Miracle-dz/UniFAR-FTUs huggingface dataset:
Medical marijuana laws and adolescent marijuana use in the United States: a systematic review and meta‐analysis

Abstract Aims To conduct a systematic review and meta‐analysis of studies in order to estimate the effect of US medical marijuana laws (MMLs) on past‐month marijuana use prevalence among adolescents. Methods A total of 2999 papers from 17 literature sources were screened systematically. Eleven studies, developed from four ongoing large national surveys, were meta‐analyzed. Estimates of MML effects on any past‐month marijuana use prevalence from included studies were obtained from comparisons of pre–post MML changes in MML states to changes in non‐MML states over comparable time‐periods. These estimates were standardized and entered into a meta‐analysis model with fixed‐effects for each study. Heterogeneity among the study estimates by national data survey was tested with an omnibus F‐test. Estimates of effects on additional marijuana outcomes, of MML provisions (e.g. dispensaries) and among demographic subgroups were abstracted and summarized. Key methodological and modeling characteristics were also described. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. Results None of the 11 studies found significant estimates of pre–post MML changes compared with contemporaneous changes in non‐MML states for marijuana use prevalence among adolescents. The meta‐analysis yielded a non‐significant pooled estimate (standardized mean difference) of −0.003 (95% confidence interval = −0.012, +0.007). Four studies compared MML with non‐MML states on pre‐MML differences and all found higher rates of past‐month marijuana use in MML states pre‐MML passage. Additional tests of specific MML provisions, of MML effects on additional marijuana outcomes and among subgroups generally yielded non‐significant results, although limited heterogeneity may warrant further study. Conclusions Synthesis of the current evidence does not support the hypothesis that US medical marijuana laws (MMLs) until 2014 have led to increases in adolescent marijuana use prevalence. Limited heterogeneity exists among estimates of effects of MMLs on other patterns of marijuana use, of effects within particular population subgroups and of effects of specific MML provisions.
Optimized Branch Current Control of Modular Multilevel Matrix Converters Under Branch Fault Conditions

The modular multilevel matrix converter (M3C) is a promising topology for high-voltage high-power applications. It features easy scalability, high-quality input and output waveforms, superior availability, etc. This letter aims to further increase the availability of the M3C when one or more of the nine branches are lost. A general nonlinear multivariable optimization model is set up to optimize the branch current configuration after the branch lost. The proposed method reduces system power capability loss after the branch failure. It achieves a smooth transition from a full M3C to a reduced topology without shutdown of the system. A M3C prototype with 27 cells is designed, and experiment results are presented to confirm the validity of this method.
Express or repress? The transcriptional dilemma of damaged chromatin

The fine modulation of transcriptional activity around DNA lesions is essential to carefully regulate the crosstalk between the activation of the DNA damage response, DNA repair and transcription, particularly when the lesion occurs next to actively transcribed genes. Recently, several studies have been carried out to investigate how DNA lesions impact on local transcription, but the emerging model remains incomplete. Transcription of genes around damaged DNA is actively downregulated by the DNA damage response through different mechanisms, which appear specific to the chromatin context, the type of DNA damage or its complexity. Intriguingly, emerging evidence also indicates that transcription of noncoding RNAs (ncRNAs) is induced at sites of DNA damage, producing small ncRNAs that are, in turn, required for a full DNA damage response activation. We discuss here these recent findings, highlighting the major unresolved questions in the field, and propose ways to reconcile these apparently contradictory observations.
Proteolysis-a characteristic of tumor-initiating cells in murine metastatic breast cancer

Tumor initiating cells (TICs) have been identified and functionally characterized in hematological malignancies as well as in solid tumors such as breast cancer. In addition to their high tumor-initiating potential, TICs are founder cells for metastasis formation and are involved in chemotherapy resistance. In this study we explored molecular pathways which enable this tumor initiating potential for a cancer cell subset of the transgenic MMTV-PyMT mouse model for metastasizing breast cancer. The cell population, characterized by the marker profile CD24+CD90+CD45−, showed a high tumorigenicity compared to non-CD24+CD90+CD45− cancer cells in colony formation assays, as well as upon orthotopic transplantation into the mammary fat pad of mice. In addition, these orthotopically grown CD24+CD90+CD45− TICs metastasized to the lungs. The transcriptome of TICs freshly isolated from primary tumors by cell sorting was compared with that of sorted non-CD24+CD90+CD45− cancer cells by RNA-seq. In addition to more established TIC signatures, such as epithelial-to-mesenchymal transition or mitogen signaling, an upregulated gene set comprising several classes of proteolytic enzymes was uncovered in the TICs. Accordingly, TICs showed high intra- and extracellular proteolytic activity. Application of a broad range of protease inhibitors to TICs in a colony formation assay reduced anchorage independent growth and had an impact on colony morphology in 3D cell culture assays. We conclude that CD24+CD90+CD45− cells of the MMTV- PyMT mouse model possess an upregulated proteolytic signature which could very well represent a functional hallmark of metastatic TICs from mammary carcinomas.
Atomic force microscopy investigation of lithium disilicate glass ceramic after various surface treatments

The aim of this study is to evaluate the influence of various surface treatments on the surface roughness of a lithium disilicate glass ceramic. A total of 25 discs of lithium disilicate glass ceramic were prepared. Specimens were divided into five groups: (1) no treatment, (2) air abrasion, (3) acid etching, (4) Nd:YAG laser irradiation and (5) Er:YAG laser irradiation. Digital images from the surfaces were obtained by means of an atomic force microscope in tapping mode. Surface roughness was measured in 10×10 μm boxes. Surface roughness data were analysed by one way analysis of variance. The air abrasion group (550±212 nm) had a significantly higher mean surface roughness value than the other groups. The acid etching group (392±157 nm) had a significantly higher mean roughness value than the control group (228±105 nm). Surface roughness of lithium disilicate glass ceramic was not increased by any of the laser irradiation treatments.
A Combined Approach of Sensor Data Fusion and Multivariate Geostatistics for Delineation of Homogeneous Zones in an Agricultural Field

To assess spatial variability at the very fine scale required by Precision Agriculture, different proximal and remote sensors have been used. They provide large amounts and different types of data which need to be combined. An integrated approach, using multivariate geostatistical data-fusion techniques and multi-source geophysical sensor data to determine simple summary scale-dependent indices, is described here. These indices can be used to delineate management zones to be submitted to differential management. Such a data fusion approach with geophysical sensors was applied in a soil of an agronomic field cropped with tomato. The synthetic regionalized factors determined, contributed to split the 3D edaphic environment into two main horizontal structures with different hydraulic properties and to disclose two main horizons in the 0–1.0-m depth with a discontinuity probably occurring between 0.40 m and 0.70 m. Comparing this partition with the soil properties measured with a shallow sampling, it was possible to verify the coherence in the topsoil between the dielectric properties and other properties more directly related to agronomic management. These results confirm the advantages of using proximal sensing as a preliminary step in the application of site-specific management. Combining disparate spatial data (data fusion) is not at all a naive problem and novel and powerful methods need to be developed.
Selective Expression of Flt3 within the Mouse Hematopoietic Stem Cell Compartment

The fms-like tyrosine kinase 3 (Flt3) is a cell surface receptor that is expressed by various hematopoietic progenitor cells (HPC) and Flt3-activating mutations are commonly present in acute myeloid and lymphoid leukemias. These findings underscore the importance of Flt3 to steady-state and malignant hematopoiesis. In this study, the expression of Flt3 protein and Flt3 mRNA by single cells within the hematopoietic stem cell (HSC) and HPC bone marrow compartments of C57/BL6 mice was investigated using flow cytometry and the quantitative reverse transcription polymerase chain reaction. Flt3 was heterogeneously expressed by almost all of the populations studied, including long-term reconstituting HSC and short-term reconstituting HSC. The erythropoietin receptor (EpoR) and macrophage colony-stimulating factor receptor (M-CSFR) were also found to be heterogeneously expressed within the multipotent cell compartments. Co-expression of the mRNAs encoding Flt3 and EpoR rarely occurred within these compartments. Expression of both Flt3 and M-CSFR protein at the surface of single cells was more commonly observed. These results emphasize the heterogeneous nature of HSC and HPC and the new sub-populations identified are important to understanding the origin and heterogeneity of the acute myeloid leukemias.
CYP2A6 metabolism in the development of smoking behaviors in young adults

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well‐validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta‐analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11–2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four‐level response of time to first cigarette after waking (>60, 31–60, 6–30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.
Structural basis for anion conduction in the calcium-activated chloride channel TMEM16A

The calcium-activated chloride channel TMEM16A is a member of a conserved protein family that comprises ion channels and lipid scramblases. Although the structure of the scramblase nhTMEM16 has defined the architecture of the family, it was unknown how a channel has adapted to cope with its distinct functional properties. Here we have addressed this question by the structure determination of mouse TMEM16A by cryo-electron microscopy and a complementary functional characterization. The protein shows a similar organization to nhTMEM16, except for changes at the site of catalysis. There, the conformation of transmembrane helices constituting a membrane-spanning furrow that provides a path for lipids in scramblases has changed to form an enclosed aqueous pore that is largely shielded from the membrane. Our study thus reveals the structural basis of anion conduction in a TMEM16 channel and it defines the foundation for the diverse functional behavior in the TMEM16 family. DOI: http://dx.doi. org/10.7554/eLife.26232. 001
An optimal color image edge detection approach

Detecting edges in color image is currently a very emerging topic in pattern recognition research. In this paper, an optimal approach for color image edge detection is introduced. The proposed technique is based on canny edge detector. The color computations are done in HSV color space. Here, the deficiencies of the traditional Canny edge detector are removed by replacing the Gaussian filter with an adaptive median filter and a type-2 fuzzy set-based technique is used for double threshold calculation in the final step of edge detection. The experimental results show the superiority of the proposed approach.
Hormone treatments in congestive heart failure

The common ultimate pathological feature for all cardiovascular diseases, congestive heart failure (CHF), is now considered as one of the main public health burdens that is associated with grave implications. Neurohormonal systems play a critical role in cardiovascular homeostasis, pathophysiology, and cardiovascular diseases. Hormone treatments such as the newly invented dual-acting drug valsartan/sacubitril are promising candidates for CHF, in addition to the conventional medications encompassing beta receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists. Clinical trials also indicate that in CHF patients with low insulin-like growth factor-1 or low thyroid hormone levels, supplemental treatment with growth hormone or thyroid hormone seems to be cardioprotective; and in CHF patients with volume overload the vasopressin antagonists can relieve the symptoms superior to loop diuretics. Furthermore, a combination of selective glucocorticoid receptor agonist and mineralocorticoid receptor antagonist may be used in patients with diuretic resistance. Finally, the potential cardiovascular efficacy and safety of incretin-based therapies, testosterone or estrogen supplementation needs to be prudently evaluated in large-scale clinical studies. In this review, we briefly discuss the therapeutic effects of several key hormones in CHF.
Genomics of adaptive divergence with chromosome‐scale heterogeneity in crossover rate

Genetic differentiation between divergent populations is often greater in chromosome centres than peripheries. Commonly overlooked, this broadscale differentiation pattern is sometimes ascribed to heterogeneity in crossover rate and hence linked selection within chromosomes, but the underlying mechanisms remain incompletely understood. A literature survey across 46 organisms reveals that most eukaryotes indeed exhibit a reduced crossover rate in chromosome centres relative to the peripheries. Using simulations of populations diverging into ecologically different habitats through sorting of standing genetic variation, we demonstrate that such chromosome‐scale heterogeneity in crossover rate, combined with polygenic divergent selection, causes stronger hitchhiking and especially barriers to gene flow across chromosome centres. Without requiring selection on new mutations, this rapidly leads to elevated population differentiation in the low‐crossover centres relative to the high‐crossover peripheries of chromosomes (“Chromosome Centre‐Biased Differentiation”, CCBD). Using simulated and empirical data, we then show that strong CCBD between populations can provide evidence of polygenic adaptive divergence with a phase of gene flow. We further demonstrate that chromosome‐scale heterogeneity in crossover rate impacts analyses beyond that of population differentiation, including the inference of phylogenies and parallel adaptive evolution among populations, the detection of genetic loci under selection, and the interpretation of the strength of selection on genomic regions. Overall, our results call for a greater appreciation of chromosome‐scale heterogeneity in crossover rate in evolutionary genomics.
Service level agreement mediation, negotiation and evaluation for cloud services in intercloud environments

The management of today’s service level agreements on the cloud market is often nontransparent and inefficient for the customer and the provider. However, service level agreements are crucial for establishing trust between all participants, especially for companies whose success depends on the purchased cloud service with its appropriated service quality. This thesis aims to improve the current situation on the cloud market in terms of providing architectural, methodological, and functional approaches with standard-based protocol specifications for dynamic and situational service level agreement management. Therefore, this thesis analyses and presents current service level agreement standards and existing implementations. Based on these results, a set of concepts and approaches for agreement and service mediation are developed and experimentally evaluated. However, all of these existing approaches either target a specific community or implement broker services with just a closed product portfolio for services delivered by a small set of providers. In order to establish a trusted provider overlay network as global marketplace for cloud services, where all participants can federate by nature, expose their product offer, and reach a wider customer community, this thesis introduces a novel concept for intercloud agreement mediation. The Agreement-Mediators in this global provider network act as neutral and autonomous entities in the cloud market and rise trust between independent providers and between providers and customers. The language and protocol for searching, negotiating, and establishing service level agreements is specified, developed, and evaluated. The outcomes of this thesis aim to increase efficiency and effectiveness for discovering cloud services of independent providers and the management of service level agreements established for each business relationship. The experimental results show significant improvements in terms of efficiency, scalability, and flexibility.
Spread Spectrum Audio Watermarking Using Multiple Orthogonal PN Sequences and Variable Embedding Strengths and Polarities

Copyright protection of audio data is a serious problem and spread spectrum (SS) based audio watermarking is a promising technology to tackle this problem. Although a number of SS-based audio watermarking methods have been reported in the literature, they cannot achieve high robustness and embedding capacity at the same time. In this paper, we propose a novel SS-based audio watermarking method that can embed a large number of watermark bits into an audio signal without compromising the robustness against common attacks. Compared with the existing audio watermarking methods, the proposed one is especially robust against severe noise addition and compression attacks, while achieving high embedding capacity. Moreover, the new audio watermarking method is computationally efficient. The validity of the proposed SS-based audio watermarking method is demonstrated by simulation results.
Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Alzheimer’s disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aβ fibrils and Aβ oligomers in vitro. Moreover, daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AβPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.
Microbial community composition along a 50 000-year lacustrine sediment sequence

Abstract For decades, microbial community composition in subseafloor sediments has been the focus of extensive studies. In deep lacustrine sediments, however, the taxonomic composition of microbial communities remains undercharacterized. Greater knowledge on microbial diversity in lacustrine sediments would improve our understanding of how environmental factors, and resulting selective pressures, shape subsurface biospheres in marine and freshwater sediments. Using high‐throughput sequencing of 16S rRNA genes across high‐resolution climate intervals covering the last 50 000 years in Laguna Potrok Aike, Argentina, we identified changes in microbial populations in response to both past environmental conditions and geochemical changes of the sediment during burial. Microbial communities in Holocene sediments were most diverse, reflecting a layering of taxa linked to electron acceptors availability. In deeper intervals, the data show that salinity, organic matter and the depositional conditions over the Last Glacial‐interglacial cycle were all selective pressures in the deep lacustrine assemblage resulting in a genetically distinct biosphere from the surface dominated primarily by Bathyarchaeota and Atribacteria groups. However, similar to marine sediments, some dominant taxa in the shallow subsurface persisted into the subsurface as minor fraction of the community. The subsequent establishment of a deep subsurface community likely results from a combination of paleoenvironmental factors that have shaped the pool of available substrates, together with substrate depletion and/or reworking of organic matter with depth. Figure. No Caption available.