Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational spectrum of ICR‐191 at the hprt locus in human lymphoblastoid cells

Human TK6 lymphoblasts were treated with the acridine derivative ICR‐191, and mutants at the hprt locus were isolated. Mutant hprt cDNA was reverse‐transcribed from mRNA, amplified by polymerase chain reaction (PCR), and sequenced. Additions of single G:C base pairs (+1 frameshift mutations) in repetitive G:C sequences were found in 82% (32/39) of the mutants. Sixteen of the +1 frameshifts analyzed were located in a single sequence of six consecutive guanine bases in exon 3. The remaining +1 frameshifts occurred at six different GGG sequences (14 mutants) and a single GGGG sequence (2 mutants) in other hprt exons. The repetitive guanine sequences that underwent frameshift mutagenesis were located in both the transcribed and nontranscribed strands of hprt. No single base deletions (‐1 frameshift mutations) were observed. Base substitutions were observed in 13% (5/39) of the clones analyzed and occurred at both G:C and A:T bases. Loss of exon 4 from the cDNA was also observed in 5% (2/39) of the mutants. Hprt mutants containing seven consecutive guanines (produced from a +1 frameshift in a GGGGGG sequence) were treated with ICR‐191 and wild‐type revertants selected in CHAT medium. Revertants were recovered at a frequency of approximately 10−7 and contained the wild‐type sequence (GGGGGG) in all clones analyzed. The observed frequency of ICR‐191‐induced ‐1 frameshift reversion in the GGGGGGG sequence was ∼500‐fold lower than the estimated frequency of +1 frameshifts observed in the wild‐type GGGGGG sequence following the same ICR‐191 treatment. These results suggest that ICR‐191 produces predominantly +1 frameshift mutations at the hprt locus in human cells. © 1994 Wiley‐Liss, Inc.
Nonsense‐mediated decay of glutathione peroxidase 1 mRNA in the cytoplasm depends on intron position

mRNA for glutathione peroxidase 1 (GPx1) is subject to cytoplasmic nonsense‐mediated decay (NMD) when the UGA selenocysteine (Sec) codon is recognized as nonsense. Here, we demonstrate by moving the sole intron of the GPx1 gene that either the Sec codon or a TAA codon in its place elicits NMD when located ≥59 bp but not ≤43 bp upstream of the intron. Therefore, the exon–exon junction of GPx1 mRNA positions the boundary between nonsense codons that do and do not elicit NMD, as has been shown for the 3′‐most junctions of mRNAs subject to nucleus‐associated NMD. We also demonstrate by using a regulatable promoter to drive GPx1 gene expression that cytoplasmic NMD is characteristic of steady‐state mRNA, in contrast to nucleus‐associated NMD. These findings clarify the mechanistic relationship between cytoplasmic and nucleus‐associated NMD and offer the first demonstration that nuclear introns can influence cytoplasmic NMD. Finally, by analyzing hybrid GPx1 genes, we disprove the idea that the cellular site of NMD is determined by the efficiency of translation initiation.
A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains

Campylobacter jejuni is a leading human enteric pathogen worldwide and despite an improved understanding of its biology, ecology, and epidemiology, limited tools exist for identifying strains that are likely to cause disease. In the current study, we used subtyping data in a database representing over 24,000 isolates collected through various surveillance projects in Canada to identify 166 representative genomes from prevalent C. jejuni subtypes for whole genome sequencing. The sequence data was used in a genome-wide association study (GWAS) aimed at identifying accessory gene markers associated with clinically related C. jejuni subtypes. Prospective markers (n = 28) were then validated against a large number (n = 3,902) of clinically associated and non-clinically associated genomes from a variety of sources. A total of 25 genes, including six sets of genetically linked genes, were identified as robust putative diagnostic markers for clinically related C. jejuni subtypes. Although some of the genes identified in this study have been previously shown to play a role in important processes such as iron acquisition and vitamin B5 biosynthesis, others have unknown function or are unique to the current study and warrant further investigation. As few as four of these markers could be used in combination to detect up to 90% of clinically associated isolates in the validation dataset, and such markers could form the basis for a screening assay to rapidly identify strains that pose an increased risk to public health. The results of the current study are consistent with the notion that specific groups of C. jejuni strains of interest are defined by the presence of specific accessory genes.
Capital Flight: Measurement and Drivers

This paper describes the nature of capital flight, the methodologies used to measure it, and its drivers. The paper presents updated estimates of the magnitude of capital flight from 39 African countries for which adequate data are available for the period 1970-2010. It gives a global context of the problem of capital flight from Africa by providing comparative indicators on capital flight and related flows for other developing regions. The paper undertakes a detailed econometric analysis of the drivers of capital flight from African countries. It explores empirically the role of domestic and external factors in driving capital flight, including structural factors, the macroeconomic environment, governance, risk and returns to investment, capital account openness, and financial development. The first objective of the study is to contribute to the literature by providing the most comprehensive analysis of capital flight from Africa that takes into account economic as well as non-economic dimensions, and recognizes the importance of both the domestic and global contexts. The second objective is to contribute to the policy debate on capital flight both in Africa and globally.
Using Reform: Conceptualizing District Initiative

This paper explores the phenomenon of district use of state reform. Past research suggests that local districts will comply minimally with mandates and respond to inducements with varying degrees of opportunism. Active use entails anticipating state responses or doing more than the state requires. Evidence is presented to illustrate that active use does exist. Existing research suggests that active users have the will and the capacity to respond positively. Will comes from a dominant coalition that believes it can set its own agenda and sees the reforms as ways to meet its own ends. Capacity comes through the formation of a temporary system that effectively manages key change functions and linkages with local schools.
The Role of Dual Embeddedness in the Innovative Performance of MNE Subsidiaries: Evidence from Brazil

This paper explores variability across a set of subsidiaries in a given local context and the same industry in terms of innovative performance as an outcome of the manner and extent to which they embed within both corporate (internal) and local (external) counterparts. By drawing on fieldwork evidence of seven subsidiaries operating in Brazil (1996-2007) it was found that: (1) subsidiaries that were able to develop knowledge-intensive linkages with specific internal and external counterparts simultaneously and based on continually increased frequency and improved quality achieved higher innovative performance levels than subsidiaries that developed such linkages with limited frequency and unchanged quality over time; and (2) some counterparts and linkages were more effective than others in terms of contributing to the subsidiaries' innovative performance. By drawing on a novel approach that explores dual embeddedness and its impacts on differences across a set of subsidiaries in terms of innovative performance over time, this paper extends our understanding of embeddedness as part of strategic asset-seeking strategies. It also provides a basis to deepen the analysis of the nuances of multiple embeddedness and its implications for the subsidiary's competitive performance.
Linking Network Coherence to Service Performance

Abstract While strategic alliances have been widely recognised as an appropriate governance mode for the co-development of capabilities, the importance of leveraging these capabilities to assemble a network of inter-linked services has been a neglected area of research. We propose network coherence as a construct to capture the degree of service consistency across the networks of the three largest global airline alliances. Employing a multi-dimensional service performance evaluation model, with a data set of over 500 customers, flying on more than 700 routes, the paper examines the impact of network coherence on customer satisfaction and market-based performance variables. The results indicate that network coherence plays a key role in improving service performance and is a useful construct in capturing a number of important service variables for airlines. The paper highlights the importance of knowledge-based capabilities in achieving competitive positioning for alliance members, exposing a number of critical challenges for global alliance networks.
THE INFLUENCE OF DISTRIBUTED LEADERSHIP ON TEACHER ORGANISATIONAL COMMITMENT: INITIAL EVIDENCE FROM VIETNAM

The present study examines the relationships between distributed leadership, demographic factors and teachers’ organisational commitment in Vietnam by using a questionnaire involving 76 teachers in three secondary schools. Consistent with previous studies, such as Bogler and Somech (2004) and Hulpia et al.(2009a), there was a significant correlation between the respondents’ perceptions of leadership distribution and their organisational commitment. Of the four independent variables examined, teacher commitment was highly correlated with and more likely to be influenced by Team leadership and Participative decision-making. Data analysis also indicates that in contrast with findings of studies conducted in Western countries, male teachers in the surveyed schools were found more committed to schools than females whilst experienced teachers showed slightly more organisational commitment than those with less experience. Cultural factors, such as gender inequality, higher respect and salaries for experienced employees were employed to shed light on these differences.
Activating Lone Parents: An Evidence-Based Policy Appraisal of Welfare-To-Work Reform in Britain

The 2008 welfare reform introduced by the previous Labour government requires (most) lone parents with older children to be available for work. This article examines the potential effect of this reform on the employment rate of lone parents and whether the age of the youngest child is a good indicator of ‘ability to work’. It suggests that reform will not lead to the desired increase as the target group is too small and the levels of multiple disadvantages within the group too high. ‘Ability to work’ needs to be conceptualised more broadly if it is to mean ‘ability to get a job’.
The 24‐h growth hormone rhythm in men: sleep and circadian influences questioned

The 24‐h rhythm of growth hormone (GH) is thought to be controlled primarily by sleep processes with a weak circadian component. This concept has been recently questioned in sleep‐deprived persons. To test the notion of a high sleep‐dependency of GH release, we established simultaneous 24‐h rhythms of GH and melatonin, a circadian marker, in night workers who form a model for challenging sleep and circadian processes. Ten day‐active subjects and 11 night workers were studied during their usual sleep–wake schedule, with sleep from 23:00 to 07:00 hours and 07:00 to 15:00 hours, respectively. Experiments were conducted in sleep rooms under continuous nutrition, bed rest, and dim light. Melatonin and GH were measured every 10 min over 24 h. In day‐active subjects, melatonin and GH showed the well‐known 24‐h profiles, with a major sleep‐related GH pulse accounting for 52.8 ± 3.5% of the 24‐h GH production and the onset of the melatonin surge occurring at 21:53 hours ± 18 min. In night workers, melatonin showed variable circadian adaptation, with the onset of secretion varying between 21:45 and 05:05 hours. The sleep‐related GH pulse was lowered, but the reduction was compensated for by the emergence of large individual pulses occurring unpredictably during waking periods, so that the total amount of GH secreted during the 24 h was constant. One cannot predict the degree of GH adaptation from the highly variable melatonin shift. These results argue against the concept that sleep processes exert a predominant influence on GH release whatever the conditions. When sleep and circadian processes are misaligned, the blunting of the sleep‐related GH pulse is counteracted, as in sleep‐deprived persons, by a compensatory mechanism promoting GH pulses during wakefulness.
Inflation, Rational Expectations and the Term Structure of Interest Rates

In a number of recent papers [11] [12],2 it has been shown that, for the United States, the behaviour of the term structure of interest rates can be explained remarkably well by combining the "Preferred Habitat" version of the Expectation Theory with a simple and readily tractable model of the formation of expectations, a model in which expected future rates are represented by a linear function of past rates. The purpose of the present paper is to generalize that approach and to strengthen the evidence supporting it in two major directions. First, we endeavour to broaden and refine the earlier analysis by making proper allowance for one additional factor, which is entirely consistent with the spirit of the model but was not duly taken into account, namely the effect of expectations of future changes in the price level. Evidence is provided that this additional factor is empirically important and that by allowing for it one can obtain a significant improvement in fit as well as a reduction in the serial correlation of the residual error. Some further improvement can also be achieved by introducing a variable intended to measure the effect of changes in the uncertainty about the future course of interest rates on the risk premium. Our second goal is to provide independent evidence in support of both the expectation theory and of our model of expectation formation and of the determinants of the risk premium, by exploring the relation between our model and the "rational expectation hypothesis". To this end we first derive expressions for the "optimal" (in the least square sense) linear forecast of all future rates, conditional upon the past history of rates of interest and rates of inflation. We show that the relation between the long rate and the history of short rates and prices which is estimated in the process of fitting our term structure equation is broadly similar to the relation that would hold if, in fact, (1) the long rate were an average of expected future rates-as called for by the expectation hypothesis-and (2) the expected future rates tended to represent optimal forecasts-as called for by the rational expectation hypothesis. These results provide strong evidence in support of both hypotheses, and of our term structure model built on them. Further
Not all Constraints are Equal: Stewardship and Boundaries of Sustainability as Viewed by First-Year Engineering Students*

The overall purpose of this research was to research attitudes and threshold concepts (key concepts or gate keeper concepts) ofbeginning engineering students towards the relationship between environment/ecology and engineering specifically towards choosing:either (a) engineering as a career to make an environmental impact or (b) choosing environmental and ecological engineering as aspecific engineering profession. The project was situated in the context of life cycle analysis and the environmental impacts of design,manufacturing, use and disposal of products. The study employed also an innovative research design: The researchers investigatedstudents’ conceptions and attitudes (and change of both) by asking students to co-design an educational game with them—through aseries of workshops. Of particular focus was the change of students’ conceptual understanding of core environmental and ecologicalconcepts during the design process. First, we reported the results of a survey of 1437 first-year engineering students at the PurdueUniversity, West Lafayette campus. The survey tested student knowledge of environmental issues, their prioritization of sustainabledevelopment in various contexts, and also explored student attitude toward change. We observed positive correlations between the highschool science courses or high school environmental education, and the average environmental knowledge scores. There was nodifference in average knowledge scores when comparing male and female students. In addition, we reported the results of an analysis ofstudents’ data as collected within the workshops. Second, we reported on preliminary findings on the participatory design workshops(n=24). The study revealed several areas of ‘troublesome’ knowledge of students.
Annexation, Local Government Spending, and the Complicating Role of Density

Annexation is often touted as a strategy to improve the overall fiscal environment of a municipality. The empirical literature on the role of annexation in municipal finance, however, has yielded inconsistent results. This article examines annexation in nearly 1,000 municipalities for its effects on local government spending. Results show that spending is influenced by annexation, but the effects on spending are complicated by accompanying changes in municipal density levels. If annexation is accompanied by higher densities, the local government will certainly experience lower increases in per-capita spending levels. However, if annexation is accompanied by lower densities, the local government may or may not experience lower increases in per-capita spending levels, depending on changes in land area relative to changes in density.
Long-term high-resolution hydrodynamical model simulation in the Gulf of Finland

Gulf of Finland is described as water body with very complex hydrography. Discharge of the largest river Neva in the eastern part of Gulf is the main cause for horizontal salinity gradient. Buoyancy driven mean cyclonic circulation varies with short term wind forced currents. The 10-year (1997–2006) simulation was done with the General Estuarine Transport Model. The horizontal resolution of the model grid was 0.5 nautical miles and 25 sigma layers in the vertical direction. The model reproduced overall seasonal cycle of temperature and salinity stratification with high inter-annual variability. Annual evolution of temperature stratification followed prevailing meteorological conditions of different years. The years with extreme meteorological conditions are well resolved by the model: the warmest (2002) and coldest (1998) summer and likewise the warm ice free winters 2000/2001 and 2001/2002. Model resolves mesoscale phenomena. Average mean surface circulation showed more persistent surface currents near the southern coast of the Gulf.
Genetic Polymorphisms of Human Flavin Monooxygenase 3 in Sulindac-Mediated Primary Chemoprevention of Familial Adenomatous Polyposis

Purpose: Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) effective in regressing adenomas in patients with familial adenomatous polyposis (FAP). However, a recent randomized trial showed that sulindac, when compared with placebo, failed to prevent the development of adenomatous polyps in genotypically positive but phenotypically negative FAP patients. The present study determined whether polymorphisms in the gene encoding flavin monooxygenase 3 (FMO3), a hepatic microsomal enzyme that inactivates sulindac, played a role in determining the efficacy of sulindac in preventing polyposis in this cohort of FAP patients. Experimental Design: Genotyping was performed on seven established FMO3 polymorphisms previously shown to have functional relevance—M66I, P153L, E158K, V257M, E305X, E308G, and R492W—in 21 and 20 FAP patients, who received sulindac and placebo, respectively. Results: None of the 41 patients exhibited heterozygous or homozygous M66I and R492W variant alleles, or homozygous P153L, V257M, and E305X variant alleles. Among sulindac-treated patients who did not develop adenomas (“responders”), 4 (33%) were homozygous for E158K and 2 (17%) were homozygous for E308G variant alleles. In contrast, none of the patients on sulindac who developed adenomas (“nonresponders”) exhibited homozygosity for either of the two variant alleles. In addition, polymorphisms in the E158K or E308G allele were associated with a significant reduction in mucosal prostanoid levels in patients treated with sulindac. Conclusions: Polymorphisms in FMO3, particularly at the E158K and E308G loci, may reduce activity in catabolizing sulindac and result in an increased efficacy to prevent polyposis in FAP.
Phases of the Canadian business cycle

In this paper we contrast a number of univariate models of Canadian GDP. We find that non-linear models are prefered to linear models, and that the most recent recession in Canada was unique in both its length and in the slow speed of recovery. We also briefly explore the link between stages of the Canadian and of the US business cycle.
Detection of neuroblastoma cells in blood.

Tumor surveillance tests are used to detect relapse and to guide the clinician in making therapeutic changes. Identification of relapse early in the course of disease may improve long-term survival. For patients with neuroblastoma, current conventional surveillance methods include radiologic testing, bone marrow analysis, physical examination, and measurement of urinary catecholamine metabolites. Immunocytologic analysis of blood for the detection of circulating tumor cells is a highly specific and sensitive method, which may prove useful in monitoring patients with neuroblastoma. In our study, circulating tumor cells were detected in seven of 10 patients with known disseminated disease at diagnosis and in six of 13 patients during therapy. In some patients, as few as two tumor cells were identified among 100,000 normal hematopoietic cells. The presence or absence of circulating neuroblasts in the 13 patients evaluated during therapy was significantly correlated with tumor relapse (P = .002). We conclude that immunocytologic analysis of blood is a sensitive method for the detection of circulating neuroblasts. We recommend that this technique be used in conjunction with other conventional methods for improved tumor detection and subsequent monitoring of neuroblastoma patients.