Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of morphosyntactic growth in typically developing toddlers: contributions of parent input and child sex.

PURPOSE Theories of morphosyntactic development must account for between-child differences in morphosyntactic growth rates. This study extends Legate and Yang's (2007) theoretically motivated cross-linguistic approach to determine if variation in properties of parent input accounts for differences in the growth of tense productivity. METHOD Fifteen toddlers (and parents) participated. None were producing tense morphemes productively at 21 months. Two dependent measures of morphosyntactic growth between 21 and 30 months were used: empirical Bayes linear coefficients at 21 months and predicted productivity scores at 30 months. Predictor variables included child sex, vocabulary, and mean length of utterance as well as 4 measures of parent language input at 21 months. RESULTS Input informativeness for tense was the most consistent predictor of morphosyntactic growth, explaining 28.3% of the unique variance in children's linear growth coefficients at 21 months and 23.0% of the unique variance in predicted tense productivity scores at 30 months. General input measures were unrelated. Child sex explained an additional 24.7% of the variance in early linear growth. Child vocabulary at 21 months did not explain a significant proportion of unique variance. CONCLUSION The findings provide evidence that input informativeness, an abstract and distributed property of input, contributes to morphosyntactic growth.
A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

Major pathogenic clonal complexes (cc) of Neisseria meningitidis differ substantially in their point prevalence among healthy carriers. We show that frequently carried pathogenic cc (e.g. sequence type ST‐41/44 cc and ST‐32 cc) depend on extracellular DNA (eDNA) to initiate in vitro biofilm formation, whereas biofilm formation of cc with low point prevalence (ST‐8 cc and ST‐11 cc) was eDNA‐independent. For initial biofilm formation, a ST‐32 cc type strain, but not a ST‐11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N‐acetylmuramyl‐l‐alanine amidase genes. In late biofilms, outer membrane phospholipase A‐dependent autolysis, which was observed in most cc, but not in ST‐8 and ST‐11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an eDNA‐dependent one yielding shear force resistant microcolonies, and an eDNA‐independent one. Based on the experimental findings and previous epidemiological observations, we hypothesize that most meningococcal cc display a settler phenotype, which is eDNA‐dependent and results in a stable interaction with the host. On the contrary, spreaders (ST‐11 and ST‐8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates.
Searching for the P/E Mean Reversion Affinity – An Application of the Flexible Fourier Approximation

The S&P 500’s Price/Earning mean reversion phenomenon seriously threatens foundations of the efficient market hypothesis. Using the Fourier approximation and regime switching models, the P/E mean reversion issue has been further investigated. The empirical findings of the threshold autoregressive model during 1871:12–2016:3, suggest that the P/E mean reversion tendency can be justified only in an economic expansion during which the P/E ratio stays afloat above its likely long-run threshold. However, the speed of adjustment toward the historical long-run equilibrium is practically non-existent in contractionary periods during which the P/E ratio tends to be below its estimated threshold.
Expression and induction by dexamethasone of ABC transporters and nuclear receptors in a human T-lymphocyte cell line

Abstract The efficacy of drugs acting within lymphocytes, like antiretroviral drugs in the treatment of HIV infection, depends on their intracellular concentrations modulated by efflux proteins like ABCB1 (P-glycoprotein). In lymphocytes, two glucocorticoids, prednisone and prednisolone, have been shown to induce ABCB1 activity. Yet, no data exist regarding dexamethasone (DEX). We report the modulation of ABC transporters and nuclear receptors’ expression by DEX in a commonly used model of human lymphocytes. CCRF-CEM cells were exposed to DEX (100 nM, 2 μM) for 24 to 72 hours. ABCB1 activity was measured using DiOC6 efflux in flow cytometry. Gene expression levels were quantified by qRT-PCR. ABCB1 activity and mRNA expression increased with DEX concentrations and incubation times. DEX (1 μM, 24 h) increased significantly ABCB1 and GR mRNA expression levels by around 8- and 3·5-fold, respectively (P<10−6). ABCB1 induction by DEX in CCRF-CEM cells suggests a potential risk of interaction in lymphocytes when associating DEX to ABCB1 substrates in antiretroviral multitherapies in vivo.
TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor

See Ginevrino and Valente (doi:10.1093/brain/awx260) for a scientific commentary on this article. Autosomal dominant torsion dystonia-1 is a disease with incomplete penetrance most often caused by an in-frame GAG deletion (p.Glu303del) in the endoplasmic reticulum luminal protein torsinA encoded by TOR1A. We report an association of the homozygous dominant disease-causing TOR1A p.Glu303del mutation, and a novel homozygous missense variant (p.Gly318Ser) with a severe arthrogryposis phenotype with developmental delay, strabismus and tremor in three unrelated Iranian families. All parents who were carriers of the TOR1A variant showed no evidence of neurological symptoms or signs, indicating decreased penetrance similar to families with autosomal dominant torsion dystonia-1. The results from cell assays demonstrate that the p.Gly318Ser substitution causes a redistribution of torsinA from the endoplasmic reticulum to the nuclear envelope, similar to the hallmark of the p.Glu303del mutation. Our study highlights that TOR1A mutations should be considered in patients with severe arthrogryposis and further expands the phenotypic spectrum associated with TOR1A mutations.
Identifying the Biological Basis of GWAS Hits for Endometriosis1

ABSTRACT Endometriosis is a common estrogen-dependent gynecological disease influenced by multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified eight genomic regions with strong evidence for association with endometriosis risk and excellent replication in multiple studies. The results represent a significant breakthrough toward understanding endometriosis. However, the significance can be realized only when the associated DNA sequence variation is linked to the altered regulation and/or function of specific genes and pathways modifying endometriosis risk. This review sets out the multiple steps required to interpret the genetic association results, identify the specific genes likely to be responsible for the altered risk within each region, and obtain the necessary genomic evidence connecting the genetic results to the target genes. Strategies include fine mapping, functional annotation, genomics, and target gene identification through gene expression, epigenetics, and cell-based studies to define direct interactions between causal single nucleotide polymorphisms (SNPs) and target genes. To help decode GWAS “hits” affecting endometriosis from multiple regions, there is an urgent need for well-powered genome-wide studies of the regulation of gene expression and epigenetic mechanisms in the endometrium and other reproductive tissues. The system genetics and genomic studies needed to follow-up GWAS signals will also provide insights into gene regulation influencing other reproductive functions. These studies require multidisciplinary research combining genetics, genomics, functional biology, and clinical research to determine the biological pathways responsible and translate the new knowledge into better outcomes for patients.
Role of the High-Affinity Zinc Uptake znuABC System in Salmonella enterica Serovar Typhimurium Virulence

ABSTRACT The Salmonella enterica serovar Typhimurium znuABC genes encoding a high-affinity zinc uptake system and its regulatory zur gene have been cloned. Salmonella serovar Typhimurium zur and znuC knockout mutants have been constructed by marker exchange. The 50% lethal dose of the znuC mutant increased when either orally or intraperitoneally inoculated in BALB/c mice, while virulence of the zur mutant decreased only when mice were intraperitoneally challenged.
The attitudes of principals of Catholic secondary schools toward teacher empowerment: A study of principals in the Western region of the national Catholic Education Association

The purpose of this study was to examine the attitudes of principals of selected Catholic secondary schools toward aspects of teacher empowerment. The Attitudes Toward Teacher Empowerment Survey was developed to measure attitudes toward empowering teachers in certain decision areas and to examine attitudes about the effects of teacher empowerment. The instrument was reviewed by two separate expert panels and sent, in final form, to 201 secondary school principals in the western region of the National Catholic Educational Association (NCEA) . The selected principals returned 161 (80.1%) usable surveys. The first part of the survey, items 1 through 29, measured principal attitudes toward empowering teachers in certain key decision areas in schools. Factor analysis reduced the data into three decision domains : (a) the manager-controlled decision domain which dealt with decisions made primarily by administrators, (b) the teacher-controlled decision domain which dealt with decisions made primarily by teachers, and (c) the
Role of intracellular Ca2+ in activation of protein kinase C during ischemic preconditioning.

BACKGROUND Activation of protein kinase C plays an important role in ischemic preconditioning. Given that protein kinase C is activated by an increase in the intracellular Ca2+ concentration ([Ca2+]i) and that myocardial ischemia and reperfusion increase [Ca2+]i, the effect of transient exposures to Ca2+ on infarct size and the effect of administration of EGTA during ischemic and alpha1-adrenoceptor-mediated preconditioning on the limitation of infarct size were investigated in the canine heart. METHODS AND RESULTS In open-chest dogs, 5 minutes after the completion of either three 5-minute infusions of CaCl2 or four 5-minute infusions of the alpha1-adrenoceptor agonist methoxamine into the coronary artery, the coronary arteries were occluded for 90 minutes; this occlusion was followed by a 6-hour reperfusion in both the Ca2+ preconditioning and methoxamine groups. Infarct sizes in the Ca2+ preconditioning (15.8+/-2.3%) and methoxamine (10.1+/-2.2%) groups were significantly (P<.01) smaller than in the control group (42.5+/-2.9%), and administration of either an inhibitor of protein kinase C (GF109203X) or an inhibitor of ecto-5'-nucleotidase (alpha,beta-methyleneadenosine 5'-diphosphate) reduced the infarct size-limiting effect of Ca2+ preconditioning. Administration of EGTA during ischemic or alpha1-adrenoceptor-mediated preconditioning inhibited both the infarct size-limiting effect and the activation of protein kinase C and ecto-5'-nucleotidase induced by these procedures. CONCLUSIONS [Ca2+]i during ischemic and alpha1-adrenoceptor-mediated preconditioning plays an important role in the infarct size-limiting effect of these procedures by activating protein kinase C and ecto-5'-nucleotidase in the canine heart.
B-cell activation and lymphoma in patients with HIV

The risk of developing non-Hodgkin lymphoma (AIDS lymphoma) is greatly increased in HIV infection. Disruption of immune function by HIV infection may contribute to lymphomagenesis by inducing (1) loss of immunoregulation of Epstein-Barr virus-infected B cells [immunoblastic and central nervous system (CNS) lymphoma] caused by loss of T-cell function, and (2) chronic B-cell hyperactivation enhancing the generation of genetic lesions (c-myc:immunoglobulin gene translocation, bcl-6 overexpression) associated with some forms of AIDS lymphoma (Burkitt lymphoma-like small noncleaved cell lymphoma and large noncleaved cell lymphoma). Also, the overproduction of B-cell–stimulatory cytokines (interleukin 10 and 6) has the potential to contribute to tumor development by supporting the growth and viability of nascent lymphoma cell clones. Therefore, HIV infection-associated B-cell hyperactivation, including direct activation of B cells by various mechanisms, and chronic overproduction of B-cell–stimulatory cytokines have the potential to contribute to the development and growth of AIDS lymphoma. Several recent reports are discussed in this review, including recent work relevant to understanding the potential of a virus-encoded cytokine-like molecule, HHV8 vIL6, to induce B-cell hyperactivation in HIV-infected people, work pointing to the potential role of a chemokine (stromal cell-derived factor 1) in lymphomagenesis, and studies on phenotypic changes in circulating B cells in HIV infection.
50-year trends in smoking-related mortality in the United States.

BACKGROUND The disease risks from cigarette smoking increased in the United States over most of the 20th century, first among male smokers and later among female smokers. Whether these risks have continued to increase during the past 20 years is unclear. METHODS We measured temporal trends in mortality across three time periods (1959-1965, 1982-1988, and 2000-2010), comparing absolute and relative risks according to sex and self-reported smoking status in two historical cohort studies and in five pooled contemporary cohort studies, among participants who became 55 years of age or older during follow-up. RESULTS For women who were current smokers, as compared with women who had never smoked, the relative risks of death from lung cancer were 2.73, 12.65, and 25.66 in the 1960s, 1980s, and contemporary cohorts, respectively; corresponding relative risks for male current smokers, as compared with men who had never smoked, were 12.22, 23.81, and 24.97. In the contemporary cohorts, male and female current smokers also had similar relative risks for death from chronic obstructive pulmonary disease (COPD) (25.61 for men and 22.35 for women), ischemic heart disease (2.50 for men and 2.86 for women), any type of stroke (1.92 for men and 2.10 for women), and all causes combined (2.80 for men and 2.76 for women). Mortality from COPD among male smokers continued to increase in the contemporary cohorts in nearly all the age groups represented in the study and within each stratum of duration and intensity of smoking. Among men 55 to 74 years of age and women 60 to 74 years of age, all-cause mortality was at least three times as high among current smokers as among those who had never smoked. Smoking cessation at any age dramatically reduced death rates. CONCLUSIONS The risk of death from cigarette smoking continues to increase among women and the increased risks are now nearly identical for men and women, as compared with persons who have never smoked. Among men, the risks associated with smoking have plateaued at the high levels seen in the 1980s, except for a continuing, unexplained increase in mortality from COPD.
Deficiency of a Transmembrane Prolyl 4-Hydroxylase in the Zebrafish Leads to Basement Membrane Defects and Compromised Kidney Function*

Prolyl 4-hydroxylases (P4Hs) catalyze the hydroxylation of collagens and hypoxia-inducible factor (HIF)-α subunits. We studied the zebrafish homologue of the recently characterized human transmembrane P4H (P4H-TM) that can hydroxylate HIF-α, but not collagens, in vitro and influence HIF-α levels in cellulo. The zebrafish P4H-TM mRNA had its highest expression in the eye and brain and lower levels in other tissues, including the kidney. Morpholino knockdown of P4H-TM in embryos resulted in a reduction in the size of the eye and head and morphological alterations in the head from 2 days postfertilization onward. In addition, pericardial edema, regarded as a sign of kidney dysfunction, developed from 3 days postfertilization onward. The phenotype was dependent on the P4H-TM catalytic activity because similar results were obtained with morpholinos targeting either translation initiation or catalytic residues of the enzyme. Structural and functional analyses of the morphant pronephric kidneys revealed fragmented glomerular basement membranes (BMs), disorganized podocyte foot processes, and severely compromised pronephric kidney function leading to proteinuria. The opacity of the eye lens was increased due to the presence of extra nuclei and deposits, and the structure of the lens capsule BM was altered. Our data suggest that P4H-TM catalytic activity is required for the proper development of the glomerular and lens capsule BMs. Many HIF target genes were induced in the P4H-TM-deficient morphants, but the observed phenotype is not likely to be mediated at least solely via the HIF pathway, and thus P4H-TM probably has additional, as yet unknown, substrates.
Brexit and the Courts: The Uncertain Fate of Constitutional Referendums in the UK

This article seeks to tell the story of the Brexit referendum and the constitutional litigation that followed it. It does so drawing on comparative material regarding the regulation of constitutional referendums as well as their implementation and litigation around contested votes elsewhere. Ultimately, the chapter argues that the EU referendum in the UK, and the Brexit process more generally, have revealed the many uncertainties underpinning the UK constitution accumulated over recent decades. These unsettled norms go to the core of the legal system. They concern: the status of EU law under UK law; the scope and limits of judicial power; the place of referendums and popular sovereignty within the constitution; and the weaknesses inherent in the latter's lack of codification. Rather than being confined to the idiosyncratic British context, however, such problems are shown to emerge wherever the voice of the people is sought to be approximated by way of referendums, and acted upon in order to bring about constitutional upheaval.
A 12-GS/s Phase-Calibrated CMOS Digital-to-Analog Converter for Backplane Communications

A 12-GS/s 8-bit digital-to-analog converter (DAC) enables 24 Gb/s signaling over conventional backplane channels. Designed in a 90-nm CMOS process, the circuit occupies an area of 670 mum times 350 mum and achieves INL and DNL of 0.31 and 0.28LSB, respectively. Measured SNDR and SFDR are 41 dB and 51 dB at 750 MHz and 32.5 dB and 35 dB at 1.5 GHz. Measured SDR and 3-dB bandwidth using 12 GS/s random data are 32 dB and 7.1 GHz, respectively. The power dissipation is 190 mW from 1-V and 1.8-V power supplies.
Role of the subthalamic nucleus in the regulation of nigral dopamine neuron activity

The influence of subthalamic nucleus (STN) afferents on dopaminergic (DA) neurons of the rat substantia nigra (SN) was investigated. Hemisections of the brain placed between the STN and the SN or located anterior to the STN caused an increase in the firing rate of DA cells without producing significant changes in their firing pattern. In contrast, electrolytic and ibotenic acid lesions of the STN resulted in 93% and 49% reductions, respectively, in the level of burst firing without affecting the firing rate of DA cells recorded in the lateral SN. Furthermore, procedures which interrupted the STN input to the SN produced rapid pacemaker‐like firing in 18% of the lateral SN DA neurons recorded. Activation of the STN using single pulses of electrical stimulation caused: (1) a 20–50 msec inhibition of DA cell firing followed by an excitation, which in 35% of DA cells was accompanied by spikes occurring in a burst‐like pattern, and (2) a short‐latency inhibition lasting 5–25 msec in 75% of non‐DA SN zona reticulata (ZR) neurons. On the other hand, stimulation of the STN for 1 minute at 20 Hz resulted in an initial decrease in DA cell burst firing followed by elevated firing rates and increased burst firing by 30–60 minutes after the stimulation. Pharmacological activation of the STN by infusion of bicuculline caused a rapid inhibition of DA cells followed by a two‐fold increase in burst firing 6–14 minutes later, whereas SN ZR cells responded with an elevation in firing rate which dissipated in 6–14 minutes. Muscimol‐induced STN inhibition produced complimentary biphasic changes in SN neuron firing: (1) an initial increase followed by a decrease in burst firing and firing rate of DA neurons and (2) a rapid inhibition followed by an excitation of ZR cells over a similar time course. Thus, the STN appears to exert a dual action on SN DA cells: (1) initial inhibition possibly mediated through STN excitation of the inhibitory SN ZR projections to DA cells, and (2) a facilitation of burst firing which may be a direct effect of excitatory STN afferents. © 1992 Wiley‐Liss, Inc.
Diagnostic Quality of 3D T2-SPACE Compared with T2-FSE in the Evaluation of Cervical Spine MRI Anatomy

BACKGROUND AND PURPOSE: Spinal anatomy has been variably investigated using 3D MRI. We aimed to compare the diagnostic quality of T2 sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with T2-FSE sequences for visualization of cervical spine anatomy. We predicted that T2-SPACE will be equivalent or superior to T2-FSE for visibility of anatomic structures. MATERIALS AND METHODS: Adult patients undergoing cervical spine MR imaging with both T2-SPACE and T2-FSE sequences for radiculopathy or myelopathy between September 2014 and February 2015 were included. Two blinded subspecialty-trained radiologists independently assessed the visibility of 12 anatomic structures by using a 5-point scale and assessed CSF pulsation artifact by using a 4-point scale. Sagittal images and 6 axial levels from C2–T1 on T2-FSE were reviewed; 2 weeks later and after randomization, T2-SPACE was evaluated. Diagnostic quality for each structure and CSF pulsation artifact visibility on both sequences were compared by using a paired t test. Interobserver agreement was calculated (κ). RESULTS: Forty-five patients were included (mean age, 57 years; 40% male). The average visibility scores for intervertebral disc signal, neural foramina, ligamentum flavum, ventral rootlets, and dorsal rootlets were higher for T2-SPACE compared with T2-FSE for both reviewers (P < .001). Average scores for remaining structures were either not statistically different or the superiority of one sequence was discordant between reviewers. T2-SPACE showed less degree of CSF flow artifact (P < .001). Interobserver variability ranged between −0.02–0.20 for T2-SPACE and −0.02–0.30 for T2-FSE (slight to fair agreement). CONCLUSIONS: T2-SPACE may be equivalent or superior to T2-FSE for the evaluation of cervical spine anatomic structures, and T2-SPACE shows a lower degree of CSF pulsation artifact.