Miracle-dz/UniFAR-FTUs huggingface dataset:
Subpathway Analysis based on Signaling-Pathway Impact Analysis of Signaling Pathway

Pathway analysis is a common approach to gain insight from biological experiments. Signaling-pathway impact analysis (SPIA) is one such method and combines both the classical enrichment analysis and the actual perturbation on a given pathway. Because this method focuses on a single pathway, its resolution generally is not very high because the differentially expressed genes may be enriched in a local region of the pathway. In the present work, to identify cancer-related pathways, we incorporated a recent subpathway analysis method into the SPIA method to form the “sub-SPIA method. ” The original subpathway analysis uses the k-clique structure to define a subpathway. However, it is not sufficiently flexible to capture subpathways with complex structure and usually results in many overlapping subpathways. We therefore propose using the minimal-spanning-tree structure to find a subpathway. We apply this approach to colorectal cancer and lung cancer datasets, and our results show that sub-SPIA can identify many significant pathways associated with each specific cancer that other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia of Genes and Genomes, we find that the pathways identified by sub-SPIA not only have the largest average degree, but also are more closely connected than those identified by other methods. This result suggests that the abnormality signal propagating through them might be responsible for the specific cancer or disease.
Searching for Answers

How do public administrators find information about the problems they confront at work? In particular, how and when do they reach across organizational boundaries to find answers? There are substantial potential obstacles to such searches for answers, especially in a system of decentralized governance such as the U.S. government. In this article, we examine the alternative mechanisms within the public sector that compensate for this dispersion of expertise, focusing on knowledge sharing across public DNA forensics laboratories. In particular, we propose that the emergence of informal interpersonal networks plays an important role in providing access to necessary expertise within a highly decentralized system. Our findings point both to the need for further research on knowledge sharing networks within the public sector as well as practical implications around the value of investments into facilitating the creation and maintenance of networks of practice.
Search for Galactic PeV Gamma Rays with the IceCube Neutrino Observatory

Gamma-ray induced air showers are notable for their lack of muons, compared to hadronic showers. Hence, air shower arrays with large underground muon detectors can select a sample greatly enriched in photon showers by rejecting showers containing muons. IceCube is sensitive to muons with energies above similar to 500 GeV at the surface, which provides an efficient veto system for hadronic air showers with energies above 1 PeV. One year of data from the 40-string IceCube configuration was used to perform a search for point sources and a Galactic diffuse signal. No sources were found, resulting in a 90% C.L. upper limit on the ratio of gamma rays to cosmic rays of 1.2 x 10(-3) for the flux coming from the Galactic plane region (-80 degrees less than or similar to l less than or similar to -30 degrees; -10 degrees less than or similar to b less than or similar to 5 degrees) in the energy range 1.2-6.0 PeV. In the same energy range, point source fluxes with E-2 spectra have been excluded at a level of (E/TeV)(2)d Phi/dE similar to 10(-12)-10(-11) cm(-2) s(-1) TeV-1 depending on source declination. The complete IceCube detector will have a better sensitivity (due to the larger detector size), improved reconstruction, and vetoing techniques. Preliminary data from the nearly final IceCube detector configuration have been used to estimate the 5-yr sensitivity of the full detector. It is found to be more than an order of magnitude better, allowing the search for PeV extensions of known TeV gamma-ray emitters.
Measuring living standards with income and consumption: evidence from the UK

This paper compares consumption and income as measures of households’ living standards using UK data. It presents evidence that income is likely to be under-recorded for households with low resources. It describes the different impressions one gets about trends in the level and inequality of living standards in the UK when using consumption, and when one adds an imputed income from housing, rather than near-cash income. It describes what different impressions one gets about the composition of households with low living standards if these are identified with consumption rather than income.
β-Actin and GAPDH housekeeping gene expression in asthmatic airways is variable and not suitable for normalising mRNA levels

Background: The use of reverse transcription-polymerase chain reaction (RT-PCR) to measure mRNA levels has led to the common use of β-actin and GAPDH housekeeping genes as denominators for comparison of samples. Expression of these genes is assumed to remain constant, so normalising for variations in processing and signal quantitation. However, it is well documented that β-actin and GAPDH expression is upregulated with proliferation, activation, and differentiation. We hypothesised that airway samples which differ in their cellular profiles and activation status have different levels of expression of GAPDH and β-actin. Methods: The mRNA for β-actin, GAPDH, and interleukin (IL)-2 was measured in bronchoalveolar lavage (BAL) fluid cells and endobronchial biopsy tissue by competitive RT-PCR in a cross sectional study of 26 normal controls and 92 asthmatic subjects. Results: For both BAL fluid cells and biopsy tissue, asthmatics overall had reduced expression of GAPDH and β-actin mRNA. In asthmatic subjects not using inhaled corticosteroids (ICS), GAPDH mRNA levels in both BAL fluid and biopsy tissue, and β-actin mRNA in BAL fluid cells were 10 times lower than samples from both normal controls and from asthmatic subjects using ICS. β-Actin mRNA in biopsy specimens showed the same pattern of expression, but asthmatic subjects not using ICS were not significantly different from those receiving ICS treatment. IL-2 mRNA levels did not differ between the subject or treatment groups but, when expressed as a ratio with β-actin, significant differences were seen. Conclusions: β-Actin and GAPDH used as denominators of gene expression quantitation in asthma research can cause confounding. Housekeeping genes need careful validation before their use in such quantitative mRNA assays.
MeCP2 Is Critical within HoxB1-Derived Tissues of Mice for Normal Lifespan

Rett syndrome is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), a transcriptional regulator. In addition to cognitive, communication, and motor problems, affected individuals have abnormalities in autonomic function and respiratory control that may contribute to premature lethality. Mice lacking Mecp2 die early and recapitulate the autonomic and respiratory phenotypes seen in humans. The association of autonomic and respiratory deficits with premature death suggests that Mecp2 is critical within autonomic and respiratory control centers for survival. To test this, we compared the autonomic and respiratory phenotypes of mice with a null allele of Mecp2 to mice with Mecp2 removed from their brainstem and spinal cord. We found that MeCP2 is necessary within the brainstem and spinal cord for normal lifespan, normal control of heart rate, and respiratory response to hypoxia. Restoration of MeCP2 in a subset of the cells in this same region is sufficient to rescue abnormal heart rate and abnormal respiratory response to hypoxia. Furthermore, restoring MeCP2 function in neural centers critical for autonomic and respiratory function alleviates the lethality associated with loss of MeCP2 function, supporting the notion of targeted therapy toward treating Rett syndrome.
MINIMUM DISTANCE ESTIMATORS FOR NONPARAMETRIC MODELS WITH GROUPED DEPENDENT VARIABLES

This Version: January 2002 This paper develops minimum distance estimators for nonparametric models where the dependent variable is known only to fall in a specified group with observable thresholds, while its true value remains unobserved and possibly censored. Such data arise commonly in major U.S and U.K data sets where, e.g., the thresholds between which earnings fall are observed, but not its level. Under minor regularity conditions identification of such a model is shown to depend on there being at least two thresholds when the model disturbance’s distribution is smooth and invertible. Estimators are motivated by conversion of the model into a set of binary choice models, each corresponding to one finite-valued threshold. This conversion illustrates that the difference of any two thresholds from a function that depends on identified components is identically zero; the function of interest is an additive component of this identity. Minimum distance estimators for possibly nonlinear functionals of the model are proposed, and shown to be consistent with a limiting distribution that is Gaussian. Estimators of the covariance matrix are provided. The estimators are applied to estimation of a problem in labor economics.
The impact of surplus free cash flow and audit quality on earnings management: The case of growth triangle countries

Purpose - – The purpose of this paper is twofold. First, it investigates whether high free-cash-flow companies with low-growth opportunities (surplus free cash flow (SFCF)) are associated with income-increasing earnings management. Second, it scrutinizes the effect of audit quality on the income-increasing earnings management and SFCF and earnings management relationship. Design/methodology/approach - – This study focusses on companies listed on the Bursa Efek Indonesia, Bursa Malaysia, and Stock Exchange of Singapore over the period 2005-2010. The cross-sectional modified Jones (1991) model is used to measure discretionary accruals (DACs) (the proxy for earnings management). SFCF is an indicator variable with firm Findings - – The empirical result provides supports for the hypothesis suggesting that company managers with high free cash flow and low-growth opportunities tend to use their discretion to select income increasing accounting choices. Investigation based on each of the three-country sub samples indicates that the relationship between SFCF and managers’ income-increasing accounting choice is applicable in Malaysia, partially applicable in Singapore but it is not valid in Indonesia. In addition, the statistical analyses based on all sample and country sub-samples indicate that audit quality has negative relationships with earnings management measure. The result of univariate analysis suggests that mean of DACs in companies audited by Big 4 auditors are significantly smaller compared to that of in non-Big 4 audited firms. However, the results of multivariate analysis suggest that audit quality has only partially significant association with earnings management. Moreover, this study finds that Big 4 auditors insignificantly moderate the SFCF-earnings management relationships. Practical implications - – This research may have implications for ASEAN economic reformers and regulators who are working on improving corporate governance and transparency in their countries and for investors who need insights about associated type of agency problems that may arise in across countries and Asian context studied. Originality/value - – Based on an approach used by Chung
The Recent Healthcare Reforms in Germany – How does the concept of partisanship explain the positions of SPD and CDU/CSU?

Since the 2000s, several healthcare reforms have been conducted within the healthcare system in Germany. These reforms aimed at decreasing healthcare costs by introducing market processes into public services, among other means. This paper examines the policy preferences and the discourse concerning the reforms of the two dominant parties in German politics, the Social Democratic Party (SPD) and the Christian Democratic Union (CDU/CSU). It aims at revealing why the parties favoured and supported the particular reform policies. The partisan preferences are determined by applying the theoretical concepts of partisanship, power resources theory and a market-oriented power resources approach. This paper utilises the qualitative method of a discourse analysis. The expected preferences of the parties are compared with the political discourse and the policy outcomes regarding market-orientation and strategies of cost containment and recalibration. It can be demonstrated that the SPD repeatedly acted in a way that contradicted the assumed partisan preferences.
Governance matters: an ecological association between governance and child mortality

Background Governance of a country may have widespread effects on the health of its population, yet little is known about the effect of governance on child mortality in a country that is undergoing urbanization, economic development, and disease control. Methods We obtained indicators of six dimensions of governance (perceptions of voice and accountability, political stability and absence of violence, government effectiveness, regulatory quality, rule of law, and control of corruption) and national under-5 mortality rates for 149 countries between 1996 and 2010. We applied a semi-parametric generalized additive mixed model to examine associations after controlling for the effects of development factors (urbanization level and economy), disease control factors (hygienic conditions and vaccination rates), health expenditures, air quality, and time. Results Governance, development, and disease control showed clear inverse relations with the under-5 mortality rate (p<0.001). Per unit increases in governance, development, and disease control factors, the child mortality rate had a 0.901-, 0.823-, and 0.922-fold decrease, respectively, at fixed levels of the other two factors. Conclusions In the effort to reduce the global under-5 mortality rate, addressing a country's need for better governance is as important as improvements in development and disease control.
2-Methoxyestradiol Induces Cell Cycle Arrest and Mitotic Cell Apoptosis in Human Vascular Smooth Muscle Cells

It has been shown that 2-methoxyestradiol (2-ME) inhibits cell proliferation and DNA synthesis in human aortic smooth muscle cells. However, the cellular mechanisms underlying the antiproliferative activity of 2-ME are unclear. The present study was performed to explore the cellular mechanisms whereby 2-ME leads to growth inhibition and apoptosis of human smooth muscle cells. Our results demonstrate that at 1 hour of treatment, 1 &mgr;mol/L 2-ME induces multiple spindles, overamplified centrosomes, and multipolar cytokinesis, whereas 10 &mgr;mol/L 2-ME causes completely damaged spindle, disorientated centrosomes, and missegregated chromosomes. At 6 hours of treatment, the mitotic index was increased and reached a maximal level, and cells with 4N DNA content (4N cells) began to accumulate. The increased mitotic cells induced by 2-ME were apoptotic as detected by both annexin V and TUNEL staining. Blockage of cells in G1/0 phase by thymidine prevented 2-ME-induced apoptosis. In addition, the increased mitotic index declined concurrently when even more 4N cells accumulated at 12 to 48 hours of treatment with 10 &mgr;mol/L 2-ME. Furthermore, in response to 2-ME, cells delayed entry into the next cell cycle and exhibited aneuploidy or micronuclei. Some aneuploidy cells continued to synthesize DNA. We conclude that 2-ME treatment not only arrests cells in mitosis and promotes mitotic cell apoptosis, but also causes cells to undergo “mitotic slippage” and endoreduplication. The induction of mitotic cell arrest and apoptosis may be a major cellular mechanism by which 2-ME inhibits proliferation of human smooth muscle cells.
Single-Dose Oral Toxicity of Fermented Scutellariae Radix Extract in Rats and Dogs

The aim of this study was to investigate the acute oral toxicity of fermented Scutellariae Radix (JKTMHGu-100) in rats and dogs. JKTM-HGu-100 was orally administered at a dose of 2,000 mg/kg in Sprague-Daw-ley rats. An escalating single-dose oral toxicity test in beagle dogs was performed at doses of 500, 1000, and 2000 mg/kg with 4-day intervals. Clinical signs, changes in body weight, mortality, and necropsy findings were examined for 2 weeks following oral administration. No toxicological changes related to the test substance nor mortality was observed after administration of a single oral dose of JKTM-HGu-100 in rats or dogs. Therefore, the approximate lethal dose (LD) for oral administration of JKTMHGu-100 in rats was considered to be over 2,000 mg/kg, and the maximum tolerance doses (MTDs) in rats and dogs were also estimated to be over 2,000 mg/kg. These results indicate that JKTM-HGu-100 shows no toxicity in rodents or non-rodents at doses of 2,000 mg/kg or less.
Complex Structures on indecomposable 6-Dimensional Nilpotent Real Lie Algebras

We show how resorting to dependable computer calculations makes it possible to compute all integrable complex structures on indecomposable 6-dimensional nilpotent real Lie algebras and their equivalence classes under the automorphism group of the Lie algebra. We also prove that the set comprised of all integrable complex structures on such a Lie algebra is a smooth submanifold of ℝ36.
KOF Working Papers

While Switzerland’s recent growth of employment was high in historical and international perspective, the reasons for this “job miracle” were not well understood. As the “miracle” was not anticipated by economic forecasters, it consequently resulted in systematic and persistent forecast errors. This paper shows that the “miracle” is related to a substantial increase in the labor intensity of economic activity. To this end, we present a number of stylized facts reflecting shifts and structural changes that affected the Swiss economy around 2000. Then, we discuss potential drivers of the “miracle” which are consistent with these facts. Finally, we demonstrate how they contribute to understand why, during the last ten years, forecasters systematically underestimated the growth of domestic employment. Finally, we highlight that immigration was not only a consequence of the “miracle”, but also an important cause, as it created additional jobs in Switzerland by raising local demand for goods and, most importantly, services. JEL-Classification: C52, E24, J21, J61
Lifetime events and posttraumatic stress disorder in 4 postconflict settings.

CONTEXT Little is known about the impact of trauma in postconflict, low-income countries where people have survived multiple traumatic experiences. OBJECTIVE To establish the prevalence rates of and risk factors for posttraumatic stress disorder (PTSD) in 4 postconflict, low-income countries. DESIGN, SETTING, AND PARTICIPANTS Epidemiological survey conducted between 1997 and 1999 among survivors of war or mass violence (aged >/=16 years) who were randomly selected from community populations in Algeria (n = 653), Cambodia (n = 610), Ethiopia (n = 1200), and Gaza (n = 585). MAIN OUTCOME MEASURE Prevalence rates of PTSD, assessed using the PTSD module of the Composite International Diagnostic Interview version 2.1 and evaluated in relation to traumatic events, assessed using an adapted version of the Life Events and Social History Questionnaire. RESULTS The prevalence rate of assessed PTSD was 37.4% in Algeria, 28.4% in Cambodia, 15.8% in Ethiopia, and 17.8% in Gaza. Conflict-related trauma after age 12 years was the only risk factor for PTSD that was present in all 4 samples. Torture was a risk factor in all samples except Cambodia. Psychiatric history and current illness were risk factors in Cambodia (adjusted odds ratio [OR], 3.6; 95% confidence interval [CI], 2.3-5.4 and adjusted OR,1.6; 95% CI, 1.0-2.7, respectively) and Ethiopia (adjusted OR, 3.9; 95% CI, 2.0-7.4 and adjusted OR, 1.8; 95% CI, 1.1-2.7, respectively). Poor quality of camp was associated with PTSD in Algeria (adjusted OR, 1.8; 95% CI, 1.3-2.5) and in Gaza (adjusted OR, 1.7; 95% CI, 1.1-2.8). Daily hassles were associated with PTSD in Algeria (adjusted OR, 1.6; 95% CI, 1.1-2.4). Youth domestic stress, death or separation in the family, and alcohol abuse in parents were associated with PTSD in Cambodia (adjusted OR, 1.7; 95% CI, 1.1-2.6; adjusted OR, 1.7; 95% CI, 1.0-2.8; and adjusted OR, 2.2; 95% CI, 1.1-4.4, respectively). CONCLUSIONS Using the same assessment methods, a wide range of rates of symptoms of PTSD were found among 4 low-income populations who have experienced war, conflict, or mass violence. We identified specific patterns of risk factors per country. Our findings indicate the importance of contextual differences in the study of traumatic stress and human rights violations.
ANALYTICAL METHOD FOR DETERMINING ERRORS IN CURRENT MEASUREMENTS WITH A ROGOWSKI COIL

Algebraic expressions are derived for the open-circuit voltage induced on a toroidal coil with unevenly spaced turns, by a sinusoidal current through its aperture. The derivation requires that the winding layer is thin, the number of turns is large, and the cross-section of the winding is rectangular. These expressions are used to determine the effects of the gap between the ends of the coil and other irregularities in the spacing of the turns on the position sensitivity, defined as the dependence of the induced voltage on the location of the current. This technique may be used to define the criteria to meet a specified upper limit for the positional sensitivity.
Computationally Efficient Robust Estimation of Sparse Functionals

Many conventional statistical procedures are extremely sensitive to seemingly minor deviations from modeling assumptions. This problem is exacerbated in modern high-dimensional settings, where the problem dimension can grow with and possibly exceed the sample size. We consider the problem of robust estimation of sparse functionals, and provide a computationally and statistically efficient algorithm in the high-dimensional setting. Our theory identifies a unified set of deterministic conditions under which our algorithm guarantees accurate recovery. By further establishing that these deterministic conditions hold with high-probability for a wide range of statistical models, our theory applies to many problems of considerable interest including sparse mean and covariance estimation; sparse linear regression; and sparse generalized linear models.
Trend Identification in Twentieth-Century U.S. Snowfall: The Challenges

Abstract There is an increasing interest in examining long-term trends in measures of snow climatology. An examination of the U.S. daily snowfall records for 1900–2004 revealed numerous apparent inconsistencies. For example, long-term snowfall trends among neighboring lake-effect stations differ greatly from insignificant to +100% century−1. Internal inconsistencies in the snow records, such as a lack of upward trends in maximum seasonal snow depth at stations with large upward trends in snowfall, point to inhomogeneities. Nationwide, the frequency of daily observations with a 10:1 snowfall-to-liquid-equivalent ratio declined from 30% in the 1930s to a current value of around 10%, a change that is clearly due to observational practice. There then must be biases in cold-season liquid-equivalent precipitation, or snowfall, or both. An empirical adjustment of snow-event, liquid-equivalent precipitation indicates that the potential biases can be statistically significant. Examples from this study show that th.