Miracle-dz/UniFAR-FTUs huggingface dataset:
UGT genomic diversity: beyond gene duplication

The human uridine diphospho (UDP)-glucuronosyltransferase (UGT) superfamily comprises enzymes responsible for a major biotransformation phase II pathway: the glucuronidation process. The UGT enzymes are located in the endoplasmic reticulum of almost all tissues, where they catalyze the inactivation of several endogenous and exogenous molecules, including bilirubin, sex steroids, numerous prescribed drugs, and environmental toxins. This metabolic pathway is particularly variable. The influence of inheritable polymorphisms in human UGT-encoding genes has been extensively documented and was shown to be responsible for a fraction of the observed phenotypic variability. Other key genomic processes are likely underlying this diversity; these include copy-number variations, epigenetic factors, and newly discovered splicing mechanisms. This review will discuss novel molecular aspects that may be determinant to UGT phenotypes.
A behaviour instantiation agent architecture

This paper presents a novel agent architecture, the VM-architecture, that chooses its actions via a behaviour instantiation mechanism inspired by Maes? s behaviour networks. The VM-architecture enables an agent, VMattie, built upon it, actively to gather information from humans using email in natural language, to compose announcements of next week? s seminars and to mail them each week to a list that she keeps updated. VMattie does all this without the supervision of a human. Implemented and tested in a UNIX environment, the system? s performance surpassed the authors? fondest hopes.
Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers.

The pharmacokinetics of iron were investigated after intravenous administration to 12 healthy volunteers of iron(III)-hydroxide sucrose complex (Venofer) as a single i.v. dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mumol/l. There was no statistically significant difference between the serum iron level before injection (0 h) and the level at 24 h after the injection. The compartment model used includes a Michaelis-Menten term and is in excellent agreement with the observed exchange of iron to transferrin and with the daily iron turnover by transferrin. The intravenously injected iron(III)-hydroxide sucrose complex led rapidly to high serum iron levels. Maximum measured levels averaged 538 mumol/l (30.0 mg/l) at 10 min after the injection. The terminal half-life of the injected iron was calculated to be 5.3 h. Mean total area under the curve (AUC) was 1491 mumol/l h, the mean residence time (MRT) was 5.5 h. The total body clearance was 20.5 ml/min. The volume of distribution of the central compartment (Vc) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vdss) was 7.31; and the volume of distribution during elimination (Vdarea) was 9.21. The calculated amount of iron transported by transferrin was 31.0 +/- 6.6 mg Fe/ 24h. In summary, the data show that the injected iron(III)-hydroxide sucrose complex is quickly cleared from the serum with a terminal half-life of approximately 5-6 h. Renal elimination of iron contributed very little to the overall elimination (in average < 5%). Renal elimination of sucrose averaged about 68 +/- 10% and 75 +/- 11% of the administered dose after 4 h and 24 h, respectively.
Quantification of the physiological and performance characteristics of on-court tennis drills

Objective: To determine the physiological responses and stroke characteristics of common on-court tennis training drills. Methods: Six high-performance players performed 1×6 repetitions of four common on-court training drills on two separate occasions; once with 30:30 seconds work:rest, and once with 60:30 seconds work:rest. Heart rate (HR), blood lactate [La−], distance covered by the player (GPS) and rate of perceived exertion (RPE) were measured before the start of each drill and after the first and last repetition. Measures of shot count and accuracy and post-impact ball velocity per drill were also recorded. Results: Significant differences were observed between drills in measures of [La−] and RPE both during ([La−] 2.1–4.4 mmol/l; RPE 2.6–5.1) and after ([La−] 4.4–10.6 mmol/l; RPE 4.3–7.6) drills, yet individual HR responses (160–182 beats/minute) were similar. Increased work times (60 v 30 seconds) also produced consistently raised [La−] and RPE responses, yet players’ average movement velocities and forehand ball speed and accuracy remained consistent. Significant decreases in forehand ball speed and accuracy were observed during higher-intensity training drills, whereas significantly lower mean movement velocities underpinned performance of less intensive drills. Conclusions: The four drills produced physiological responses that reflect previously reported normal or maximal matchplay demands. These results point to the adaptations possible with adjustment of training drill type and load specific to matchplay demands or training phase.
Activation of AMP‐activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders

It is now becoming evident that the liver has an important role in the control of whole body metabolism of energy nutrients. In this review, we focus on recent findings showing that AMP‐activated protein kinase (AMPK) plays a major role in the control of hepatic metabolism. AMPK integrates nutritional and hormonal signals to promote energy balance by switching on catabolic pathways and switching off ATP‐consuming pathways, both by short‐term effects on phosphorylation of regulatory proteins and by long‐term effects on gene expression. Activation of AMPK in the liver leads to the stimulation of fatty acid oxidation and inhibition of lipogenesis, glucose production and protein synthesis. Medical interest in the AMPK system has recently increased with the demonstration that AMPK could mediate some of the effects of the fat cell‐derived adiponectin and the antidiabetic drugs metformin and thiazolidinediones. These findings reinforce the idea that pharmacological activation of AMPK may provide, through signalling and metabolic and gene expression effects, a new strategy for the management of metabolic hepatic disorders linked to type 2 diabetes and obesity.
The Greenhouse Effect in Central North America: If Not Now, When?

Climate models with enhanced greenhouse gas concentrations have projected temperature increases of 2� to 4�C, winter precipitation increases of up to 15 percent, and summer precipitation decreases of 5 to 10 percent in the central United States by the year 2030. An analysis of the climate record over the past 95 years for this region was undertaken in order to evaluate these projections. Results indicate that temperature has increased and precipitation decreased both during winter and summer, and that the ratio of winter-to-summer precipitation has decreased. The signs of some trends are consistent with the projections whereas others are not, but none of the changes is statistically significant except for maximum and minimum temperatures, which were not among the parameters predicted by the models. Statistical models indicate that the greenhouse winter and summer precipitation signal could have been masked by natural climate variability, whereas the increase in the ratio of winter-to-summer precipitation and the higher rates of temperature change probably should have already been detected. If the models are correct it will likely take at least another 40 years before statistically significant precipitation changes are detected and another decade or two to detect the projected changes of temperature.
Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer.

PURPOSE Although models exist that place patients into discrete groups at various risks for disease recurrence after surgery for prostate cancer, we know of no published work that combines pathologic factors to predict an individual's probability of disease recurrence. Because clinical stage and biopsy Gleason grade only approximate pathologic stage and Gleason grade in the prostatectomy specimen, prediction of prognosis should be more accurate when postoperative information is added to preoperative variables. Therefore, we developed a postoperative nomogram that allows more accurate prediction of probability for disease recurrence for patients who have received radical prostatectomy as treatment for prostate cancer, compared with the preoperative nomogram we previously published. PATIENTS AND METHODS By Cox proportional hazards regression analysis, we modeled the clinical and pathologic data and disease follow-up for 996 men with clinical stage T1a-T3c NXM0 prostate cancer who were treated with radical prostatectomy by a single surgeon at our institution. Prognostic variables included pretreatment serum prostate-specific antigen level, specimen Gleason sum, prostatic capsular invasion, surgical margin status, seminal vesicle invasion, and lymph node status. Treatment failure was recorded when there was either clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on this set of men and a separate sample of 322 men from five other surgeons' practices from our institution. RESULTS Cancer recurrence was noted in 189 of the 996 men, and the recurrence-free group had a median follow-up period of 37 months (range, 1 to 168 months). The 7-year recurrence-free probability for the cohort was 73% (95% confidence interval, 68% to 76%). The predictions from the nomogram appeared to be accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (ie, a comparison of the predicted probability with the actual outcome) of 0.89. CONCLUSION A postoperative nomogram has been developed that can be used to predict the 7-year probability of disease recurrence among men treated with radical prostatectomy.
From Financial Crisis to Global Recovery

Preface1. Financial Crisis Origin2. Banking Sector Stress Tests: United States Versus the European Union3. Is the U.S. Economy on the Mend? 4. Global Recovery Prospects: North America and Europe, Asia, and South America5. Hedge Funds and Derivatives, Credit Default Swaps, and Rating Agencies6. U.S. and EU Regulatory Proposals: How Strict? How Cooperative? 7. The Dollar's Future as a Reserve Currency8. The Great Depression and the Current Financial Crisis9. The Future of American CapitalismNotesIndex
Pseudomonas aeruginosa sodA and sodB mutants defective in manganese- and iron-cofactored superoxide dismutase activity demonstrate the importance of the iron-cofactored form in aerobic metabolism

The consumption of molecular oxygen by Pseudomonas aeruginosa can lead to the production of reduced oxygen species, including superoxide, hydrogen peroxide, and the hydroxyl radical. As a first line of defense against potentially toxic levels of endogenous superoxide, P. aeruginosa possesses an iron- and manganese-cofactored superoxide dismutase (SOD) to limit the damage evoked by this radical. In this study, we have generated mutants which possess an interrupted sodA (encoding manganese SOD) or sodB (encoding iron SOD) gene and a sodA sodB double mutant. Mutagenesis of sodA did not significantly alter the aerobic growth rate in rich medium (Luria broth) or in glucose minimal medium in comparison with that of wild-type bacteria. In addition, total SOD activity in the sodA mutant was decreased only 15% relative to that of wild-type bacteria. In contrast, sodB mutants grew much more slowly than the sodA mutant or wild-type bacteria in both media, and sodB mutants possessed only 13% of the SOD activity of wild-type bacteria. There was also a progressive decrease in catalase activity in each of the mutants, with the sodA sodB double mutant possessing only 40% of the activity of wild-type bacteria. The sodA sodB double mutant grew very slowly in rich medium and required approximately 48 h to attain saturated growth in minimal medium. There was no difference in growth of either strain under anaerobic conditions. Accordingly, the sodB but not the sodA mutant demonstrated marked sensitivity to paraquat, a superoxide-generating agent. P. aeuroginosa synthesizes a blue, superoxide-generating antibiotic similar to paraquat in redox properties which is called pyocyanin, the synthesis of which is accompanied by increased iron SOD and catalase activities (D.J. Hassett, L. Charniga, K. A. Bean, D. E. Ohman, and M. S. Cohen, Infect. Immun. 60:328-336, 1992). Pyocyanin production was completely abolished in the sodB and sodA sodB mutants and was decreased approximately 57% in sodA mutants relative to that of the wild-type organism. Furthermore, the addition of sublethal concentrations of paraquat to wild-type bacteria caused a concentration-dependent decrease in pyocyanin production, suggesting that part of the pyocyanin biosynthetic cascade is inhibited by superoxide. These results suggest that iron SOD is more important than manganese SOD for aerobic growth, resistance to paraquat, and optimal pyocyanin biosynthesis in P. aeruginosa.
Assessing the Vulnerability of Emerging Asia to External Demand Shocks: The Role of China

The paper assesses the vulnerability of China to external shocks via the indirect negative effect of a slow-down in exports on domestic demand for investment. In the last decade China has increased its dependence on external demand, particularly from the advanced countries; at the same time it has become a primary destination market for goods produced in the rest of emerging Asia. Since 2001 investment expenditures have represented a key driver of Chinese GDP growth; as a very large share of activity in the manufacturing sector is export oriented, we expect fixed capital investment in this sector to be highly related to exports. Overcoming serious shortcomings in available data, we estimate an investment equation for the period 1993-2006 and find an elasticity of investment to exports in the manufacturing sector in the range between 0.9 and 1. Taking into account the dominant contribution of capital accumulation to Chinese GDP growth, we conclude that the growth effects of an external demand shock could become significant when taking into account the domestic investment channel.
Enhancing private enforcement of Australia's corporate continuous disclosure regime: why unshackling litigation funders makes eminent sense

With a view to protecting the interests of investors in public companies more effectively, current Australian corporate law imposes on certain market participants a duty of continuous disclosure of key financial and other information concerning the business and affairs of a company. This is designed to promote transparency and, ultimately, foster a fair, efficient and competitive capital market environment. If this lofty objective is to be achieved, it is imperative that the law relating to continuous disclosure is robustly enforced. Private parties can play a significant role in this regard. By complementing the enforcement efforts of public regulatory authorities, the private enforcement process increases the chances that violations of the law will be found out and pursued. In the recent case of Brookfield Multiplex Limited v International Litigation Funding Partners Pte Ltd (2009) 27 ACLC 1610; [2009] FCAFC 147, the Full Federal Court of Australia considered shareholder class litigation facilitated by commercial litigation funders to challenge an alleged failure to observe the continuous disclosure laws. The majority made a finding characterising the actions of the class litigants, their lawyers and the litigation funders as giving rise to a managed investment scheme subject to regulation under the Corporations Act 2001 (Cth). If allowed to stand, this decision has the potential to discourage the funding of private litigation seeking to challenge suspected contraventions of the continuous disclosure regime. A reduction in private enforcement is, in turn, likely to lead to less than optimum enforcement of the law. As well, unless reversed, the decision is likely to discourage the use of the class action procedure in proceedings seeking to enforce the law in this area. Given the important role that class actions play in resolving in one law suit the claims of numerous individuals having a common legal position, the decision is apt to undermine judicial efficiency. These are very weighty matters. In order to overcome these problems, the Commonwealth Government has announced its intention to introduce reforms to alleviate the regulatory burden introduced by the Full Federal Court. This development is most welcome. By reforming the law to remove the undesirable effects of the Multiplex decision, policy makers will serve the interests of investors and society generally better. This paper considers the impact of the Multiplex decision and explores ways in which the law can be reformed to overcome its effects.
Do IPOs Face Higher Accounting-Related Litigation Risk? Evidence from Restatements

I compare litigation risks related to restated IPO prospectus financials and a matched sample of restated non-IPO financial statements. I find that investors are more likely to sue IPO companies than non-IPO companies and that the higher litigation rate in IPOs stems from companies with error-type restatements. In addition, I find IPO suits are more likely to be settled than non-IPO suits. Overall, these results are consistent with plaintiff attorney’s incentives driving the filing of lawsuits and suggest a potential explanation for why IPO issuers provide higher quality financial reporting. The prospect of higher litigation risk provides ex ante incentives for IPO companies to mitigate accounting errors and thus improve financial reporting quality compared to non-IPO companies. I am grateful to my dissertation committee—Michael Willenborg (Chair), Assaf Eisdorfer, David Weber, and Yanhua (Sunny) Yang—for their continuous guidance and support. I thank Dain Donelson, Todd Kravet, Jeremy McClane, Logan Steele, Kexin Zheng, Ying Zhou, and workshop participants at the University of Connecticut for their insightful comments. All errors are my own.
Identification of Free Radicals by Spin Trapping with DEPMPO and MCPIO Using Tandem Mass Spectrometry

This study evaluates the use of a pyrroline (DEPMPO) and an imidazole (MCPIO) spin trap for the detection of hydroxyl and biomolecule (a peptide and a phospholipid) free radical adducts by electrospray ionization mass spectrometry (ESI-MS). The hydroxyl and biomolecule free radical adducts were detected using a quadrupole time-of-flight (QToF) and a linear ion trap (LIT) mass spectrometers. In the presence of hydroxyl radical, the mass spectrum obtained for each of the spin traps, DEPMPO and MCPIO, showed the presence of ions that could be attributed to hydroxyl and peroxyl radicals. Further characterisation by tandem mass spectrometry (MS/MS) also revealed the presence of hydroxy–hydroxyl adducts. Based on the results described here, we show that DEPMPO is a better spin trap for free radical trapping and detection by mass spectrometry mainly because adducts show increased signal intensity. The ESI-MS spectra obtained for DEPMPO and MCPIO in the presence of biomolecule radicals (peptide and phospholipid) show molecular ions of DEPMPO and MCPIO adducts, which were characterised by MS/MS. Both carbon centred radicals and oxygen centred radicals were efficiently trapped by the two spin traps and analysis of QToF-MS/MS spectra allowed the location of the radical position in either the peptide or in the phospholipid fatty acyl chain. However, the MS/MS spectra of MCPIO adducts were more informative than DEPMPO adducts. The LIT-MS/MS spectra only shows typical peptide and phospholipid fragmentation, which is difficult for the structural characterisation of the spin adduct. In this study, the DEPMPO and MCPIO adducts were identified either in nitrone or hydroxylamine form, which are electron spin resonance (ESR) silent forms. The results described here show that both spin traps coupled with detection by mass spectrometry are valuable tools for trapping radicals of biomolecules. Furthermore, the acquired data provide valuable information on the presence of adducts (hydroxyl and biomolecule) that are ESR silent. This is especially important considering the complexity of the radical species in a biological environment and the presence of reducing compounds that convert the spin adducts to silent ESR forms.
Learner Modeling Based on Bayesian Networks

The work presented in this chapter lies within Learner modeling in an adaptive ed‐ ucational system construed as a computational modeling of the learner. All actions of the learner in a learning situation on an adaptive hypermedia systems are not limited to valid or invalid actions (true and false), but they are a set of actions that characterize the learning path of his formation. Thus, we cannot represent the infor‐ mation from the system of each learner using relative data. It requires putting our work in a probabilistic context due to the changes in the learner model information during formation. We propose in this work to use Bayesian networks as a probabil‐ istic framework to resolve the issue of dynamic management and update of the learner model. The experiments and results presented in this work are arguments in favor of our hypothesis, and can also promote reusing the modeling obtained through different systems and similar modeling situations.
CBFAST- Efficient Clustering Based Extended Fast Feature Subset Selection Algorithm for High Dimensional Data

The recent increase of data poses a major challenge in data extracting. High dimensional data contains high degree of irrelevant and redundant information. Feature selection is the process of eliminating such irrelevant and redundant data set with respect to the task to be performed. Several features selection techniques are used to improve the efficiency and performance of various machine learning algorithms. There are several methods that have been proposed to extract features from such high dimensional data. This paper proposes Clustering based extended Fast Feature Selection method to extract features from high dimensional data. The proposed algorithm Semi- supervised learning which is useful to partition the data in appropriate clusters. Also it selects the most frequent feature subset from the input.