Miracle-dz/UniFAR-FTUs huggingface dataset:
Recognition and removal of oxidized guanines in duplex DNA by the base excision repair enzymes hOGG1, yOGG1, and yOGG2.

8-Oxo-7,8-dihydroguanine (OG) is susceptible to further oxidation in vitro to form two secondary oxidation products, guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). Previous work from this laboratory has shown that OG, Gh, and Sp are recognized and excised from duplex DNA substrates by the Escherichia coli DNA repair enzyme Fpg. In this report, we extend these studies to the functionally related eukaryotic OG glycosylases (OGG) from yeast and humans: yOGG1, yOGG2, and hOGG1. The hOGG1 enzyme was active only toward the removal of 8-oxoguanine, exhibiting a 1000-fold faster rate of removal of 8-oxoguanine from OG.C-containing duplexes relative to their OG.A counterparts. Duplexes containing Gh or Sp opposite any of the four natural bases were not substrates for the hOGG1 enzyme. In contrast, both yOGG1 and yOGG2 enzymes removed Gh and Sp in a relatively efficient manner from an 18 bp duplex. No significant difference was observed in the rate of reaction of Gh- and Sp-containing duplexes with yOGG1. However, yOGG2 removed Sp at a faster rate than Gh. Both yOGG enzymes exhibit a negligible dependence on the base opposite the lesion, suggesting that the activity of these enzymes may be promutagenic. Surprisingly, in the 18 bp sequence context, both yOGG enzymes did not exhibit OG removal activity. However, both removed OG in a 30 bp duplex with a different sequence surrounding the OG. The wide range of repair efficiencies observed by these enzymes with different substrates in vitro suggests that this could greatly affect the mutagenicity of these lesions in vivo. Indeed, the greater efficiency of the yOGG proteins for removal of the further oxidized products, Gh and Sp, over their 8-oxoguanine parent, suggests that these lesions may be the preferred substrates in vivo.
Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study.

AIMS To determine and evaluate QTc intervals in electrocardiograms (ECGs) of former heroin addicts, currently in methadone maintenance treatment (MMT), as previous reports suggest that methadone may prolong QTc intervals, thus possibly increasing the risk for Torsade de pointes (TdP). DESIGN Cross-sectional study. SETTING Between January 2003 and September 2004, patients on a steady dose of methadone for at least 2 weeks were studied. PARTICIPANTS This study is a subset of 153 patients, of whom 151 patients participated in a study of high methadone doses and serum levels. A total of 138 patients in MMT for a minimum of 100 days up to 10.7 years, receiving 40-290 mg/day methadone dose, participated. MEASUREMENTS Patients had an ECG at the time when blood was drawn for determination of serum methadone levels at around 24 hours after the last oral methadone dose. Corrected-QT intervals (QTc) were calculated using the Bazett formula. FINDINGS Of 138 patients studied, 98 (71%) were male. Mean QTc interval was 418.3 +/- 32.8 milliseconds (ms). Mean methadone dose was 170.9 +/- 50.3 mg/day and mean serum methadone level was 708.2 +/- 363.1 ng/ml. Methadone dose and serum levels did not correlate with QTc. Three patients had QTc intervals above 500 ms ('prolonged'). After 2 +/- 0.4 years of follow-up, two patients died; they were two of three patients with very prolonged QTc. Causes of death were not attributed to cardiac origin. An additional 19 patients had QTc intervals of between 450 and 499 ms ('possibly prolonged'). None of these QTc > or = 450 ms patients had any cardiac problems. Methadone doses of all 22 patients were > 120 mg/day. CONCLUSIONS Methadone maintenance is generally safe; however, the possible toxicity of high dose (> 120 mg/day) should be monitored for QTc.
Technical ability to treat male factor infertility must not overtake academic knowledge

EDITOR—We were alarmed by Kurinczuk et al's findings that infants born after intracytoplasmic sperm injection are twice as likely as other infants to have a major birth defect and nearly 50% more likely to have a minor defect.1 Our unit has been concerned about the safety of intracytoplasmic sperm injection,2 and this concern has been voiced by other units. We previously suggested that routine karyotyping should …
The overdue promise of short tandem repeat variation for heritability

Short tandem repeat (STR) variation has been proposed as a major explanatory factor in the heritability of complex traits in humans and model organisms. However, we still struggle to incorporate STR variation into genotype-phenotype maps. Here, we review the promise of STRs in contributing to complex trait heritability, and highlight the challenges that STRs pose due to their repetitive nature. We argue that STR variants are more likely than single nucleotide variants to have epistatic interactions, reiterate the need for targeted assays to accurately genotype STRs, and call for more appropriate statistical methods in detecting STR-phenotype associations. Lastly, somatic STR variation within individuals may serve as a read-out of disease susceptibility, and is thus potentially a valuable covariate for future association studies.
Canadian City Housing Prices and Urban Market Segmentation

The authors provide a detailed empirical analysis of Canadian city housing prices. They examine the long-run relationship between city house prices in Canada from 1981 to 2005 as well as idiosyncratic relations between city prices and city-specific variables. The results suggest that city house prices are only weakly correlated in the long run, and that there is a disconnect between house prices and interest rates. City-specific variables such as union wage levels, new-housing prices, and the issuance of building permits tend to be positively related to city existing-house prices. Surprisingly, there is mixed evidence with respect to standard measures of economic activity, such as labour force and per capita GDP.
High‐grade malignant stricture is predictive of esophageal tumor stage risks of endosonographic evaluation

Background. Endosonography is very accurate for the preoperative staging of esophageal carcinoma. Approximately 20–38% of patients with esophageal carcinoma present with high‐grade malignant strictures that preclude passage of the dedicated echoendoscope. In patients with such strictures, endosonographic staging of esophageal tumors may be performed after aggressive esophageal dilatation. However, aggressive dilatation and passage of the echoendoscope in patients with high‐grade malignant strictures is not without risk. A detailed assessment of the tumor stage in patients presenting with high‐grade malignant stenoses has not been previously reported to the authors' knowledge.
Aging and Clinical Pharmacology: Implications for Antidepressants

The elderly frequently have changes in pharmacokinetics, sensitivity to medications, homeostatic reserve (ability to tolerate physiological challenges), exposure to multiple medications, and adherence. All of these age‐associated factors can potentially influence total exposure to medication, adverse effects, and subsequent treatment outcome. Most clinical trials are performed with healthy, younger adults. Extrapolating the results of these trials to the elderly may be inappropriate, particularly for the antidepressant treatment of depression. The authors review these age‐associated differences and discuss their implications for antidepressant use in older adults.
From the real world to real words: the METEO case

Machine Translation (MT) is the focus of extensive scientific in- vestigations driven by regular evaluation campaigns, but which are mostly oriented towards a somewhat artificial task: translating news articles into En- glish. In this paper, we investigate how well current MT approaches deal with a real-world task. We have rationally reconstructed one of the only MT systems in daily production use: the METEO system. We show how a combination of a sentence-based memory approach, a phrase-based statisti- cal engine and a neural-network rescorer can give results comparable to those of the current system while offering a faster development cycle and arguably better customization possibilities.
Nasopharyngeal carcinoma in Brunei Darussalam : low incidence among the Chinese and an evaluation of antibodies to Epstein-Barr virus antigens as

Introduction: Little or no information is available on the prevalence of nasopharyngeal carcinoma (NPC) among different ethnic groups in Brunei, or how useful plasma IgA antibodies are against viral capsid antigen (VCA) and early antigen (EA) in the diagnosis of NPC, even though they are routinely measured in patients suspected to have NPC. Methods: The National Cancer Registry at Raja Isteri Pengiran Anak Saleha (RIPAS) Hospital was used to identify NPC patients diagnosed between 2000 and 2006. Clinical data and antibody test results for 38 NPC patients and for nine patients suspected of NPC but later diagnosed as negative for NPC by biopsy (control group) were obtained from the Oncology and Histopathology Departments at RIPAS Hospital. Results: The annual incidence rates for NPC among the major ethnic groups in Brunei were determined and compared to data from Singapore and Peninsular Malaysia. The most significant finding was that the average annual incidence of NPC among Bruneian Chinese males (4.1 per 100,000 persons) was significantly lower than that for Chinese males from Singapore (15.9) and Peninsular Malaysia (19.6). IgA anti-VCA and IgA anti-EA were sensitive and specific to NPC in Brunei in accordance with studies elsewhere. The measurement of IgA antibodies against VCA by ELISA was the better serological test for NPC. However, many stage IV NPC cases did not possess IgA anti-VCA and IgA anti-EA. Conclusion: Determining the factors that are responsible for a lower incidence of NPC among Chinese males in Brunei Darussalam may be useful for formulating measures to reduce NPC incidence elsewhere. The possible tendency for the loss of IgA antibodies against VCA and EA in advanced stages of NPC needs to be established with a larger number of patients, and the causes elucidated, in order to better understand the disease process in NPC.
Myostatin in tendon maintenance and repair

Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.
Elaboração da Metodologia de Aplicação do Teste de Tetrazólio para Avaliação da Viabilidade das Sementes de Coquinho-azedo

O Cerrado apresenta uma diversidade de especies com potencial de exploracao, dentre estas o coquinho-azedo, Butia capitata (Mart) Becc, destaca-se pela sua importância socioeconomica e ambiental. No entanto, a germinacao do coquinho e lenta e desuniforme, tal fator associado a carencia de estudos cientificos, limita a utilizacao da especie. Um dos fatores que interferem significativamente na germinacao de uma especie e a viabilidade dos embrioes. Dessa forma, o presente trabalho teve como objetivo estabelecer um padrao de aplicacao do tetrazolio, visando propiciar uma metodologia eficiente para analisar a viabilidade das sementes de coquinho-azedo. Para tanto, foram avaliados tres metodos de preparo das sementes (endosperma, seccao longitudinal do endosperma e extracao do embriao) sobre tres concentracoes da solucao de tetrazolio (1,0%; 0,5% e 1,0%) e tres periodos diferenciados de embebicao (2, 4 e 6 horas) na ausencia de luz a uma temperatura ambiente. Pelos resultados, verificou-se que a extracao do embriao e posterior embebicao em solucao de tetrazolio a uma concentracao de 0,5% por um periodo de quatro horas permitiu a melhor visualizacao da coloracao dos tecidos.
Change in plasma levels of vitamin D after consumption of cod-liver and fresh cod-liver oil as part of the traditional north Norwegian fish dish “Molje”

Objective. To assess changes in plasma 25-hydroxy vitamin D (25(OH)D) concentrations after ingestion of «Mølje», a traditional north Norwegian fish dish rich in vitamin D. Methods. Thirty-three volunteers all living in the city of Tromsø, located in northern Norway (latitude 69°), were served a “Mølje” meal consisting of cod, hard roe, cod liver, and fresh cod-liver oil. The amounts of liver, and cod-liver oil consumed were weighed and recorded. Blood samples were collected before the meal, and at 4 hours, 12 hours and 5 days after it. The cod liver and cod-liver oil were analysed for vitamin D content and the plasma samples for the metabolite 25(OH)D. Trends in plasma 25(OH)D levels during the five-day observation period were analysed. The study was conducted at the beginning of April of 2000. Results. Among the 33 participating subjects, 69.7% had baseline plasma 25(OH)D concentrations below 50 nmol/l and for one-quarter of the subjects, they were < 37.5 nmol/l. The participants who acknowledged taking cod-liver oil supplements had significantly higher aseline 25(OH)D plasma levels at the outset of the study compared to those reporting not doing so (p=0.02). Changes in plasma 25(OH)D levels relative to baseline concentrations were significantly associated with the body mass index (p<0.01). Conclusion. Vitamin D status in populations living in circumpolar areas needs more research to investigate to what degree people living in the Arctic areas are at increased risk for vitamin D insufficiency and to determine the role of the traditional diet in preventing such deficiency.
Predicting cognitive sequelae in survivors of critical illness with cognitive screening tests.

RATIONALE Survivors of critical illness have a high rate of cognitive impairments that may persist years after hospital discharge. Data are lacking regarding whether cognitive screening tests administered at hospital discharge can be used to predict which critically ill patients are likely to have long-term cognitive sequelae. OBJECTIVES This prospective study assessed whether two cognitive screening tests, the Mini-Mental State Examination (MMSE) and Mini-Cog, administered at hospital discharge, predict cognitive sequelae in survivors of critical illness 6 months after hospital discharge. METHODS Seventy critically ill patients completed the MMSE and Mini-Cog just before hospital discharge. Of these 70 patients, 53 completed a neuropsychological battery 6 months after hospital discharge. MEASUREMENTS AND MAIN RESULTS At hospital discharge, 45 patients (64%) had impaired performance on the MMSE (score < 27, mean = 24.4) and 32 (45%) on the Mini-Cog. Twenty-seven patients (39%) were impaired on both the MMSE and Mini-Cog, whereas only 20 patients (28%) had scores in the normal range on both tests. Cognitive sequelae occurred in 57% of survivors (30 of 53) at 6 months, with predominant dysfunction in the memory (38%) and executive (36%) domains. Logistic regression analyses showed that neither the MMSE nor the Mini-Cog predicted cognitive sequelae at 6 months. CONCLUSIONS A large number of critically ill survivors had cognitive impairments, as assessed by the MMSE and Mini-Cog, at hospital discharge. However, the MMSE and Mini-Cog scores did not predict long-term cognitive sequelae at 6-month follow-up and cannot be used as surrogate endpoints for long-term cognitive impairment.
Towards goal-driven behaviour control of multi-robot systems

The task-level control of mobile robots in uncertain environments demand high adaptivity and cognitive capabilities that allow for flexible decision making and planning. This work introduces the ROS Hybrid Behaviour Planner (RHBP). RHBP combines the advantages of a reactive and adaptive behaviour-based layer with a formal symbolic planner that enables appropriate goal pursuance. Here, we present the first development stage of our system that enables more adaptive multi-robot decision making and planning in the widely used Robot Operating System (ROS) ecosystem.
Estimating the loss in expectation of life due to cancer using flexible parametric survival models

A useful summary measure for survival data is the expectation of life, which is calculated by obtaining the area under a survival curve. The loss in expectation of life due to a certain type of cancer is the difference between the expectation of life in the general population and the expectation of life among the cancer patients. This measure is used little in practice as its estimation generally requires extrapolation of both the expected and observed survival. A parametric distribution can be used for extrapolation of the observed survival, but it is difficult to find a distribution that captures the underlying shape of the survival function after the end of follow‐up. In this paper, we base our extrapolation on relative survival, because it is more stable and reliable. Relative survival is defined as the observed survival divided by the expected survival, and the mortality analogue is excess mortality. Approaches have been suggested for extrapolation of relative survival within life‐table data, by assuming that the excess mortality has reached zero (statistical cure) or has stabilized to a constant. We propose the use of flexible parametric survival models for relative survival, which enables estimating the loss in expectation of life on individual level data by making these assumptions or by extrapolating the estimated linear trend at the end of follow‐up. We have evaluated the extrapolation from this model using data on four types of cancer, and the results agree well with observed data. Copyright © 2013 John Wiley & Sons, Ltd.
ALTERED PTERIN PATTERNS IN PHOTOBEHAVIORAL MUTANTS OF Phycomyces blakesleeanus *

Abstract— Pterins were extracted with methanol from sporangiophores of the lower fungus Phycomyces blakesleeanus and separated and identified by high performance liquid chromatography (HPLC) with fluorescence detection. The following pterins were found and identified for the wild‐type strain NRRL1555: carboxypterin (6.7 × 10‐6M), neopterin (4.2 × 10‐7M), xanthopterin (5.3 × 10‐6M), biopterin (3.9 × 10‐7M), pterin (9.1 × 10‐7M), and 6,7‐dimethylpterin (1.2 × 10‐6M). The HPLC elution profiles of the wild type were compared to a set of phototropism mutants (genotype mad) with specific defects in the light‐transduction pathway. The mutant profiles were qualitatively similar to those of the wild type. Quantitative differences were, however, discerned for madA, madC, and madH mutants. The madA mutation was associated with increased amounts of biopterin and 6,7‐dimethylpterin and a reduction of neopterin, pterin, xanthopterin, and unidentified pterins eluting at 14–18 min. The stimulatory effect of the madA mutation on biopterin and 6,7‐dimethylpterin appears to be compensated by a secondary mutation (pde) which is responsible for the loss of 75% of adenosine 3',5'‐cyclic monophosphate (cAMP)‐phosphodiesterase activity. In a madA pde double mutant the amounts of biopterin and 6,7‐dimethylpterin fell below the wild‐type level. These results suggest that an increased level of endogenous cAMP represses the biosynthesis of these pterins. The madC mutation increased the amounts of biopterin and xanthopterin and that of the unidentified pterins which could be derivatized to carboxypterin. Single madB mutations had, compared to the wild type, two times higher amounts of biopterin and two times lower amounts of neopterin. In a madH mutant the identified pterins occurred at normal concentrations while the total pool of pterins and of unidentified pterins were elevated. Complex changes of the pterin pattern were obtained in various double mad‐mutants suggesting that some mad gene products synergistically control the pterin content. The results of this and the accompanying paper (Hohl et al., 1992, Photochem. Photobiol.55) show that some of the mad genes affect pterin as well as flavin levels in Phycomyces. We propose that photoreception of Phycomyces requires a balanced and precisely controlled ratio of endogenous pterins and flavins. For some of the mutants the relative excess of certain pterins may cause the known sensitivity changes in the near‐UV.
Gamma Knife surgery for brain metastases from gastrointestinal cancer.

OBJECT Brain metastases from gastrointestinal cancers are rare. However, the incidence is increasing because patients with gastrointestinal carcinoma tend to live longer due to earlier diagnosis and more effective treatment of systemic disease. The purpose of this study was to evaluate the efficacy of Gamma Knife surgery (GKS) for the treatment of brain metastases from gastrointestinal cancers. METHODS The authors performed a retrospective review of 40 patients (18 women and 22 men) who had undergone GKS to treat a total of 118 metastases from gastrointestinal cancers between January 1996 and December 2006. The mean patient age was 58.7 years, and the mean Karnofsky Performance Scale (KPS) score was 70. There were 7 patients with esophageal cancer, 25 with colon cancer, 5 with rectal cancer, 2 with pancreatic cancer, and 1 with gastric cancer. Nineteen patients were treated with whole-brain radiotherapy and/or local brain radiotherapy before GKS. Twenty-four patients had extracranial metastases, and 3 had an additional primary cancer. The mean metastatic brain tumor volume was 4.3 cm3, and the mean maximum tumor dose varied from 17.1 to 76.7 Gy (mean 41.8 Gy). RESULTS Follow-up imaging studies were available in 25 patients with a total of 90 treated metastases. The results demonstrate a tumor control rate of 91%. The median survival time was 6.7 months, and the 6-month and 1-year survival rates were 55 and 25%, respectively. A univariate analysis revealed that the KPS score (<or=70 vs >or=80) was significant (p=0.018) for improved survival. CONCLUSIONS Results in this series suggest that GKS can be an effective tool for the treatment of brain metastases from gastrointestinal cancer.