Miracle-dz/UniFAR-FTUs huggingface dataset:
Co-estimating Reticulate Phylogenies and Gene Trees from Multi-locus Sequence Data

The multispecies network coalescent (MSNC) is a stochastic process that captures how gene trees grow within the branches of a phylogenetic network. Coupling the MSNC with a stochastic mutational process that operates along the branches of the gene trees gives rise to a generative model of how multiple loci from within and across species evolve in the presence of both incomplete lineage sorting (ILS) and reticulation (e.g., hybridization). We report on a Bayesian method for sampling the parameters of this generative model, including the species phylogeny, gene trees, divergence times, and population sizes, from DNA sequences of multiple independent loci. We demonstrate the utility of our method by analyzing simulated data and reanalyzing three biological data sets. Our results demonstrate the significance of not only co-estimating species phylogenies and gene trees, but also accounting for reticulation and ILS simultaneously. In particular, we show that when gene flow occurs, our method accurately estimates the evolutionary histories, coalescence times, and divergence times. Tree inference methods, on the other hand, underestimate divergence times and overestimate coalescence times when the evolutionary history is reticulate. While the MSNC corresponds to an abstract model of “intermixture,” we study the performance of the model and method on simulated data generated under a gene flow model. We show that the method accurately infers the most recent time at which gene flow occurs. Finally, we demonstrate the application of the new method to a 106-locus yeast data set. [Multispecies network coalescent; reticulation; incomplete lineage sorting; phylogenetic network; Bayesian inference; RJMCMC. ]
Neighborhood Design, Physical Activity, and Wellbeing: Applying the Walkability Model

Neighborhood design affects lifestyle physical activity, and ultimately human wellbeing. There are, however, a limited number of studies that examine neighborhood design types. In this research, we examine four types of neighborhood designs: traditional development, suburban development, enclosed community, and cluster housing development, and assess their level of walkability and their effects on physical activity and wellbeing. We examine significant associations through a questionnaire (n = 486) distributed in Tucson, Arizona using the Walkability Model. Among the tested neighborhood design types, traditional development showed significant associations and the highest value for walkability, as well as for each of the two types of walking (recreation and transportation) representing physical activity. Suburban development showed significant associations and the highest mean values for mental health and wellbeing. Cluster housing showed significant associations and the highest mean value for social interactions with neighbors and for perceived safety from crime. Enclosed community did not obtain the highest means for any wellbeing benefit. The Walkability Model proved useful in identifying the walkability categories associated with physical activity and perceived crime. For example, the experience category was strongly and inversely associated with perceived crime. This study provides empirical evidence of the importance of including vegetation, particularly trees, throughout neighborhoods in order to increase physical activity and wellbeing. Likewise, the results suggest that regular maintenance is an important strategy to improve mental health and overall wellbeing in cities.
Facial image feature extraction using support vector machines

In this paper, we present an approach that unifies sub-space feature extraction and support vector classification for face recognition. Linear discriminant, independent component and principal component analyses are used for dimensionality reduction prior to introducing feature vectors to a support vector machine. The performance of the developed methods in reducing classification error and providing better generalization for high dimensional face recognition application is demonstrated.
Closed-loop Pushing with Fast Model Identification

We propose a framework for performing single contact point planar pushing with unknown pressure distribution. The problem is challenging due to the stochastic and under-actuated system properties. Using as few as two data points, our method can estimate the control-related model parameters. To achieve posture stabilization, we use differential dynamic programming and replan with updated model when large deviation occurs. We demonstrate empirical success in posture stabilization and robustness with respect to different pressure distributions.
Oligomannose-Rich Membranes of Dying Intestinal Epithelial Cells Promote Host Colonization by Adherent-Invasive E. coli

A novel mechanism is revealed by which clinical isolates of adherent-invasive Escherichia coli (AIEC) penetrate into the epithelial cell layer, replicate, and establish biofilms in Crohn's disease. AIEC uses the FimH fimbrial adhesin to bind to oligomannose glycans on the surface of host cells. Oligomannose glycans exposed on early apoptotic cells are the preferred binding targets of AIEC, so apoptotic cells serve as potential entry points for bacteria into the epithelial cell layer. Thereafter, the bacteria propagate laterally in the epithelial intercellular spaces. We demonstrate oligomannosylation at two distinct sites of a glycoprotein receptor for AIEC, carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6 or CD66c), on human intestinal epithelia. After bacterial binding, FimH interacts with CEACAM6, which then clusters. The presence of the highest-affinity epitope for FimH, oligomannose-5, on CEACAM6 is demonstrated using LC-MS/MS. As mannose-dependent infections are abundant, this mechanism might also be used by other adherent-invasive pathogens.
Trust in Automated Vehicles

Abstract Increasing degrees of automation in on-road vehicles bear great potential for heightened driver safety and traffic efficiency in both the near and far future. The more the driver delegates control to the vehicle, the more salient the issue of trust in automated technology becomes. Misaligned trust can lead to mishandling of automation controls in individual instances and decreases the general acceptance of on-road automation on a broader scale. In this paper, we apply insights from trust research for dynamic web service interaction to the novel automated driving domain, in order to scope the problem space regarding trust in automated vehicles. We conclude that the appropriate communication of trustworthiness, the necessity to calibrate trust, the importance of intervention capabilities by the driver, and the unambiguous transparency of locus of control are all important aspects when in comes to understanding trust in automated vehicles.
Does the Enigmatic Wightia Belong to Paulowniaceae (Lamiales)?

The familial placement of Wightia has been controversial in the Lamiales, and the genus is currently placed in Paulowniaceae in APG IV. Phylogenetic analyses of Wightia and its close relatives in Lamiales are conducted using sequences of the complete chloroplast genomes as well as sequence data from nine chloroplast DNA regions (atpB, matK, ndhF, psbBTNH, rbcL, rps4, rps16 intron, trnL-F, and trnV-atpE) and one mitochondrial gene rps3. The maximum likelihood and Bayesian analyses do not support a close relationship between Wightia and Paulownia of Paulowniaceae; instead the enigmatic Wightia is sister to Phrymaceae with strong support in all analyses. Hence Wightia should not be placed in Paulowniaceae. Because morphological data show Wightia’s affinity to both Phrymaceae and Paulowniaceae and prior nrITS data suggest its sister relationship to Paulownia of Paulowniaceae, it is likely that Wightia may have had a hybrid origin between early lineages of Phrymaceae and Paulowniaceae. It is therefore the best to exclude Wightia from Paulowniaceae and place the genus as unassigned until further nuclear data to test the hybrid hypothesis. The seven species of Paulownia constitute a monophyletic group, and Paulowniaceae is supported to be a monogeneric family, consistent with a series of morphological and floral development characters. The genus Brandisia, which was sometimes regarded as a close relative of Wightia, is supported to be nested within Orobanchaceae, as sister to Pterygiella. This sister relationship can be corroborated by fruit, seed and pollen morphological characters.
Intra-tumor heterogeneity of MLH1 promoter methylation revealed by deep single molecule bisulfite sequencing

A single tumor may contain cells with different somatic mutations. By characterizing this genetic heterogeneity within tumors, advances have been made in the prognosis, treatment and understanding of tumorigenesis. In contrast, the extent of epigenetic intra-tumor heterogeneity and how it influences tumor biology is under-explored. We have characterized epigenetic heterogeneity within individual tumors using next-generation sequencing. We used deep single molecule bisulfite sequencing and sample-specific DNA barcodes to determine the spectrum of MLH1 promoter methylation across an average of 1000 molecules in each of 33 individual samples in parallel, including endometrial cancer, matched blood and normal endometrium. This first glimpse, deep into each tumor, revealed unexpectedly heterogeneous patterns of methylation at the MLH1 promoter within a subset of endometrial tumors. This high-resolution analysis allowed us to measure the clonality of methylation in individual tumors and gain insight into the accumulation of aberrant promoter methylation on both alleles during tumorigenesis.
Surveillance and Genomics of Toxigenic Vibrio cholerae O1 From Fish, Phytoplankton and Water in Lake Victoria, Tanzania

The occurrence of toxigenic Vibrio cholerae O1 during a non- outbreak period in Lake Victoria was studied and genetic characteristics for environmental persistence and relatedness to pandemic strains were assessed. We analyzed 360 samples of carps, phytoplankton and water collected in 2017 during dry and rainy seasons in the Tanzanian basin of Lake Victoria. Samples were tested using PCR (ompW and ctxA) with DNA extracted from bacterial isolates and samples enriched in alkaline peptone water. Isolates were screened with polyvalent antiserum O1 followed by antimicrobial susceptibility testing. Whole genome sequencing and bioinformatics tools were employed to investigate the genomic characteristics of the isolates. More V. cholerae positive samples were recovered by PCR when DNA was obtained from enriched samples than from isolates (69.0% vs. 21.3%, p < 0.05), irrespectively of season. We identified ten V. cholerae O1 among 22 ctxA-positive isolates. Further studies are needed to serotype the remaining ctxA-positive non-O1 strains. Sequenced strains belonged to El Tor atypical biotype of V. cholerae O1 of MLST ST69 harboring the seventh pandemic gene. Major virulence genes, ctxA, ctxB, zot, ace, tcpA, hlyA, rtxA, ompU, toxR, T6SS, alsD, makA and pathogenicity islands VPI-1, VPI-2, VSP-1, and VSP-2 were found in all strains. The strains contained Vibrio polysaccharide biosynthesis enzymes, the mshA gene and two-component response regulator proteins involved in stress response and autoinducers for quorum sensing and biofilm formation. They carried the SXT integrative conjugative element with phenotypic and genotypic resistance to aminoglycoside, sulfamethoxazole, trimethoprim, phenicol, and quinolones. Strains contained a multidrug efflux pump component and were resistant to toxic compounds with copper homeostasis and cobalt-zinc-cadmium resistance proteins. The environmental strains belonged to the third wave of the seventh pandemic and most are genetically closely related to recent outbreak strains from Tanzania, Kenya, and Uganda with as low as three SNPs difference. Some strains have persisted longer in the environment and were more related to older outbreak strains in the region. V. cholerae O1 of outbreak potential seem to persist in Lake Victoria through interactions with fish and phytoplankton supported by the optimum water parameters and intrinsic genetic features enhancing survival in the aquatic environment.
Brain mechanisms of sensory and vicarious pain

The aim of the Thesis was to study the brain circuits representing sensory and vicarious pain. Experiments with functional magnetic resonance imaging were conducted to study neural activity patterns evoked by both stimulus modalities. Sensory pain was induced to subjects by applying noxious heat to right foot, while pictures of painful feet were used to arouse vicarious pain. Sensory pain was modeled in three different ways within the framework of the general linear model: The event-like model assumes that brain’s pain-circuits are activated only during noxious stimulus, while the two other models that used long and intermediate blocks additionally assume, to different degrees, that also expectation of pain activates the same circuits. Both sensory and vicarious pain triggered robust neural activity increase in partly overlapping but mostly neighboring clusters in an area extending bilaterally from midcingulate cortex to supplementary motor area. The self-related pain cluster located slightly posterior to the otherrelated cluster. Stimulus-modality-specific brain regions exhibiting increased activation included somatosensory cortex and bilateral anterior insula for sensory pain and occipital cortex for vicarious pain. Among the tested models of pain perception, the event-like model yielded results that most closely match previously reported findings. Overall, the results of the Thesis accord with prior literature, and thus confirm the suitability of the selected stimuli and experimental design for studying brain circuits representing pain. Helppromotion is suggested to account for the partly shared neural representations of sensory and vicarious pain. The results and the model’s straightforward interpretability strongly support the use of the event-like model in future studies investigating brain activity reflecting sensory pain.
Adjusting to the GDPR: The Impact on Data Scientists and Behavioral Researchers

Rapid growth in the availability of behavioral big data (BBD) has outpaced the speed of updates to ethical research codes and regulation of data privacy and human subjects' data collection, storage, and use. The introduction of the European Union's (EU's) General Data Protection Regulation (GDPR) in May 2018 will have far-reaching effects on data scientists and researchers who use BBD, not only in the EU, but around the world. Consequently, many companies are struggling to comply with the Regulation. At the same time, academics interested in research collaborations with companies are finding it more difficult to obtain data. In light of the importance of BBD in both industry and academia, data scientists and behavioral researchers would benefit from a deeper understanding of the GDPR's key concepts, definitions, and principles, especially as they apply to the data science workflow. We identify key GDPR concepts and principles and describe how they can impact the work of data scientists and researchers in this new data privacy regulation era.
Assessing and Interpreting Reliability

For research to produce meaningful results, variables must be measured in a reliable manner. Reliability of a measurement indicates the degree to which the outcome can be reproduced in repeated occasions under the same conditions. While the theoretical consistency of measurements may seem straightforward, it is actually more complicated than often appreciated by applied researchers. This editorial is the next installment in a series on statistical methods in headache research. In this introduction to the concept, we describe the nature of reliability, the use of reliability in headache research, and common problems related to reliability. While the field of reliability is truly an extensive area with its own statistical research, this editorial is meant to serve as a starting point for readers of the Journal and researchers interested in the topic.
Connexin 43 hemichannels and pannexin‐1 channels contribute to the α‐synuclein‐induced dysfunction and death of astrocytes

Diverse studies have suggested that cytoplasmic inclusions of misfolded α‐synuclein in neuronal and glial cells are main pathological features of different α‐synucleinopathies, including Parkinson's disease and dementia with Lewy bodies. Up to now, most studies have focused on the effects of α‐synuclein on neurons, whereas the possible alterations of astrocyte functions and neuron–glia crosstalk have received minor attention. Recent evidence indicates that cellular signaling mediated by hemichannels and pannexons is critical for astroglial function and dysfunction. These channels constitute a diffusional route of communication between the cytosol and the extracellular space and during pathological scenarios they may lead to homeostatic disturbances linked to the pathogenesis and progression of different diseases. Here, we found that α‐synuclein enhances the opening of connexin 43 (Cx43) hemichannels and pannexin‐1 (Panx1) channels in mouse cortical astrocytes. This response was linked to the activation of cytokines, the p38 MAP kinase, the inducible nitric oxide synthase, cyclooxygenase 2, intracellular free Ca2+ concentration ([Ca2+]i), and purinergic and glutamatergic signaling. Relevantly, the α‐synuclein‐induced opening of hemichannels and pannexons resulted in alterations in [Ca2+]i dynamics, nitric oxide (NO) production, gliotransmitter release, mitochondrial morphology, and astrocyte survival. We propose that α‐synuclein‐mediated opening of astroglial Cx43 hemichannels and Panx1 channels might constitute a novel mechanism involved in the pathogenesis and progression of α‐synucleinopathies.
Subgroup distortion of 3-manifold groups

In this paper, we compute the subgroup distortion of all finitely generated subgroups of all finitely generated 3 3 -manifold groups, and the subgroup distortion in this case can only be linear, quadratic, exponential and double exponential. It turns out that the subgroup distortion of a subgroup of a 3 3 -manifold group is closely related to the separability of this subgroup.
SurfaceBrush

Popular Virtual Reality (VR) tools allow users to draw varying-width, ribbonlike 3D brush strokes by moving a hand-held controller in 3D space. Artists frequently use dense collections of such strokes to draw virtual 3D shapes. We propose SurfaceBrush, a surfacing method that converts such VR drawings into user-intended manifold free-form 3D surfaces, providing a novel approach for modeling 3D shapes. The inputs to our method consist of dense collections of artist-drawn stroke ribbons described by the positions and normals of their central polylines, and ribbon widths. These inputs are highly distinct from those handled by existing surfacing frameworks and exhibit different sparsity and error patterns, necessitating a novel surfacing approach. We surface the input stroke drawings by identifying and leveraging local coherence between nearby artist strokes. In particular, we observe that strokes intended to be adjacent on the artist imagined surface often have similar tangent directions along their respective polylines. We leverage this local stroke direction consistency by casting the computation of the user-intended manifold surface as a constrained matching problem on stroke polyline vertices and edges. We first detect and smoothly connect adjacent similarly-directed sequences of stroke edges producing one or more manifold partial surfaces. We then complete the surfacing process by identifying and connecting adjacent similarly directed edges along the borders of these partial surfaces. We confirm the usability of the SurfaceBrush interface and the validity of our drawing analysis via an observational study. We validate our stroke surfacing algorithm by demonstrating an array of manifold surfaces computed by our framework starting from a range of inputs of varying complexity, and by comparing our outputs to reconstructions computed using alternative means.
A New Method for Atlanta World Frame Estimation

In this paper, we propose a new Atlanta frame estimation method by considering the relationship between vertical direction and horizontal directions. Unlike previous solutions, our method does not solve all the directions at one time. On the contrary, it estimates the directions sequentially. Concretely, our method first searches the vertical direction in $\mathbb{S}^2$ globally, then estimates the horizontal directions in one-dimension. As a consequence, the dimensionality of each subproblem problem is low and it can be solved efficiently. In other words, the running time of our method will not greatly increase as the number of horizontal directions increases. The advantages of our method are validated via testing on both synthetic and real-world data.
Magnetic Separation and Antibiotics Selection Enable Enrichment of Cells with ZFN/TALEN-Induced Mutations

The ability to enrich cells with targeted mutations greatly facilitates the process of using engineered nucleases, including zinc-finger nucleases and transcription activator-like effector nucleases, to construct such cells. We previously used surrogate reporters to enrich cells containing nuclease-induced mutations via flow cytometry. This method is, however, limited by the availability of flow cytometers. Furthermore, sorted cells occasionally fail to form colonies after exposure to a strong laser and hydrostatic pressure. Here we describe two different types of novel reporters that enable mutant cell enrichment without the use of flow cytometers. We designed reporters that express H-2Kk, a surface antigen, and the hygromycin resistance protein (HygroR), respectively, when insertions or deletions are generated at the target sequences by the activity of engineered nucleases. After cotransfection of these reporters and the engineered nuclease-encoding plasmids, H-2Kk- and HygroR-expressing cells were isolated using magnetic separation and hygromycin treatment, respectively. We found that mutant cells were drastically enriched in the isolated cells, suggesting that these two reporters enable efficient enrichment of mutants. We propose that these two reporters will greatly facilitate the use of engineered nucleases in a wider range of biomedical research.
BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer’s disease

Significance BACE1 is a rate-limiting enzyme for amyloid beta polypeptide production, which plays a crucial role in Alzheimer’s disease (AD) pathogenesis. However, how this essential protease is posttranslationally regulated remains incompletely understood. In the current study, we show that K501 residue on BACE1, a ubiquitin modification site, is also competitively SUMOylated. We discovered that SUMOylation of BACE1 augments its stability and enzymatic activity, resulting in senile plaque formation and cognitive defect. Identification of the posttranslational modification on BACE1 provides insight into the molecular mechanism in AD. Amyloid beta (Aβ) is a major pathological marker in Alzheimer’s disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aβ production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aβ production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.