority of cells (85%) were neurones and most were immunoreactive to oxytocin or to vasopressin (AVP). 2. The resting [Ca2+]i of the majority (80%) of the neurones remained stable while 20% of the neurones displayed spontaneous [Ca2+]i oscillations which disappeared in low‐Ca2+ (100 nM) EGTA buffer. 3. Addition of 100 nM oxytocin increased the [Ca2+]i in both stable and oscillating cells. Two types of responses were observed: (i) a sustained response with [Ca2+]i being maintained at an elevated level and (ii) a brief response with [Ca2+]i quickly returning to a near‐resting level. Responses were reproducible, dose dependent and blocked with a specific oxytocin antagonist. 4. Removal of extracellular Ca2+ did not block the oxytocin response. In EGTA buffer, application of thapsigargin (200 nM) onto oxytocin‐sensitive cells induced an increase in [Ca2+]i and inhibited the oxytocin response. These effects were not induced by other intracellular Ca2+ mobilizers such as tBuBHQ (see Methods) or caffeine. 5. In conclusion, half of the SO cells respond to oxytocin with a rise in [Ca2+]i. The effect is mediated by oxytocin receptors and results from release of Ca2+ from thapsigargin‐sensitive stores.
Point: a glucose tolerance test is important for clinical practice.

There is no doubt that clinical, symptomatic diabetes is a risk factor for cardiovascular disease (CVD) and all-cause mortality. It has also been shown that the risk is graded across the entire range of hyperglycemia (1,2). However, it has been debated during the last decades whether asymptomatic, unrecognized diabetes, or even a lesser degree of hyperglycemia, increases the risk of CVD and death. Traditionally, investigators who studied the association between hyperglycemia and the development of diabetic complications focused on fasting glucose levels (3). Until the 1980s, the standards for measuring blood glucose concentration varied, HbA1c was not available, and consequently, the results between the studies were conflicting. Now that we have data from the multitude of studies in which recommended standards have been applied (4,5), it has been possible to get a clearer picture of the matter. A plethora of recent studies from diverse populations have demonstrated that asymptomatic hyperglycemia is an independent risk factor (6–10). Hyperglycemia, however, is not a simple issue. Blood glucose has a strong diurnal variation; it also varies seasonally and changes with age. Hyperglycemia can be determined at least in three ways by measuring fasting glucose, postchallenge (or postprandial) glucose, and HbA1c. The first is by definition the lowest glucose level during the day, during a few early morning hours. HbA1c indicates the mean glycemic level during a lengthy period of time—several weeks or months—summarizing both fasting and postprandial glucose levels. Postchallenge glucose level shows the magnitude of glucose elevation (peak) after the glucose load, lasting 1–3 h. If one eats the usual three meals a day, the postprandial glycemia usually lasts from 6 to 9 h a day (11). Even though there are moderate correlations between these parameters of glycemia, in the general …
Center for Economic Institutions Working Paper Series

We examine the pyramidal ownership structure of a large sample of newly listed Chinese companies controlled by local governments or private entrepreneurs. Both types of the owners use layers of intermediate companies to control their firms. However, their pyramiding behaviors are likely affected by different property rights constraints. Local governments are constrained by the Chinese laws prohibiting free transfer of state ownership. Pyramiding allows them to credibly decentralize their firm decision rights to firm management without selling off their ownership. Private entrepreneurs are constrained by their lack of access to external funds. Pyramiding creates internal capital markets that help relieving their external financing constraints. Our empirical results support these conjectures. Local governments build more extensive corporate pyramids when they are less burdened with fiscal or unemployment problems, when they have more long-term goals, and when their firm decisions are more subject to market and legal disciplines. The more extensive pyramids are also associated with smaller “underpricing” when the firms go public. Entrepreneur owners construct more complex corporate pyramids when they do not have a very deep pocket – as indicated by their personal wealth.
Detection of BRAF V600E mutation by pyrosequencing

Introduction: Detection of the V600E hotspot mutation in BRAF oncogene is extremely useful for the screening of hereditary non‐polyposis colorectal cancer (Lynch's syndrome) and for the prediction of sensitivity to MEK inhibitors. Here we describe a method for detecting this mutation based upon pyrosequencing technology. Methods: The efficiency of pyrosequencing for detecting BRAF V600E mutations was compared with the conventional dideoxy sequencing method in 12 tumour cell lines and in 108 colorectal tumours. Results: The results from pyrosequencing were 100% concordant with those from dideoxy sequencing. This method was capable of detecting BRAF V600E mutations at a much lower ratio of mutant to wild‐type alleles (1:50) than dideoxy sequencing (1:5) while being considerably faster and less expensive. Conclusions: Pyrosequencing offers a specific, sensitive, rapid and cost‐effective alternative to dideoxy sequencing for the detection of BRAF V600E mutations in clinical tumour specimens.
Public sector reforms and management control systems in a developing country: a case study of a large state enterprise in Nigeria

In recent years, public sector reforms with its New Public Management (NPM) doctrine have attracted the attention of policy makers, practitioners and academics around the world. In the developing countries, these reforms are usually engineered and imposed by the international financial community such as the World Bank and the International Monetary Fund (IMF). One of the main components of NPM is changes in management control systems (MCS) as it is believed that by adopting new MCS better transparency and accountability will ensue. This has resulted in the introduction of private sector accounting practices into the public sectors in order to enhance efficiency, effectiveness and transparency, and also to change the orientation of public sector managers towards managerialism. Using a large state enterprise in Nigeria, hypothetical called Nigeria State Company (NSC) as a case study, this thesis seeks to explore and understand the Nigerian public sector reforms and how these reforms impacts on the MCS of the organisation. The thesis explores the various MCS introduced, the processes of their implementation and how these systems function in the day-to-day decision making of the organisation.
Probabilistic assessment of the performance of combined sewer systems

Too optimistic impression Usually, serviceability of a sewer system is assessed on the basis of model results because of insufficiency of measurements. Serviceability is defined as “The ability of an asset to deliver a specific service to customers”. The services offered by a sewer system consist of protection of public health and prevention of flooding provided that the quality of the environment is safeguarded. Hydraulic performance is assessed on the basis of calculations (e.g. combined sewer overflows (CSOs) and flooding) that support interventions reducing environmental and economic damage. Visual inspections (e.g. closed circuit television (CCTV) data) in combination with predictions of remaining service life determine whether rehabilitation is necessary. However, this approach has several shortcomings. Firstly, uncertainties in knowledge of system structure, system dimensions and determinative processes are ignored. Secondly, natural variability of rainfall is not considered. Thirdly, system performance is often described with imperfect models assuming that assets are not liable to failure, such as blockage of conduits due to ingress of soil or root intrusion, subsidence of conduits and technical failure of pumps. Finally, it assumes that deficiencies can be (visually) detected and quantified. All this leads to a too optimistic impression of sewer performance.
Fish or Fowl?: Collegial Processes in Managerialist Institutions

Academic promotion is a curious fish. Most employees - including general staff in higher education institutions - would expect that an appointment to a middle management position (with responsibility for managing 20 staff and a budget of $2 million) would be made for the medium term if not indefinitely, and only after systematic selection from amongst candidates with extensive preparation for the post. On the other hand, they would expect that a pay increase for meritorious performance, if available at all, would be decided annually, largely at the discretion of the employee's supervisor, following a largely informal process. For academics, however, the position is almost completely reversed. As we shall see in greater detail below, appointment as head of a school or department is usually short term, still largely by an informal process for which the main qualification seems not to be management experience and expertise, but the confidence of one's peers. Heads of school might be described in short hand as collegial appointments, although to a managerialist they would appear to be the amateurish appointment of amateurs. In contrast, academics' pay increases for meritorious performance - academic promotions - are made after the most thorough scrutiny of applicants' performance and academic merit. This paper compares the processes for appointing heads of academic schools or departments with those for promoting academic staff in Australian higher education institutions. It considers the future of these largely collegial processes within increasing managerialist institutions.
Generalized Shwartzman Reaction Induced by Liquoid in the Rat

Summary In an autoradiographic study the number of DNA-synthesizing aortic endothelial cells was compared 48 hours after an intravenous injection of the acidic polymer Liquoid or saline in rats. Doses of 1.5-2 mg per 100 g body weight produced a 14-fold increase in DNA-synthesizing endothelial cells and the generalized Shwartzman reaction. These results show that Liquoid causes severe endothelial injury.
Susceptibility to Smoking among Adolescents and Its Implications for Mexico’s Tobacco Control Programs. Analysis of the Global Youth Tobacco Survey 2003–2004 and 2006–2007

Smoking prevention efforts should either prevent target groups from becoming susceptible to smoking or prevent susceptible adolescents from progressing to becoming regular smokers. To describe the prevalence of susceptibility to smoking among never smoker students from cities that applied the GYTS in 2003 and 2006. The GYTS uses a two-stage cluster sample survey design that produces representative samples of students aged 12–15 years enrolled in public, private, and technical schools. The survey was undertaken at 399 schools in 9 cities. The GYTS surveyed 33,297 students during the academic years 2003–04 and 2006–07. Among never smokers, about 25% are likely to initiate smoking in the next 12 months. There are no differences in susceptibility to smoking by gender. When comparing results from 2003 and 2006, the susceptibility index has not changed, but for one city. The GYTS results are useful for monitoring susceptibility to smoking among adolescents and provide evidence for strengthening the efforts of tobacco control programs in Mexico.
A.I.R.A.P. - Alternative Views on Alternative Investments

This paper investigates issues of risk-adjusted performance, value added and leverage for hedge funds. It applies AIRAP (Alternative Investments Risk Adjusted Performance), which is the power utility implied certain return that a risk-averse investor would trade off for holding risky assets, to hedge fund indices and individual hedge fund data. Inferences are made about the value added by hedge funds and the difference between directional and non-directional strategies. Evidence of non-normality, higher moment risks and the trade-off between mean-variance profile vis-a-vis skewness and kurtosis is noted across style categories. Further, survivorship bias is estimated across style categories in the first four moments.
The Effects Of Market Integration On Global Risk Sharing: Examining Market Reactions To Cataclysmic Events

There are a number of cataclysmic events that stand out as markedly catastrophic enough to cause significant unrest in investors‘ outlook on the stability of the market. In today‘s increasingly integrated global market, the key concern for investors in adjusting for such situations is to spread their portfolio risk across different risk bases in order to reduce unwanted effects from the idiosyncrasy of a particular part of their portfolios. Using the event study method and ICAPM-derived measure of market integration, I find that there is evidence for market integration‘s global risk sharing effect on abnormal returns from cataclysmic events, specifically in regard to natural disasters and terrorist attacks. There is, however, no evidence of risk-diffusing effects beyond the event day, even for relatively short post-event windows of 6 and 11 days. This seems to suggest that market integration as motivated by global risk sharing is only effective to disperse the initial shock of a cataclysmic event.
Soil moisture effect on microwave emission of forest canopies

In this paper, experimental results obtained on two forest plots in Tuscany (Italy) by using the IROE/IFAC multi-frequency dual-polarized microwave radiometer are reported. The sensitivity of L-band microwave emission to both forest biomass and soil moisture content under canopies is investigated. A radiative transfer model, which considers vegetation as an ensemble of disks and cylinders over a soil surface, has been used to interpret the obtained results. A good agreement between experimental data and model simulations has been obtained. A further analysis has been carried out by applying the model for predicting the soil moisture under natural forests with moderate biomass.
The Membrane-anchored Serine Protease Prostasin (CAP1/PRSS8) Supports Epidermal Development and Postnatal Homeostasis Independent of Its Enzymatic Activity*

Background: Prostasin is a membrane-anchored serine protease with essential functions in epithelial development and homeostasis. Results: Mice expressing enzymatically inactive endogenous prostasin, unlike prostasin null mice, display normal tissue development and homeostasis. Conclusion: Essential in vivo functions of prostasin are independent of the catalytic activity of prostasin. Significance: Prostasin may have a unique role as an allosteric regulator of other membrane-anchored proteases. The membrane-anchored serine protease prostasin (CAP1/PRSS8) is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis. Here, we report the surprising finding that prostasin executes these functions independent of its own enzymatic activity. Prostasin null (Prss8−/−) mice lack barrier formation and display fatal postnatal dehydration. In sharp contrast, mice homozygous for a point mutation in the Prss8 gene, which causes the substitution of the active site serine within the catalytic histidine-aspartate-serine triad with alanine and renders prostasin catalytically inactive (Prss8Cat−/Cat− mice), develop barrier function and are healthy when followed for up to 20 weeks. This striking difference could not be explained by genetic modifiers or by maternal effects, as these divergent phenotypes were displayed by Prss8−/− and Prss8Cat−/Cat− mice born within the same litter. Furthermore, Prss8Cat−/Cat− mice were able to regenerate epidermal covering following cutaneous wounding. This study provides the first demonstration that essential in vivo functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease.
Intraocular Pressure Outcomes Following Transscleral Diode Cyclophotocoagulation Using Long and Short Duration Burns

Purpose:The purpose of this study was to compare outcomes of transscleral diode cyclophotocoagulation using short duration (SD) versus longer duration (LD) treatment. Patients and Methods:Data were collected retrospectively on patients with glaucoma who underwent cyclophotocoagulation with LD (4000 ms) treatment with variable power ⩽1000 mW versus SD using 1500 ms with variable power ⩽2000 mW. The outcome measures included: intraocular pressure (IOP) at 12 months, decrease in number of antiglaucoma medications, complications and visual acuity (VA) at the final follow-up visit. Results:There were 71 patients and 70 patients in the SD and LD groups, respectively. The mean IOP±SD pretreatment baseline was 33±10 versus 36±10 mm Hg for SD and LD groups, respectively (P>0.05). At 1 year postoperatively, the IOP decreased significantly in both groups (16.7 vs. 17.4 mm Hg for SD and LD, respectively; P<0.0001). This decrease in IOP was comparable between groups (P=0.5). The average number of IOP lowering medications were 2.5 and 2.9 at baseline in the SD and LD groups, respectively, and decreased to 1.3 in both groups (P=0.83). The mean LogMAR VA decreased significantly from 1.87 at baseline to 1.96 at 1 year in the SD group (P=0.276), and 2.03 to 2.3 (P⩽0.001) in the LD group, this change was comparable (0.19; P=0.075) between the 2 groups. Complications were also comparable. Conclusions:Both LD and SD burns during cyclophotocoagulation effectively lowered IOP at 1 year. Neither treatment resulted in a greater reduction of IOP. LD treatment appeared to result in a decrease in VA and greater postoperative inflammation.
An Empirical Analysis of Cross-Listing Decisions in Share-Issue Privatizations: Evidence from Developed and Developing Countries

Frequently the largest equity offerings in the world, share-issue privatizations (SIPs) are sometimes conducted entirely on domestic exchanges and are sometimes cross-listed on foreign exchanges. In this paper, we examine the determinants of a privatizing government’s actions regarding whether to cross-list. Using data from 821 SIPs from 76 countries during 1985-2007, we identify firm-level and institution-level factors that affect the cross-listing decisions in these equity offerings. The data indicate that offering size, industry, and product market are the firm-level characteristics most closely related to the cross-listing decisions. We also find that institution-level factors (such as the country’s level of economic development and capital market development) significantly impact the likelihood of cross-listings in share-issue privatizations. We further identify that the factors affecting cross-listing decisions vary significantly between developed and developing nations.