Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcription-modulated repair in Escherichia coli evident with UV-induced mutation spectra in supF.

We have determined several mutation spectra with the supF sequence after UV mutagenesis in Escherichia coli. The cells were either mfd(+) or mfd(-) and grown in defined or complex medium. The tRNA supF gene was expressed from the plasmid pZ189 or pLS1D (similar to pLS189, a variant of pZ189, but with a tac promoter for supF). Most of the mutations with either plasmid could be attributed to possible targeting photoproducts at dipyrimidine sites in the transcribed (TS) or non-transcribed (NTS) DNA strand with differential characteristics relevant to the repair process "mutation frequency decline" (MFD): (1) with pZ189, targeting sites in TS were favored over sites in NTS in all conditions except after an explicit MFD incubation with mfd(+) cells, when there was a majority in NTS; (2) with pLS1D (tac promoter), there was always a marked bias for targeting sites in TS and this was not altered by an MFD incubation; and (3) with pLS1D, spectra with mfd(-) cells vis-à-vis wild-type indicated a notable shift in the position of a hot-spot (both targeting sites in TS) and an increase in deletion mutations. The results support the Selby-Sancar idea that transcription-coupled nucleotide excision repair (TCR) at tRNA genes accounts for MFD and can be inhibited by rapid transcription. During interference of TCR by rapid transcription, however, the presence or absence of functional Mfd protein (transcription-repair coupling factor) can still influence the pattern of mutation, e.g. alter the position of a hot-spot in pLS1D. Only when a tRNA promoter is modulated by an MFD condition is transcription at a rate conducive to TCR. There were several deletion mutations with pLS1D between direct repeats (not present in pZ189) and a model for their production by UV damage is suggested. The spectra with pZ189 in E. coli had similarities with those published for UV mutagenesis in human cells, e.g. mutations at positions approximately 124 and 156.
Reordering Models for Statistical Machine Translation : A Literature Survey

In this survey, we briefly study various reordering models that are used with statistical translation models. Reordering model is one of the important component of any statistical machine translation system. Problem of reordering is NP-Hard itself. In this survey, we study various reordering approaches that can be used to solve this problem. We first study simple distortion-based reordering which is used with phrasebased and factor-based models. Next, we discuss limitations of this distance-based approach. Then we introduce a new source-reordering based approach to handle the reorderings based on structural information of the input text. We study how to use parse trees and shallow parsing for source-side reordering.
Inflammatory Bowel Disease : Serologic Markers and Pharmacogenomic and Metabolic Assessment of Thiopurine Therapy

I. Aetna considers TPMT gene mutation or TPMT phenotypic assays (e.g., Prometheus TPMT Genetics, Prometheus TPMT Enzyme) medically necessary prior to initiation of 6mercaptopurine or azathioprine therapy. Only 1 genotypic or phenotypic assay of TPMT activity is necessary per member per lifetime. TPMT gene mutation assays and TPMT phenotypic assays are considered experimental and investigational for all other indications because their effectiveness for indications other than the one listed above has not been established.
Decoherence, delocalization, and irreversibility in quantum chaotic systems.

Decoherence in quantum systems which are classically chaotic is studied. The Arnold cat map and the quantum kicked rotor are chosen as examples of linear and nonlinear chaotic systems. The Feynman-Vernon influence functional formalism is used to study the effect of the environment on the system. It is well-known that quantum coherence can obliterate many chaotic behavior in the corresponding classical system. But interaction with an environment can under general circumstances quickly diminish quantum coherence and reenact many classical chaotic behavior. How effective decoherence works to sustain chaos, and how the resultant behavior qualitatively differs from the quantum picture depend on the coupling of the system with the environment and the spectral density and temperature of the environment. We show how recurrence in the quantum cat map is lost and classical ergodicity is recovered due to the effect of the environment. Quantum coherence and diffusion suppression are instrumental to dynamical localization for the kicked rotor. We show how environment-induced effects can destroy this localization. Such effects can also be understood as resulting from external noises driving the system. Peculiar to decohering chaotic systems is the apparent transition from reversible to irreversible dynamics. We show such transitions in the quantum cat map and the kicked rotor and distinguish it from apparent irreversibility originating from dynamical instability and imprecise measurements. By performing a time reversal on and followng the quantum kicked rotor dynamics numerically, we whow how the oth
A Comparative study of condition indices and heavy metals in perna viridis populations at Sebatu and Muar, Peninsular Malaysia

This study compared some allometric parameters (shell length, shell width, shell height, total dry weight of soft tissues, condition index and heavy metals (Cd, Cu, Pb and Zn) in the different soft tissues of Perna viridis collected from Sebatu and Muar estuary. It was found that the total dry weight of soft tissues and condition index of mussels collected from Sebatu were significantly (p<0.05) higher than those in Muar. The significantly (p<0.05) higher concentrations of Cu in most soft tissues and some of Cd indicated a higher bioavailability of Cu and Cd at Muar than Sebatu. In addition, the significantly (p<0.05) higher levels of Cu, Cd, Zn and Pb in surface sediments collected from Muar supported the observable anthropogenic impacts at Muar than Sebatu and hence, higher metal contamination at Muar than Sebatu. The higher condition index value in mussels recorded in Sebatu than in Muar was believed to be a result of higher metal contamination at Muar estuary.
Family involvement in nursing homes: effects on stress and well-being

While it is clear that families remain involved in the lives of loved ones following placement in a nursing home, little research has examined whether visiting and the provision of care has effects on the emotional stress and psychological well-being of family members. Utilizing pre-placement and post-placement data from the Caregiver Stress and Coping Study (n = 185) as well as a theoretical framework to delineate the manifestation of caregiver stress (i.e., the stress process model), the goal of this analysis was to determine whether frequency of visits and provision of personal and instrumental activities of daily living assistance following institutionalization were related to post-placement emotional distress, family conflict, and psychological well-being among family members. Following control of a wide array of pre-placement and post-placement covariates, multiple regression models found that visiting was negatively associated with post-placement role overload; moreover, the provision of instrumental activities of daily living help was negatively related to loss of intimate exchange at post-placement. The results suggest that family involvement following institutionalization may operate differently than when in the community, and add to the literature emphasizing the positive implications of family involvement in residential long-term care.
How I Do It: Treatment of Plantar Calluses and Corns With an Erbium-Doped Yttrium Aluminum Garnet Laser

This study was conducted with 70 patients admitted to the Department of Dermatology, Istanbul Medipol University, Turkey, with plantar callus between 2012 and 2014. After approval by the ethics committee, 102 lesions were retrospectively evaluated. Patients providedwritten informedconsent. Forpatientsagedbelow 18, informed consent was obtained from a parent or legal guardian. Patients who had a serious systemic disease or were pregnant or potentially pregnant and those with a history of epilepsy, preexisting melanoma, or hypertrophic scar formationdue to traumatic process predisposition to hemorrhage or immunological disorder were excluded from the study.
Reproducibility of Tumor Uptake Heterogeneity Characterization Through Textural Feature Analysis in 18F-FDG PET

18F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Methods: Double baseline 18F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland–Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. Results: The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of −2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of −22.5% to 3.1% and −1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Conclusion: Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these 18F-FDG PET–derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.
Nitrate supplementation enhances the contractile properties of human skeletal muscle.

PURPOSE Dietary nitrate supplementation positively affects cardiovascular function at rest and energy metabolism during exercise in humans and has recently also been reported to markedly enhance the in vitro contractile properties of mouse fast-twitch muscle. The aim of this study was to investigate the effects of short-term nitrate supplementation on the in vivo contractile properties of the skeletal muscle and voluntary muscle function of humans. METHODS In a double-blind, randomized, crossover design, 19 healthy untrained men (21 ± 3 yr) ingested a nitrate-rich concentrated beetroot juice (NIT; nitrate dosage, approximately 9.7 mmol·d) and a placebo (PLA) for seven consecutive days. After the last supplementation dose, force was recorded while participants completed a series of voluntary and involuntary (electrically evoked) unilateral isometric contractions of the knee extensors. RESULTS NIT enhanced the peak force response to low-frequency electrical stimulation, as follows: maximal twitch (NIT, 149 ± 41 N, vs PLA, 138 ± 37 N; P = 0.008; effect size, r (ES) = 0.56) and submaximal 1- to 20-Hz contractions (5%-10%, ES = 0.53-0.63). Whereas explosive (rising phase) force production during the first 50 ms of evoked maximal twitch and octet contractions (eight electrical impulses at 300 Hz) was also 3%-15% greater after NIT compared with that after PLA (P = 0.023-0.048, ES = 0.52-0.59), explosive voluntary force remained similar (P = 0.510, ES = 0.16). Maximum voluntary force was also unchanged after NIT (P = 0.539, ES = 0.15). CONCLUSIONS These results indicate that 7 d of dietary nitrate supplementation enhanced the in vivo contractile properties of the human skeletal muscle. Specifically, nitrate supplementation improved excitation-contraction coupling at low frequencies of stimulation and enhanced evoked explosive force production but did not affect maximum or explosive voluntary force production in untrained individuals.
Scanning The Business Environment For Information: A Grounded Theory Approach

This thesis examines the scanning of the business environment for information by a sample of Portuguese chemical companies. Nineteen companies were studied and forty senior managers were interviewed during 1992. The methodology used coupled the multiple case study approach with the grounded theory method of qualitative analysis. The grounded theory proposed in this thesis comprises three main components: the categories, the principal relationships among them and the contextual factors that shape the categories and relationships. Variability among companies is explained by a few key relationships among these categories. Environmental scanning is the phenomenon under study and constitutes the core category, to which the other six categories that emerged out of the qualitative data analysis were related: perceived environmental change and strategic change, information consciousness and information climate, organizational outwardness and individual exposure to information. The relationships identified among these categories contribute to understanding how managerial perceptions of environmental change affect strategic change and also how internal factors of an organizational, as well as of an individual, nature influence the environmental scanning activity. From an internal perspective, the contextual factors include company history and culture; from an external perspective, those factors include the overall economic, social, cultural and political conditions that characterize modem Portugal and shape those organizations, to a certain extent. This research unravelled three main issues concerning the problematic of environmental scanning in Portuguese chemical companies: 1) The scanning focus and scanning mode used by managers are inappropriate to deal with the important discontinuities they perceive in their business environment; 2) The integration of environmental information with internally-generated information is achieved only at top level, by means of senior managers' ability to relate and integrate disparate data provided by the functional areas; 3) Organizational culture emerged as an important factor in the analysis of information issues within organizations. However, the fact that the three ''best'' companies have developed different sorts of information cultures suggests that there is not a "best" culture: different cultures may be required for different contexts.
Improving multitasking assessment in healthy older adults using a prop-based version of the Breakfast task

ABSTRACT Computerized cognitive assessment is becoming increasingly more common in clinical neuropsychological assessment and cognitive neuropsychological research. A number of computerized tasks now exist to assess multitasking abilities that are essential for everyday tasks such as cooking, shopping, or driving, but little is known about whether these tasks are appropriate for assessing older adults’ multitasking. The present study directly compared age effects on multitasking when assessed using a computerized and a prop-based version of Craik and Bialystok’s (2006) Breakfast task. Twenty participants aged 18 to 24 years and 20 participants aged 60 to 79 years were assessed on both versions of the Breakfast task. While age-related decrements in multitasking performance were found using the computerized task, significant age differences were not found on the majority of measures when the prop-based version was administered. The results suggest that age-related deficits in multitasking will be less when more contextualized, noncomputer based tasks are used.
Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors.

BACKGROUND HER2 mutations and amplifications have been identified as oncogenic drivers in lung cancers. Dacomitinib, an irreversible inhibitor of HER2, EGFR (HER1), and HER4 tyrosine kinases, has demonstrated activity in cell-line models with HER2 exon 20 insertions or amplifications. Here, we studied dacomitinib in patients with HER2-mutant or amplified lung cancers. PATIENTS AND METHODS As a prespecified cohort of a phase II study, we included patients with stage IIIB/IV lung cancers with HER2 mutations or amplification. We gave oral dacomitinib at 30-45 mg daily in 28-day cycles. End points included partial response rate, overall survival, and toxicity. RESULTS We enrolled 30 patients with HER2-mutant (n = 26, all in exon 20 including 25 insertions and 1 missense mutation) or HER2-amplified lung cancers (n = 4). Three of 26 patients with tumors harboring HER2 exon 20 mutations [12%; 95% confidence interval (CI) 2% to 30%] had partial responses lasting 3+, 11, and 14 months. No partial responses occurred in four patients with tumors with HER2 amplifications. The median overall survival was 9 months from the start of dacomitinib (95% CI 7-21 months) for patients with HER2 mutations and ranged from 5 to 22 months with amplifications. Treatment-related toxicities included diarrhea (90%; grade 3/4: 20%/3%), dermatitis (73%; grade 3/4: 3%/0%), and fatigue (57%; grade 3/4: 3%/0%). One patient died on study likely due to an interaction of dacomitinib with mirtazapine. CONCLUSIONS Dacomitinib produced objective responses in patients with lung cancers with specific HER2 exon 20 insertions. This observation validates HER2 exon 20 insertions as actionable targets and justifies further study of HER2-targeted agents in specific HER2-driven lung cancers. CLINICALTRIALSGOV NCT00818441.
Reactivation of L1 retrotransposon by benzo(a)pyrene involves complex genetic and epigenetic regulation

Benzo(a)pyrene (BaP), is an environmental pollutant present in tobacco smoke and a byproduct of fossil fuel combustion which likely contributes to the tumorigenic processes in human cancers including lung and esophageal. Long Interspersed Nuclear Element-1 (LINE-1) or L1 is a mobile element within the mammalian genome that propagates via a “copy-and-paste” mechanism using reverse transcriptase and RNA intermediates. L1 is strongly expressed during early embryogenesis and then silenced as cells initiate differentiation programming. Although the complex transcriptional control mechanisms of L1 are not well understood, L1 reactivation has been described in several human cancers and following exposure of mouse or human cells to BaP. In this study we investigated the molecular mechanisms and epigenetic events that regulate L1 reactivation following BaP exposure. We show that challenge of HeLa cells with BaP induces early enrichment of the transcriptionally-active chromatin markers histone H3 trimethylated at lysine 4 (H3K4Me3) and histone H3 acetylated at lysine 9 (H3K9Ac), and reduces association of DNA methyltransferase-1 (DNMT1) with the L1 promoter. These changes are followed by proteasome-dependent decreases in cellular DNMT1 expression and sustained reduction of cytosine methylation within the L1 promoter CpG island. Pharmacological inhibition of the proteasome signaling pathway with the inhibitor MG132 blocks degradation of DNMT1 and alters BaP-mediated histone epigenetic modifications. We conclude that genetic reactivation of L1 by BaP involves an ordered cascade of epigenetic events that begin with nucleosomal histone modifications and is completed with alterations in DNMT1 recruitment to the L1 promoter and reduced DNA methylation of CpG islands.
Geographical distribution and host range of entomophthorales infecting the green spruce aphid Elatobium abietinum Walker in Iceland.

Entomophthora planchoniana and Neozygites fresenii caused infection in populations of the green spruce aphid, Elatobium abietinum, in Iceland. On this aphid species En. planchoniana was exclusively found in the western part of Iceland, while N. fresenii was exclusively found in the eastern part of Iceland. This discrete and nearly nonoverlapping geographical distribution correlates with the distribution of two different populations of El. abietinum found in Iceland. On other aphid species N. fresenii, En. planchoniana, Pandora neoaphidis, and Conidiobolus obscurus were documented throughout the country. Transmission experiments showed that Pa. neoaphidis and En. planchoniana could infect the eastern population of El. abietinum, although they have never been found on this population in nature. This strongly indicates that there is little or no interaction among El. abietinum, other aphids, and their respective entomophthoralean fungi in the field. Furthermore, this study is the first to record epizootics caused by N. fresenii and En. planchoniana in the subpolar region.
Is There a Role for mTOR Inhibitors in Renal Transplantation?

S irolimus (SRL) was approved for use as an immunosuppressive agent in kidney transplant recipients (KTRs) in Europe in the US and in 1999. SRL binds to the immunophilin, FK Binding Protein-12, to generate an immunosuppressive complex. This complex inhibits the activation of the mammalian target of rapamycin (mTOR), a key regulatory kinase. In 2010, the Food and Drug Administration approved the second mTOR inhibitor (mTORi) everolimus, for KTRs. However, after more than 20 years of clinical trials and experience, transplant physicians have yet to firmly establish the role of mTORi in KTRs. In 2013, less than 5% of KTRs in the United States were on an mTORi at 1-year posttransplant. The pivotal registration trials with SRL were done with cyclosporine as the adjuvant immunosuppressant and without therapeutic drug monitoring of the mTORi. Compared with azathioprine or placebo, SRL demonstrated efficacy, however at a cost of decreased renal function related to the combined exposure of the mTORi and the calcineurin inhibitor (CNI). Over the next decade, clinical research with SRL focused on CNI avoidance or withdrawal in hopes of minimizing CNI nephrotoxicity. Although the outcomes were mixed, there was an emerging signal of less malignancy in the cohort of KTRs exposed to SRL. With the arrival of the second mTORi everolimus, there was a repetition of the CNI withdrawal trials done 10 to 15 years earlier with SRL. Although some improvement in eGFR could be demonstrated, this “benefit” diminished over time. Compared with CNIs, to date, there has been no evidence demonstrating any clear advantage of mTORi in terms of patient or allograft survival. mTORi use has been limited by a high rate of intolerance and untoward side-effects. Whether in clinical practice or clinical trials, the discontinuation rate of mTORi is approximately 25% because of side effects including: apthous ulcers, pneumonitis, fatigue, edema (with or without proteinuria), biochemical, and hematological abnormalities. Over the last 15 years, an accumulating body of evidence has emerged suggesting that mTORi in KTRs could reduce the rate or recurrence of both nonmelanoma skin cancer and other malignancies. Given the ubiquitous nature of the