Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of DASH Diet With Cardiovascular Risk Factors in Youth With Diabetes Mellitus: The SEARCH for Diabetes in Youth Study

Background— We have shown that adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is related to blood pressure in youth with type 1 and type 2 diabetes mellitus. We explored the impact of the DASH diet on other cardiovascular disease risk factors. Methods and Results— Between 2001 and 2005, data on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein particle density, apolipoprotein B, body mass index, waist circumference, and adipocytokines were ascertained in 2130 youth aged 10 to 22 years with physician-diagnosed diabetes mellitus. Dietary intake was assessed by food frequency questionnaire, categorized into the DASH food groups, and assigned an adherence score. Among youth with type 1 diabetes mellitus, higher adherence to the DASH diet was significantly and inversely associated with low-density lipoprotein/high-density lipoprotein ratio and A1c in multivariable-adjusted models. Youth in the highest adherence tertile had an estimated 0.07 lower low-density lipoprotein/high-density lipoprotein ratio and 0.2 lower A1c levels than those in the lowest tertile adjusted for confounders. No significant associations were observed with triglycerides, low-density lipoprotein particle density, adipocytokines, apolipoprotein B, body mass index Z score, or waist circumference. Among youth with type 2 diabetes mellitus, associations were observed with low-density lipoprotein particle density and body mass index Z score. Conclusions— The DASH dietary pattern may be beneficial in the prevention and management of cardiovascular disease risk in youth with diabetes mellitus.
Characterization of the Interaction Domains between the Phosphoprotein and the Nucleoprotein of Human Metapneumovirus

Human metapneumovirus (HMPV) is a leading cause of severe respiratory infections in children but also affects human populations of all ages worldwide. Currently, no vaccine or efficient antiviral treatments are available for this pneumovirus. ABSTRACT Human metapneumovirus (HMPV) causes severe respiratory diseases in young children. The HMPV RNA genome is encapsidated by the viral nucleoprotein (N), forming an RNA-N complex (NNuc), which serves as the template for genome replication and mRNA transcription by the RNA-dependent RNA polymerase (RdRp). The RdRp is formed by the association of the large polymerase subunit (L), which has RNA polymerase, capping, and methyltransferase activities, and the tetrameric phosphoprotein (P). P plays a central role in the RdRp complex by binding to NNuc and L, allowing the attachment of the L polymerase to the NNuc template. During infection these proteins concentrate in cytoplasmic inclusion bodies (IBs) where viral RNA synthesis occurs. By analogy to the closely related pneumovirus respiratory syncytial virus (RSV), it is likely that the formation of IBs depends on the interaction between HMPV P and NNuc, which has not been demonstrated yet. Here, we finely characterized the binding P-NNuc interaction domains by using recombinant proteins, combined with a functional assay for the polymerase complex activity, and the study of the recruitment of these proteins to IBs by immunofluorescence. We show that the last 6 C-terminal residues of HMPV P are necessary and sufficient for binding to NNuc and that P binds to the N-terminal domain of N (NNTD), and we identified conserved N residues critical for the interaction. Our results allowed us to propose a structural model for the HMPV P-NNuc interaction. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of severe respiratory infections in children but also affects human populations of all ages worldwide. Currently, no vaccine or efficient antiviral treatments are available for this pneumovirus. A better understanding of the molecular mechanisms involved in viral replication could help the design or discovery of specific antiviral compounds. In this work, we have investigated the interaction between two major viral proteins involved in HMPV RNA synthesis, the N and P proteins. We finely characterized their domains of interaction and identified a pocket on the surface of the N protein, a potential target of choice for the design of compounds interfering with N-P complexes and inhibiting viral replication.
Interannual variability of tropospheric NO2 column over central Europe — observations from SCIAMACHY and GEM-AQ model simulations

Spatial and temporal variability of NO2 tropospheric column over Europe was analyzed for a 3 year period (2008–2010) based on monthly average observations from SCIAMACHY and the GEM-AQ model results. The GEM-AQ model was run in a global variable configuration with a resolution of ∼15 km over Central Europe. Spatial averaged time series were calculated for two selected regions in Western and Central Europe in order to assess the seasonal and interannual variability of the tropospheric NO2. The spatial pattern is similar near large emission sources for consecutive years. However, in remote regions there are differences due to interannual variability of meteorological conditions. Highest tropospheric NO2 column values (over 150 × 1015 molecules/cm2) were persistent over the Benelux and over most of the European agglomerations. The general agreement between modelled and observed NO2 column is good. In the remote areas, the modelled NO2 column shows weaker gradients than the observed field.
The diversity , structure and function of heritable adaptive 1 immunity sequences in the Aedes aegypti genome 2 3

The diversity, structure and function of heritable adaptive 1 immunity sequences in the Aedes aegypti genome 2 3 Zachary J. Whitfield1*, Patrick T. Dolan1,2*, Mark Kunitomi1*#, Michel Tassetto1, 4 Matthew G. Seetin3, Steve Oh3, Cheryl Heiner3, Ellen Paxinos3, and Raul 5 Andino1 6 7 1 Department of Microbiology and Immunology, University of California, 600 16th 8 Street, GH-S572, UCSF Box 2280, San Francisco, California 94143-2280, USA. 9
BRAF V600E Is a Determinant of Sensitivity to Proteasome Inhibitors

A critical step toward defining tailored therapy in patients with cancer is the identification of genetic interactions that may impair—or boost—the efficacy of selected therapeutic approaches. Cell models able to recapitulate combinations of genetic aberrations are important to find drug–genotype interactions poorly affected by the heterogeneous genetics of human tumors. In order to identify novel pharmacogenomic relationships, we employed an isogenic cell panel that reconstructs cancer genetic scenarios. We screened a library of 43 compounds in human hTERT-HME1 epithelial cells in which PTEN or RB1 were silenced in combination with the targeted knockin of cancer-associated mutations in EGFR, KRAS, BRAF, or PIK3CA oncogenes. Statistical analysis and clustering algorithms were applied to display similar drug response profiles and mutation-specific patterns of activity. From the screen, we discovered that proteasome inhibitors show selectivity toward BRAF V600E–mutant cells, irrespective of PTEN or RB1 expression. Preferential targeting of BRAF-mutant cells by proteasome inhibitors was corroborated in a second BRAF V600E isogenic model, as well as in a panel of colorectal cancer cell lines by the use of the proteasome inhibitor carfilzomib. Notably, carfilzomib also showed striking in vivo activity in a BRAF-mutant human colorectal cancer xenograft model. Vulnerability to proteasome inhibitors is dependent on persistent BRAF signaling, because BRAF V600E blockade by PLX4720 reversed sensitivity to carfilzomib in BRAF-mutant colorectal cancer cells. Our findings indicated that proteasome inhibition might represent a valuable targeting strategy in BRAF V600E–mutant colorectal tumors. Mol Cancer Ther; 12(12); 2950–61. ©2013 AACR.
Effects of Strength Training on Post-Pubertal Adolescent Distance Runners

33 Purpose: Strength training activities have consistently been shown to improve running 34 economy (RE) and neuromuscular characteristics, such as force producing ability and maximal 35 speed, in adult distance runners. However the effects on adolescent (<18 years) runners remains 36 elusive. This randomized control trial aimed to examine the effect of strength training on 37 several important physiological and neuromuscular qualities associated with distance running 38 performance. Methods: Participants ( n =25, 13 female, 17.2 ±1.2 years) were paired according 39 to their sex and RE and randomly assigned to a ten week strength training group (STG), or a 40 control group (CG) who continued their regular training. The STG performed twice weekly 41 sessions of plyometric, sprint and resistance training in addition to their normal running. 42 Outcome measures included body mass, maximal oxygen uptake ( 𝑉̇ O 2max ), speed at 𝑉̇ O 2max , 43 running economy (quantified as energy cost), speed at fixed blood lactate concentrations 44 (sFBLC), 20 m sprint, and maximum voluntary contraction (MVC) during an isometric quarter- 45 squat. Results: Eighteen participants (STG, n =9, 16.1 ±1.1 years; CG, n =9, 17.6 ±1.2 years) 46 completed the study. The STG displayed small improvements (3.2-3.7%, ES: 0.31-0.51) in 47 running economy that were inferred as ‘possibly beneficial’ for an average of three submaximal 48 speeds. Trivial or small changes were observed for body composition variables, 𝑉̇ O 2max and 49 s 𝑉 ̇ O 2max , however the training period provided likely benefits to sFBLC in both groups. 50 Strength training elicited a very likely benefit and a possible benefit to sprint time (ES: 0.32) 51 and MVC (ES: 0.86) respectively. Conclusion: Ten weeks of strength training added to the 52 programme of a post-pubertal distance runner was highly likely to improve maximal speed, 53 and enhances running economy by a small extent, without deleterious effects on body 54 composition or other aerobic parameters.
Guanfu Base A, an Antiarrhythmic Alkaloid of Aconitum coreanum, Is a CYP2D6 Inhibitor of Human, Monkey, and Dog Isoforms

Guanfu base A (GFA) is a novel heterocyclic antiarrhythmic drug isolated from Aconitum coreanum (Lèvl.) rapaics and is currently in a phase IV clinical trial in China. However, no study has investigated the influence of GFA on cytochrome P450 (P450) drug metabolism. We characterized the potency and specificity of GFA CYP2D inhibition based on dextromethorphan O-demethylation, a CYP2D6 probe substrate of activity in human, mouse, rat, dog, and monkey liver microsomes. In addition, (+)-bufuralol 1′-hydroxylation was used as a CYP2D6 probe for the recombinant form (rCYP2D6), 2D1 (rCYP2D1), and 2D2 (rCYP2D2) activities. Results show that GFA is a potent noncompetitive inhibitor of CYP2D6, with inhibition constant Ki = 1.20 ± 0.33 μM in human liver microsomes (HLMs) and Ki = 0.37 ± 0.16 μM for the human recombinant form (rCYP2D6). GFA is also a potent competitive inhibitor of CYP2D in monkey (Ki = 0.38 ± 0.12 μM) and dog (Ki = 2.4 ± 1.3 μM) microsomes. However, GFA has no inhibitory activity on mouse or rat CYP2Ds. GFA did not exhibit any inhibition activity on human recombinant CYP1A2, 2A6, 2C8, 2C19, 3A4, or 3A5, but showed slight inhibition of 2B6 and 2E1. Preincubation of HLMs and rCYP2D6 resulted in the inactivation of the enzyme, which was attenuated by GFA or quinidine. Beagle dogs treated intravenously with dextromethorphan (2 mg/ml) after pretreatment with GFA injection showed reduced CYP2D metabolic activity, with the Cmax of dextrorphan being one-third that of the saline-treated group and area under the plasma concentration–time curve half that of the saline-treated group. This study suggests that GFA is a specific CYP2D6 inhibitor that might play a role in CYP2D6 medicated drug-drug interaction.
Ecohydrology-a challenging multidisciplinary research perspective / Ecohydrologie: une perspective stimulante de recherche multidisciplinaire

Abstract Ecohydrology is the science that studies the mutual interaction between the hydrological cycle and ecosystems. Such an interaction is especially intense in water-controlled ecosystems, where water may be a limiting factor, not only because of its scarcity, but also because of its intermittent and unpredictable appearance. Soil moisture is the key variable modulating the complex dynamics of the climate-soil-vegetation system and controlling the spatial and temporal patterns of vegetation. In this note the authors' perspective to the field is discussed and some open questions are outlined.
Oscillatory and Aperiodic Neural Activity Jointly Predict Language Learning

Abstract Memory formation involves the synchronous firing of neurons in task-relevant networks, with recent models postulating that a decrease in low-frequency oscillatory activity underlies successful memory encoding and retrieval. However, to date, this relationship has been investigated primarily with face and image stimuli; considerably less is known about the oscillatory correlates of complex rule learning, as in language. Furthermore, recent work has shown that nonoscillatory (1/ƒ) activity is functionally relevant to cognition, yet its interaction with oscillatory activity during complex rule learning remains unknown. Using spectral decomposition and power-law exponent estimation of human EEG data (17 women, 18 men), we show for the first time that 1/ƒ and oscillatory activity jointly influence the learning of word order rules of a miniature artificial language system. Flexible word-order rules were associated with a steeper 1/ƒ slope, whereas fixed word-order rules were associated with a shallower slope. We also show that increased theta and alpha power predicts fixed relative to flexible word-order rule learning and behavioral performance. Together, these results suggest that 1/ƒ activity plays an important role in higher-order cognition, including language processing, and that grammar learning is modulated by different word-order permutations, which manifest in distinct oscillatory profiles.
Hydraulic geometry and maximum flow efficiency as products of the principle of least action

Basic flow relationships have previously been seen to be insufficient to explain the self-adjusting mechanism of alluvial channels and as a consequence extremal hypotheses have been incorporated into the analyses. In contrast, this study finds that by introducing a channel form factor (width/depth ratio), the self-adjusting mechanism of alluvial channels can be illustrated directly with the basic flow relations of continuity, resistance and sediment transport. Natural channel flow is able to reach an optimum state (Maximum Flow Efficiency (MFE), defined as the maximum sediment transporting capacity per unit available stream power) with regard to the adjustment of channel form such that rivers exhibit regular hydraulic geometry relations at dominant or bankfull stage. Within the context of MFE, this study offers support for the use of the concepts of maximum sediment transporting capacity (MSTC) and minimum stream power (MSP). Furthermore, this study indicates that the principle of least action is able to provide a physical explanation for the existence of MFE, MSTC and MSP. Potential energy is minimized and consequently sediment transport is maximized in alluvial channels. Copyright © 2000 John Wiley & Sons, Ltd.
Landslides in coastal areas of Italy

Abstract Of the more than 8000 km of coasts in Italy, about 35% consist of cliffs and rocky shores. On them many villages are located, some of them dating back to Roman or Greek times. Typical natural hazards along these coastal areas are rock falls, slides and debris flows. They induce locally extremely high levels of risk, as shown by the many disasters that have occurred in recent time. This paper provides a first portrait over the whole of Italy of (1) the number and distribution of coastal landslides; (2) their typologies; (3) their state of activity; (4) the most common damage and exposed elements; and (5) the most typical mitigation measures. This information has been largely derived from the IFFI archive (Italian Landslides Inventory). Geographic information system processing has allowed us to identify 4135 landslides affecting a large portion of the Italian cliffed coasts. The damage evaluation, based on the AVI archive (inventory of information on sites historically affected by landslides and floods in Italy for the period 1918–2000), has shown the extent of the problem: there have been 408 casualties in the 20th century and 713 significant disruptions of the rail and road networks. A more detailed analysis has been carried out in three sample areas to illustrate the basic factors controlling the genesis and evolution of slope instabilities in the various coastal settings.
Spatial configuration, spatial cognition and spatial behaviour : the role of architectural intelligibility in shaping spatial experience.

This thesis investigates the role of spatial configuration in shaping resident's experience of their neighbourhood. Studies to date have found that spatial configuration affects spatial behaviour and movement patterns (e.g., Hillier et al, 1993), however there has been little investigation of the cognitive processes that might underlie this relationship. Other research into cognition of the urban environment suggests that local spatial factors may play a role in cognitive processes (e.g., Hart & Moor, 1973), however these studies have not addressed global spatial configuration in quantitative terms. No studies to date have sought to integrate cognitive, behavioural and configurational factors within a single framework. Using Hillier's (1996) definition of intelligibility as the relationship between local and global configurational factors, this thesis investigates the relationship between resident's cognition, observed patterns of movement and the spatial configuration of an area. Two adjacent areas in Hampstead Garden Suburb in North London were investigated in detail. One area is relatively intelligible, the other less so. Structured interview surveys were carried out with local residents to elicit aspects of their cognition of the local area and detailed observations were made of movement patterns in the two neighbourhoods. Analysis of the spatial characteristics of the two areas using 'space syntax' methods provided a common basis for analyses of these data. The findings confirm that spatial configuration, spatial cognition and space use patterns are all related to one another. The main finding is that the degree of intelligibility of the area is the most significant intervening variable in relations between the three variables. The more intelligible area showed more powerful correlations between spatial configuration and patterns of movement, as well as giving rise to perceptions of greater legibility and increased neighbourhood size by local residents. Strong correlations were also identified between residents' cognitive maps and observed patterns of movement in the area. The correlations were again found to be stronger in the intelligible area than the unintelligible area. These findings suggest that spatial configuration may play an important role in determining people's daily spatial experience by increasing or reducing their sense of autonomy. By reducing the ability to predict either one's precise location within his/her global context, or the likely behaviour of others in space, unintelligible urban configurations may result in perceptions of a lesser sense of personal control over one's own actions in the environment. The thesis concludes that 'architectural intelligibility' may be a basic aspect in achieving human spatial needs.
Dose estimates of occupational radiation exposure during radioguided surgery of Tc-99m-PSMA-labeled lymph nodes in recurrent prostate cancer

Abstract Aim [99mTc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99mTc- activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. Methods In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p. i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of 99mTc-PSMA-I&S in patients was determined from repeated dose rate measurements to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10). The surgeon’s finger dose Hp(0.07) is estimated from radioactivity measured in resected lymph nodes. Potenzial incorporations were estimated for an activity of 10 MBq. Results From the first 6 subsequent patients, an effective half-life of 4.15 h was observed. Assuming an operation time 24 h p. i. , the OAR was 550 MBq. Operations lasting in average 2 h in a distance of 0.25 m to the patient imply a body dose for surgeons of 4.16 µSv per procedure. Based on these estimates, the surgeon’s Hp(10) is less than 1 mSv per year with up to 241 operations per year. Hp(0.07) and potential incorporation of activity do not lead to further limitations. Summary All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.
Investigation of the Fate of Type I Angiotensin Receptor after Biased Activation

Biased agonism on the type I angiotensin receptor (AT1-R) can achieve different outcomes via activation of G protein–dependent and –independent cellular responses. In this study, we investigated whether the biased activation of AT1-R can lead to different regulation and intracellular processing of the receptor. We analyzed β-arrestin binding, endocytosis, and subsequent trafficking steps, such as early and late phases of recycling of AT1-R in human embryonic kidney 293 cells expressing wild-type or biased mutant receptors in response to different ligands. We used Renilla luciferase–tagged receptors and yellow fluorescent protein–tagged β-arrestin2, Rab5, Rab7, and Rab11 proteins in bioluminescence resonance energy transfer measurements to follow the fate of the receptor after stimulation. We found that not only is the signaling of the receptor different upon using selective ligands, but the fate within the cells is also determined by the type of the stimulation. β-arrestin binding and the internalization kinetics of the angiotensin II–stimulated AT1-R differed from those stimulated by the biased agonists. Similarly, angiotensin II–stimulated wild-type AT1-R showed differences compared with a biased mutant AT1-R (DRY/AAY AT1-R) with regards to β-arrestin binding and endocytosis. We found that the differences in the internalization kinetics of the receptor in response to biased agonist stimulation are due to the differences in plasma membrane phosphatidylinositol 4,5-bisphosphate depletion. Moreover, the stability of the β-arrestin binding is a major determinant of the later fate of the internalized AT1-R receptor.