Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of osteoblast differentiation by transcription factors

Runx2, osterix, and β‐catenin are essential for osteoblast differentiation. Runx2 directs multipotent mesenchymal cells to an osteoblastic lineage, and inhibits them from differentiating into the adipocytic and chondrocytic lineages. After differentiating to preosteoblasts, β‐catenin, osterix, and Runx2 direct them to immature osteoblasts, which produce bone matrix proteins, blocking their potential to differentiate into the chondrocytic lineage. Runx2 inhibits osteoblast maturation and the transition into osteocytes, keeping osteoblasts in an immature stage. Other transcription factors including Msx1, Msx2, Dlx5, Dlx6, Twist, AP1(Fos/Jun), Knox‐20, Sp3, and ATF4 are also involved in osteoblast differentiation. To gain an understanding of bone development, it is important to position these transcription factors to the right places in the processes of osteoblast differentiation. J. Cell. Biochem. 99: 1233–1239, 2006. © 2006 Wiley‐Liss, Inc.
Patient‐derived mouse xenografts from pediatric liver cancer predict tumor recurrence and advise clinical management

Identification of new treatments for relapsing pediatric cancer is an unmet clinical need and a societal challenge. Liver cancer occurrence in infancy, 1.5 for million children per year, falls far below the threshold of interest for dedicated drug development programs, and this disease is so rare that it is very difficult to gather enough children into a phase II clinical trial. Here, we present the establishment of an unprecedented preclinical platform of 24 pediatric liver cancer patient‐derived xenografts (PLC‐PDXs) from 20 hepatoblastomas (HBs), 1 transitional liver cell tumor (TCLT), 1 hepatocellular carcinoma, and 2 malignant rhabdoid tumors. Cytogenetic array and mutational analysis of the parental tumors and the corresponding PLC‐PDXs show high conservation of the molecular features of the parental tumors. The histology of PLC‐PDXs is strikingly similar to that observed in primary tumors and recapitulates the heterogeneity of recurrent disease observed in the clinic. Tumor growth in the mouse is strongly associated with elevated circulating alpha‐fetoprotein (AFP), low rate of necrosis/fibrosis after treatment, and gain of chromosome 20, all indicators of resistance to chemotherapy and poor outcome. Accordingly, the ability of a tumor to generate PLC‐PDX is predictive of poor prognosis. Exposure of PLC‐PDXs to standards of care or therapeutic options already in use for other pediatric malignancies revealed unique response profiles in these models. Among these, the irinotecan/temozolomide combination induced strong tumor regression in the TCLT and in a model derived from an AFP‐negative relapsing HB. Conclusion: These results provide evidence that PLC‐PDX preclinical platform can strongly contribute to accelerate the identification and diversification of anticancer treatment for aggressive subtypes of pediatric liver cancer. (Hepatology 2016;64:1121‐1135)
Differences between Macrolide-Resistant and -Susceptible Streptococcus pyogenes: Importance of Clonal Properties in Addition to Antibiotic Consumption

ABSTRACT A steady decline in macrolide resistance among Streptococcus pyogenes (group A streptococci [GAS]) in Portugal was reported during 1999 to 2006. This was accompanied by alterations in the prevalence of macrolide resistance phenotypes and in the clonal composition of the population. In order to test whether changes in the macrolide-resistant population reflected the same changing patterns of the overall population, we characterized both macrolide-susceptible and -resistant GAS associated with a diagnosis of tonsillo-pharyngitis recovered in the period from 2000 to 2005 in Portugal. Pulsed-field gel electrophoresis (PFGE) profiling was the best predictor of emm type and the only typing method that could discriminate clones associated with macrolide resistance and susceptibility within each emm type. Six PFGE clusters were significantly associated with macrolide susceptibility: T3-emm3-ST406, T4-emm4-ST39, T1-emm1-ST28, T6-emm6-ST382, B3264-emm89-ST101/ST408, and T2-emm2-ST55. Four PFGE clusters were associated with macrolide resistance: T4-emm4-ST39, T28-emm28-ST52, T12-emm22-ST46, and T1-emm1-ST28. We found no evidence for frequent ongoing horizontal transfer of macrolide resistance determinants. The diversity of the macrolide-resistant population was lower than that of susceptible isolates. The differences found between the two populations suggest that the macrolide-resistant population of GAS has its own dynamics, independent of the behavior of the susceptible population.
Sense and sensibility: the scaleable minifab

The objective of the scaleable minifab is cost competitive, low risk IC manufacturing to satisfy a business need. This paper analyzes the capital and operating costs of a fab, and shows how the data can be used to improve the cost structures of modular IC manufacturing while containing capital risk. A modular fab can limit capital risk by allowing capacity to be added in an incremental way when needed. The paper shows that the cost per wafer is higher for the smaller fab as predicted by economics of scale. In addition, the lower wafer cost benefit of economies of scale is overshadowed by the cost penalty of under-utilization of fab capacity. This suggests that a fab should be designed in a modular way, starting small in size and growing in modules when needed. Keeping utilization high will result in a lower average wafer cost than a larger fab with economies of scale and lower utilization.
Category-theoretic quantitative compositional distributional models of natural language semantics

This thesis is about the problem of compositionality in distributional semantics. Distributional semantics presupposes that the meanings of words are a function of their occurrences in textual contexts. It models words as distributions over these contexts and represents them as vectors in high dimensional spaces. The problem of compositionality for such models concerns itself with how to produce representations for larger units of text by composing the representations of smaller units of text. This thesis focuses on a particular approach to this compositionality problem, namely using the categorical framework developed by Coecke, Sadrzadeh, and Clark, which combines syntactic analysis formalisms with distributional semantic representations of meaning to produce syntactically motivated composition operations. This thesis shows how this approach can be theoretically extended and practically implemented to produce concrete compositional distributional models of natural language semantics. It furthermore demonstrates that such models can perform on par with, or better than, other competing approaches in the field of natural language processing. There are three principal contributions to computational linguistics in this thesis. The first is to extend the DisCoCat framework on the syntactic front and semantic front, incorporating a number of syntactic analysis formalisms and providing learning procedures allowing for the generation of concrete compositional distributional models. The second contribution is to evaluate the models developed from the procedures presented here, showing that they outperform other compositional distributional models present in the literature. The third contribution is to show how using category theory to solve linguistic problems forms a sound basis for research, illustrated by examples of work on this topic, that also suggest directions for future research.
Revisiting the pathways to retirement: a latent structure model of the dynamics of transition from work to retirement

ABSTRACT A dynamic latent structure model of the work–retirement transition process was identified, focusing on transitions of work and retirement status for men and women aged 51–74 years. Using the Health and Retirement Study data (1998–2004), latent transition analysis was used to identify a best fitting model capturing work–retirement statuses in four samples defined by age and sex. The prevalence of each status was described and the dynamic transition probabilities within the latent structure were examined. Using multinomial logistic regression, socio-demographic, health, family and occupational factors were assessed to determine how each was related to the likelihood of occupying a specific latent status at baseline. Results showed that study respondents were classified into distinct groups: full retiree, partial retiree or part-time worker, full-time worker, work-disabled or home-maker. The prevalence of full retiree status increased, while the prevalence for full-time worker status decreased over time for both men and women. Membership rates in the work-disabled and partial retiree status were generally consistent, with decreased probabilities of the work-disabled status in the older age groups and increased probabilities of partial retirees among younger men. Our findings indicated that many older Americans experience multiple transitions on the pathway to retirement. Future research on late-life labour-force transitions should evaluate the impact of the recent Great Recession and examine the role of larger socio-economic contexts.
A potential model for early stages of chromosomal evolution via concentric Robertsonian fans: a large area of polymorphism in southern short-tailed shrews (Blarina carolinensis)

Western Tennessee contains unusually highly polymorphic populations of southern short-tailed shrews (Blarina carolinensis). We previously documented eight Robertsonian translocations (ROBs) accounting for a variation in diploid number from 46 in most of this species’ range to 34–40 in western Tennessee. We have now expanded our study to include data from adjacent areas in Tennessee and Mississippi, 10 localities in all. The new data show a variation in diploid number ranging from 31 to 41, four new ROBs (for a total of 12), and the novel finding of monobrachial translocations in this group. All animals collected from this large area (extending over 12,000 km2) had some level of ROBs, and none represented the 2n = 46 form seen in other parts of the range of this species. Because other species of shrews (genus Sorex) are not affected in the same area, the factors and/or selective forces causing this extensive polymorphism in B. carolinensis must be unique to this species and to this geographic area. Some ROBs were found throughout this large area of over 12,000 km2. Other translocations (including those with monobrachial homology) were located in one or two localities in this large area, and still other translocations were intermediate in their distribution. There was a concentric pattern to the evolution and presumed spreading of the ROBs. This allowed us to expand the concept of a Robertsonian “fan,” introduced by Matthey (1970), to that of concentric evolution of multiple fusion fans: ROBs likely arose independently, separated temporally and geographically, and radiated into surrounding populations to create this complex zone of polymorphism. This is an active process in its infancy, and it is not as mature as that seen in European studies of Mus and Sorex.
Effect of Glipizide on Insulin Secretion and Insulin Metabolism in Obese Type II Diabetic Patient

this study was designed to explore the short-term effect of glipizide on insulin secretion and metabolism. Plasma insulin and C-peptide levels in the fasting state and after a 100-g oral glucose load were measured in 17 obese newly diagnosed type II (non-insulin-dependent) diabetic subjects before and after 1 mo of treatment with glipizide (15 mg/day). Plasma glucose levels decreased significantly after treatment with glipizide. Plasma insulin and C-peptide concentrations in the fasting state did not change after glipizide treatment. Also, postglucose plasma insulin levels did not change after glipizide, whereas postglucose plasma C-peptide concentrations significantly increased. A significant relationship was found between the increase in C-peptide plasma levels and the decrease in glycemic profile after glucose load following glipizide treatment. The relation between plasma C-peptide and insulin incremental areas after the oral glucose load significantly increased after treatment. These results suggest that in obese type II diabetic patients, 1 mo of treatment with glipizide potentiates the (β-cell response to oral glucose load and increases insulin metabolism, probably within the liver.
Infrastructure Network Development, Re-territorialization Processes and Multilevel Territorial Governance: A Case Study in Northern Italy

Abstract Infrastructure networks play a crucial role in the construction of the territory because they create connections among places and define spatial systems in physical and economic as well as political terms. The development of mobility networks activate the re-definition of the constituting relations of territories (de-territorialization and re-territorialization processes) and interact with the re-scaling of territorial governance; new actors appear on the scene and places take part in ‘multiple spatialities’. Territorial planning has to face the new infrastructure proposals within multilevel governance processes. This paper addresses these issues on the basis of a case study regarding a proposal for a ‘territorial platform’, named Ti-Bre, between the Brenner axis and the Tuscany harbour system, in Italy. This is a new connection that may change traditional transport flows, challenging regional and sectoral visions and plans as well as territorial cooperation processes, and requiring appropriate assessment of environmental and economic sustainability.
Beta risk estimation of companies listed on the Ghana stock exchange

Purpose - The purpose of this paper is to estimate the Beta Risk Coefficient of 32 listed companies (shares), which are included in the Ghana Stock Exchange (GSE All Share Index). Design/methodology/approach - This research investigated some of the issues that can affect beta estimates (the measurement of returns, the choice of market index used, the length of estimation period, the sampling interval, the issue of normality, autocorrelation, the effect of thin trading, seasonality and stability) by using 32 listed companies. The methodology used was the Market model and some of the beta estimation techniques used included Scholes-Williams' beta, Dimson's beta, and Fowler-Rorke's beta. Findings - The empirical results generally confirm the evidence by various researchers in the literature reviewed. However, the tests for the effect of thin trading and the effect of seasonality reject the null hypothesis ( Originality/value - The study has about 95 per cent originality since the authors went into the field to gather all the data needed and did all the analysis.
Testing web-based solutions for improving reading tasks in students with dyslexia

This work is aimed at assessing whether and how we can improve the level of web pages accessibility for dyslexic users, and to determine which new requisites could be added to the current ones proposed in the Italian Stanca Act in Italy, whose standards derive from the WCAG 2.0 guidelines for disabilities. In order to achieve this goal, we designed a test targeted to students diagnosed with dyslexia. Results showed that improvements may be reached taking into account a set of parameters not specifically considered by WCAG 2.0.
Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion.

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900-1500), an afternoon nap (1400-2000), or an evening nap (1900-0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.
Insulin stimulates phosphatidylinositol-3-kinase activity in rat adipocytes.

Phosphatidylinositol (PtdIns) 3-kinase is thought to participate in the signal transduction pathways initiated by the activation of receptor tyrosine kinases including the insulin receptor. To approach the physiological relevance of this enzyme in insulin signaling, we studied the activation of PtdIns-3-kinase in adipocytes, a major insulin target tissue for glucose transport and utilisation. To analyze possible interactions of the enzyme with cellular proteins, immunoprecipitations with the following antibodies were performed: (a) anti-phosphotyrosine antibodies, (b) two antibodies to the 85-kDa subunit of PtdIns-3-kinase (p85) and (c) an antibody to the 185-kDa major insulin receptor substrate (p185). We show that in cell extracts from adipocytes exposed to insulin, and after immunoprecipitation with an anti-phosphotyrosine antibody and an antibody to p85, we are able to detect a PtdIns-3-kinase activity stimulated by the hormone. Similarly, after immunoprecipitation with an antibody to p185, an increase in the PtdIns-3-kinase activity could be demonstrated. Taken together these results suggest that, upon insulin stimulation of fat cells, PtdIns-3-kinase itself is tyrosine phosphorylated and/or associated with an insulin receptor substrate, such as p185, which could function as a link between the insulin receptor and PtdIns-3-kinase. The PtdIns-3-kinase was activated within 1 min of exposure to insulin, and the half-maximal effect was reached at the same concentration, i.e. 3 nM, as for stimulation of the insulin receptor kinase. Subcellular fractionation showed that PtdIns-3-kinase activity was found both in the membranes and in the cytosol. Further, immunoprecipitation with an antibody to p85, which possesses the capacity to activate PtdIns-3-kinase, suggests that the presence of the enzyme in the membrane may be due to an insulin-induced recruitment of the PtdIns-3-kinase from the cytosol to the membrane. Finally, we used isoproterenol, which exerts antagonistic effects on insulin action. This drug was found to inhibit both the PtdIns-3-kinase and the insulin receptor activation by insulin, suggesting that the activation of the PtdIns-3-kinase was closely regulated by the insulin receptor tyrosine kinase. The occurrence of an insulin-stimulated PtdIns-3-kinase in adipocytes leads us to propose that this enzyme might be implicated in the generation of metabolic responses induced by insulin.
Effects of pH and aeration on gamma-poly(glutamic acid) formation by Bacillus licheniformis in controlled batch fermentor cultures.

Bacillus licheniformis ATCC 9945A was grown on Medium E in batch fermentations in which the pH was maintained at 5.5. , 6.5, 7.4, and 8.25. The effects of pH on cell growth, carbon source utilization, and gamma-polyglutamic acid (gamma-PGA) production, molecular weight, and polymer stereochemistry were determined. The gamma-PGA yield was highest (15 g/L, 96 h growth time) at pH 6.5. The increase in gamma-PGA formation at pH 6.5 corresponded with a relatively high specific production rate at high gamma-PGA concentration (0.09 h(-1), approximately 15 g/L gamma-PGA). In contrast, the specific gamma-PGA production rates at fermentor pH values of 5.5 and 7.4 decreased significantly for gamma-PGA fermentor yields > approximately 5 g/L. Interestingly, alteration of the medium pH had little to no significant effects on the product quality as measured by stereochemical composition and molecular weight. While glutamate and glycerol utilization were similar as a function of pH, citrate consumption increased at pH 6.5, indicating that the formation of gamma-PGA from citrate at pH 6.5 was of increased importance. The effect of aeration was evaluated by increasing the agitation speed (250 to 800 rpm) and aeration rate (0.5 to 2.0 L/min) at pH 6.5, the pH of maximal gamma-PGA production. Increased aeration resulted in doubling of the cell dry weights (2 to 4 g/L), increasing gamma-PGA yields (6.3 to 23 g/L by 48 h) and increasing in the maximum gamma-PGA-specific production rate (0.09 to 0.11 h(-1)). Other effects of increased agitation included a rapid depletion of glutamate and citrate (by 50 h) and a decrease in product molecular weight. Despite the increase in agitation and aeration, oxygen limitation of the culture was not avoided, because the partial pressure decreased to <1.0% by 29 h.
Changes in hemodynamic and neuro-humoral control cause cardiac damage in 1 kidney , 1 clip hypertensive mice

Sympathovagal balance and baroreflex control of heart rate (HR) were evaluated during the development (one and four weeks) of one kidney, one clip (1K1C) hypertension in conscious mice. The development of cardiac hypertrophy and fibrosis was also examined. Overall variability of systolic arterial pressure (AP) and HR in the time domain and baroreflex sensitivity were calculated from basal recordings. Methyl atropine and propranolol allowed the evaluation of the sympathovagal balance to the heart and the intrinsic HR. Staining of renal angiotensin II in the kidney and plasma renin activity (PRA) were also evaluated. One and four weeks after clipping, the mice were hypertensive and tachycardic, and exhibited elevated sympathetic and reduced vagal tone. The intrinsic HR was elevated only one week after clipping. Systolic AP variability was elevated while HR variability and baroreflex sensitivity were reduced one and four weeks after clipping. Renal angiotensin II staining and PRA were elevated only one week after clipping. Concentric cardiac hypertrophy was observed one and four weeks, while cardiac fibrosis was observed only at 4 weeks after clipping. In conclusion, these data further support previous findings in the literature and provide new features of neuro-humoral changes during the development of 1K1C hypertension in mice. In addition, the 1K1C hypertensive model in mice can be an important tool for studies evaluating the role of specific genes relating to dependent and non-dependent angiotensin II hypertension in transgenic mice.
Performance in the Hedge Funds Industry

In this study, we analyze the performance persistence of hedge funds over short- and long-term horizons. Using a non-parametric test, we first observe that the Relative Value and the Specialist Credit strategies contain the highest proportion of outperforming managers. We next analyze the performance persistence of portfolios ranked according to their average past returns. Persistence is mainly observed over one- to three-month holding periods but rapidly vanishes as the formation or the holding period is lengthened. We finally examine long-term risk-adjusted returns persistence of hedge fund portfolio within an APT framework. This leads us to detect a slight overreaction pattern that is more pronounced among the directional hedge fund strategies.