Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrative transformation of Candida albicans, using a cloned Candida ADE2 gene

Candida albicans is a diploid dimorphic yeast with no known sexual cycle. The development of a DNA transformation system would greatly improve the prospects for genetic analyses of this yeast. Plasmids were isolated from a Candida Sau3A partial library which complements the ade2-1 and ade2-5 mutations in Saccharomyces cerevisiae. These plasmids contain a common region, part of which, when subcloned, produces ade2 complementation. Among the small number of auxotrophs previously isolated in C. albicans, red adenine-requiring mutants had been identified by several groups. In two of these strains, the cloned Candida DNA transformed the mutants to ADE+ at frequencies of 0.5 to 5 transformants per micrograms of DNA. In about 50% of the transformants, plasmid DNA sequences became stably integrated into the host genome and, in the several cases analyzed by Southern hybridization, the DNA was integrated at the site of the ADE2 gene in one of the chromosomal homologs.
The Impact of IFRS on the Role of Auditors in Earnings Quality of European Companies

Prior studies suggest earnings quality increases when audit quality increases. We test whether such a relation is affected by institutional factors, such as the use of International Financial Reporting Standards (IFRS), which is regarded as a superior set of accounting standards. We use and analyze data of firms in the European Union from 2000 to 2007. Our findings are consistent with previous research that earnings quality has improved after the adoption of IFRS. However, our further tests indicate that IFRS have more impact on earnings quality of companies with non-Big 4 auditors. We also find the difference in earnings quality between Big 4 and non-Big 4 audited financial statements is reduced under IFRS. Our explanation for the results is that IFRS allow less alternative accounting treatments than local standards, which restrict managers’ opportunity for earnings management. Financial reports under IFRS are more comparable, transparent and investors have more confidence in IFRS. Thus, there is less demand for large auditors to reduce information asymmetry between managers and investors in an IFRS dominated reporting environment. Our evidence suggests the relationship between audit quality and earnings quality varies with institutional factors. In our context, the positive association of high quality audits and high quality earnings weakens as the strength of accounting standards increases. Our results are robust when we control for other influences on earnings quality, particularly for managerial incentives for earning management.
The Treatment of Hepatitis C- An Introduction to the Use of New Medicines.

An editorial accompanying the article “Treatment Options in Hepatitis C — The Current State of the Art,” by Stefan Zeuzem in this issue of Deutsches Ärzteblatt International course, gives priority to advanced stages of disease, and spreads the cost of treatment over a period of up to two decades. Sofosbuvir, the first highly effective drug against hepatitis C, is very expensive (3). When it was introduced in Germany, the price of treatment added up to more than €100 000 per patient; since then, the monthly costs have remained essentially the same, but a reduction of the required duration of treatment has lowered the overall price per patient to €40 000—50 000. The high price is due to systemic features of new drug introduction in Germany. The initial price can be set by the manufacturers themselves. They are liable to their shareholders, who expect a return on their investment; often, as in the case of sofosbivir, this investment involves a financial gamble in the form of patent purchases or corporate acquisitions (4). From an economic perspective, the market for breakthrough drugs is not really free and competi tive. Although similarly effective drugs may come out within a few years, like for the interferon-free treatment of hepatitis C, for kinase and immune checkpoint inhibitors in oncology, and for combination therapy for HIV, these drugs generally cost no less than their predecessors. The situation seems about to change in the case of hepatitis C, as the combined preparation of grazoprevir with elbasvir is indeed lower-priced. In Germany, the the mandatory early risk-benefit assessment of new drugs, as specified by the the Pharmaceutical Market Reorganization Act (Arznei mittelmarktneuordnungsgesetz, AMNOG) of 2010, has had an unfavorable effect on the initial drug prices. The decisions of the Joint Federal Committee (Gemeinsamer Bundesausschuss, G-BA) according to this law provide the basis for subsequent rebate negotiations between healthinsurance carriers and drug companies; thus, the price at market entry has a large influence on the final price (5). Moreover, early ratings of drug benefits have become so rapid and efficient, with more than 200 of them carried out to date, that the German prices are used as reference values in many other countries. W hen Deutsches Ärzteblatt International invited me to write an editorial on the treatment of hepatitis C, I hesitated. The topic is evidently relevant not only to gastroenterology, but also to my own specialty, hematology/oncology; it is, however, currently surrounded by emotionally charged debate, sparked by the many new drugs against hepatitis C and their high prices. For both specialties, the availability of new treatment options coincides with major progress in our understanding of the disease. Yet discussions of how patients with hepatitis C should be treated are often narrowly centered on the question of drug costs, and the views expressed on the matter are often rigid and partisan. We can learn much from the way the new drugs for hepatitis C have been dealt with up to now.
SIGIR 2014 workshop on temporal, social and spatially-aware information access (#TAIA2014)

Spatial and temporal context are increasingly important as users rely more on mobile devices to access information on the Web. Although information access applications are becoming more context-savvy, users’ expectations are far ahead of current capabilities. For example, users expect a given application to understand the nature of their current immediate surroundings, while many systems have trouble drawing an accurate map of a city, or assigning a geographic and temporal scope to a web document. Successfully incorporating spatial and temporal context into the retrieval and user models opens up a universe of hyperlocal scenarios. Users provide an unprecedented volume of detailed, and continuously updated information about where they are, what they are doing, who they are with, and what they are thinking and feeling about their current activities. The provision of this stream creates an informal contract between the user and the information access application that the user will provide the information, but the application must provide results that are contextually relevant. Many of the research questions about how to understand and employ user context have yet to be answered. We bring together practitioners and researchers, in a program centered around short papers, keynote speakers, and discussion of recent breakthroughs and challenges in spatial and temporal information access, from algorithmic and architectural perspectives.
A FEM-Formulation for Virtual Reality Applications

Primljeno (Received): 2011-10-10 Prihvaćeno (Accepted): 2011-12-20 Original scientific paper Virtual reality (VR), as a novel technology, represents one of the most powerful tools to assist or even play the major role in many areas, such as development of new designs, training medical practitioners or assembly operators, entertaining industry, etc. On the other hand, the finite element method (FEM) imposed itself as an essential technical support for the needs of computing flexible bodies’ deformational behavior. FEM together with CAD are important ingredients of VR. In the VR applications that imply interactive simulations with flexible bodies included, the efficiency of FEM formulations is of crucial importance. The paper presents a co-rotational FEM-formulation developed to meet the needs of simulating geometrically nonlinear deformational behavior at interactive frame rates. It is presented here in combination with a rather simple linear tetrahedral element. The formulation is enriched with a coupled-mesh technique to enable the usage of rougher FEM models to compute deformational behavior of complex geometries. The advantages of an iterative solver and the solution procedure for both static and dynamic analyses are discussed.
Regional Analysis of the Magnetization Transfer Ratio of the Brain in Mild Alzheimer Disease and Amnestic Mild Cognitive Impairment

BACKGROUND AND PURPOSE: Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. MATERIALS AND METHODS: Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. RESULTS: Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine–based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio–related features, especially between patients with Alzheimer disease versus healthy subjects. CONCLUSIONS: Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease.
A Psycholinguistic Model for the Marking of Discourse Relations

Discourse relations can either be explicitly marked by discourse connectives (DCs), such as therefore and but , or implicitly conveyed in natural language utterances. How speakers choose between the two options is a question that is not well understood. In this study, we propose a psycholinguistic model that predicts whether or not speakers will produce an explicit marker given the discourse relation they wish to express. Our model is based on two information-theoretic frameworks: (1) the Rational Speech Acts model, which models the pragmatic interaction between language production and interpretation by Bayesian inference, and (2) the Uniform Information Density theory, which advocates that speakers adjust linguistic redundancy to maintain a uniform rate of information transmission. Specifically, our model quantifies the utility of using or omitting a DC based on the expected surprisal of comprehension, cost of production, and availability of other signals in the rest of the utterance. Experiments based on the Penn Discourse Treebank show that our approach outperforms the state-of-the-art performance at predicting the presence of DCs (Patterson and Kehler, 2013), in addition to giving an explanatory account of the speaker’s choice.
IT VALUE AND RISK PADA PT. X FINANCE

Sebagai perusahaan pembiayaan kendaraan terbesar di Indonesia dilihat dari perolehan laba bersih dan jumlah aset perusahaan, PT. X Finance terus bertekad untuk menjadi perusahaan pembiayaan kelas dunia. Untuk mewujudkan tujuan tersebut, strategi yang dilakukan oleh PT. X Finance diantaranya dengan memanfaatkan Teknologi Informasi (TI) dalam semua kegiatan operasionalnya. Nilai IT (IT Value) pada perusahaan dapat dilihat dari beberapa variabel, diantaranya firm performance, firm value dan competitive advantage dari perusahaan. Dalam penerapan TI tidak semuanya akan berjalan sesuai dengan tujuan perusahaan, sehingga akan menimbulkan risiko. Untuk mengantisipasi atau mengurangi kemungkinan terjadi risiko tersebut, perlu adanya suatu manajemen resiko. Salah satu penerapan manajemen resiko TI (IT Risk) di PT. X Finance dapat menggunakan standar ISO 31000. Implementasinya mencakup penentuan konteks resiko, asesmen resiko, penanganan, review dan monitoring terhadap risiko.
Concentrations of Progesterone, Follistatin, and Follicle-Stimulating Hormone in Peripheral Plasma Across the Estrous Cycle and Pregnancy in Merino Ewes That Are Homozygous or Noncarriers of the Booroola Gene1

Abstract The circulating concentrations of progesterone, FSH, and follistatin across the estrous cycle and gestation were compared in Australian merino sheep that were homozygous for the Booroola gene, FecB, or were noncarriers. The Booroola phenotype is due to a point mutation in the bone morphogenetic protein receptor 1B. Progesterone concentrations began to rise earlier and were higher in the Booroola ewes than in the noncarriers on most days of the luteal phase but not during the follicular phase of the cycle. Follistatin concentrations remained unchanged across the estrous cycle in both groups of ewes, with no differences between genotypes. FSH concentrations were higher in Booroola ewes than in noncarrier ewes on most days of the estrous cycle, with a significantly higher and broader peak of FSH around the time of estrus. Progesterone concentrations were significantly higher in early and midgestation in Booroola ewes but were lower toward the end of gestation than those in noncarriers. FSH declined in both groups across gestation, with lower concentrations of FSH in Booroola ewes during midgestation. Follistatin remained unchanged across gestation in Booroola ewes and noncarrier ewes with a twin pregnancy but declined across gestation in noncarrier ewes with a singleton pregnancy. These results suggest that follistatin concentration is not regulated by the FecB gene during the estrous cycle and pregnancy but is influenced by the number of fetuses. However, the FecB gene appears to positively affect both progesterone and FSH during the estrous cycle and across pregnancy, which suggests that bone morphogenetic proteins play an important role in the regulation of both hormones.
Initial Experiments in Data-Driven Morphological Analysis for Finnish

This paper presents initial experiments in data-driven morphological analysis for Finnish using deep learning methods. Our system uses a character based bidirectional LSTM and pretrained word embeddings to predict a set of morphological analyses for an input word form. We present experiments on morphological analysis for Finnish. We learn to mimic the output of the OMorFi analyzer on the Finnish portion of the Universal Dependency treebank collection. The re-sults of the experiments are encouraging and show that the current approach has potential to serve as an extension to existing rule-based analyzers
Information Versus Strategic Reporting: Determinants of the Disclosure of Pro Forma Earnings by Large German Corporations

This paper investigates the determinants of firms’ decisions to disclose ‘pro forma’ earnings, voluntarily performance metrics, in a largely unregulated setting, the German capital market. For a sample of earnings releases published by large German firms, we address the role of informative and strategic motives for the disclosure of such voluntary performance metrics, and investigate effects of first-time IFRS adoption. Results indicate that incentives to meet earnings benchmarks play a significant role in the decision to disclose pro forma earnings and are positively associated with relative reporting emphasis assigned to these metrics. On the other hand, we find no evidence that firms use pro forma earnings to compensate for low quality of reported GAAP earnings. Consistent with an informative endeavor, voluntary adopters of IFRS are significantly less likely to use pro forma earnings disclosures and to assign reporting emphasis than mandatory adopters. Taken together, these results suggest that regulatory concern may be warranted, and point out the need for further capital markets based studies.
Recent Advances in the Chemical Composition of Propolis

Propolis is a honeybee product with broad clinical applications. Current literature describes that propolis is collected from plant resins. From a systematic database search, 241 compounds were identified in propolis for the first time between 2000 and 2012; and they belong to such diverse chemical classes as flavonoids, phenylpropanoids, terpenenes, stilbenes, lignans, coumarins, and their prenylated derivatives, showing a pattern consistent with around 300 previously reported compounds. The chemical characteristics of propolis are linked to the diversity of geographical location, plant sources and bee species.
Katrina and the Core Challenges of Disaster Response

VOL. 30:1 WINTER 2006 As Hurricanes Katrina, Rita, and Wilma successively lashed the gulf coast starting in late August 2005, nature’s fury exposed serious weaknesses in the United States’ emergency response capabilities. These problems were not simply the failure of particular places or leaders to be ready for disaster but rather an indication of more fundamental issues. These must be addressed if the country is to be ready for serious challenges that may lie ahead, whether severe natural disasters, outbreaks of emergent infectious disease, or renewed terrorist attacks. Not all emergencies pose this magnitude of challenge. In the United States, the initial—and usually major—responsibility for disaster response rests with local authorities. This “bottom-up” system of emergency management has a long history and continues to make sense in most circumstances. Because local governments are proximate to disaster sites and have at least some emergency capacity, they can respond quickly to initial alerts. They have detailed knowledge of local conditions, and in many cases have agreements for mutual aid to secure additional help rapidly from nearby jurisdictions. Aid from state or national sources is provided mainly when local
ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack

Background and Purpose— Several risk scores have been developed to predict the stroke risk after transient ischemic attack (TIA). However, the validation of these scores in different cohorts is still limited. The objective of this study was to elucidate whether these scores were able to predict short-term and long-term risks of stroke in patients with TIA. Methods— From the Fukuoka Stroke Registry, 693 patients with TIA were followed up for 3 years. Multivariable-adjusted Cox proportional hazards model was used to assess the hazard ratio of risk factors for stroke. The discriminatory ability of each risk score for incident stroke was estimated by using C-statistics and continuous net reclassification improvement. Results— The multivariable-adjusted Cox proportional hazards model revealed that dual TIA and carotid stenosis were both significant predictors for stroke after TIA, whereas abnormal diffusion-weighted image was not. ABCD3 (C-statistics 0.61) and ABCD3-I (C-statistics 0.66) scores improved the short-term predictive ability for stroke (at 7 days) compared with the ABCD2 score (C-statistics 0.54). Addition of intracranial arterial stenosis (at 3 years, continuous net reclassification improvement 30.5%; P<0.01) and exclusion of abnormal diffusion-weighted imaging (at 3 years, continuous net reclassification improvement 24.0%; P<0.05) further improved the predictive ability for stroke risk until 3 years after TIA. Conclusions— The present study demonstrates that ABCD3 and ABCD3-I scores are superior to the ABCD2 score for the prediction of subsequent stroke in patients with TIA. Addition of neuroimaging in the ABCD3 score may enable prediction of long-term stroke risk after TIA.
Genetic Confirmation that the H5 Protein Is Required for Vaccinia Virus DNA Replication

ABSTRACT The duplication of the poxvirus double-stranded DNA genome occurs in cytoplasmic membrane-delimited factories. This physical autonomy from the host nucleus suggests that poxvirus genomes encode the full repertoire of proteins committed for genome replication. Biochemical and genetic analyses have confirmed that six viral proteins are required for efficient DNA synthesis; indirect evidence has suggested that the multifunctional H5 protein may also have a role. Here we show that H5 localizes to replication factories, as visualized by immunofluorescence and immunoelectron microscopy, and can be retrieved upon purification of the viral polymerase holoenzyme complex. The temperature-sensitive (ts) mutant Dts57, which was generated by chemical mutagenesis and has a lesion in H5, exhibits defects in DNA replication and morphogenesis under nonpermissive conditions, depending upon the experimental protocol. The H5 variant encoded by the genome of this mutant is ts for function but not stability. For a more precise investigation of how H5 contributes to DNA synthesis, we placed the ts57 H5 allele in an otherwise wild-type viral background and also performed small interfering RNA-mediated depletion of H5. Finally, we generated a complementing cell line, CV-1–H5, which allowed us to generate a viral recombinant in which the H5 open reading frame was deleted and replaced with mCherry (vΔH5). Analysis of vΔH5 allowed us to demonstrate conclusively that viral DNA replication is abrogated in the absence of H5. The loss of H5 does not compromise the accumulation of other early viral replication proteins or the uncoating of the virion core, suggesting that H5 plays a direct and essential role in facilitating DNA synthesis. IMPORTANCE Variola virus, the causative agent of smallpox, is the most notorious member of the Poxviridae family. Poxviruses are unique among DNA viruses that infect mammalian cells, in that their replication is restricted to the cytoplasm of the cell. This physical autonomy from the nucleus has both cell biological and genetic ramifications. Poxviruses must establish cytoplasmic niches that support replication, and the genomes must encode the repertoire of proteins necessary for genome synthesis. Here we focus on H5, a multifunctional and abundant viral protein. We confirm that H5 associates with the DNA polymerase holoenzyme and localizes to the sites of DNA synthesis. By generating an H5-expressing cell line, we were able to isolate a deletion virus that lacks the H5 gene and show definitively that genome synthesis does not occur in the absence of H5. These data support the hypothesis that H5 is a crucial participant in cytoplasmic poxvirus genome replication.