Miracle-dz/UniFAR-FTUs huggingface dataset:
Inactivation of p21-Activated Kinase 2 (Pak2) Inhibits the Development of Nf2-Deficient Malignant Mesothelioma

Malignant mesotheliomas (MM) show frequent somatic loss of the NF2 tumor suppressor gene. The NF2 product, Merlin, is implicated in several tumor-related pathways, including p21-activated kinase (PAK) signaling. Merlin is both a phosphorylation target for PAK and a negative regulator of this oncogenic kinase. Merlin loss results in PAK activation, and PAK inhibitors hold promise for the treatment of NF2-deficient tumors. To test this possibility in an in vivo genetic system, Nf2f/f;Cdkn2af/f mice were crossed to mice with conditional knockout of Pak2, a highly expressed group I Pak member. Cohorts of these animals were injected in either the thoracic or peritoneal cavities with adeno-Cre virus to delete floxed alleles in the mesothelial lining. Loss of Pak2 resulted in a markedly decreased incidence and delayed onset and progression of pleural and peritoneal MMs in Nf2;Cdkn2a-deficient (NC) mice, as documented by Kaplan-Meier survival curves and in vivo bioluminescent imaging. RNA-seq revealed that MMs from NC;Pak2-/- mice showed downregulated expression of genes involved in several oncogenic pathways (Wnt, Akt) when compared to MMs from mice retaining Pak2. Kinome profiling showed that, as compared to NC MM cells, NC;Pak2-/- MM cells had multiple kinase changes indicative of an epithelial to mesenchymal transition. Collectively, these findings suggest that NC;Pak2-/- MMs adapt by reprogramming their kinome and gene signature profiles to bypass the need for PAK activity via the activation of other compensatory oncogenic kinase pathways. The identification of such secondary pathways offers opportunities for rational combination therapies to circumvent resistance to anti-PAK drugs.
Centrosomal localization of DNA damage checkpoint proteins

During mitosis, the phosphatidylinositol‐3 (PI‐3) family‐related DNA damage checkpoint kinases ATM and ATR were found on the centrosomes of human cells. ATRIP, an interaction partner of ATR, as well as Chk1 and Chk2, the downstream targets of ATR or ATM, were also localized to the centrosomes. Surprisingly, the DNA‐PK inhibitor vanillin enhanced the level of ATM on centrosomes. Accordingly, DNA‐PKcs, the catalytic subunit of DNA‐PK, was also found on the centrosomes. Vanillin altered the phosphorylation of Chk2 in the centrosomes and in whole cell extracts. Nucleoplasmic ATM co‐immunoprecipitated with Ku70/86, the DNA binding subunits of DNA‐PK, while vanillin diminished this association. Vanillin did not affect microtubule polymerization at the centrosomes but, surprisingly, caused a transient enhancement of α‐tubulin foci in the nucleus. Interestingly, γ‐tubulin was also present in the nucleus and co‐immunoprecipitated with ATR or BRCA1. DNA damage led to a reduction of the mentioned checkpoint proteins on the centrosomes but increased the level of γ‐tubulin at this organelle. Taken together, these results indicate that DNA damage checkpoint proteins may control the formation of γ‐tubulin and/or the kinetics of microtubule formation at the centrosomes, and thereby couple them to the DNA damage response. J. Cell. Biochem. 101: 451–465, 2007. © 2006 Wiley‐Liss, Inc.
Efficient metaheuristic for multi-product disassembly lot sizing problem with lost sales

Disassembly planning aims to determine the quantity of end-of-life products in order to satisfy the demand of leaf items over a given planning horizon while minimizing several costs. Disassembly planning problem with two levels, multi-products type and capacity constraints is treated by developing a linear programming model. The objective of this model is to minimize the sum of the fixed costs of disassembly, inventory holding cost of components and lost sales cost. In order to solve it, we propose an efficient optimization method based on genetic algorithm and Fix-and-Optimize heuristic. Our contribution is both the development of a new model allowing lost sales, and then we propose a new approach to solve it for all instances adapted from literature.
Absence of IL‐6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL‐6 receptors by Epstein‐Barr virus in vitro

Interleukin‐6 (IL‐6) is a cytokine which is necessary for the differentiation of activated B cells and growth of early haemopoietic progenitors. It is used for ex‐vivo expansion of myeloid progenitors in the setting of high‐dose chemotherapy with autologous bone marrow transplantation (BMT). Expression of the IL‐6 receptor (IL‐6R) was examined in six fresh Burkitt’s lymphoma (BL) cell preparations and 12 BL cell lines by reverse transcriptase polymerase chain reaction (RT‐PCR) and flow cytometry (FCM). Inducibility of IL‐6R mRNA expression by Epstein‐Barr virus (EBV) was studied by comparing two uninfected cell lines with the same cell lines infected by EBV. The phenotype of the BL cells lines was analysed by FCM and by proliferation assays in the presence of anti‐IgM antibodies.
The impact of hypoalbuminemia in kidney-pancreas transplant recipients.

BACKGROUND Hypoalbuminemia is associated with poorer outcomes in renal transplantation. Diabetes can compound hypoalbuminemia's detrimental effects. Kidney-pancreas transplantation alters the diabetic milieu; yet, some patients continue to be hypoalbuminemic. METHODS We retrospectively analyzed 232 patients who underwent simultaneous kidney-pancreas transplantation (SPK) between 1993 and 1997 to determine the incidence and clinical correlates of hypoalbuminemia in SPK recipients. Post-SPK hypoalbuminemia was defined as a serum albumin level < or =3.5 g/dl. Univariate analyses were performed to determine whether post-SPK hypoalbuminemia was associated with pre-SPK variables. The effect of albumin level and hypoalbuminemia on the risk of post-SPK events (cardiac events, cytomegalovirus [CMV] infection, rejection, readmission, kidney and pancreas graft failure, and death) was examined with a Cox proportional hazards model. RESULTS The study population consisted of 149 men and 83 women. Average follow-up was 2.0+/-1.3 years. Hypoalbuminemia (serum albumin level < or =3.5 g/dL) was most common early after SPK (3 months: 44% of evaluable patients were hypoalbuminemic; 12 months: 15.3%; 36 months: 8.3%). Acute rejection episodes and readmission were the most common adverse events after SPK transplantation. There were 24 episodes of renal allograft loss and only 5 cardiac events. Ten SPK recipients died during the study time period. SPK-related hypoalbuminemia was associated with an increased risk for CMV infection (risk ratio [RR] 2.5; P<0.02), renal graft failure (RR 2.41; P=0.05), pancreas graft failure (RR 3.66; P=0.01), and a trend toward an increased risk for death (RR 2.8; P=0.19). CONCLUSIONS Post-SPK hypoalbuminemia resolves over time in many patients. Persistent post-SPK hypoalbuminemia is associated with an increased risk for CMV infection, graft loss, and a trend toward decreased survival. Efforts to improve nutrition, as it may affect hypoalbuminemia in SPK recipients, may be one strategy for improving SPK outcomes.
Ectopic D-type cyclin expression induces not only DNA replication but also cell division in Arabidopsis trichomes

Although the mechanisms controlling the two cell-cycle checkpoints G1-S and G2-M are well studied, it remains elusive how they are linked in higher eukaryotes. In animals, D-type cyclins have been implicated in the control of cell-cycle progression in mitotic as well as in endoreduplicating cells. By contrast, we show that the expression of the D-type cyclin CYCD3;1 in endoreduplicating Arabidopsis trichome cells not only induced DNA replication but also cell divisions.
Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging-a pilot study.

BACKGROUND Anthracyclines are potent chemotherapeutics burdened by their cardiotoxicity. So far no marker to detect early cardiac damage exists. We tested the ability of magnetic resonance imaging (MRI) to show early changes in myocardial signal and cardiac function after anthracycline therapy. METHODS Twenty-two patients with normal cardiac function were investigated by MRI before and 3 and 28 days after anthracycline chemotherapy. Contrast enhanced fast spin echo images were obtained to characterize myocardial enhancement. Left ventricular ejection fraction was measured by MRI in contiguous short-axis planes. RESULTS All patients remained clinically stable. Ejection fraction decreased from 67.8% +/- 1.4% to 58.9% +/- 1.9% after 28 days (P < .05). The relative myocardial contrast enhancement increased from 3.8 +/- 0.4 to 6.9 +/- 1.1 (P < .01). An increase of the enhancement of >5 on day 3 compared with baseline predicted a significant loss of ejection fraction at 28 days (67.5% +/- 2.8% to 51.4% +/- 5.6%, mean difference 16.1% +/- 6.6%; P < .05), whereas an increase of +5 was not associated with a significant loss of ejection fraction (67.6% +/- 1.7% to 62.5% +/- 1.4%, mean difference 4.1% +/- 2.6%; P not significant). CONCLUSIONS MRI detects early changes in myocardial contrast and slightly deteriorating cardiac function in patients receiving anthracyclines. Larger patient cohorts and longer follow-up are needed to evaluate MRI as a predictor for anthracycline cardiotoxicity.
Memory training and memory improvement in Alzheimer's disease: rules and exceptions

Alzheimer’s disease (AD) results in a global memory dysfunction that involves (a) retrieval of information encoded in a particular temporal-spatial context, or episodic memory; (b) retrieval of overlearned context-free information, or semantic memory; and (c) retrieval of information without conscious awareness, or implicit memory (1,2). However, as with many other groups of individuals suffering from memory deficits, the most pronounced deficit in AD, especially early in the disease process, is seen in tasks tapping episodic memory (e.g., free recall or recognition of verbal and nonverbal infomation) (3). Not only do AD patients perform extremely poorly in the bulk of episodic memory tasks, but unlike their healthy aged counterparts, they have also been found to fail to benefit from a variety of different forms of environmental and cognitive support for remembering (4). A selection of studies demonstrating such failures to utilize memory support in AD is shown in Table 1. The basic message from Table 1 is that, irrespective of whether organizational instructions, verbal mediators etc. are provided, AD patients tend to perform at the same low level as in baseline conditions in which these forms of support are lacking. Note that all forms of cognitive support listed in Table 1 have been found to improve memory considerably in healthy older adults (5,6).
Does the Provision of Non-audit Services Affect Auditor Independence and Audit Quality? Evidence from Bahrain

The main aim of this research is to investigate perceptions of respondents (auditors, accountants and financial managers) on the effect of provision of non-audit services (NAS) to audit clients companies upon auditor independence and audit quality. This study expands on previous work done on the effects of providing non-audit services upon auditorsA­ independence and audit quality in Bahrain, which considered as an important subject for both auditing firms and auditing profession. This paper provides insights on the factors which explain the impact of the provision of non-audit services upon auditor independence and audit quality in Bahrain. To achieve the objectives of the research, a questionnaire was prepared and disseminated to a sample of 250 respondents. The results indicate that respondents are supporting the idea that A¬independence of auditor is impaired with providing non-audit serviceA®. Kruskal-Wallis Test revealed that only respondentsA­ occupation is associated with their perceptions. Providing empirical evidence on this issue within the Bahraini environment, as a member of the Gulf Cooperation Council countries, may add a new dimension to the accounting and auditing literature. As the study analysed only one country (Bahrain); generalisation of the results might be a limitation. Future research studies should consider other countries in the region and to include respondents in other non-listed companies with more recent data which may lead to different results.
Are There Economies of Scale in Municipal Government Expenditures?

One factor that is relevant to determining the optimal size of local government is whether there are economies of diseconomies of scale in municipal government expenditures. This paper examines the question by analyzing municipal government expenditures of 487 municipalities with populations greater than 50,000. At first glance it appears that municipal expenditures are characterized by diseconomies of scale, but because there is a close correlation between total population and population density, one must be careful to make sure that the effects attributed to total population are not in fact due to variations in population density. When cities are divided into groups by population density so that they are not compared with other cities with very different densities, the evidence for diseconomies of scale goes away. It appears that after variation in density is taken into account, municipal government expenditures are characterized by constant returns to scale. Thus, there is no reason to think that either consolidations or secessions at the local level would appreciably affect per capita government expenditures.
Ease of Access and Usefulness of Transfer Information on Community College Websites in Texas

Many first-time community college entrants aspire to earn a bachelor’s degree, but few do. To transfer, students often must overcome information constraints to navigate bureaucratic hurdles and conflicting requirements. For a sample of 20 Texas community colleges, we reviewed college websites, assessing the ease of access and usefulness of online transfer information, and spoke to key transfer personnel about the information provided to students. We used a qualitative case study approach to triangulate findings from our data sources. Approximately two thirds of colleges in the sample fell below the highest standard on our rubric for either ease of access or usefulness, indicating room for improvement at most institutions. Many personnel we interviewed recognized the strengths and limitations of their college’s online information, though several were ambivalent regarding the need for improving online transfer information, arguing that the availability of online information alone is insufficient for successful transfer and not as important as face-to-face advising. Our research illustrates the need for colleges to develop and update their online information with care, determining which information students need to transfer (including transfer guides for partner programs/colleges), how students might search for that information, and ensuring that necessary transfer information is available and up-to-date. The framework provided by our rubric may guide institutions in the evaluation of their online transfer information.
[Mental disease related to belief in being possessed by the "Zar" spirit].

The belief in being possessed by the "Zar" spirit is widespread in East and Central Africa, particularly in Sudan and Ethiopia. It also affects Jews living in Ethiopia, as well as those who have immigrated to Israel. According to this belief, being possessed by Zar is the cause of almost all somatic and mental disturbances. Zar exorcism, rituals, language and the clinical syndromes of 13 cases of Zar possession treated in our outpatient clinic are described. Of the 13, 8 were neurotic and the rest atypical psychotics, who except for 1, remitted quickly. Of the 13, 9 were married, 6 were males and 8 were 40 or older. All had a history of Zar possession while still in Ethiopia, and in the immediate families of 8 there were others with a history of Zar possession. 8 of the cases spoke in a peculiar "Zar language. " In all cases the new episode of Zar possession appeared during the first 2 years of living in Israel. The differential diagnosis of DSM-III R categories in relation to Zar possession illness, and anthropological and sociopsychological implications of the illness in Israel as compared to Ethiopia are discussed. According to an accepted theory, Zar possession is found in the weaker strata of Amharic society. In Ethiopia, therefore, it was the women who were usually affected. In Israel, there has been a dramatic emancipation of the Ethiopian woman, and men were relegated to lower status. For these reasons, in Israel it is the men among the Ethiopian immigrants who are more susceptible to the condition. We find it important to combine both traditional and modern therapeutic modalities in treating Zar possession.
The Role of Macrophage-Inducible C-Type Lectin in Different Stages of Chronic Liver Disease

The macrophage-inducible C-type lectin (mincle) is part of the innate immune system and acts as a pattern recognition receptor for pathogen-associated molecular patterns (PAMPS) and damage-associated molecular patterns (DAMPs). Ligand binding induces mincle activation which consequently interacts with the signaling adapter Fc receptor, SYK, and NF-kappa-B. There is also evidence that mincle expressed on macrophages promotes intestinal barrier integrity. However, little is known about the role of mincle in hepatic fibrosis, especially in more advanced disease stages. Mincle expression was measured in human liver samples from cirrhotic patients and donors collected at liver transplantation and in patients undergoing bariatric surgery. Human results were confirmed in rodent models of cirrhosis and acute-on-chronic liver failure (ACLF). In these models, the role of mincle was investigated in liver samples as well as in peripheral blood monocytes (PBMC), tissues from the kidney, spleen, small intestine, and heart. Additionally, mincle activation was stimulated in experimental non-alcoholic steatohepatitis (NASH) by treatment with mincle agonist trehalose-6,6-dibehenate (TDB). In human NASH, mincle is upregulated with increased collagen production. In ApoE deficient mice fed high-fat western diet (NASH model), mincle activation significantly increases hepatic collagen production. In human cirrhosis, mincle expression is also significantly upregulated. Furthermore, mincle expression is associated with the stage of chronic liver disease. This could be confirmed in rat models of cirrhosis and ACLF. ACLF was induced by LPS injection in cirrhotic rats. While mincle expression and downstream signaling via FC receptor gamma, SYK, and NF-kappa-B are upregulated in the liver, they are downregulated in PBMCs of these rats. Although mincle expressed on macrophages might be beneficial for intestinal barrier integrity, it seems to contribute to inflammation and fibrosis once the intestinal barrier becomes leaky in advanced stages of chronic liver disease.
Long time immunogenicity of measles vaccine in the vaccination era: An open question

ABSTRACT After WHO European Region determined the 2005 – 2010 Strategic Plan for measles elimination, the number of reported measles cases in Europe fell dramatically. This decrease is related to the vaccination strategy carried out by European countries. This extensive immunization strategy changes the epidemiological patter and could influence the effectiveness and the long-time immunogenicity of the vaccine. To evaluate the long-time immunogenicity of the measles vaccine in the vaccination era, a pilot study among vaccinated blood donors in Apulia was designed. Of 174 enrolled patients, 93.7% presented an anti-measles IgG titer positive. GMT seems to increase by age (p = 0.001). The GMT seems to increase by age and this could be related to the exposition to natural boosters, that was more probable before the beginning of universal mass vaccination against measles. Future studies have to focus the correlation between GMT and age.
Design of a Socio-economic Processes Monitoring System Based on Network Analysis and Big Data

Socio-economic policy should satisfy the interests of the society as much as possible and contribute to improving the quality of life. This actualizes the role of developing the theoretical and methodological foundations for building an innovative information system for monitoring the socio-economic situation and population responses. The study built and tested an algorithm for supporting management decisions based on the collection of large data sets of socio-economic information based on the principles of the digital economy and processing them through network analysis. The algorithm is focused on building a monitoring system that presupposes a synergy of the authorities and the society, not only in its pensionary part, but also among the masses, which are diverse in their representativeness. The result of the study was the formation of a theoretical and methodological framework for creating a system for making management decisions and assessing the effectiveness of the activities of government bodies, based on the principles of reflection of the final beneficiaries of economic policy.
Holistic perspectives on learning and knowledge : An awarding body perspective.

This study took a grounded theory approach with the aim of developing a more holistic approach to learning and knowledge. There has been a lot written about learning and knowledge but very little has been written looking at the complex entanglement of the two. The research was very much grounded in the data whilst remaining sensitive to the theory of complexity. This study wanted to reject the simplistic and often mechanistic views of learning and knowledge and wanted to explore the more complex entanglement. This was done by taking data from three focus groups each consisting of 4-6 individuals. In addition a sense making workshop consisting of 5 individuals then helped to code and cluster the data which helped support the researcher's findings. At the time the research environment was going through a climate of change faced with huge financial pressures due to the economic downturn whilst still carrying the scars from previous litigation. The findings suggest that learning and knowledge is a very complex entanglement which is far more elaborate and complex than the theory immediately implies. These insights are discussed with reference to academic theory and a number of implications for business were identified. Overall the study supports a more integrated consideration of organisational learning and knowledge which should be applied in practice. If implemented effectively, should provide a more unique and sustainable competitive advantage, through a more effective workforce.