Miracle-dz/UniFAR-FTUs huggingface dataset:
Repression of c-Myc and inhibition of G1 exit in cells conditionally overexpressing p300 that is not dependent on its histone acetyltransferase activity

p300 and cAMP response element binding protein (CREB)-binding protein (CBP) are two highly homologous, conserved transcriptional coactivators, and histone acetyltransferases (HATs) that link chromatin remodeling with transcription. Cell transformation by viral oncogene products such as adenovirus E1A and SV40 large T antigen depends on their ability to inactivate p300 and CBP. To investigate the role of p300 in cell-cycle progression, we constructed stable rat cell lines, which conditionally overexpress p300 from a tetracycline-responsive promoter. When p300 was induced in these cells, serum-stimulated S-phase entry was significantly inhibited. The inhibition of S-phase induction was associated with down-regulation of c-Myc, but not of c-Fos or c-Jun. Simultaneous overexpression of c-Myc and p300 before serum stimulation reversed the inhibition of S-phase induction to a significant level, indicating that the inhibition of c-Myc to a large extent is responsible for the p300 inhibition of G1 exit. Similar studies with stable rat cell lines that overexpress a mutant p300, which lacks the HAT activity, showed that the intrinsic HAT activity of p300 is not required for the negative regulation of c-Myc or G1. These findings, and our previously published results (Kolli, S., Buchmann, A. M., Williams, J., Weitzman, S. & Thimmapaya, B. (2001) Proc. Natl. Acad. Sci. USA 98, 4646–4651), establish an important negative regulatory role for p300 in c-Myc expression that may be important in maintaining the cells in the G0/G1 phase of the cell cycle.
Georouting and Delta-Gathering: Efficient Data Propagation Techniques for GeoSensor Networks

We consider the issue of query and data propagation i the context of geosensor networks over geo-aware sensors. In such networks, techniques for efficient propagation of queries and data play a significant role in reducing energy consumption. Georoutingis a new technique for the broadcasting of l calized data and queriesin geo-aware sensor networks; it makes use of the existing query routing tree, and does not involve the creation of any additional communication channels. In addition to localized broadcasting, georouting is useful for (nonlocalized) broadcasting spatial data, greatly reducing the amount of communication, and hence energy consumption, during broadcasts. We demonstrate its effectiveness empirically, having implemented this technique. In addition to broadcasting queries and data to the sensors, we consider data gathering, where data is being transmitted from the sensors back towards the central processor. Delta-gatheringis a new technique for reducing the amount of communication during data gathering. Finally, we apply our delta-gathering approach toward the problem of sensor datavisualization. We present sensor terrainsas a preferable alternative to isoline-based visualization ( contour maps ) for this problem.
IMPACT OF ENTREPRENEURIAL ORIENTATION ON STRATEGIC ALLIANCES AND THE ROLE OF TOP MANAGEMENT

The management literature draws attention to the gap of strategic alliances (SA) in the paradigm of entrepreneurial orientation (EO). The aim of this paper is to propose a model where EO is associated with SA, this relationship being influenced by its predecessor (top management), and EO working as a multidimensional construct. Data collected from 101 Brazilian firms were analyzed using structural equation modeling and supported those hypotheses. Improving firms’ EO, particularly risk taking (RT), is important in order to promote SA. Obviously, top management can influence SA, but firms with an RT competence are more likely to promote SAs and conduct their implementation. Therefore, the present study offers the following contributions: (1) consolidating the EO construct by using it in a multidimensional way in a reflexive model, particularly the risk dimension; (2) advancing studies relating EO and SA by showing that top management has a significant influence on the EO-SA relationship; (3) the model used is robust and representative of the field of strategy and entrepreneurship as it explained 25.5% of the EO-SA relationship; (4) we suggest that EO should be used to increase SA and firm performance, which can reduce entrance barriers and business risks, particularly for small and medium-sized enterprises (SMEs).
AE 2 isoforms in rat kidney : immunohistochemical localization and regulation in response to chronic NH 4 Cl loading

Sebastian Frische, Alexander S. Zolotarev, Young-Hee Kim, Jeppe Praetorius, Seth Alper, Søren Nielsen, and Susan M. Wall The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C; Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C, Denmark; Department of Medicine, Harvard Medical School, Molecular and Vascular Medicine Unit and Renal Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; and Emory University School of Medicine, Renal Division, Atlanta, Georgia 30322
Delivering Knowledge across Boundaries: A Process Model of Knowledge Delivery in Offshoring Projects

The lack of understanding on how to successfully deliver knowledge across boundaries in global offshoring projects, and on why the vendors cannot fully absorb the knowledge delivered from clients, is a gap in the existing literature that may account for the inefficient mechanisms used to deliver knowledge by clients and the shift of project management strategy from total outsourcing to global teamwork. To address this gap, an integrated framework is proposed to explain how the different types and amounts of knowledge are delivered across boundaries between vendors and clients in the outsourcing arrangements by combining the framework of knowledge boundaries and absorptive capacity. Applying the new theoretical lenses to analyze the case of BankCo offshore outsourcing project, the stages are identified, through which various types of knowledge are delivered from clients to vendors by sequential processes in each stage. In particular, our study reveals that the strategic shift from total global offshore outsourcing project to global distributed teamwork lends its opportunity to the hindrance of pragmatic boundary and insufficient knowledge absorptive capacity of the vendor organizations.
Design and characterization of a 10 cm annular array transducer for high intensity focused ultrasound (HIFU) applications

A large transducer to generate high intensity focused ultrasound (HIFU) for surgery via tissue ablation is described. Designed to address the need for therapeutic applications into deep tissue, the device operates at 1.25 MHz. In order to increase focus-to-entrance intensity ratios, the design was optimized to have a natural focal distance of 10 cm at f/1.0. Variable focus is achieved by phasing the array, and particular care was exercised to maximize the range of focal distances that can be achieved with a limited number of amplifiers and elements, using a constant-phase delay design. Design approach and tradeoffs are discussed, with emphasis on comparing theoretical calculations with test performance
The effects of cytochrome P450 induction by xenobiotics on endobiotic metabolism in pre-clinical safety studies

The induction of hepatic cytochrome P450 (CYP) enzymes, conjugating enzymes, and drug transporters involved in the phase I–III metabolism of xenobiotics is frequently encountered in pre-clinical drug safety studies. As xenobiotics, new drug entities can serve as ligands to three major nuclear receptors; the aryl hydrocarbon receptor (AhR), the constitutive androstane receptor (CAR), and the pregnane X receptor (PXR). These act as xenosensors that often coordinate gene expression with several other nuclear receptors normally involved in endobiotic metabolism. A subsequent gene activation cascade can result in altered liver weights and histopathology and, in some cases, reduced therapeutic efficacy if the drug under test is also a substrate for the induced metabolic enzymes. In humans, CYP induction can result in therapeutic failure for autoinducers or drug–drug interactions if the pharmacokinetic and pharmacodynamic properties of co-administered drugs are altered because they are substrates for the induced enzymes. In addition to CYP gene expression, nuclear receptor proteins regulate the expression of complex gene networks, and therefore mediate the metabolism and modify the effects of steroid hormones, fat-soluble vitamins, and free fatty acids on the metabolic, reproductive, and developmental processes of mammals. CAR and PXR also regulate hepatic energy metabolism through cross-talk with insulin- or glucagon-responsive transcription factors. This review examines the perturbation of these endogenous regulatory systems by xenobiotic CYP inducers, which have potential pathophysiological consequences ranging from alterations in the biological clock to adverse effects on the cardiovascular system of pre-clinical species.
Genetic Diversity in German and European Populations: Looking for Substructures and Genetic Patterns

A classical case-control study is a powerful and cost-efficient approach to detect association of genetic markers with complex disease phenotypes. However, only a small fraction of significant association results has been replicated by other studies. Undetected genetic substructures in the population may be one of the reasons for spurious or biased results. The German "Genomic Control" study aims at detecting genetic differentiation between one Southern German population, represented by the KORA study (KORA Survey S4 (1999/2001)), and two Northern German populations (SHIP, Greifswald, and POPGEN, Schleswig-Holstein). Relevant population-substructures will be assessed, as well as their influence on case-control studies. Since KORA samples are used as controls for different German genetic association studies, the knowledge gained through this Genomic Control project will influence the planning of further genetic association studies. A second project, the European LD study, deals with the detection and comparison of linkage disequilibrium (LD) patterns in the human genome for eight distinct European populations. In general, a conservation of LD patterns across European samples can be observed for most gene regions. However, there are chromosomal regions with variable LD structure which may have implications on the fine-mapping of genes in different populations.
Effect of Gravity on Movement and Muscle Characteristics for Daily Occupational Performance in Sitting and Side-Lying Positions in Adults

The purpose of this study was to compare differences in the activation of biceps and triceps, if any, in patients with stroke in a simple reaching and grasping task under two body orientations, one performed under constant gravity and the other against gravity. Twenty healthy adults from the midwestern United States were randomly assigned to either an against gravity (sitting) or a constant gravity (side-lying) body orientation in a within-subject repeated measure design. Each participant performed the task of moving a filled soda can from a fixed start and end position. The results showed that the reaching velocity was significantly lower (p < .0001) and muscle activations of biceps and triceps as measured by surface electromyography were significantly less pronounced (p < .00001) in the side-lying position compared to the sitting position. The data suggest that the muscle activation patterns differ under different biomechanical constraints created by different gravity situations. Thus, the same functional task done in different body orientations may not necessarily fully recruit the same muscle groups in all orientations.
TERT Promoter Mutations Lead to High Transcriptional Activity under Hypoxia and Temozolomide Treatment and Predict Poor Prognosis in Gliomas

Objective This study explored the effects of telomerase reverse transcriptase (TERT) promoter mutations on transcriptional activity of the TERT gene under hypoxic and temozolomide (TMZ) treatment conditions, and investigated the status and prognostic value of these mutations in gliomas. Methods The effect of TERT promoter mutations on the transcriptional activity of the TERT gene under hypoxic and TMZ treatment conditions was investigated in glioma cells using the luciferase assay. TERT promoter mutations were detected in 101 glioma samples (grades I–IV) and 49 other brain tumors by sequencing. TERT mRNA expression in gliomas was examined by real-time PCR. Hazard ratios from survival analysis of glioma patients were determined relative to the presence of TERT promoter mutations. Results Mutations in the TERT promoter enhanced gene transcription even under hypoxic and TMZ treatment conditions, inducing upregulation of TERT mRNA expression. Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age. Conclusion TERT promoter mutations were specific to gliomas. TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. These findings demonstrate that TERT promoter mutations are novel prognostic markers for gliomas that can inform prospective therapeutic strategies.
Historical response rates, reinforcement context, and behavioral persistence

Historical Response Rates, Reinforcement Context, and Behavioral Persistence Chata A. Dickson In several studies, historically lower-rate responding has been found to be more persistent than historically higherrate responding (e.g., Lattal, 1989; Nevin, 1974). In these studies, historical response-rate differences were generated by reinforcement schedules (e.g., fixed-ratio [FR] and differential-reinforcement-of-low-rates-ofresponding [DRL]) that directly affect response rate. The current study was conducted with pigeons pecking keys to determine whether this finding would hold when response-rate differences were generated by the context of reinforcement, such as a concurrently available source of reinforcement or schedule of response-independent food. In each of 3 experiments, a history-building condition was followed by a history-testing condition. In Experiment 1, history building consisted of a multiple-concurrent (variable interval [VI] 40-s VI 20-s, VI 40-s VI 80-s) schedule, and history testing consisted of a multiple fixed interval (FI) 40-s, FI 40-s. It was expected that response rate would be lower on the VI 40-s schedule that was paired with the VI 20-s than the VI 40-s that was paired with the VI 80-s (cf. Belke, 1992), however, large differences in response rate on the two VI 40-s schedules were not obtained. The rate and temporal distribution of historically lower-rate responding initially changed more rapidly than did higherrate responding in each of the four pigeons. In attempt to increase the difference in response rate across the two components of the multiple schedule, in Experiment 2, history building consisted of a multiple concurrent (VI 40-s Tandem VI FR, VI 40-s Tandem VI DRL), and history testing consisted of a multiple (FI 40-s, FI 40-s). Schedule values were adjusted in attempt to obtain response-rate differences, but the programmed rate of reinforcement was always equal on the VI 40-s alternative across the two components. Again, large differences in response rate on the two VI 40-s schedules were not obtained. The rate of historically lower-rate responding changed more rapidly in three of the four pigeons, and the temporal distribution of historically lower-rate responding changed more gradually than did higher-rate responding. In Experiment 3, history building consisted of a multiple mixed VI 30-s variable time (VT) 30-s, VI 30-s schedule, and history testing consisted of a multiple FI 30-s, FI 30-s. The VT schedule provided the contextual schedule designed to reduce response rate in the same component. In this case, larger response-rate differences across the two components were obtained. Lower-rate responding was less persistent, both in terms of rate and temporal distribution of responding. Results are discussed in terms of factors shown to determine resistance to change, and the importance of understanding relations between schedules of reinforcement and resultant response organization.
AN ENERGETIC AGN OUTBURST POWERED BY A RAPIDLY SPINNING SUPERMASSIVE BLACK HOLE OR AN ACCRETING ULTRAMASSIVE BLACK HOLE

Powering the 1062 erg nuclear outburst in the MS0735.6+7421 cluster central galaxy by accretion with a 10% mass-to-energy conversion efficiency implies that its putative supermassive black hole (SMBH) grew by ∼6 × 108 M☉ over the past 100 Myr. Guided by data at several wavelengths, we place upper limits on the amount of cold gas and star formation near the nucleus of <109 M☉ and <2 M☉ yr−1, respectively. These limits imply that an implausibly large fraction of the preexisting cold gas in the inner several kpc must have been consumed by its SMBH at the rate of ∼3–5 M☉ yr−1 during the past 100 Myr while leaving no trace of star formation. Such a high accretion rate would be difficult to maintain by stellar accretion or the Bondi mechanism, unless the black hole mass approaches 1011 M☉. Furthermore, its feeble nuclear luminosities in the UV, I, and X-ray bands compared to its enormous mechanical power are inconsistent with rapid accretion onto a ∼5 × 109 M☉ black hole. We suggest instead that the active galactic nucleus (AGN) outburst is powered by angular momentum released from a rapidly spinning black hole. The rotational energy and power available from a spinning black hole are consistent with the cavity and shock energetics inferred from X-ray observations. A maximally spinning 109 M☉ black hole contains enough rotational energy, ∼1062 erg, to quench a cooling flow over its lifetime and to contribute significantly to the excess entropy found in the hot atmospheres of groups and clusters. Two modes of AGN feedback may be quenching star formation in elliptical galaxies centered in cooling halos at late times. An accretion mode that operates in gas-rich systems, and a spin mode operating at modest accretion rates. The spin conjecture may be avoided in MS0735 by appealing to Bondi accretion onto a central black hole whose mass greatly exceeds 1010 M☉. The host galaxy's unusually large 3.8 kpc stellar core radius (light deficit) may witness the presence of an ultramassive black hole.
Detection and Prevention of Malicious Activities on RDBMS Relational Database Management Systems

Insider attacks formed the biggest threaten against database management systems. There are many mechanisms have been developed to detect and prevent the insider attacks called Detection of Malicious Activities in Database Systems DEMIDS. The DEMIDS consider as one of the last defenses mechanism of the database security system. There are many mechanisms that have been developed to detect and prevent the misuse activi- ties like delete, and update data on the database systems. These mechanisms utilize auditing and profiling methods to detect and prevent the malicious activities. However these mechanisms still have problems to detect the misuse activities such as limit to detect the malicious data on authorized com- mands. This study will address these problems by propose a mechanism that utilizes dependency relationship among items to detect and prevent the malicious data by calculate a number of relations among data items. If the number of relations among items is not allowed any modification or deletion then the mechanism will detect activity as malicious activity. The evaluation parameters such as detect, false positive and false negative rate use to evaluate the accuracy of proposed mechanism.
Examining the Role of Social Cognitive Constructs in Religion's Effect on Alcohol Use

(ABSTRACT) Previous research has shown that individuals who are more religious use alcohol less than those who are less religious. The purpose of the current study was to investigate the relationship between various dimensions of religion and alcohol use, including an examination of the potential mediating role of social cognitive constructs in that relationship. It was hypothesized that: 1) Individuals who were more religious would drink alcohol less often, consume fewer drinks per drinking day, and experience fewer alcohol-related problems than those who were less religious. 2) Individuals who utilized more self-regulatory strategies, had higher self-efficacy, had less positive and more negative expectancies of alcohol use, and had standards of more moderate alcohol use would report less frequent alcohol use, fewer drinks per drinking day, and fewer alcohol-related problems. 3) Individuals who reported greater religiosity would utilize drinking self-regulatory strategies more frequently, have higher self-efficacy for avoiding heavy alcohol use, have less positive and more negative outcome expectancies regarding alcohol use, and have standards of more moderate alcohol use. 4) The relationships between the dimensions of religiosity and the alcohol use indices would be mediated by the social cognitive constructs. Three hundred and thirty-four college students completed a number of self-report questionnaires assessing alcohol use, religiosity dimensions, and social cognitive iii constructs. Results were consistent with, and expanded upon, previous research by demonstrating that various dimensions of religiosity were inversely related to, and also multivariate predictors of, the quantity and frequency of alcohol use and the experience of alcohol-related problems in a sample of college students. Findings further suggested that this relationship was completely mediated by several social cognitive constructs including self-efficacy, outcome expectancies, internal standards regarding alcohol use, and the use of self-regulatory strategies. Limitations of the study and suggestions for future research are discussed. iv Acknowledgments First and foremost, I would like to give God the glory for this major accomplishment and thank Him for guiding and supporting me throughout this endeavor. Next I would like to thank my advisor, Bob Stephens, for his leadership, teaching, and encouragement over the past 6 years. You are truly a wonderful advisor, mentor, and friend. I would also like to acknowledge two undergraduate students, Elizabeth Ashley and Kristin McCants, whose help with regard to data collection and data entry for this project was indispensable-I would not have been able to complete the study without your assistance. A special thanks to my …
On Near Optimality of the Set of Finite-State Controllers for Average Cost POMDP

We consider the average cost problem for partially observable Markov decision processes (POMDP) with finite state, observation, and control spaces. We prove that there exists an e-optimal finite-state controller (FSC) functionally independent of initial distributions for any e > 0, under the assumption that the optimal liminf average cost function of the POMDP is constant. As part of our proof, we establish that if the optimal liminf average cost function is constant, then the optimal limsup average cost function is also constant, and the two are equal. We also discuss the connection between the existence of nearly optimal finite-history controllers and two other important issues for average cost POMDP: the existence of an average cost that is independent of the initial state distribution, and the existence of a bounded solution to the constant average cost optimality equation.