Miracle-dz/UniFAR-FTUs huggingface dataset:
Measurements of optical tissue properties using integrating sphere technique

The optical properties of white matter human brain, canine prostate and pig liver were measured in the wavelength range 330-1100 nm. The measurements were carried out in native as well as in coagulated tissues. We used the double integrating sphere technique to provide reflection and transmission measurements and a special homogenising technique to prepare the tissue. The optical properties were evaluated using an inverse Monte- Carlo simulation, considering the geometry of the experimental set-up. All tissues show characteristic absorption bands at 420 nm and 550 nm, related to the strong absorption of haemoglobin. After coagulation the scattering increases drastically while absorption remains nearly unchanged. The anisotropy factor g increases with increasing wavelength and drops down slightly after coagulation. The wavelength behaviour of tissue scattering has been compared with theoretical calculations (Mie-theory), showing that ideal spheres with an diameter between 0.6 and 0.8 pm fit best to the experimental results.
Rapid Clozapine Blood Level Determination in a National Health Service Trust

Neuropsychiatric symptoms including depression, apathy and psychosis occur frequently in patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia, but whether the use of rivastigmine is effective earlier in the disease course is unclear. The aim of this systematic review was to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia.
Differences in Chromatic Sensitivity Estimated Using Static and Dynamic Colour Stimuli

Abstract The current study reports on a novel computerised colour vision test employing static and dynamic stimuli. The aim of the study was to assess if static and dynamic stimuli result in comparable chromatic discrimination thresholds when participant’s age is taken into account. Participants (n = 20) were 21 to 77 years old, had normal colour vision and no history of any eye disease. They all participated in two sessions estimating chromatic sensitivity with static and dynamic stimuli, respectively, with six directions in colour space varying either along the red-green (RG) or yellow- blue (YB) directions. We found no significant differences in chromatic thresholds along a tritan axis obtained with static and dynamic stimuli. However, along protan and deitan axes, chromatic thresholds were lower if estimated using static stimuli than those estimated using the dynamic stimuli. As anticipated, chromatic sensitivity decreased with age and with greater chromatic sensitivity loss along the tritan confusion line. Research results suggest that differences between chromatic thresholds measured with static and dynamic stimuli become more apparent with increasing age of study participant.
Fluid mobilization of rare earth elements, Th, and U during the terrestrial alteration of H chondrites

The chemical effects of terrestrial alteration, with a particular focus on lithophile trace elements, were studied for a set of H chondrites displaying various degrees of weathering from fresh falls to altered finds collected from hot deserts. According to their trace element distributions, a considerable fraction of rare earth elements (REEs), Th, and U resides within cracks observed in weathered meteorite specimens. These cracks appear to accumulate unbound REEs locally accompanied by Th and U relative to the major element abundances, especially P and Si. The deposition of Ce is observed in cracks in the case of most of the weathered samples. Trace element maps visually confirm the accumulation of these elements in such cracks, as previously inferred based on chemical leaching experiments. Because the positive Ce anomalies and unbound REE depositions in cracks occur in all weathered samples studied here while none of such features are observed in less altered samples including falls (except for altered fall sample Nuevo Mercurio), these features are interpreted to have been caused by terrestrial weathering following chemical leaching. However, the overall effects on the bulk chemical composition remain limited as the data for all Antarctic meteorites studied in this work (except for heavily weathered sample A 09516, H6) are in good agreement with published data for unaltered meteorites.
Efficient Density-peaks Clustering Algorithms on Static and Dynamic Data in Euclidean Space

Clustering multi-dimensional points is a fundamental task in many fields, and density-based clustering supports many applications because it can discover clusters of arbitrary shapes. This article addresses the problem of Density-Peaks Clustering (DPC) in Euclidean space. DPC already has many applications, but its straightforward implementation incurs O(n2) time, where n is the number of points, thereby does not scale to large datasets. To enable DPC on large datasets, we first propose empirically efficient exact DPC algorithm, Ex-DPC. Although this algorithm is much faster than the straightforward implementation, it still suffers from O(n2) time theoretically. We hence propose a new exact algorithm, Ex-DPC++, that runs in o(n2) time. We accelerate their efficiencies by leveraging multi-threading. Moreover, real-world datasets may have arbitrary updates (point insertions and deletions). It is hence important to support efficient cluster updates. To this end, we propose D-DPC for fully dynamic DPC. We conduct extensive experiments using real datasets, and our experimental results demonstrate that our algorithms are efficient and scalable.
An Automated Data-driven Machine Intelligence Framework for Mining Knowledge To Classify Fake News Using NLP

The rapid spread of fake news has become a serious concern over the internet. In recent years, social media platforms are widely used for news consumption. These platforms are excellent for their low-cost accessibility and rapid dissemination of news. Contrariwise, it encourages the rapid propagation of ’fake news,’ or low-quality news containing intentionally misleading content. The quick dissemination of fake news has the potential to have devastating consequences for individuals and society as a whole. Therefore, to overcome this problem, this paper proposed an artificial intelligence framework that incorporates ensembles of deep learning features for the classification of fake news. Deep learning approaches such as Multilayer Perceptron (MLP), Convolutional Neural Networks (CNN), and Bidirectional Long Short Term Memory (BILSTM) have been used to extract local and sequential features. To obtain relevant features at the word level, these approaches are initialized using pretrained GLOVE word embedding, which results in, three base learners as GLOVE+MLP, GLOVE+CNN, and GLOVE+BiLSTM. Moreover, to extract features at the sentence level, Bidirectional Encoder Representations from Transformers (BERT) are adopted, which results in, three more base learners as BERT+MLP, BERT+CNN, BERT+BiLSTM. In total, six models are employed as base learners. Later, predictions from the best of these models are ensembled and performance is computed using ensembling techniques. Overall, we have investigated nine ensembling techniques, including weighted voting, bagging, boosting, stacked ensembles like SVC, and logistic regression. The performance is computed using four publicly available datasets regarding the macro average f1-score. We observed that soft weighted voting-based ensemble outperformed other models on three datasets achieving an f1-score of 92.99% (McIntyre), 95.22% (Kaggle), and 78.3% (Gossipcop).
Signal Structure for a Class of Nonlinear Dynamic Systems

Signal Structure for a Class of Nonlinear Dynamic Systems Meilan Jin Department of Computer Science, BYU Master of Science Signal structure is a partial structure representation for dynamic systems. It characterizes the causal relationship between manifest variables and is depicted in a weighted graph, where the weights are dynamic operators. Earlier work has defined signal structure for linear time-invariant systems through dynamical structure function. This thesis focuses on the search for the signal structure of nonlinear systems and proves that the signal structure reduces to the linear definition when the systems are linear. Specifically, this work: 1. Defines the complete computational structure for nonlinear systems. 2. Provide a process to find the complete computational structure given a state space model. 3. Define the signal structure for dynamic systems in general. 4. Provide a process to find the signal structure for a class of dynamic systems from their complete computational structure.
Critical parameters of the delivery in Ten Pin bowling / Rizal Mohd Razman

This exploratory study examined the possible important parameters for high level bowlers in three main areas - physical attribute, kinematics and movement variability. Consideration of the 'critical' parameters was made by looking at the variables that best distinguished the elite from the semi-elite bowlers using the discriminant function analysis. The study had an applied perspective in terms of the applications of the results and findings. Elite and semielite bowlers were grouped by their bowling score average (BSave), with participants scoring 200 pin falls and above assigned to the elite group. A total of 18 elite bowlers (M=10, F=8; BSave 213.2±6.80), 12 semi-elite bowlers (M=7, F=5; BSave 181.3±9.36) and 33 sedentary university students (M=14, F=19) representing the normal population were recruited. Ten anthropometric measurements and seven strength tests were conducted but there were no identifiable critical parameter of physical attributes for better bowlers as it was not possible to successfully distinguish between elite and semi-elite bowlers. However, differences were found when compared to the normal population, whereby the bowlers were heavier, had longer limbs, had stronger forearm internal rotation and arm flexion. A four-camera, 100 Hz, video-based 3D motion capture system was utilised for technique analysis. A total of 43 discrete kinematic variables were gathered from the motion analysis, out of which it was concluded that the two bowling groups had similar kinematic patterns for the majority of segments, with the exception of the shoulder and elbow regions. Discriminant analysis revealed that there were three critical kinematic variables, which showed an estimated 76.7% success rate for cross-validated classification in distinguishing the elite and semi-elite bowlers. From the discrete kinematic data, the within-subject inter-trial variability was also extracted to compare movement consistency. Consequently, 41 absolute variability variables were examined with a number of differences observed between the elite and semi-elite bowlers especially at the base (foot region) and the wrist, both of which are the most distal segments. The discriminant analysis highlighted four critical variability variables, with an estimated 76.7% success rate in distinguishing bowling playing level. It was concluded that the critical parameters of delivery for good bowling performance were faster shoulder velocity at front foot strike, faster elbow velocity at release, lower wrist height at release, more consistent foot lateral position at front foot strike, more consistent wrist lateral position at release, more varied foot slide distance, and more varied wrist superior-inferior position at release. Finally, as a consequence of the vast data gathered from this study, anthropometric and strength normative data, as well as kinematics and absolute variability measures for high level bowlers in Malaysia have been established and are readily available as a reference.
Par3/Bazooka binds NICD and promotes Notch signalling during Drosophila development

The conserved bazooka (baz/par3) gene acts as a key regulator of asymmetrical cell divisions across the animal kingdom. Associated Par3/Baz-Par6-aPKC protein complexes are also well known for their role in the establishment of apical/basal cell polarity in epithelial cells. Here we define a novel, positive function of Baz/Par3 in the Notch pathway. Using Drosophila wing and eye development, we demonstrate that Baz is required for Notch signaling activity and optimal transcriptional activation of Notch target genes. Baz appears to act independently of aPKC in these contexts, as knockdown of aPKC does not cause Notch loss-of-function phenotypes. Using transgenic Notch constructs, our data positions Baz activity downstream of activating Notch cleavage steps and upstream of Su(H)/CSL transcription factor complex activity on Notch target genes. We demonstrate a biochemical interaction between NICD and Baz, suggesting that Baz is required for NICD activity before NICD binds to Su(H). Taken together, our data define a novel role of the polarity protein Baz/Par3, as a positive and direct regulator of Notch signaling through its interaction with NICD.
Single-cell analysis of signalling and transcriptional responses to type I interferons

Type I interferons (IFNs) play crucial roles in antiviral defence, autoinflammation and cancer immunity. The human genome encodes 17 different type I IFNs that all signal through the same receptor. Non-redundant functions have been reported for some type I IFNs. However, whether different type I IFNs induce different responses remains largely unknown. We stimulated human peripheral blood mononuclear cells (PBMCs) with recombinant type I IFNs to address this question in multiple types of primary cells. We analysed signalling responses by mass cytometry and changes in gene expression by bulk and single-cell RNA sequencing. We found cell-type specific changes in the phosphorylation of STAT transcription factors and in the gene sets induced and repressed upon type I IFN exposure. We further report that the magnitude of these responses varied between different type I IFNs, whilst qualitatively different responses to type I IFN subtypes were not apparent. Taken together, we provide a rich resource mapping signalling responses and IFN-regulated genes in immune cells. Highlights Mass cytometry and scRNAseq analysis of human PBMCs stimulated with type I IFNs Cell type-specific phosphorylation of STAT proteins and induction of ISGs Different type I IFNs induce qualitatively similar responses that vary in magnitude Identification of ten core ISGs, up-regulated by all cell types in response to all type I IFNs In brief Rigby et al. provide a single-cell map of signalling and transcriptomic responses to type I IFNs in ex vivo stimulated human PBMCs. Different cell types responded in unique ways but differences between different type I IFNs were only quantitative. These rich datasets are available via an easy-to-use interactive interface (https://rehwinkellab.shinyapps.io/ifnresource/). Graphical abstract
Histone deacetylation and cytosine methylation compartmentalize heterochromatic regions in the genome organization of Neurospora crassa

Chromosomes must correctly fold in eukaryotic nuclei for proper genome function. Eukaryotic organisms hierarchically organize their genomes, including in the fungus Neurospora crassa, where chromatin fiber loops compact into Topologically Associated Domain (TAD)-like structures formed by heterochromatic region aggregation. However, insufficient data exists on how histone post-translational modifications, including acetylation, affect genome organization. In Neurospora, the HCHC complex (comprised of the proteins HDA-1, CDP-2, HP1, and CHAP) deacetylates heterochromatic nucleosomes, as loss of individual HCHC members increases centromeric acetylation and alters the methylation of cytosines in DNA. Here, we assess if the HCHC complex affects genome organization by performing Hi-C in strains deleted of the cdp-2 or chap genes. CDP-2 loss increases intra– and inter-chromosomal heterochromatic region interactions, while loss of CHAP decreases heterochromatic region compaction. Individual HCHC mutants exhibit different patterns of histone post-translational modifications genome-wide: without CDP-2, heterochromatic H4K16 acetylation is increased, yet smaller heterochromatic regions lose H3K9 trimethylation and gain inter-heterochromatic region interactions; CHAP loss produces minimal acetylation changes but increases heterochromatic H3K9me3 enrichment. Loss of both CDP-2 and the DIM-2 DNA methyltransferase causes extensive genome disorder, as heterochromatic-euchromatic contacts increase despite additional H3K9me3 enrichment. Our results highlight how the increased cytosine methylation in HCHC mutants ensures genome compartmentalization when heterochromatic regions become hyperacetylated without HDAC activity. Significance Statement The mechanisms driving chromosome organization in eukaryotic nuclei, including in the filamentous fungus Neurospora crassa, are currently unknown, but histone post-translational modifications may be involved. Histone proteins can be acetylated to form active euchromatin while histone deacetylases (HDACs) remove acetyl marks to form silent heterochromatin; these heterochromatic regions cluster, forming strong interactions, in Neurospora genome organization. Here, we show that mutants of a heterochromatin-specific HDAC, HCHC, increase heterochromatic histone acetylation genome-wide and contact probability between distant heterochromatic loci. HCHC loss also impacts cytosine methylation, and in strains lacking both the HCHC and cytosine methylation, heterochromatic regions interact more with euchromatin. Our results suggest cytosine methylation normally functions to segregate silent and active loci when heterochromatic acetylation increases.
Topology-dependent DNA binding

DNA stores our genetic information and is ubiquitous in biological and biotechnological applications, where it interacts with binding partners ranging from small molecules to large macromolecular complexes. Binding is modulated by mechanical strains in the molecule and, in turn, can change the local DNA structure. Frequently, DNA occurs in closed topological forms where topology and supercoiling add a global constraint to the interplay of binding-induced deformations and strain-modulated binding. Here, we present a quantitative model of how the global constraints introduced by DNA topology modulate binding and create a complex interplay between topology and affinity. We focus on fluorescent intercalators, which unwind DNA and enable direct quantification via fluorescence detection. Using bulk measurements, we show that DNA supercoiling can increase or decrease intercalation relative to an open topology depending on ligand concentration and the initial topology. Our model quantitatively accounts for observations obtained using psoralen for UV-induced DNA crosslinking, which is frequently used to quantify supercoiling in vivo. Finally, we observe topology-dependent binding in a single-molecule assay, which provides direct access to binding kinetics and DNA supercoil dynamics. Our results have broad implications for the detection and quantification of DNA and for the modulation of DNA binding in cellular contexts.
Small extracellular vesicles promote stiffness-mediated metastasis

Tissue stiffness is a critical prognostic factor in breast cancer and is associated with metastatic progression. Here we show an alternative and complementary hypothesis of tumor progression whereby physiological matrix stiffness affects the quantity and protein cargo of small EVs produced by cancer cells, which in turn drive their metastasis. Primary patient breast tissue produces significantly more EVs from stiff tumor tissue than soft tumor adjacent tissue. EVs released by cancer cells on matrices that model human breast tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4, ITGα6β1, CD44) compared to EVs from softer normal tissue (0.5 kPa; soft EVs), which facilitates their binding to extracellular matrix (ECM) protein collagen IV, and a 3-fold increase in homing ability to distant organs in mice. In a zebrafish xenograft model, stiff EVs aid cancer cell dissemination through enhanced chemotaxis. Moreover, normal, resident lung fibroblasts treated with stiff and soft EVs change their gene expression profiles to adopt a cancer associated fibroblast (CAF) phenotype. These findings show that EV quantity, cargo, and function depend heavily on the mechanical properties of the extracellular microenvironment. Graphical Abstract
The elusive role of herpesviruses in Alzheimer’s disease: current evidence and future directions

Abstract Alzheimer’s disease (AD) is the most common cause of dementia. While pathologic hallmarks, such as extracellular beta-amyloid plaques, are well-characterized in affected individuals, the pathogenesis that causes plaque formation and eventual cognitive decline is not well understood. A recent resurgence of the decades-old “infectious hypothesis” has garnered increased attention on the potential role that microbes may play in AD. In this theory, it is thought that pathogens such as viruses may act as seeds for beta-amyloid aggregation, ultimately leading to plaques. Interest in the infectious hypothesis has also spurred further investigation into additional characteristics of viral infection that may play a role in AD progression, such as neuroinflammation, latency, and viral DNA integration. While a flurry of research in this area has been recently published, with herpesviruses being of particular interest, the role of pathogens in AD remains controversial. In this review, the insights gained thus far into the possible role of herpesviruses in AD are summarized. The challenges and potential future directions of herpesvirus research in AD and dementia are also discussed.
MPK4 mediated phosphorylation of PIF4 controls thermosensing by regulation of H2A.Z deposition in Arabidopsis

Plants have the ability to perceive a slight upsurge in ambient temperature and respond by undergoing morphological changes, such as elongated hypocotyls and early flowering. The dynamic functioning of PHYTOCHROME INTERACTING FACTOR4 (PIF4) in thermomorphogenesis has been well established, although the regulatory pathway involved in thermosensing is not deciphered completely. In our study, we demonstrate that an increase in temperature from 22℃ to 28℃ induces the phosphorylation of PIF4 by MITOGEN-ACTIVATED PROTEIN KINASE 4 (MPK4) which shows high expression and activation at 28℃. Apparently, phosphorylated PIF4 represses the expression of ACTIN-RELATED PROTEIN 6 (ARP6) that is required for mediating histone variant H2A.Z deposition at its target gene loci. We demonstrate that variation of ARP6 expression in PIF4 phosphor -null and phosphor-mimetic seedlings affects hypocotyl growth and flowering at 22℃ and 28℃. Further, we show that change in ARP6 expression affects H2A.Z deposition at the loci of genes involved in hypocotyl elongation using PIF4 phosphor -null and phosphor-mimetic seedlings. Interestingly, the expression of MPK4 is also controlled by H2A.Z deposition in temperature dependent manner. Taken together, our findings highlight the cumulative molecular interplay between MPK4, PIF4, and chromatin modification by ARP6-mediated H2A.Z deposition as a regulatory mechanism of thermosensing.