Miracle-dz/UniFAR-FTUs huggingface dataset:
Modelling Binary Data

INTRODUCTION Some Examples The Scope of this Book Use of Statistical Software STATISTICAL INFERENCE FOR BINARY DATA The Binomial Distribution Inference about the Success Probability Comparison of Two Proportions Comparison of Two or More Proportions MODELS FOR BINARY AND BINOMIAL DATA Statistical Modelling Linear Models Methods of Estimation Fitting Linear Models to Binomial Data Models for Binomial Response Data The Linear Logistic Model Fitting the Linear Logistic Model to Binomial Data Goodness of Fit of a Linear Logistic Model Comparing Linear Logistic Models Linear Trend in Proportions Comparing Stimulus-Response Relationships Non-Convergence and Overfitting Some other Goodness of Fit Statistics Strategy for Model Selection Predicting a Binary Response Probability BIOASSAY AND SOME OTHER APPLICATIONS The Tolerance Distribution Estimating an Effective Dose Relative Potency Natural Response Non-Linear Logistic Regression Models Applications of the Complementary Log-Log Model MODEL CHECKING Definition of Residuals Checking the Form of the Linear Predictor Checking the Adequacy of the Link Function Identification of Outlying Observations Identification of Influential Observations Checking the Assumption of a Binomial Distribution Model Checking for Binary Data Summary and Recommendations OVERDISPERSION Potential Causes of Overdispersion Modelling Variability in Response Probabilities Modelling Correlation Between Binary Responses Modelling Overdispersed Data A Model with a Constant Scale Parameter The Beta-Binomial Model Discussion MODELLING DATA FROM EPIDEMIOLOGICAL STUDIES Basic Designs for Aetiological Studies Measures of Association Between Disease and Exposure Confounding and Interaction The Linear Logistic Model for Data from Cohort Studies Interpreting the Parameters in a Linear Logistic Model The Linear Logistic Model for Data from Case-Control Studies Matched Case-Control Studies MIXED MODELS FOR BINARY DATA Fixed and Random Effects Mixed Models for Binary Data Multilevel Modelling Mixed Models for Longitudinal Data Analysis Mixed Models in Meta-Analysis Modelling Overdispersion Using Mixed Models EXACT METHODS Comparison of Two Proportions Using an Exact Test Exact Logistic Regression for a Single Parameter Exact Hypothesis Tests Exact Confidence Limits for bk Exact Logistic Regression for a Set of Parameters Some Examples Discussion SOME ADDITIONAL TOPICS Ordered Categorical Data Analysis of Proportions and Percentages Analysis of Rates Analysis of Binary Time Series Modelling Errors in the Measurement of Explanatory Variables Multivariate Binary Data Analysis of Binary Data from Cross-Over Trials Experimental Design COMPUTER SOFTWARE FOR MODELLING BINARY DATA Statistical Packages for Modelling Binary Data Interpretation of Computer Output Using Packages to Perform Some Non-Standard Analyses Appendix A: Values of logit(p) and probit(p) Appendix B: Some Derivations Appendix C: Additional Data Sets References Index of Examples Index
Iterative Two- and One-Dimensional Methods for Three-Dimensional Neutron Diffusion Calculations

Abstract Two methods are proposed for solving the three-dimensional neutron diffusion equation by iterating between solutions of the two-dimensional (2-D) radial and one-dimensional (1-D) axial solutions. In the first method, the 2-D/1-D equations are coupled using a current correction factor (CCF) with the average fluxes of the lower and upper planes and the axial net currents at the plane interfaces. In the second method, an analytic expression for the axial net currents at the interface of the planes is used for planar coupling. A comparison of the new methods is made with two previously proposed methods, which use interface net currents and partial currents for planar coupling. A Fourier convergence analysis of the four methods was performed, and results indicate that the two new methods have at least three advantages over the previous methods. First, the new methods are unconditionally stable, whereas the net current method diverges for small axial mesh size. Second, the new methods provide better convergence performance than the other methods in the range of practical mesh sizes. Third, the spectral radii of the new methods asymptotically approach zero as the mesh size increases, while the spectral radius of the partial current method approaches a nonzero value as the mesh size increases. Of the two new methods proposed here, the analytic method provides a smaller spectral radius than the CCF method, but the CCF method has several advantages over the analytic method in practical applications.
Fully parallel adaptive finite element simulation using the simplified spherical harmonics approximations for frequency-domain fluorescence-enhanced optical imaging

Fluorescence-enhanced optical imaging/tomography may play an important role in preclinical research and clinical diagnostics as a type of optical molecular. Time- and frequency-domain measurement can acquire more measurement information, reducing the ill-posedness and improving the reconstruction quality of fluorescence-enhanced optical tomography. Although the diffusion approximation (DA) theory has been extensively in optical imaging, high-order photon migration models must be further investigated for application to complex and small tissue volumes. In this paper, a frequency-domain fully parallel adaptive finite element solver is developed with the simplified spherical harmonics (SPN) approximations. To fully evaluate the performance of the SPN approximations, a fast tetrahedron-based Monte Carlo simulator suitable for complex heterogeneous geometries is developed using the convolution strategy to realize the simulation of the fluorescence excitation and emission. With simple and real digital mouse phantoms, the results show that the significant precision and speed improvements are obtained from the parallel adaptive mesh evolution strategy.
High-κ gate dielectrics: Current status and materials properties considerations

Many materials systems are currently under consideration as potential replacements for SiO2 as the gate dielectric material for sub-0.1 μm complementary metal–oxide–semiconductor (CMOS) technology. A systematic consideration of the required properties of gate dielectrics indicates that the key guidelines for selecting an alternative gate dielectric are (a) permittivity, band gap, and band alignment to silicon, (b) thermodynamic stability, (c) film morphology, (d) interface quality, (e) compatibility with the current or expected materials to be used in processing for CMOS devices, (f) process compatibility, and (g) reliability. Many dielectrics appear favorable in some of these areas, but very few materials are promising with respect to all of these guidelines. A review of current work and literature in the area of alternate gate dielectrics is given. Based on reported results and fundamental considerations, the pseudobinary materials systems offer large flexibility and show the most promise toward success.
Inference Based on Imputed Failure Times for the Proportional Hazards Model with Interval-Censored Data

Abstract We propose an approach to the proportional hazards model for interval-censored data in which parameter estimates are obtained by solving estimating equations that are the partial likelihood score equations for the full-data proportional hazards model, averaged over all rankings of imputed failure times consistent with the observed censoring intervals. Imputed failure times are generated using a parametric estimate of the baseline distribution; the parameters of the baseline distribution are estimated simultaneously with the proportional hazards regression parameters. Although a parametric form for the baseline distribution must be specified, simulation studies show that the method performs well even when the baseline distribution is misspecified. The estimating equations are solved using Monte Carlo techniques. We present a recursive stochastic approximation scheme that converges to the zero of the estimating equations; the solution has a random error that is asymptotically normally distributed w.
Vitamin A-treated natural killer cells reduce interferon-gamma production and support regulatory T cell differentiation

Natural killer (NK) cells are innate cytotoxic lymphocytes that contribute to immune responses against stressed, transformed or infected cells. NK cell effector functions are regulated by microenvironmental factors, including cytokines, metabolites and nutrients. Vitamin A is an essential micronutrient that plays an indispensable role in embryogenesis and development, but was also reported to regulate immune responses. However, the role of vitamin A in regulating NK cell functions remains poorly understood. Here, we show that the most prevalent vitamin A metabolite, all-trans retinoic acid (atRA), induces transcriptional and functional changes in NK cells leading to altered metabolism and reduced IFN-γ production in response to a wide range of stimuli. atRA-exposed NK cells display a reduced ability to support dendritic cell (DC) maturation and to eliminate immature DCs. Moreover, they support the polarization and proliferation of regulatory T cells. These results imply that in vitamin A-enriched environments, NK cells can acquire regulatory-like functions and might promote tolerogenic immunity and/or immunosuppression.
Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis

Central nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important yet challenging to study due to disease leisions’ locations and other complexities. Utilizing the powerful spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular haemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications. Our data identified three main 3D global pseudospace-time trajectory bundles which represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex induced by experimental intraventricular haematoma stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH. These results are informative in understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injuries and strategizing more effective clinical management regimens. The bioinformatics strategies will also be useful for the study of other CNS diseases.
Non-micelle-like Amyloid Aggregate Stabilizes Amyloid β (1-42) Growth Nuclei Formation

Protein aggregate formations are essential processes to regulate biochemical networks in the cell, while anomalously formed aggregates such as amyloid fibrils cause serious neuronal diseases. It has been discussed for a quarter century that protein crowding milieus, such as micelle-like aggregates, promote the formation of growth nuclei, fibril-growth competent aggregates which trigger rapid growth of pathogenic amyloid fibrils, but the mechanisms are still elusive, in particular at microscopic level. In this study, we examined the long-standing problem by employing atomistic molecular dynamics simulations for amyloid β(1-42) (Aβ42), the paradigmatic amyloid-forming peptide. First, we constructed an atomistic model of Aβ42 growth nuclei in Aβ42 aggregate milieu, the pentameric Aβ42 protomer dimer surrounded by 40 Aβ42 monomers. Next, we simulated Aβ42 monomer dissociation from the Aβ42 growth nuclei and examined the effect of Aβ42 aggregate milieu on the process. Aβ42 aggregates spatially restrict Aβ42 monomer dissociation pathways, while such spatial restriction itself does not significantly suppress Aβ42 monomer dissociation from the growth nuclei. Rather, Aβ42 aggregate milieus thermodynamically stabilize an Aβ42 monomer binding to the growth edge by making atomic contacts with the monomer and contributes to stable formation of growth nuclei. A part of the aggregate milieu anchors dissociating monomer to the remaining part of growth nuclei, suggesting cooperative suppression of Aβ42 monomer dissociation from Aβ42 growth nuclei. Since the Aβ42 aggregate milieu does not take a micelle-like configuration, we here discuss a new mechanism for stable formation of Aβ42 growth nuclei in the presence of aggregate milieu.
A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells

Toxoplasma gondii secretes protein effectors to subvert the human immune system sufficiently to establish a chronic infection. Relative to murine infections, little is known about which parasite effectors disarm human immune responses. Here we used targeted CRISPR screening to identify secreted protein effectors required for parasite survival in IFNγ-activated human cells. Independent screens were carried out using two Toxoplasma strains which differ in virulence in mice, leading to the identification of effectors required for survival in IFNγ-activated human cells. We identify the secreted protein GRA57 and two other proteins, GRA70 and GRA71, that together form a complex which enhances the ability of parasites to persist in IFNγ-activated human foreskin fibroblasts (HFFs). Components of the protein machinery required for export of Toxoplasma proteins into the host cell were also found to be important for parasite resistance to IFNγ in human cells, but these export components function independently of the identified protein complex. Host-mediated ubiquitination of the parasite vacuole has previously been associated with increased parasite clearance from human cells, but we find that vacuoles from GRA57, GRA70 and GRA71 knockout strains are surprisingly less ubiquitinated by the host cell. We hypothesise that deletion of this trimeric complex renders parasites hypersensitive to remaining ubiquitination, resulting in increased parasite clearance.
Habitat edges affect tree diversity more than biomass regeneration in a reforested wet neotropical timber plantation

About half of all forests are tropical and secondary, making tropical forest regeneration integral to future forests. Tree stand biomass and taxonomic richness can recover in a few decades, but relative abundances may lag indefinitely. Since most forests are within a km of a habitat edge, edge effects likely affect community composition regeneration. However, most studies assess how degraded edges affect intact forests, leaving it unclear whether higher-quality edges could facilitate regeneration of nearby degraded forests. Notably, higher quality edges near intact forests could promote processes like dispersal and wood biomass accumulation that effectively accelerate succession, leading to better performance of shade-tolerant taxa compared to pioneer taxa in the early stages of forested plantation regeneration. This study addressed how wet tropical forested plantation regeneration was affected by distance to adjacent intact forest edge. It was hypothesized that old timber plantations facilitate regeneration by increasing available shade, favoring the presence and biomass of later-successional taxa, ultimately changing community composition overall. A wet neotropical timber plantation reforested after 20 years and adjacent to primary forest was censused for trees along a 300 m edge distance gradient, and analysis matched identified taxa to broad dispersal mode and wood density traits using relevant literature. As distance from primary forest edge increased, stem and wood density tended to increase significantly, with ~10% variation explained, while biomass and canopy light surprisingly tended to stay the same. Stand tree richness also tended to increase significantly, but diversity decreased steeply and non-linearly, explained in part by wood density, and taxonomic composition varied notably. Finally, tree taxa associated with both early and late successional stages decreased significantly, as well as genus Ficus, but biomass by dispersal mode did not tend to change. Overall this study supports that stand composition is less resilient and more subject to edge effects than biomass and richness, suggesting that global forests will likely be distinctly new assemblages in the future, with timber and biodiversity trade-offs occurring based on local and regional management activity.
Golgi fragmentation – One of the earliest organelle phenotypes in Alzheimer’s disease neurons

Alzheimer’s disease (AD) is the most common cause of dementia, with no current cure. Consequently, alternative approaches focusing on early pathological events in specific neuronal populations, besides targeting the well-studied amyloid beta (Aβ) accumulations and Tau tangles, are needed. In this study, we have investigated disease phenotypes specific to glutamatergic forebrain neurons and mapped the timeline of their occurrence, by implementing familial and sporadic human induced pluripotent stem cell models as well as the 5xFAD mouse model. We recapitulated characteristic late AD phenotypes, such as increased Aβ secretion and Tau hyperphosphorylation, as well as previously well documented mitochondrial and synaptic deficits. Intriguingly, we identified Golgi fragmentation as one of the earliest AD phenotypes, indicating potential impairments in protein processing and post-translational modifications. Computational analysis of RNA sequencing data revealed differentially expressed genes involved in glycosylation and glycan patterns, whilst total glycan profiling revealed minor glycosylation differences. This indicates general robustness of glycosylation besides the observed fragmented morphology. Importantly, we identified that genetic variants in Sortilin-related receptor 1 (SORL1) associated with AD could aggravate the Golgi fragmentation and subsequent glycosylation changes. In summary, we identified Golgi fragmentation as one of the earliest disease phenotypes in AD neurons in various in vivo and in vitro complementary disease models, which can be exacerbated via additional risk variants in SORL1. Graphical Abstract
The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition

Eukaryotic cells achieve proteostasis by ensuring their protein requirements are met through tight control of TORC1 activity. Upon TORC1 inhibition, degradative activity is increased, and protein synthesis is reduced through inhibition of translation initiation, to maintain cell viability. Here, we show that the ribosome-associated complex (RAC)/Ssb chaperone system is required to maintain proteostasis and cell viability under TORC1 inhibition, in yeast. In the absence of the Hsp40 cochaperone Zuo1, translation does not decrease in response to loss of TORC1 activity. The functional interaction between Zuo1 and its Hsp70 partner, Ssb, is required for proper translational control and proteostasis maintenance upon TORC1 inhibition. Further, we have found that the rapid degradation of eIF4G following TORC1 inhibition is prevented in zuo1Δ cells, contributing to decreased survival in these conditions. Our findings suggest a new role for RAC/Ssb in regulating translation in response to changes in TORC1 signalling.
Multiple antagonist calcium-dependent mechanisms control CaM kinase-1 subcellular localization in a C. elegans thermal nociceptor

Nociceptive habituation is a conserved process through which pain-sensitivity threshold is adjusted based on past sensory experience and which may be dysregulated in human chronic pain conditions. Noxious heat habituation in C. elegans involves the nuclear translocation of CaM kinase-1 (CMK-1) in the FLP thermo-nociceptors neurons, causing reduced animal heat sensitivity and avoidance responses. The phosphorylation of CMK-1 on T179 by CaM kinase kinase-1 (CKK-1) is required for nuclear entry. Recently, we identified a specific Nuclear Export Sequence (NES) required to maintain CMK-1 in the cytoplasm at rest (20 °C) and showed that Ca2+/CaM binding is sufficient to enhance CMK-1 affinity for IMA-3 via a specific Nuclear Localization Signal (NLS) in order to promote nuclear entry after persistent heat stimulation (90 min at 28°C) (Ippolito et al., 2021). Here, we identified additional functional NES and NLS on CMK-1, whose activity can counteract previously identified elements. Furthermore, we clarify the relationship between the CaM-binding-dependent and T179-dependent effects. T179 phosphorylation can promotes nuclear entry both downstream of CaM-binding and as part of an independent/parallel pathway. Moreover, T179 phosphorylation can also produce the opposite effect by promoting nuclear export. Taken together, our studies show that multiple calcium-dependent regulatory mechanisms converge to bias the activity pattern across a network of NES/NLS elements, in order to activate CMK-1 nucleo-cytoplasmic shuttling, change its localization equilibrium and actuate stimulation-dependent nociceptive plasticity.
Differentiation and admixture of Fagus sylvatica L. and Fagus orientalis Lipsky in a northern German forest – learning from pioneer forest work

Tree species are suffering from changing and stressful environmental conditions worldwide. Fagus sylvatica L. , one of the most common Central European deciduous tree species showed symptoms of crown damage, a reduction in growth and increased mortality following the severe recent drought years. For Germany Fagus orientalis Lipsky, a closely related species with higher drought tolerance, originating from south-eastern Europe, Turkey, the Greater Caucasus region and the Hyrcanian forest, has been proposed as an alternative with high future potential. The translocation of pre-adapted planting material has been proposed as a tool to mitigate negative effects of climate change. This approach can be beneficial but might also harbor risks. Taking advantage of F. orientalis trees planted over 100 years ago in the forest district of Memsen, Germany, we set out to study admixture between the two beech species and the direction of gene flow. Furthermore, we used a range-wide dataset of F. sylvatica and F. orientalis provenances to determine the origin of the introduced trees. Using a combination of nuclear EST-SSRs and one chloroplast SSR marker with species-specific variants, we could show that interspecific gene flow was going in both directions. In most cases, F. sylvatica was the pollen donor which is likely explained by the higher abundance of this species producing vast amounts of pollen. The planted trees originated from the Greater Caucasus region and showed strong genetic divergence from German F. sylvatica populations. In the future, gene flow patterns as well as hybrid performance from different provenances should be tested in additional stands and in comparison to F. sylvatica provenances from southern Europe to assess the suitability of Oriental beech for the mitigation of climate change impacts.