Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationships of Attention and Executive Functions to Oral Language, Reading, and Writing Skills and Systems in Middle Childhood and Early Adolescence

Relationships between attention/executive functions and language learning were investigated in students in Grades 4 to 9 (N = 88) with and without specific learning disabilities (SLDs) in multiword syntax in oral and written language (OWL LD), word reading and spelling (dyslexia), and subword letter writing (dysgraphia). Prior attention-deficit/hyperactivity disorder (ADHD) diagnosis was correlated only with impaired handwriting. Parental ratings of inattention, but not hyperactivity, correlated with measures of written language but not oral language. Sustaining switching attention correlated with writing the alphabet from memory in manuscript or by keyboard and fast copying of a sentence with all the letters of the alphabet. Multiple regressions based on a principal component for composites of multiple levels of language (subword, word, and syntax/text) showed that measures of attention and executive function involving language processing rather than ratings of attention and executive function not specifically related to language accounted for more variance and identified more unique predictors in the composite outcomes for oral language, reading, and writing systems. Inhibition related to focused attention uniquely predicted outcomes for the oral language system. Findings are discussed in reference to implications for assessing and teaching students who are still learning to pay attention to heard and written language and self-regulate their language learning during middle childhood and adolescence.
Achieving the tobacco endgame: evidence on the hardening hypothesis from repeated cross-sectional studies in New Zealand 2008–2014

Introduction The hardening hypothesis proposes that as smoking prevalence declines the proportion of ‘hardcore’ or ‘hardened’ smokers will increase. The possible constructs of hardening include reduced motivation to quit, increased levels of addiction, increased levels of disadvantage and reduced quit rates among continuing smokers. Most previous studies have investigated only a single facet of the hypothesis. We used data from a national population monitor to test the hypothesis using measures across all four hardening constructs. Methods We analysed data from a biennial population-based survey of New Zealand adults (aged 15 years+) from 2008 to 2014. Data were collected through face-to-face computer-assisted personal interviews. Results During a period of reducing smoking prevalence, there were no statistically significant changes in indicators of hardening including the proportion of smokers who were unmotivated to quit, unable to quit despite repeated attempts or receiving state benefits or on a low income. Quit rates did not change significantly over the study period. For 2014 versus 2008, the OR for recent (within last 1–12 months) quitting was 1.14 (95% CI 0.53 to 2.46) and for sustained (within previous 13–24 months) quitting was 1.88 (95% CI 0.78 to 4.54). Conclusions This study provides evidence that robust tobacco control strategies that result in substantial declines in smoking prevalence are not accompanied by the hypothesised increase in ‘hardcore’ or ‘hardened’ smokers who are more addicted and less motivated and able to quit. The findings suggest that there is no need for substantial change in approach to achieve New Zealand's Smokefree 2025 goal on the grounds that the smoker population is becoming increasingly hardened.
Design of a controlled release liquid formulation of lamotrigine

Background and the purpose of the study Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. Methods Multiple (w/o/w) emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency (EE), morphology, zeta potential (ZP), polydispersity index (PI), rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure (MES) test and strychnine induced seizure (SIS) pattern test and results were compared with marketed formulation. Results The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. Major Conclusion Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy.
Association of PD-1/PD-L axis expression with cytolytic activity, mutational load, and prognosis in melanoma and other solid tumors

Significance The Cancer Genome Atlas datasets were used in the current study to explore the relationship of programmed death ligand-1 (PD-L1) expression, a cytotoxic T-cell gene signature, and mutational load to each other, to immunoactive factors, such as programmed cell death protein-1 (PD-1), PD-L2, and other checkpoint molecules, and to survival across multiple solid tumor types. We found that PD-L2 expression is more closely related to an ongoing host immune response in certain tumor types than PD-L1. Notably, mutational load was not immediately related to inflammation in any tumor type studied, and was inferior to an inflamed tumor microenvironment for predicting survival in patients with metastatic melanoma. Our findings also indicate the need for biomarker assays that are tumor-type–specific and include both expression studies and genomic profiling. Programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade has led to remarkable and durable objective responses in a number of different tumor types. A better understanding of factors associated with the PD-1/PD-L axis expression is desirable, as it informs their potential role as prognostic and predictive biomarkers and may suggest rational treatment combinations. In the current study, we analyzed PD-L1, PD-L2, PD-1, and cytolytic activity (CYT) expression, as well as mutational density from melanoma and eight other solid tumor types using The Cancer Genome Atlas database. We found that in some tumor types, PD-L2 expression is more closely linked to Th1/IFNG expression and PD-1 and CD8 signaling than PD-L1. In contrast, mutational load was not correlated with a Th1/IFNG gene signature in any tumor type. PD-L1, PD-L2, PD-1, CYT expression, and mutational density are all positive prognostic features in melanoma, and conditional inference modeling revealed PD-1/CYT expression (i.e., an inflamed tumor microenvironment) as the most impactful feature, followed by mutational density. This study elucidates the highly interdependent nature of these parameters, and also indicates that future biomarkers for anti–PD-1/PD-L1 will benefit from tumor-type–specific, integrated, mRNA, protein, and genomic approaches.
The Role of Error Processing in the Contextual Interference Effect During the Training of Perceptual-Cognitive Skills

The contextual interference (CI) effect refers to the learning benefits that occur from a random compared with blocked practice order. In this article, the cognitive effort explanation for the CI effect was examined by investigating the role of error processing. In 2 experiments, a perceptual-cognitive task was used in which participants anticipated 3 different tennis skills across a pretest, 3 practice sessions, and retention test. During practice, the skills were presented in either a random or blocked practice order. In Experiment 1, cognitive effort was examined using a probe reaction time (RT) task. In Experiment 2, cognitive effort was manipulated for 2 groups by inserting a cognitively demanding secondary task into the intertrial interval. The CI effect was found in both experiments as the random groups displayed superior learning in the retention test compared with the blocked groups. Cognitive effort during practice was greater in random compared to blocked practice groups in Experiment 1. In Experiment 2, greater decrements in secondary task performance following an error were reported for the random group when compared with the blocked group. The suggestion is that not only the frequent switching of tasks in randomized orders causes increased cognitive effort and the CI effect, but it is also error processing in combination with task switching. Findings extend the cognitive effort explanation for the CI effect and propose an alternative hypothesis highlighting the role of error processing.
Protein S Regulates Neural Stem Cell Quiescence and Neurogenesis

Neurons are continuously produced in brains of adult mammalian organisms throughout life—a process tightly regulated to ensure a balanced homeostasis. In the adult brain, quiescent Neural Stem Cells (NSCs) residing in distinct niches engage in proliferation, to self‐renew and to give rise to differentiated neurons and astrocytes. The mechanisms governing the intricate regulation of NSC quiescence and neuronal differentiation are not completely understood. Here, we report the expression of Protein S (PROS1) in adult NSCs, and show that genetic ablation of Pros1 in neural progenitors increased hippocampal NSC proliferation by 47%. We show that PROS1 regulates the balance of NSC quiescence and proliferation, also affecting daughter cell fate. We identified the PROS1‐dependent downregulation of Notch1 signaling to correlate with NSC exit from quiescence. Notch1 and Hes5 mRNA levels were rescued by reintroducing Pros1 into NCS or by supplementation with purified PROS1, suggesting the regulation of Notch pathway by PROS1. Although Pros1‐ablated NSCs show multilineage differentiation, we observed a 36% decrease in neurogenesis, coupled with a similar increase in astrogenesis, suggesting PROS1 is instructive for neurogenesis, and plays a role in fate determination, also seen in aged mice. Rescue experiments indicate PROS1 is secreted by NSCs and functions by a NSC‐endogenous mechanism. Our study identifies a duple role for PROS1 in stem‐cell quiescence and as a pro‐neurogenic factor, and highlights a unique segregation of increased stem cell proliferation from enhanced neuronal differentiation, providing important insight into the regulation and control of NSC quiescence and differentiation. Stem Cells 2017;35:679–693
SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a

Ras proteins play vital roles in numerous biological processes and Ras mutations are found in many human tumors. Understanding how Ras proteins are regulated is important for elucidating cell signaling pathways and identifying new targets for treating human diseases. Here we report that one of the K-Ras splice variants, K-Ras4a, is subject to lysine fatty acylation, a previously under-studied protein post-translational modification. Sirtuin 2 (SIRT2), one of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent lysine deacylases, catalyzes the removal of fatty acylation from K-Ras4a. We further demonstrate that SIRT2-mediated lysine defatty-acylation promotes endomembrane localization of K-Ras4a, enhances its interaction with A-Raf, and thus promotes cellular transformation. Our study identifies lysine fatty acylation as a previously unknown regulatory mechanism for the Ras family of GTPases that is distinct from cysteine fatty acylation. These findings highlight the biological significance of lysine fatty acylation and sirtuin-catalyzed protein lysine defatty-acylation.
MicroRNAs in cutaneous melanoma: Role as diagnostic and prognostic biomarkers

Melanoma is the leading cause of skin cancer deaths in the United States, and its incidence has been rising steadily for the past 30 years (Aftab, Dinger, & Perera, 2014). A more complete understanding of the molecular mechanisms that drive melanomagenesis is crucial to improve diagnosis, prognostication, and treatment of this disease. Given that melanoma survival rates are better when the disease is detected early, precise diagnostic tests for early melanoma detection would be extremely useful. In addition, as survival rates decrease drastically when the disease becomes metastatic, improved tools to more precisely identify high‐risk patients as well as to predict treatment response are necessary. The role of microRNAs (miRNAs) in melanoma biology could be the key. miRNA expression profiling has identified several miRNAs that play a crucial role in melanoma cell proliferation, migration, and invasion, as well as miRNAs involved in apoptosis and in the immune response. Here we review the most current data on the miRNAs involved in melanoma as well as their potential roles as diagnostic and prognostic biomarkers of this disease.
Developing a test-bed for robust research governance of geoengineering: the contribution of ocean iron biogeochemistry

Geoengineering to mitigate climate change has long been proposed, but remains nebulous. Exploration of the feasibility of geoengineering first requires the development of research governance to move beyond the conceptual towards scientifically designed pilot studies. Fortuitously, 12 mesoscale (approx. 1000 km2) iron enrichments, funded to investigate how ocean iron biogeochemistry altered Earth's carbon cycle in the geological past, provide proxies to better understand the benefits and drawbacks of geoengineering. The utility of these iron enrichments in the geoengineering debate is enhanced by the GEOTRACES global survey. Here, we outline how GEOTRACES surveys and process studies can provide invaluable insights into geoengineering. Surveys inform key unknowns including the regional influence and magnitude of modes of iron supply, and stimulate iron biogeochemical modelling. These advances will enable quantification of interannual variability of iron supply to assess whether any future purposeful multi-year iron-fertilization meets the principle of ‘additionality’ (sensu Kyoto protocol). Process studies address issues including upscaling of geoengineering, and how differing iron-enrichment strategies could stimulate wide-ranging biogeochemical outcomes. In summary, the availability of databases on both mesoscale iron-enrichment studies and the GEOTRACES survey, along with modelling, policy initiatives and legislation have positioned the iron-enrichment approach as a robust multifaceted test-bed to assess proposed research into climate intervention. This article is part of the themed issue ‘Biological and climatic impacts of ocean trace element chemistry’.
Sources of Parent-Child Transmission of Drug Abuse: Path Analyses of Not-Lived-With Parental, Stepparental, Triparental, and Adoptive Families

Abstract To clarify the origins of parent-child resemblance for drug abuse (DA), using national Swedish data, we fit path models to information on DA in parents and children from six informative family types: i) not-lived-with father, ii) not-lived-with mother, iii) stepfather, iv) stepmother, v) triparental, and vi) adoptive. From these families, we estimated parent-offspring resemblance reflecting the effects of genes + rearing, genes only, and rearing only. The estimates of parent-offspring correlations were statistically homogenous across family types. The weighted estimate of the father-offspring correlation for DA for genes + rearing, genes-only, and rearing-only relationships were, respectively, +0.26, +0.19, and +0.06. Parallel figures for mother-offspring relationships were +0.19, +0.13, and +0.09. In both genes + rearing and genes-only parent-offspring relationships, DA correlations were stronger for fathers than for mothers. Both genetic and environmental factors contribute substantially to parent-offspring resemblance for DA and seem to be additive.
Calibration Procedure for Attenuation Coefficient Measurements in Highly Opaque Media Using Infrared Focal Plane Array (IRFPA) Spectroscopy

The purpose of this article is to present a new calibration procedure for spectroscopic measurements using an infrared focal plane array (IRFPA) spectrometer on highly opaque middle-wave infrared (MWIR) media. The procedure is based on the properties of the IRFPA camera and especially the integration time (IT), which is the main parameter that can be adjusted to control the sensitivity of the measurements. The goal of the paper is to experimentally validate this dependence with the direct reference intensity light coming out of the IR monochromator in order to predict the spectrum shape and intensity level in a range out of the camera saturation. This method allows determining spectrum used as background for transmittance calculation. It has been applied in the case of measurement of water transmittance, which is a highly opaque medium and whose measurement requires high ITs. The main result is the ability to take an IR spectroscopic imaging measurement through 300 µm of water and the determination of its transmittance with sufficient sensitivity due to the proposed calibration procedure. This procedure allows the possibility of transitory studies in heterogeneous aqueous media.
LARP4 mRNA codon-tRNA match contributes to LARP4 activity for ribosomal protein mRNA poly(A) tail length protection

Messenger RNA function is controlled by the 3' poly(A) tail (PAT) and poly(A)-binding protein (PABP). La-related protein-4 (LARP4) binds poly(A) and PABP. LARP4 mRNA contains a translation-dependent, coding region determinant (CRD) of instability that limits its expression. Although the CRD comprises <10% of LARP4 codons, the mRNA levels vary >20 fold with synonymous CRD substitutions that accommodate tRNA dynamics. Separately, overexpression of the most limiting tRNA increases LARP4 levels and reveals its functional activity, net lengthening of the PATs of heterologous mRNAs with concomitant stabilization, including ribosomal protein (RP) mRNAs. Genetic deletion of cellular LARP4 decreases PAT length and RPmRNA stability. This LARP4 activity requires its PABP-interaction domain and the RNA-binding module which we show is sensitive to poly(A) 3'-termini, consistent with protection from deadenylation. The results indicate that LARP4 is a posttranscriptional regulator of ribosomal protein production in mammalian cells and suggest that this activity can be controlled by tRNA levels.
Training Range Environmental Evaluation and Characterization System (TREECS)

Abstract : Active military ranges contain munitions constituents (MC) and metal contamination that affect the usability and functionality of training facilities. Residues and disturbances from range operations can adversely impact the environment, including human and ecological health which require a variety of assessment tools to evaluate. Such impacts can also affect environmental compliance and range sustainment. Most Army live-fire training and testing ranges also have unique environments in which low-order and dud munitions may cause random and highly uncertain sources of MC contamination. Additionally, these ranges are under increased regulatory scrutiny, which in extreme cases has resulted in limitations being placed on training. The Training Range Environmental Evaluation and Characterization System (TREECS) has been developed by the Engineer Research and Development Center (ERDC) to assist Army analysts in managing ranges in such a manner that comply with environmental quality (EQ) objectives for toxic constituent stressors. The system hosts environmental characterization, risk management and evaluation tools and integrates the results for ease-of-use and reliability for MC. Specifically, the system automates conceptual model formulation and model parameter population across scales and pathways; formulates and couples first principle MC fate/transport-transformation-sequestration models with hydraulic models; and provides a single tool that bridges the gap between migration assessment and risk management and range sustainment. TREECS is currently being tested for use in the Army's Operational Range Assessment Program (ORAP). This presentation will discuss the overall TREECS framework and capabilities along with a case study demonstrating those capabilities.
TGFβ signaling confers sorafenib resistance via induction of multiple RTKs in hepatocellular carcinoma cells

Transforming growth factor β (TGFβ) is a multifunctional cytokine which is importantly implicated in hepatocarcinogenesis. The current study provides novel evidence that TGFβ upregulates the expression of multiple receptor tyrosine kinases (RTKs), including IGF1R, EGFR, PDGFβR, and FGFR1 in human hepatocellular carcinoma (HCC) cells. This, in turn, sensitized HCC cells to individual cognate RTK ligands, leading to cell survival. Our data showed that the TGFβ‐mediated increase in growth factor sensitivity led to evasion of apoptosis induced by the mutikinase inhibitor, sorafenib. Conversely, we observed that inhibition of the TGFβ signaling pathway by LY2157299, a TGFβRI kinase inhibitor, enhanced sorafenib‐induced apoptosis, in vitro. Our findings disclose an important interplay between TGFβ and RTK signaling pathways, which is critical for hepatocellular cancer cell survival and resistance to therapy. © 2016 Wiley Periodicals, Inc.
Grand Advantage

We study the role of family wealth for children’s educational achievement using novel Swedish register data. In particular, we focus on the relationship between grandparents’ wealth and their grandchildren’s educational achievement. Doing so allows us to reliably establish the independent role of wealth in contributing to long-term inequalities in opportunity. We use regression models with extensive controls to account for observed socioeconomic characteristics of families, cousin fixed effects to net out potentially unobserved grandparent effects, and marginal structural models to account for endogenous selection. We find substantial associations between grandparents’ wealth and their grandchildren’s grade point averages (GPA) in the 9th grade that are only partly mediated by parents’ socioeconomic characteristics and wealth. Our findings indicate that family wealth inequality—even in a comparatively egalitarian context like Sweden—has profound consequences for the distribution of opportunity across multiple generations. We posit that our estimates of the long-term consequences of wealth inequality may be conservative for nations other than Sweden, like the United States, where family wealth—in addition to its insurance and normative functions—allows the direct purchase of educational quality and access.
Rapid DNA replication origin licensing protects stem cell pluripotency

Complete and robust human genome duplication requires loading MCM helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but G1 length varies widely among cell types. Using quantitative single cell analyses we found that pluripotent stem cells with naturally short G1 phases load MCM much faster than their isogenic differentiated counterparts with long G1 phases. During the earliest stages of differentiation towards all lineages, MCM loading slows concurrently with G1 lengthening, revealing developmental control of MCM loading. In contrast, ectopic Cyclin E overproduction uncouples short G1 from fast MCM loading. Rapid licensing in stem cells is caused by accumulation of the MCM loading protein, Cdt1. Prematurely slowing MCM loading in pluripotent cells not only lengthens G1 but also accelerates differentiation. Thus, rapid origin licensing is an intrinsic characteristic of stem cells that contributes to pluripotency maintenance.