Miracle-dz/UniFAR-FTUs huggingface dataset:
Studies of the repair of O6-alkylguanine and O4-alkylthymine in DNA by alkyltransferases from mammalian cells and bacteria.

O6-Methylguanine in DNA is repaired by the action of a protein termed O6-alkylguanine-DNA alkyltransferase (AT) which transfers the methyl group to a cysteine residue in its own sequence. Since the cysteine which is methylated is not regenerated rapidly, if at all, the capacity for repair of O6-methylguanine is limited by the number of molecules of the AT available within the cell. The level and inducibility of the AT differed greatly in different mammalian cell types and species with the highest levels in human tissues and in liver and the lowest levels in brain. Only a small induction occurred in rat liver in response to exposure to alkylating agents. In E. coli such exposure increased the activity more than 100-fold. The At was not specific for methyl groups but also removed ethyl, 2-hydroxyethyl, n-propyl, isopropyl and n-butyl groups from the O6-position in DNA. The protein isolated from E. coli removed methyl groups much more rapidly than the larger alkyl groups but the mammalian AT isolated from rat liver showed much less difference in rate with adducts of different size. Ethyl and n-propyl groups were removed by the rat liver AT only three to four times more slowly than methyl groups. Another important difference between the bacterial and mammalian ATs is that the bacterial protein was also able to remove methyl groups from the O4-position of thymine in methylated DNA or poly(dT) but the AT from rat liver or human fibroblasts did not repair O4-methylthymidine. (ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension.

We studied the hemodynamic, neurohumoral, and biochemical effects of the novel angiotensin type 1 (AT1) receptor antagonist irbesartan in 86 untreated patients with essential hypertension on a normal sodium diet. According to a double-blind parallel group trial, patients were randomized to a once-daily oral dose of the AT1 receptor antagonist (1, 25, or 100 mg) or placebo after a placebo run-in period of 3 weeks. Randomization medication was given for 1 week. Compared with placebo, 24-hour ambulatory blood pressure did not change with the 1-mg dose, and it fell (mean and 95% confidence interval) by 7.0 (4.2-9.8)/6.1 (3.9-8.1) mm Hg with the 25-mg dose and by 12.1 (8.1-16.2)/7.2 (4.9-9.4) mm Hg with the 100-mg dose. Heart rate did not change during either dose. With the 25-mg dose, the antihypertensive effect was attenuated during the second half of the recording, and with the 100-mg dose, it was maintained for 24 hours. Baseline values of renin and the antihypertensive response to the 25- and 100-mg doses were well correlated (r = .68, P < .01). Renin did not change with the 1-mg dose, but it rose threefold to fourfold with the 25-mg dose and fourfold to fivefold with the 100-mg dose 4 to 6 hours after administration. With the 100-mg dose, renin was still elevated twofold 24 hours after dosing. The changes in renin induced by the AT1 receptor antagonist were associated with parallel increments in angiotensin I and angiotensin II. Aldosterone, despite AT1 receptor blockade, did not fall. (ABSTRACT TRUNCATED AT 250 WORDS)
Rescued expression of WIF-1 in gallbladder cancer inhibits tumor growth and induces tumor cell apoptosis with altered expression of proteins

As a highly conserved metabolic pathway, the Wnt signaling pathway is involved in cell differentiation, proliferation and several other processes. In normal cells, this pathway is suppressed, and abnormal activation is often associated with tumor occurrence and development. In certain types of tumor, Wnt inhibitory factor 1 (WIF-1), an inhibitor of the Wnt pathway, inhibits tumor growth. However, the effect of the expression of WIF-1 on gallbladder cancer remains to be fully elucidated. In the current study, reverse transcription-quantitative polymerase chain reaction and western blotting were conducted. The present study demonstrated that, in gallbladder cancer, WIF-1 generally exhibited low levels of expression as a result of gene promoter methylation. Treatment with the drug, 5-aza-2-deoxycytidine, increased the expression of WIF-1 in the GBC-SD gallbladder cell line. In addition, a WIF-1-expression plasmid was transfected into GBC-SD cells, and it was found that cell proliferation, invasion and metastasis declined significantly, whereas the apoptotic rate increased. A nude mouse tumor transplantation experiment showed that the oncogenicity of the GBC-SD cells expressing WIF-1 was substantially lower, compared with that of the untransfected GBC-SD cells and of GBD-SD cells expressing the control plasmid. A fluorescent protein chip experiment showed that the restored expression of WIF-1 affected the expression of several cellular proteins. These alterations may explain the different biological behavior of the tumor cells expressing WIF-1. As an effective inhibitory factor of the Wnt signaling pathway, WIF-1 modulated the expression of proteins controlling the proliferation, apoptosis and metastasis of gallbladder tumor cells, thus suppressing the tumor. Therefore, WIF-1 may be an effective treatment target for gallbladder cancer.
The Development of Cortical Sensitivity to Visual Word Forms

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7–12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.
NADPH oxidase complex-derived reactive oxygen species, the actin cytoskeleton, and Rho GTPases in cell migration.

SIGNIFICANCE Rho GTPases are historically known to be central regulators of actin cytoskeleton reorganization. This affects many processes including cell migration. In addition, members of the Rac subfamily are known to be involved in reactive oxygen species (ROS) production through the regulation of NADPH oxidase (Nox) activity. This review focuses on relationships between Nox-regulated ROS, Rho GTPases, and cytoskeletal reorganization, in the context of cell migration. RECENT ADVANCES It has become clear that ROS participate in the regulation of certain Rho GTPase family members, thus mediating cytoskeletal reorganization. CRITICAL ISSUES The role of the actin cytoskeleton in providing a scaffold for components of the Nox complex needs to be examined in the light of these new advances. During cell migration, Rho GTPases, ROS, and cytoskeletal organization appear to function as a complex regulatory network. However, more work is needed to fully elucidate the interactions between these factors and their potential in vivo importance. FUTURE DIRECTIONS Ultrastructural analysis, that is, electron microscopy, particularly immunogold labeling, will enable direct visualization of subcellular compartments. This in conjunction with the analysis of tissues lacking specific Rho GTPases, and Nox components will facilitate a detailed examination of the interactions of these structures with the actin cytoskeleton. In combination with the analysis of ROS production, including its subcellular location, these data will contribute significantly to our understanding of this intricate network under physiological conditions. Based on this, in vivo and in vitro studies can then be combined to elucidate the signaling pathways involved and their targets.
Square free values of the order function

Given a ∈ Z \{ ±1, 0}, we consider the problem of enumerating the integers m coprime to a such that the order of a modulo m is square free. This question is raised in analogy to a result recently proved jointly with F. Saidak and I. Shparlinski where square free values of the Carmichael function are studied. The technique is the one of Hooley that uses the Chebotarev Density Theorem to enumerate primes for which the index ip(a )o fa modulo p is divisible by a given integer.
Angioplasty : A Potential Role of Tissue Factor Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After

Belle, Michael D. Ezekowitz, Régis Bordet, Sophie Susen, Brigitte Jude and Delphine Emmanuelle Jeanpierre, Thierry Le Tourneau, Isabelle Six, Christophe Zawadzki, Eric Van Angioplasty : A Potential Role of Tissue Factor Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2003 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Circulation doi: 10.1161/01.CIR. 0000089370.84709. 51 2003;108:1740-1745; originally published online September 22, 2003; Circulation. http://circ.ahajournals. org/content/108/14/1740 World Wide Web at: The online version of this article, along with updated information and services, is located on the
Discretionary Measures and Automatic Stabilizers in the Croatian Fiscal Policy

Abstract The role of fiscal policy as a tool to stabilize business cycle fluctuations has been at the center of recent public debates. If governments allow automatic fiscal stabilizers to work fully in a downswing but fail to resist the temptation to spend cyclical revenue increases during an upswing, the stabilizers may lead to bias toward budget positions. This paper assesses to what extent some items of the Croatian central government budget operate to smooth the business cycle. For disentangling automatic stabilizers from discretionary measures, this research relies on the European Commission methodology. Results show that the structural budget balance was on average 1.74% of GDP in deficit in the period between 1995 and 2009. Automatic stabilisation in Croatia is relatively weak and supplemented by discretionary measures, which led to “destabilizing” the economic activity in a pro-cyclical manner in Croatia in several observed periods.
Computing discrete logarithms in high-genus hyperelliptic Jacobians in provably subexponential time

We provide a subexponential algorithm for solving the discrete logarithm problem in Jacobians of high-genus hyperelliptic curves over finite fields. Its expected running time for instances with genus g and underlying finite field Fq satisfying g ≥ ϑ log q for a positive constant ϑ is given by O(e(f(√1+3/2ϑ + √3/2ϑ) + o(1)) √(g log q) log (g log q)) The algorithm works over any finite field, and its running time does not rely on any unproven assumptions.
Information-accessing furniture to make our everyday lives more comfortable

We present a concept for information equipment called information-accessing furniture. We have developed an embedded module to be assembled into tables, mirrors, and walls. It can be easily assembled into furniture or other interior components because it is a package of information processing units, input/output units, and other optional units. This concept enables building information equipment designed to match a surrounding environment, and offers an intuitive interface to users, thus helping them to obtain information easily while doing routine activities. We developed several different prototypes with embedded modules and studied their applications. Some comments we received during interviews with end-users and interior designers are also presented 1 .
Ketamine and propofol differentially inhibit human neuronal K+ channels

Background and objective Interaction of intravenous anaesthetic agents with voltage-dependent potassium channels significantly correlates with clinical concentrations. If potassium channels were to play an important part in anaesthesia, one might expect different effects at the molecular level of those anaesthetics that show different clinical effects. Our aim was to analyse the interaction of general anaesthetics with voltage-dependent K channels. Methods Whole cell patch-clamp experiments were analysed in detail in order to compare the effects of two clinically diverse intravenous hypnotics, ketamine and propofol, on voltage-dependent potassium channels in human neuroblastoma SH-SY5Y cells. Results Both anaesthetics inhibited the potassium conductance in a concentration-dependent and reversible manner with IC50-values of 300 µM and 45 µM for ketamine and propofol respectively. Whereas ketamine shifted the midpoint of current activation by maximally 14 mV to more hyperpolarized potentials, propofol had the opposite effect on the activation midpoint. Current inhibition by ketamine increased with voltage but decreased with propofol at higher membrane potentials. Propofol but not ketamine induced concentration-dependent but voltage-independent decline, akin to inactivation, of the voltage-dependent potassium channels. Conclusions The anaesthetics differed not only in their clinical profiles but they also showed differential actions on voltage-dependent potassium channels in several ways. This provides additional evidence for the hypothesis that voltage-dependent potassium channels play an important role in anaesthesia.
Abnormal Left-Sided Orbitomedial Prefrontal Cortical–Amygdala Connectivity during Happy and Fear Face Processing: A Potential Neural Mechanism of Female MDD

Background: Pathophysiologic processes supporting abnormal emotion regulation in major depressive disorder (MDD) are poorly understood. We previously found abnormal inverse left-sided ventromedial prefrontal cortical–amygdala effective connectivity to happy faces in females with MDD. We aimed to replicate and expand this previous finding in an independent participant sample, using a more inclusive neural model, and a novel emotion processing paradigm. Methods: Nineteen individuals with MDD in depressed episode (12 females), and 19 healthy individuals, age, and gender matched, performed an implicit emotion processing and automatic attentional control paradigm to examine abnormalities in prefrontal cortical–amygdala neural circuitry during happy, angry, fearful, and sad face processing measured with functional magnetic resonance imaging in a 3-T scanner. Effective connectivity was estimated with dynamic causal modeling in a trinodal neural model including two anatomically defined prefrontal cortical regions, ventromedial prefrontal cortex, and subgenual cingulate cortex (sgACC), and the amygdala. Results: We replicated our previous finding of abnormal inverse left-sided top-down ventromedial prefrontal cortical–amygdala connectivity to happy faces in females with MDD (p = 0.04), and also showed a similar pattern of abnormal inverse left-sided sgACC–amygdala connectivity to these stimuli (p = 0.03). These findings were paralleled by abnormally reduced positive left-sided ventromedial prefrontal cortical–sgACC connectivity to happy faces in females with MDD (p = 0.008), and abnormally increased positive left-sided sgACC–amygdala connectivity to fearful faces in females, and all individuals, with MDD (p = 0.008; p = 0.003). Conclusion: Different patterns of abnormal prefrontal cortical–amygdala connectivity to happy and fearful stimuli might represent neural mechanisms for the excessive self-reproach and comorbid anxiety that characterize female MDD.
Overlapping Resilient HG Control for Uncertain Time-Delayed Systems

The paper presents the expansion-contraction relations within the Inclusion Principle for a class of continuoustime state-delayed uncertain systems when considering HP state memoryless control with additive controller uncertainty. All uncertainties are supposed to be time-varying norm bounded. The main contribution is the derivation of conditions under which a resilient HP control law designed in the expanded space is contracted into the initial system preserving simultaneously both the robust quadratic stability of closed-loop systems and the value of the HP-norm disturbance attenuation bound. A LMI delay independent procedure is supplied for control design. The results are specialized into the overlapping decentralized control setting which enables to construct robust HP resilient block tridiagonal state feedback controllers.
Validation of a Mathematical Model of Gene Transcription in Aggregated Cellular Systems: Application to L1 Retrotransposition

We present a methodology aimed at partial validation and accuracy-precision assessment of a mathematical model of gene transcription at the cellular level. The method is based on the analysis of time-series measurements aggregated over a large number of cells. Such measurements are typically obtained via reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. The validation procedure presented herein uses as an example data on L1 retrotransposon gene in HeLa cells. The procedure compares model predicted values with the RT-PCR data for L1 by means of the standard Bayesian statistical techniques with the help of modern Markov-Chain Monte-Carlo methodology.
The Phonology and Morphology of Arabic

1. Introduction 2. The Phoneme System of Arabic 3. Phonological Features 4. Syllable Structure and Syllabification 5. Word Stress 6. Morphology 7. Morphology 2 8. Lexical Phonology 9. Post-Lexical Phonology 10. Emphasis References Index of Authors Index of Subjects
Serum CA19-9 Is Significantly Upregulated up to 2 Years before Diagnosis with Pancreatic Cancer: Implications for Early Disease Detection

Purpose: Biomarkers for the early detection of pancreatic cancer are urgently needed. The primary objective of this study was to evaluate whether increased levels of serum CA19-9, CA125, CEACAM1, and REG3A are present before clinical presentation of pancreatic cancer and to assess the performance of combined markers for early detection and prognosis. Experimental Design: This nested case–control study within the UKCTOCS included 118 single and 143 serial serum samples from 154 postmenopausal women who were subsequently diagnosed with pancreatic cancer and 304 matched noncancer controls. Samples were split randomly into independent training and test sets. CA19-9, CA125, CEACAM1, and REG3A were measured using ELISA and/or CLIA. Performance of markers to detect cancers at different times before diagnosis and for prognosis was evaluated. Results: At 95% specificity, CA19-9 (>37 U/mL) had a sensitivity of 68% up to 1 year, and 53% up to 2 years before diagnosis. Combining CA19-9 and CA125 improved sensitivity as CA125 was elevated (>30 U/mL) in approximately 20% of CA19-9–negative cases. CEACAM1 and REG3A were late markers adding little in combined models. Average lead times of 20 to 23 months were estimated for test-positive cases. Prediagnostic levels of CA19-9 and CA125 were associated with poor overall survival (HR, 2.69 and 3.15, respectively). Conclusions: CA19-9 and CA125 have encouraging sensitivity for detecting preclinical pancreatic cancer, and both markers can be used as prognostic tools. This work challenges the prevailing view that CA19-9 is upregulated late in the course of pancreatic cancer development. Clin Cancer Res; 21(3); 622–31. ©2014 AACR.
REC-STA: Reconfigurable and Efficient Chip Design With SMO-Based Training Accelerator

Sequential minimal optimization (SMO) and Karush-Kuhn-Tucker condition are often used to solve learning problems in support vector machines. However, during hardware implementation of the SMO algorithm, enhancing chip performance without excessively increasing chip area is often a crucial issue. The solution proposed in this paper is a novel reconfigurable and efficient chip design with SMO-based training accelerator (REC-STA). Two novel methods used in the proposed REC-STA are trimode coarse-grained reconfigurable architecture (TCRA) and triple finite-state-machine with dynamic scheduling The first method modifies the baseline SMO design by developing trimode reconfigurable architectures with parallel and pipeline computing capabilities. The second method provides a schedule for efficient reconfiguration of the TCRA. Use of these methods can remove kernel cache design. For chip manufacturing, the implementation of the REC-STA is synthesized, placed, and routed using the TSMC 0.18-μm technology library. The core size is 2.94 mm × 2.94 mm and the power consumption is 77.3 mW. Compared with the baseline design, the FPGA simulation results show that the proposed architecture requires 50% less memory and 31% fewer gate counts but provides a 16-fold improvement in training performance. The experimental results confirm the efficacy of the proposed architecture and methods.
Heterogeneous Genomic Differentiation Between Walking-Stick Ecotypes: “Isolation by Adaptation” and Multiple Roles for Divergent Selection

Abstract Genetic differentiation can be highly variable across the genome. For example, loci under divergent selection and those tightly linked to them may exhibit elevated differentiation compared to neutral regions. These represent “outlier loci” whose differentiation exceeds neutral expectations. Adaptive divergence can also increase genome-wide differentiation by promoting general barriers to neutral gene flow, thereby facilitating genomic divergence via genetic drift. This latter process can yield a positive correlation between adaptive phenotypic divergence and neutral genetic differentiation (described here as “isolation-by-adaptation”). Here, we examine both these processes by combining an AFLP genome scan of two host plant ecotypes of Timema cristinae walking-sticks with existing data on adaptive phenotypic divergence and ecological speciation in these insects. We found that about 8% of loci are outliers in multiple population comparisons. Replicated comparisons between population-pairs using the same versus different host species revealed that 1–2% of loci are subject to host-related selection specifically. Locus-specific analyses revealed that up to 10% of putatively neutral (nonoutlier) AFLP loci exhibit significant isolation-by-adaptation. Our results suggest that selection may affect differentiation directly, via linkage, or by facilitating genetic drift. They thus illustrate the varied and sometimes nonintuitive contributions of selection to heterogeneous genomic differentiation.
A contribution to the empirics of welfare growth

Abstract This paper compares the determinants of economic growth and ‘full’ income growth. Our main result is that determinants may differ or have very different impact on welfare outcomes as compared to economic outcomes. Human capital plays a bigger role in determining the former, so that policies targeting human capital might have a greater effect on the welfare of societies than one would think by looking at their impact on economic growth alone. The same goes for health institutions and a number of other factors. Initial income has a greater impact on ‘full’ income growth than on real income per capita growth, implying even faster convergence than previously found, after conditioning for economic, health-related, institutions-related, and geographic cross-country differences. Overall, we strongly reject the hypothesis that the coefficient estimates for the impact of our set of explanatory variables on ‘full’ income growth is the same as for income growth. We conclude that there exist systematic differences for the impact of a number of factors on economic versus welfare growth outcomes.