Miracle-dz/UniFAR-FTUs huggingface dataset:
Assay Reproducibility and Interindividual Variation for 15 Serum Estrogens and Estrogen Metabolites Measured by Liquid Chromatography–Tandem Mass Spectrometry

Background: Interindividual differences in estrogen metabolism may partially account for differences in risks of estrogen-responsive cancers. We conducted a proof-of-performance study to assess the reproducibility of a LC/MS-MS method for measurement of 15 serum estrogens and metabolites (all 15 termed EM) in total (conjugated+unconjugated) and unconjugated forms and describe interindividual variation. Methods: Interindividual variation in serum EM profiles was evaluated for 20 premenopausal women, 15 postmenopausal women, and 10 men. Replicate aliquots from 10 premenopausal women, 5 postmenopausal women, and 5 men were assayed eight times over 4 weeks. Components of variance were used to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC). Results: In postmenopausal women and men, median EM concentrations were similar and substantially lower than that in premenopausal women. Within each sex/menopausal group, the sum of all EM varied 5- to 7-fold across extreme deciles. Some EM had greater variation; total estrone varied approximately 12-fold in premenopausal and postmenopausal women. Unconjugated estradiol varied 17-fold in postmenopausal women but only 5-fold in premenopausal women and men. CVs reflecting variation across replicate measures for individuals were <5% for most EM, but higher in some individuals with a low EM concentration. Overall laboratory CVs for all but one EM were <2% and ICCs were >99% for all EM in each group. Conclusions: The serum EM assay has excellent laboratory reproducibility. In premenopausal women, postmenopausal women, and men, interindividual variation in EM measures is substantially greater than laboratory variation. Impact: The serum EM assay is suitable for epidemiologic application. See all the articles in this CEBP Focus section, “Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology. ” Cancer Epidemiol Biomarkers Prev; 23(12); 2649–57. ©2014 AACR.
The Tax Benefits of Relaxing the Long-Only Constraint: Do They Come from Character or Deferral?

In this study, we propose a decomposition of the total tax benefit (or liability) of a strategy into what we define as character and deferral components. Our decomposition is mathematically straightforward and intuitive, and it allows for a quick and informative assessment of tax benefits of different tax-aware strategies without modeling various investor-specific situations. We use this character-deferral decomposition to identify the source of tax benefits resulting from relaxation of the long-only constraint. Our empirical evidence shows that, for tax-aware strategies, relaxing the long-only constraint results in a drastic increase in their tax benefits, in particular owing to an increase in the character benefit. We conclude that tax-aware relaxed-constraint strategies are more attractive to taxable investors than their long-only counterparts.
NMDA receptors on zebrafish Mauthner cells require CaMKII‐α for normal development

Calcium/calmodulin dependent protein kinase 2 (CaMKII) is a multifunctional protein that is highly enriched in the synapse. It plays important roles in neuronal functions such as synaptic plasticity, synaptogenesis, and neural development. Gene duplication in zebrafish has resulted in the occurrence of seven CaMKII genes (camk2a, camk2b1, camk2b2, camk2g1, camk2g2, camk2d1, and camk2d2) that are developmentally expressed. In this study, we used single cell, real‐time quantitative PCR to investigate the expression of CaMKII genes in individual Mauthner cells (M‐cells) of 2 days post fertilization (dpf) zebrafish embryos. We found that out of seven different CaMKII genes, only the mRNA for CaMKII‐α was expressed in the M‐cell at detectable levels, while all other isoforms were undetectable. Morpholino knockdown of CaMKII‐α had no significant effect on AMPA synaptic currents (mEPSCs) but decreased the amplitude of NMDA mEPSCs. NMDA events exhibited a biexponential decay with τfast ≈ 30 ms and τslow ≈ 300 ms. Knockdown of CaMKII‐α specifically reduced the amplitude of the slow component of the NMDA‐mediated currents (mEPSCs), without affecting the fast component, the frequency, or the kinetics of the mEPSCs. Immunolabelling of the M‐cell showed increased dendritic arborizations in the morphants compared with controls, and knockdown of CaMKII‐α altered locomotor behaviors of touch responses. These results suggest that CaMKII‐α is present in embryonic M‐cells and that it plays a role in the normal development of excitatory synapses. Our findings pave the way for determining the function of specific CaMKII isoforms during the early stages of M‐cell development. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 145–162, 2015
Bacterial N-Glycosylation Efficiency Is Dependent on the Structural Context of Target Sequons*

Site selectivity of protein N-linked glycosylation is dependent on many factors, including accessibility of the modification site, amino acid composition of the glycosylation consensus sequence, and cellular localization of target proteins. Previous studies have shown that the bacterial oligosaccharyltransferase, PglB, of Campylobacter jejuni favors acceptor proteins with consensus sequences ((D/E)X1NX2(S/T), where X1,2 ≠ proline) in flexible, solvent-exposed motifs; however, several native glycoproteins are known to harbor consensus sequences within structured regions of the acceptor protein, suggesting that unfolding or partial unfolding is required for efficient N-linked glycosylation in the native environment. To derive insight into these observations, we generated structural homology models of the N-linked glycoproteome of C. jejuni. This evaluation highlights the potential diversity of secondary structural conformations of previously identified N-linked glycosylation sequons. Detailed assessment of PglB activity with a structurally characterized acceptor protein, PEB3, demonstrated that this natively folded substrate protein is not efficiently glycosylated in vitro, whereas structural destabilization increases glycosylation efficiency. Furthermore, in vivo glycosylation studies in both glyco-competent Escherichia coli and the native system, C. jejuni, revealed that efficient glycosylation of glycoproteins, AcrA and PEB3, depends on translocation to the periplasmic space via the general secretory pathway. Our studies provide quantitative evidence that many acceptor proteins are likely to be N-linked-glycosylated before complete folding and suggest that PglB activity is coupled to general secretion-mediated translocation to the periplasm. This work extends our understanding of the molecular mechanisms underlying N-linked glycosylation in bacteria.
Teaching schools as teacher education laboratories

This study emanated from the Integrated Strategic Planning Framework for Teacher Education and Development in South Africa . This Framework proposes that teaching schools should be established in the country to improve the teaching practicum component of pre-service teacher education. A generic qualitative study was undertaken to explore the affordances of a teaching school to enable student teacher learning for the teaching profession. The overarching finding of the study is that a teaching school holds numerous affordances for enabling meaningful student teacher learning for the teaching profession. However, the full affordances of a teaching school will not be realised if a teaching school is viewed merely as a practicum site. Foregrounding a laboratory view of practice work in a teaching school could enable true research-oriented teacher education. A teaching school as a teacher education laboratory would imply a deliberate inclusion of cognitive apprenticeship and an inquiry orientation to learning in the schoo
Numerical investigation of low level OSNR estimation based on gaussian fitting and non-linear least squares on AAH in noisy optical communication links

An extended digital estimation approach of optical signal to noise ratio (OSNR) based on statistical analysis of asynchronous amplitude histograms (AAH) of the received optical signal is presented and numerically investigated. Accurate OSNR estimation on highly noisy optical transmission link is achieved. Furthermore, the proposed OSNR estimation approach may be digitally adjusted to any Cartesian modulation format such as multilevel phase shift keying and quadrature amplitude modulated optical signals without degrading estimation accuracy. The OSNR estimation methodology is based on kernel density estimation with Gaussian kernels and non-linear least-squares regression (NLLS). Heuristic searches are no longer needed and the process becomes more reliable and robust. Reported results show accurate OSNR estimation with less than 15% error estimation on the simulated OSNR value for different signal modulation formats, exhibiting a more confident estimation system, with comparable results among formats because of the statistical nature histogram instead of the regular counting bins histogram.
Restorative justice for victims: inherent limits?

ABSTRACT Campaigners for restorative justice suggest that we should deal with criminal behaviour by encouraging those responsible to repair the harm they have caused and that those who cause and suffer harm should be at the centre of deliberation and decision making. This paper explores ‘internal’ obstacles to achieving this goal: structural weaknesses in the case for restorative justice. The focus is on contradictions in the way the campaign for restorative justice has thought about the role of victims in restorative encounters. Involvement of victims is crucial for two quite different reasons: they have an essential role to play in the reform of offenders and they need to be involved to benefit from the healing effects of restorative encounters. Tensions between these two ways of thinking about the rationale for victim involvement have been insufficiently acknowledged. This hampers the campaign for restorative justice from achieving its loftier ambitions.
Dynamic enhancer function in the chromatin context

Enhancers serve as critical regulatory elements in higher eukaryotic cells. The characterization of enhancer function has evolved primarily from genome‐wide methodologies, including chromatin immunoprecipitation (ChIP‐seq), DNase‐I hypersensitivity (DNase‐seq), digital genomic footprinting (DGF), and the chromosome conformation capture techniques (3C, 4C, and Hi‐C). These population‐based assays average signals across millions of cells and lead to enhancer models characterized by static and sequential binding. More recently, fluorescent microscopy techniques, including fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single molecule tracking (SMT), reveal a highly dynamic binding behavior for these factors in live cells. Furthermore, a refined analysis of genomic footprinting suggests that many transcription factors leave minimal or no footprints in chromatin, even when present and active in a given cell type. In this study, we review the implications of these new approaches for an accurate understanding of enhancer function in real time. In vivo SMT, in particular, has recently evolved as a promising methodology to probe enhancer function in live cells. Integration of findings from the many approaches now employed in the study of enhancer function suggest a highly dynamic view for the action of enhancer activating factors, viewed on a time scale of milliseconds to seconds, rather than minutes to hours. WIREs Syst Biol Med 2018, 10:e1390. doi: 10.1002/wsbm.1390
Do different scales measure the same construct? Three Sense of Coherence scales

Background: Different scales claim to measure the construct “Sense of Coherence”. Results from these scales have been compared without knowing whether they measure the same construct. This article compares two versions of Antonovsky’s original scale (SOC-13 and SOC-29), translated into Swedish, and a three-item scale (SOC-3) that claims to measure Sense of Coherence. Methods: The data were analysed in a cross-sectional setting. The study consisted of university students studying social work (n = 395). Results: The original scales had no distribution problems in differentiating Sense of Coherence. The SOC-3 had severe distribution problems. The two versions of the original Sense of Coherence scale had an acceptable reliability (Cronbach’s α; SOC-29 = 0.93, SOC-13 = 0.89). The SOC-3 scale did not have an acceptable reliability (Cronbach’s α = 0.39). SOC-29 and SOC-13 had a high intercorrelation (r = 0.96, p<0.001). The SOC-3 significantly correlated with SOC-29 (r = −0.72, p<0.001) and SOC-13 (r = −0.67, p<0.001), but the magnitude was significantly lower than the intercorrelation between SOC-29 and SOC-13 (Fisher’s z-transformation, p<0.001). Conclusions: Because scales that claim to measure the same construct are not always interchangeable, researchers should make sure they compare results from studies that use the same scales.
Post-processing of dynamic gadolinium-enhanced magnetic resonance imaging exams of the liver: explanation and potential clinical applications for color-coded qualitative and quantitative analysis

The purpose of this article is to explain and illustrate the current status and potential applications of automated and color-coded post-processing techniques for the analysis of dynamic multiphasic gadolinium-enhanced magnetic resonance imaging (MRI) of the liver. Post-processing of these images on dedicated workstations allows the generation of time–intensity curves (TIC) as well as color-coded images, which provides useful information on (neo)-angiogenesis within a liver lesion, if necessary combined with information on enhancement patterns of the surrounding liver parenchyma. Analysis of TIC and color-coded images, which are based on pharmacokinetic modeling, provides an easy-to-interpret schematic presentation of tumor behavior, providing additional characteristics for adequate differential diagnosis. Inclusion of TIC and color-coded images as part of the routine abdominal MRI workup protocol may help to further improve the specificity of MRI findings, but needs to be validated in clinical decision-making situations. In addition, these tools may facilitate the diagnostic workup of disease for detection, characterization, staging, and monitoring of antitumor therapy, and hold incremental value to the widely used tumor response criteria.
Analyzing the response to epidemics: concept of evidence-based Haddon matrix

Purpose The purpose of this paper is to propose a novel evidence-based Haddon matrix that identifies intervention options for organizations and governments responding to an epidemic in a developing economy. Design/methodology/approach A literature review of articles published within a year of the cholera outbreak in Haiti. Two separate types of literature sources are used – academic and non-academic – to apprehend the value and role of interventions implemented and/or identified. Findings The Haddon matrix helps break down the challenges involved in the containment of an epidemic into smaller, manageable components. This research shows that the matrix enables visualization of past evidence, help dissect various informational sources, and increase collaboration across humanitarian organizations. It will also serve as a building block for academics to identify new research directions to respond to epidemic outbreaks. Research limitations/implications The analysis focuses on the cholera epidemic in Haiti. Future work will be directed to generalize the identified recommendations and insights to a broader context. Originality/value This paper presents an evidence-based Haddon matrix that infers recommendations and insights based on past evidence for each phase (pre-event, response, and post-event) and factor (agent, host, physical environment, and socio-cultural environment) of an epidemic and for various stakeholders (humanitarian organizations, governments, and academics). The matrix provides a structured framework to identify interventions and best practices to address challenges during an epidemic outbreak.
Genetic Factors and Neurocognitive Traits

ABSTRACT Genetic contributions to phenotypic variation in general intelligence have been studied extensively. Less research has been conducted on genetic contributions to specific cognitive abilities, such as attention, memory, working memory, language, and motor functions. However, the existing data indicate a significant role of genetic factors in these abilities. Stages of information processing, such as sensory gating, early sensory registration, and cognitive analysis, also show evidence of genetic contributions. Recent molecular studies have begun to identify candidate genes for specific cognitive functions. Future research, identifying endophenotypes based on cognitive profiles of neuropsychiatric disorders, may also assist in the detection of genes that increase susceptibility to major psychiatric disorders.
Venous Thromboembolism and Cancer Risk among Elderly Adults in the United States

Background: Few studies have evaluated cancer risk following venous thromboembolism (VTE). Both VTE and cancer disproportionately affect older adults. Methods: Using linked Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we evaluated 1.2 million cancer cases and 200,000 controls (66–99 years old, 1992–2005). VTEs occurring before selection were identified using Medicare claims. Logistic regression was used to estimate ORs. Results: VTE was present in 2.5% of cases and 2.2% of controls. VTE was associated with risk of cancers of the lung [OR = 1.18; 95% confidence interval (CI), 1.12–1.23], stomach (OR = 1.19; 95% CI, 1.09–1.30), small intestine (OR = 1.42; 95% CI, 1.17–1.71), colon (OR = 1.25; 95% CI, 1.18–1.31), gallbladder (OR = 1.39; 95% CI, 1.16–1.67), pancreas (OR = 1.53; 95% CI, 1.43–1.64), soft tissue (OR = 1.43; 95% CI, 1.21–1.68), ovary (OR = 1.35; 95% CI, 1.22–1.50), and kidney/renal pelvis (OR = 1.34; 95% CI, 1.23–1.46), and melanoma (OR = 1.17; 95% CI, 1.08–1.27), non-Hodgkin lymphoma (OR = 1.27; 95% CI, 1.20- 1.35), myeloma (OR = 1.48; 95% CI, 1.35–1.63), and acute myeloid leukemia (OR = 1.35; 95% CI, 1.19–1.54). Strongest risks were observed within 1 year of VTE diagnosis, but risks were elevated more than 6 years after VTE for colon cancer (OR = 1.24; 95% CI, 1.12–1.37), pancreatic cancer (OR = 1.33; 95% CI, 1.15–1.54), and myeloma (OR = 1.35; 95% CI, 1.10–1.66). Few differences in risk were observed by VTE subtype. Cancers of the lung, stomach, and pancreas were more likely to have distant metastases within one year after VTE. Conclusion: Among elderly adults, cancer risk is elevated following VTE diagnosis. Impact: Short-term associations with cancer are likely driven by enhanced screening following VTE and reverse causation. While obesity, other comorbidities, and smoking cannot be excluded as explanations, longer-term elevations for select cancers suggest that some VTEs may be caused by cancer precursors. Cancer Epidemiol Biomarkers Prev; 23(5); 774–83. ©2014 AACR.
US Monetary Policy, Global Risk Aversion, and New Zealand Funding Conditions

Instrumenting US monetary shocks with fed funds future contracts and extracting global risk sentiment from VIX, this paper uses a structural vector autoregression framework to estimate the causal impact of US monetary policy on New Zealand financial and real sectors. The paper finds that 20 basis points increase in US one-year rate leads to about 14 and 59 percent increase in domestic and external funding spreads of New Zealand banks, respectively. The paper also finds that credit default swap spread rises contemporaneously following a US monetary tightening shock. Similar patterns are documented in Australia, Canada, Sweden and United Kingdom. These results suggest the existence of a global financial cycle underpinned by US monetary policy, and prompt the reassessment of the relevance of Mundellian trilemma in an increasingly globalised economic system.
The Structural Relationship Between Two Motor Sequences Practiced Close in Time Impacts Offline Facilitation

ABSTRACT Robust offline gains occur during explicit motor sequence learning. However practice of a motor sequence, other than the target sequence, within 4–6 hr after initial practice interferes with these gains. This work assessed if experiencing supplemental practice of spatially or motorically similar sequences influenced the extent of offline gain. A contemporary model of sequence learning assumes that exposure to a spatially but not motor-related sequence would not compromise stabilization of the memory for the target sequence, thus, would have minimal impact on the resultant offline gain and possibly amplify overnight gains. As anticipated, a reliable offline improvement was observed for the target motor sequence in the absence of practice with an alternative motor sequence. This gain was significantly reduced when the learner experienced additional practice with either a novel or motorically similar sequence. There was no evidence of heightened overnight gain for the target sequence from intervening practice with a spatially similar sequence. Thus, the expression of offline improvement is not necessarily eliminated if practice of an alternative motor sequence is encountered shortly after a target sequence. However, the structure of the motor sequence faced during intervening practice can impact the resultant postpractice consolidation processes reflected in the eventual expression of offline facilitation.