Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensity-free Convolutional Temporal Point Process: Incorporating Local and Global Event Contexts

Event prediction in the continuous-time domain is a crucial but rather difficult task. Temporal point process (TPP) learning models have shown great advantages in this area. Existing models mainly focus on encoding global contexts of events using techniques like recurrent neural networks (RNNs) or self-attention mechanisms. However, local event contexts also play an important role in the occurrences of events, which has been largely ignored. Popular convolutional neural networks, which are designated for local context capturing, have never been applied to TPP modelling due to their incapability of modelling in continuous time. In this work, we propose a novel TPP modelling approach that combines local and global contexts by integrating a continuous-time convolutional event encoder with an RNN. The presented framework is flexible and scalable to handle large datasets with long sequences and complex latent patterns. The experimental result shows that the proposed model improves the performance of probabilistic sequential modelling and the accuracy of event prediction. To our best knowledge, this is the first work that applies convolutional neural networks to TPP modelling.
Asymptotic curves on B-surfaces according to type-2 bishop frame in the sol space

Abstract In this paper, we study B— surfaces of biharmonic constant Π2— slope curves according to type-2 Bishop in the . We characterize asymptotic curves on B— surfaces of biharmonic constant Π2— slope curves in terms of their Bishop curvatures. Finally, we find out their explicit parametric equations in the .
Near-wall turbulence intensity as $Re_\tau \rightarrow \infty$

In this study, asymptotic scaling of near-wall streamwise turbulence intensity $\overline{u'u'}/u_\tau^2$ ($u_\tau$ is the friction velocity) is theoretically explored. The three scalings previously proposed are first reviewed with their derivation and physical justification: 1) $\overline{u'u'}/u_\tau^2 \sim \ln Re_\tau$ ($Re_\tau$ is the friction velocity); 2) $\overline{u'u'}/u_\tau^2 \sim 1/U_\infty^+$ ($U_\infty^+$ is the inner-scaled freestream velocity in boundary layer); 3) $\overline{u'u'}/u_\tau^2 \sim Re_\tau^{-1/4}$. A new analysis is subsequently developed based on velocity spectrum, and two possible scenarios are identified based on the asymptotic behaviour of the outer-scaling part of the near-wall velocity spectrum. In the former case, the outer-scaling part of the spectrum is assumed to reach a non-zero constant as $Re_\tau \rightarrow \infty$, and it results in the scaling of $\overline{u'u'}/u_\tau^2 \sim \ln Re_\tau$, both physically and theoretically consistent with the classical attached eddy model. In the latter case, a sufficiently rapid decay of the outer-scaling part of the spectrum with $Re_\tau$ is assumed due to the effect of viscosity, such that $\overline{u'u'}/u_\tau^2<\infty$ for all $Re_\tau$. The following analysis yields $\overline{u'u'}/u_\tau^2 \sim 1/\ln Re_\tau$, asymptotically consistent with the scaling of $\overline{u'u'}/u_\tau^2 \sim 1/U_\infty^+$. The scalings are further verified with the existing simulation and experimental data and those from a quasilinear approximation (Holford \emph{et al.}, 2023, \texttt{arXiv:2305.15043}), the spectra of which all appear to favour $\overline{u'u'}/u_\tau^2 \sim 1/\ln Re_\tau$, although new datasets for $Re_\tau \gtrsim O(10^4)$ would be necessary to conclude this issue.
Hereditäre Lebererkrankungen: Morbus Wilson und Hämochromatose

Morbus Wilson und die HFE-assoziierte Hämochromatose sind autosomal-rezessiv vererbte Stoffwechselkrankheiten der Leber. Die Kenntnis der Symptomatik und Diagnostik ist wichtig, um diese Erkrankungen möglichst früh erkennen und behandeln zu können. Bei der Hämochromatose kann die frühzeitige Diagnose Endorganschädigungen verhindern. Insbesondere Morbus Wilson wird aufgrund seines breiten Symptomspektrums häufig spät erkannt.
Die nichtalkoholische Steatohepatitis (NASH) als Ursache erhöhter Leberwerte

Die nichtalkoholische Steatohepatitis (NASH) ist die progrediente Verlaufsform der nichtalkoholischen Fettlebererkrankung (NAFLD) und durch eine erhöhte entzündliche Aktivität gekennzeichnet, die in einer Leberfibrose bzw. Leberzirrhose resultieren kann. NASH-Aktivität und Leberfibrose sind die prognoserelevanten Risikofaktoren, sodass eine rationale Stufendiagnostik, Identifikation von Risikopersonen und ein zielgerichteter Einsatz der therapeutischen Möglichkeiten entscheidend ist.
Erhöhte Leberwerte: eine differenzialdiagnostische Herausforderung

Die Abklärung erhöhter Leberwerte gehört zum Kerngebiet der Hepatologie und ist eine differenzialdiagnostische Herausforderung. Erhöhte Leberwerte können das laborchemische Korrelat einer Vielzahl von Lebererkrankungen, aber auch aus physiologischen oder extrahepatischen Ursachen erhöht sein. Eine rationale Herangehensweise ist notwendig, um eine Überdiagnostik zu vermeiden, ohne seltene Lebererkrankungen zu übersehen.
Digital harmonic holographic microscope for the study of nanostructures in nonlinear regime

Digital holography is an imaging technique that enables a 3-dimensional reconstruction of the electromagnetic field scattered by an object in both amplitude and phase. We demonstrated its use in microscopy in linear regime for the full 3-D mapping of the field scattered by single nanostructures such as nano-antennas and near-field probes. Holography is a technique based on interferences, which can be obtained at the laser illumination wavelength, but also with Second Harmonic Generation (SHG), since the latter is produced in a coherent process. Here, we describe the development of a harmonic holographic microscope for single-shot mapping of the second harmonic 3D radiation pattern near samples with nonzero second harmonic susceptibilities. The knowledge of the scattered field (amplitude and phase) in a given plane (that of the camera) allows its reconstruction in any other plane using e.g. the angular spectrum representation of the optical fields, and assuming propagation in homogeneous media, a process called 3D numerical back-propagation [6]. In addition to providing 3D reconstruction, thus enhancing the imaging capabilities beyond those of back focal-plane imaging, the harmonic holography microscope also benefits from an amplification effect since the signal from the sample is multiplied by an intense reference in the interference term, making the method particularly well suited to measure the weak SHG signals. After a first validation on dielectric samples made of nonlinear micro-crystals and cornea collagen, we are implementing the technique to obtain SHG fields radiated by plasmonic nano-antennas.
Soliton Raman shift wavelength tuning through the pump pulse polarization control

In addition to the well-known problem related to the growing demands in telecom fiber optical data transmission lines with extended bandwidth in recent years the researchers developed an interest in mode-locked fiber lasers of 1600-1700 nm spectral region in a number of biomedical applications. The known approach to get the generation in this range uses the Er-doped fiber mode-locked seed source of telecom range. The output ultrashort pulse then propagates in nonlinear optical fiber with anomalous dispersion undergoing the Raman shift to the longer wavelengths. We propose a method to control the characteristics of the output Raman soliton spectrum adjusting the polarization of the pump pulse at the input of the nonlinear fiber. We have shown that this method allows to tune the wavelength of the output spectrum maximum in the whole range (1600-1700 nm) while the output power remains constant. Our simulation results agree with experimental observations.
‘Boots’ theory: why mental health initiatives need to address economic inequalities

Mental health promotion initiatives can be costly – but so too are the consequences of poor mental health. For this editorial I want to unpack the ‘boots’ theory of socioeconomic unfairness, and explore its implications for mental health funding. Boots theory has been around for some time, but I only came across it recently. For those who are equally unaware, boots theory explains how the wealthy can afford to live cheaply while the poor cannot. The theory is called ‘boots’, because of how Terry Pratchett, in his 1993 book Men at Arms, initially described it:
Deciphering the genetic interactions between Pou4f3, Gfi1, and Rbm24 in maintaining mouse cochlear hair cell survival

Mammals harbor a limited number of sound-receptor hair cells (HCs) that cannot be regenerated after damage. Thus, investigating the underlying molecular mechanisms that maintain HC survival is crucial for preventing hearing impairment. Intriguingly, Pou4f3-/- or Gfi1-/-HCs form initially but then rapidly degenerate, whereas Rbm24-/-HCs degenerate considerably later. However, the transcriptional cascades involving Pou4f3, Gfi1, and Rbm24 remains undescribed. Here, we demonstrate that Rbm24 expression is completely repressed in Pou4f3-/- HCs but unaltered in Gfi1-/- HCs, and further that the expression of both POU4F3 and GFI1 is intact in Rbm24-/- HCs. Moreover, by using in vivo mouse transgenic reporter assays, we identify three Rbm24 enhancers to which POU4F3 binds. Lastly, through in vivo genetic testing of whether Rbm24 restoration alleviates the degeneration of Pou4f3-/-HCs, we show that ectopic Rbm24 alone cannot prevent Pou4f3-/-HCs from degenerating. Collectively, our findings provide new molecular and genetic insights into how HC survival is regulated.
Genome-wide identification of notochord enhancers comprising the regulatory landscape of the brachyury locus in mouse

The node and notochord are important signaling centers organizing dorso-ventral patterning of cells arising from neuro-mesodermal progenitors forming the embryonic body anlage. Due to the scarcity of notochordal progenitors and notochord cells, a comprehensive identification of regulatory elements driving notochord-specific gene expression has been lacking. Here we have used ATAC-seq analysis of FACS-purified notochordal cells from TS12-13 mouse embryos to identify 8921 putative notochord enhancers. In addition, we established a new model for generating notochordal cells in culture, and found 3728 of these enhancers occupied by the essential notochordal regulators Brachyury (T) and/or Foxa2. We describe the regulatory landscape of the T locus comprising 10 putative enhancers occupied by these factors and confirmed the regulatory activity of 3 of these elements. Moreover, we characterized one new notochord enhancer, termed TNE2, in embryos. TNE2 complements the loss of TNE in the trunk notochord, and is essential for notochordal cell proliferation and differentiation in the tail. Our data demonstrate the essential role of Foxa2 in switching T expressing cells from a NMP/mesodermal trajectory to the notochordal fate. Summary statement Combining multi-omics assays of purified embryonic and in vitro generated cells we identified thousands of notochord enhancers comprising TNE2 essential for T expression and tail development of the mouse embryo.
Model-free Identification of Phenotype-Relevant Variables From Dose Response Data

Complex phenotypic changes occur during development and in response to injury and disease. Identifying key regulators of phenotypic change is a shared aim of many different fields of research, including life history, tissue regeneration, and cancer. These examples of phenotypic change involve coordinated changes in cellular behaviors and associated changes in gene expression which if disrupted, can alter and even block completion of the phenotypic transition. Experimental treatments that effectively block the completion of a phenotypic transition can be quantitatively manipulated to identify key regulatory genes through changes in transcriptional dose response. In this paper, we present a “model free” approach to identify “bifurcation-like” behaviors of key regulatory genes by tracking spikes in their transcriptional sensitivities. Genes that exhibit such behavior are predicted to comprise nodes in subnetworks or modules that regulate the phenotypic transition. We applied our method to an in-silico data set where we also studied the impact of noise in the predictions. We also applied the method to a gene expression data that were collected during tail regeneration in axolotls. Our code for gene identification, which can be extended more generally to other component variables of complex phenotypic change, is freely available via the following GitHub site github.com/alanavc/id-vars-from-resp-data.
Multiprotein Assemblies, Phosphorylation and Dephosphorylation in Neuronal Cytoskeleton

Filament systems are comprised of fibrous and globular cytoskeletal proteins and are key elements regulating cell shape, rigidity, and dynamics. The cellular localization and assembly of neurofilaments depend on phosphorylation by kinases. The involvement of the BRCA1 (Breast cancer associated protein 1)/BARD1 (BRCA1-associated RING domain 1) pathways in Alzheimer disease (AD) is suggested by colocalization studies. In particular, BRCA1 accumulation within neurofibrillary tangles and colocalization with tau aggregates in the cytoplasm of AD patients implicates the involvement of mutant forms of BRCA1/BARD1 proteins in disease pathogenesis. The purpose of this study is to show that the location of mutations in the translated BARD1, specifically within ankyrin repeats, has strong correlation with the Cdk5 motifs for phosphorylation. Mapping of the mutation sites on the protein’s three-dimensional structure and estimation of the backbone dihedral angles show transitions between the canonical helical and extended conformations of the tetrapeptide sequence of ankyrin repeats. Clustering of mutations in BARD1 ankyrin repeats near the N-termini of the helices with T/SXXH motifs provides a basis for conformational transitions that might be necessary to ensure the compatibility of the substrate with active site geometry and accessibility of the substrate to the kinase. Ankyrin repeats are interaction sites for phosphorylation-dependent dynamic assembly of proteins including those involved in transcription regulation and signaling, and present potential targets for the design of new drugs.
Mitochondrial genome fragmentation is correlated with increased rates of molecular evolution

Animal mitochondrial genomes (mitogenomes) typically exhibit a highly conserved gene content and organisation, with genes encoded on a single circular chromosome. However, many species of parasitic lice (Insecta: Phthiraptera) are notable exceptions, having mitogenomes fragmented into multiple circular chromosomes. To understand the process of mitogenome fragmentation, we conducted a large-scale genomic study of a major group of lice, Amblycera, with extensive taxon sampling. Analyses of the evolution of mitogenome structure across a phylogenomic tree of 90 samples from 53 genera, revealed evidence for multiple independent origins of mitogenome fragmentation, some inferred to have occurred less than five million years ago. We leveraged these many independent origins of fragmentation to compare the rates of DNA substitution and gene rearrangement, specifically contrasting branches with fragmented and non-fragmented mitogenomes. We found that lineages with fragmented mitochondrial genomes had significantly higher rates of mitochondrial sequence evolution. In addition, lineages with fragmented mitochondrial genomes were more likely to have mitogenome gene rearrangements than those with single-chromosome mitochondrial genomes. By combining phylogenomics and mitochondrial genomics we provide a detailed portrait of mitogenome evolution across this group of insects with a remarkably unstable mitogenome structure, identifying processes of molecular evolution that are correlated with mitogenome fragmentation. Author Summary Mitochondria are organelles that play a key role in providing energy to cells essential for life. The structure of the mitochondrial genome is conserved across most animal groups, being a single circular chromosome containing 37 genes. Deviations from this structure are typically detrimental and associated with some human diseases. However, in very few animal groups, the mitochondrial genome is fragmented into multiple circular chromsomes. In one group of insects, parasitic lice, fragmentation varies among species, with some having a complete circular genome and others having their mitochondrial genome fragmented in two or more smaller chromosomes. Here, we use whole genome sequencing reads to analyze an unprecedented number of species from a diverse group of lice (Amblycera) that exhibits both single-chromosome and fragmented mitochondrial genomes to understand how this fragmentation evolved. We found that fragmentation evolved many times independently in this group and this fragmentation is correlated faster rates mitochondrial molecular evolution and with an increased frequency of gene rearrangement. We also provide evidence that the rate of mitochondrial genome fragmentation changes over time. Altogether, our combination of broad sampling and phylogenomic and comparative analyses provide new insights into the mechanisms and dynamics of mitochondrial genome fragmentation.
Site-specific acetylation of polynucleotide kinase 3’-phosphatase (PNKP) regulates its distinct role in DNA repair pathways

Mammalian polynucleotide kinase 3’-phosphatase (PNKP) is a dual-function DNA end-processing enzyme with 3’-phosphatase and 5’-kinase activities, which generate 3’-OH and 5’-phosphate termini respectively, as substrates for DNA polymerase and DNA ligase to complete DNA repair. PNKP is thus involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes, which involve distinct sets of proteins. In this study, we report that PNKP is acetylated at two lysine (K142 and K226) residues. While K142 (AcK142) is constitutively acetylated by p300, CBP acetylates K226 (AcK226) only after DSB induction. Co-immunoprecipitation analysis using antibodies specific for PNKP peptides containing AcK142 or AcK226 of PNKP showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP only with DSBR proteins. Although acetylation at these residues did not significantly affect the enzymatic activity of PNKP in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage, specifically in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington’s Disease (HD)-based mouse model, K142, but not K226, was acetylated. This observation is consistent with the reported degradation of CBP but not p300 in HD cells. Moreover, genomes of HD cells progressively accumulated DSBs specifically in the transcribed genes. Chromatin-immunoprecipitation analysis using anti-AcK142 or anti-AcK226 antibodies demonstrated an association of Ac-PNKP with the transcribed genes, consistent with PNKP’s role in transcription-coupled repair. Thus, our findings collectively demonstrate that acetylation at two lysine residues located in different domains of PNKP regulates its functionally distinct role in BER/SSBR vs. DSBR.
Structure of R&D capital expenditure and national total factor productivity

Abstract This paper examines the relationship between the structure of R&D fixed capital spending, measured as the ratio of the private sector to public sector R&D capital expenditure, and national total factor productivity. It employs South African data for the period 1965 to 2019. This study employs the non-linear distributed lag modelling framework to cater for non-linearities in the relationship. The findings, first, suggest that the ratio of private sector to public sector R&D capital spending has a positive effect on total factor productivity. Second, the structure of R&D capital spending has large asymmetric effects on national total factor productivity, with negative changes dominating positive changes. Negative changes in the structure of R&D capital spending negatively influence total factor productivity, but positive changes have positive effects. Both in the short run and the long run, cumulative multipliers indicate that negative changes in the structure of R&D capital spending dominate positive changes by a very large margin. The findings imply that the private sector must become more dominant than the public sector in R&D capital spending in the national system of innovation.
Unheard risk: considering the role of intrusive cognitions in relapse

Abstract Substance use disorders (SUD) represent a pervasive and ongoing public health crisis responsible for many deaths and hospitalizations each year. Despite decades of research, we have yet to develop an effective cross-substance treatment model. Many who seek and enter treatment for SUD end up relapsing despite their intentions. Inconsistency in treatment success necessitates the identification of novel, universal therapeutic targets in the underlying core mechanisms of SUD. Determining the cognitive mechanisms which promote addictive behaviors is an essential first step to fully understand relapse and maintenance in SUD. The goal of the current review is to explore underlying cognitive processes which prolong SUD despite treatment. Through this, we propose a mechanistic model for how intrusive cognitions may jeopardize symptom improvement and SUD treatment success via risky decision making. Intrusive cognitions - images, words, memories, or impulses - demand little cognitive effort, and lend themselves to quick action and decisions. In the current paper, we present evidence which shows how intrusive cognitions, poorly inhibited, could impair the decision making process in SUD and lead to subsequent addictive behaviors.
Re-examining the corporate governance – Firm performance nexus: Fresh evidence from a causal mediation analysis

Abstract The role that corporate governance (CG) plays in contributing to firm performance enhancements has been widely acknowledged. However, the conduit through which CG is able to affect firm performance is an emergent theme. This paper re-examines the relationship between corporate governance (CG) and firm performance via means of causal mediation analysis using financial reporting quality (FRQ) as a mediator. The study samples 104 companies listed on the respective stock markets of nine sub-Saharan African countries, and collects annual reports data spanning over a period of 2007 to 2019 for analysis using causal mediation. The study finds that a causal relationship exists between CG and firm performance, albeit through the transmission mechanism of FRQ. Again, the study finds that CG positively affects firm performance both directly and indirectly through the mediation of FRQ. The study is useful in highlighting for mangers and CG practitioners attention, an important channel through which CG would favourably affect firm performance, being FRQ. The current study is unique, in that it is the first panel multi-cross-country investigation within Africa to introduce FRQ in the study of the relationship between CG and firm performance. It therefore extends the agency theory by employing FRQ as a mediating variable in the CG—firm performance nexus within the African context.