Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Prognosis of Quality of Life in Dogs Diagnosed With Mild to Moderate Elbow Dysplasia in Sweden

Objective: The objective of this study was to increase knowledge regarding long-term prognosis of mild to moderate elbow dysplasia (ED) using a canine orthopedic index. Study Design: Cross-sectional observational study. Sample Population: Sixty dogs randomly selected from each of five different breeds and three ED groups: ED0 (control), ED1, and ED2, based on the Kennel Club's screening results. The total number of selected dogs was 900 (60*5*3). Methods: Questionnaires were administered to owners by telephone interview. Bayesian network modeling was used to assess the relation between ED grade, treatment options, dog demographics, and quality-of-life indicators. Results: Seven hundred sixty-five questionnaires were collected (85% response rate), of which 61 concerned dogs euthanized due to osteoarthritis. There was no direct association between ED grade and owner's perceived quality of life, but ED1 and ED2 dogs were more likely to receive veterinary care and subsequent NSAID treatment compared to ED0 dogs. A significant association was found between the occurrence of euthanasia due to orthopedic disease and ED scores 1 and 2 in the sample (p < 0.001). Conclusion: The degree of osteoarthritis was not directly associated with the canine orthopedic index, except for ED2 and lameness score. It can be speculated that owners who paid closer attention to orthopedic symptoms and perceived them as impairing their dogs' lives were also more likely to seek veterinary care and get treatment, irrespective of the ED grading. Impact: ED1-graded dogs had a lower risk than might be expected to develop visible clinical symptoms and showed a similar quality of life as dogs with ED0. ED2-graded dogs were more likely than ED0-graded dogs to have their lives impaired by lameness, according to the owners' perception.
The Rocketbox Library and the Utility of Freely Available Rigged Avatars

As part of the open sourcing of the Microsoft Rocketbox avatar library for research and academic purposes, here we discuss the importance of rigged avatars for the Virtual and Augmented Reality (VR, AR) research community. Avatars, virtual representations of humans, are widely used in VR applications. Furthermore many research areas ranging from crowd simulation to neuroscience, psychology, or sociology have used avatars to investigate new theories or to demonstrate how they influence human performance and interactions. We divide this paper in two main parts: the first one gives an overview of the different methods available to create and animate avatars. We cover the current main alternatives for face and body animation as well introduce upcoming capture methods. The second part presents the scientific evidence of the utility of using rigged avatars for embodiment but also for applications such as crowd simulation and entertainment. All in all this paper attempts to convey why rigged avatars will be key to the future of VR and its wide adoption.
The Quest for Hemispheric Asymmetries Supporting and Predicting Executive Functioning

Abstract This narrative review addresses the neural bases of two executive functions: criterion setting, that is, the capacity to flexibly set up and select task rules and associations between stimuli, responses, and nonresponses, and monitoring, that is, the process of continuously evaluating whether task rules are being applied optimally. There is a documented tendency for criterion setting and monitoring to differentially recruit left and right lateral prefrontal regions and connected networks, respectively, above and beyond the specific task context. This model, known as the ROtman–Baycrest Battery to Investigate Attention (ROBBIA) model, initially sprung from extensive neuropsychological work led by Don Stuss. In subsequent years, multimodal lines of empirical investigation on both healthy individuals and patients with brain damage, coming from functional neuroimaging, EEG, neurostimulation, individual difference approaches, and, again, neuropsychology, so to “complete the circle,” corroborated the functional mapping across the two hemispheres as predicted by the model. More recent electrophysiological evidence has further shown that hemispheric differences in intrinsic prefrontal dynamics are able to predict cognitive performance in tasks tapping these domain-general functions. These empirical contributions will be presented together with contrasting evidence, limits, and possible future directions to better fine-tune this model and extend its scope to new fields.
Life history patterns and biology of the slender mongoose (Galerella sanguinea) in the Kalahari Desert

The mongoose family (Herpestidae) has provided a wealth of data on life history patterns and behavior of its more social species but little is known about the many solitary mongoose species. Here, we provide the 1st longterm data on life history patterns and the biology of the solitary slender mongoose (Galerella sanguinea) in the Kalahari Desert, South Africa. Slender mongooses are strictly diurnal, solitary foragers, opportunistically hunting vertebrates and invertebrates. Life history patterns, such as a prolonged period of offspring dependence, including age at 1st emergence, at 1st foraging, and at weaning, compared to social meerkats (Suricata suricatta), seem to be an adaptation to their mainly solitary life style.
Range and Topology Mutation Based Wireless Agility

Wireless is a key component in most of today's network infrastructures. Yet, it is highly susceptible to network attacks because wireless communication and infrastructure, such as Access Point(AP) and clients, can be easily discovered and targeted. Particularly,the static nature of the wireless AP topology and its configuration offers a significant advantage to adversaries to identify network targets and plan devastating attacks such as denial of service or eavesdropping. This is critically important in hostile military environment in which soldiers depend on wireless infrastructure for communication and coordination. In this paper, we present formal foundations for two wireless agility techniques: (1) Random Range Mutation (RNM) that allows for periodic changes of AP coverage range randomly, and (2) Random Topology Mutation (RTM) that allows for random motion and placement of APs in the wireless infrastructure. The goal of these techniques is to proactively defend against targeted attacks (e.g.,DoS and eavesdropping) by forcing the wireless clients to change their AP association randomly. We apply Satisfiability Modulo Theories (SMT) and Answer Set Programming (ASP) based constraint solving methods that allow for optimizing wireless AP mutation while maintaining service requirements including coverage, security and energy properties under incomplete information about the adversary strategies. Our evaluation validates the feasibility,scalability, and effectiveness of the formal methods based technical approaches.
Estrogen‐related receptor β activation and isoform shifting by cdc2‐like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma

Glioblastoma (GBM; grade 4 glioma) is a highly aggressive and incurable tumor. GBM has recently been characterized as highly dependent on alternative splicing, a critical driver of tumor heterogeneity and plasticity. Estrogen‐related receptor β (ERR‐β) is an orphan nuclear receptor expressed in the brain, where alternative splicing of the 3' end of the pre‐mRNA leads to the production of 3 validated ERR‐β protein products: ERR‐β short form (ERR‐βsf), ERR‐β2, and ERR‐β exon 10 deleted. Our prior studies have shown the ERR‐β2 isoform to play a role in G2/M cell cycle arrest and induction of apoptosis, in contrast to the function of the shorter ERR‐βsf isoform in senescence and G1 cell cycle arrest. In this study, we sought to better define the role of the proapoptotic ERR‐β2 isoform in GBM. We show that the ERR‐β2 isoform is located not only in the nucleus but also in the cytoplasm. ERR‐β2 suppresses GBM cell migration and interacts with the actin nucleation‐promoting factor cortactin, and an ERR‐β agonist is able to remodel the actin cytoskeleton and similarly suppress GBM cell migration. We further show that inhibition of the splicing regulatory cdc2‐like kinases in combination with an ERR‐β agonist shifts isoform expression in favor of ERR‐β2 and potentiates inhibition of growth and migration in GBM cells and intracranial tumors. —Tiek, D. M. , Khatib, S. A. , Trepicchio, C. J., Heckler, M. M. , Divekar, S. D. , Sarkaria, J. N. , Glasgow, E. , Riggins, R. B. Estrogen‐related receptor β activation and isoform shifting by cdc2‐like kinase inhibition restricts migration and intracranial tumor growth in glioblastoma. FASEB J. 33, 13476–13491 (2019). www.fasebj. org
Strenghtening Content Security Policy via Monitoring and URL Parameters Filtering

Content Security Policy (CSP) is a security mechanism for mitigating content injection attacks. It makes it possible to specify the origins of content allowed to load in a webpage. Upon enforcement, CSP-compliant browsers would block content not matching the CSP. Previous works have demonstrated limitations of CSP that can lead to security violations. We observe that CSP bypasses (due to JSONP and open redirects) can be linked to the fact that in CSP specification, URL parameters are considered safe by default. In particular, the ability to bypass partially whitelisted origins using HTTP redirections has been rendered possible starting from CSP2 for privacy purposes (not to reveal redirection URLs), while this can lead to security holes. In this work, we discuss 4 extensions to strengthen CSP via a monitoring mechanism: the ability to selectively exclude whitelisted content, express more fine grained checks on URL arguments, explicitly prevent redirections to partially whitelisted origins, and an efficient reporting mechanism to collect content that are allowed by a CSP enforced on a webpage. We show that using CSP along with these extensions improves the security of web applications and overcomes known weaknesses of the current CSP specification. We demonstrate the feasibility of our proposals by an implementation using service workers.
Automatic Discovery and Synthesis of Checksum Algorithms from Binary Data Samples

Reverse engineering unknown binary message formats is an important part of security research. Error detecting codes such as checksums and Cyclic Redundancy Check codes (CRCs) are commonly added to messages as a guard against corrupt or untrusted input. Before an analyst can manufacture input for software which uses checksums they must discover the algorithm to calculate a valid checksum. To address this need, we have developed a program synthesis based approach for detecting and reverse-engineering checksum algorithms automatically. Our approach takes a small set of binary messages as input and automatically returns a Python implementation of the checksum algorithm if one can be found. Our approach first performs a search over the message space to identify the location of the checksum and then uses program synthesis to identify the operations performed on the message to compute the checksum. We return to the user runnable code to both calculate a checksum from a message and to validate a message according to the checksum algorithm. We generate unit tests, allowing the user to validate the synthesized checksum algorithm is correct with regard to the input messages. We created the Tufts Checksum Corpus comprised of 12 checksum inference questions collected from posts on reverse engineering question and answer sites and 2 instances of common internet protocol checksums. Our approach successfully synthesized the underlying checksum algorithms for 12 out of 14 cases in our test suite.
Functional Analysis of Nuclear Factor Y in the Wing-Dimorphic Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae)

Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor with the ability to bind to a CCAAT box in nearly all eukaryotes. However, the function of NF-Y in the life-history traits of insects is unclear. Here, we identified three NF-Y subunits, NlNF-YA, NlNF-YB, and NlNF-YC, in the wing-dimorphic brown planthopper (BPH), Nilaparvata lugens. Spatio-temporal analysis indicated that NlNF-YA, NlNF-YB, and NlNF-YC distributed extensively in various body parts of fourth-instar nymphs, and were highly expressed at the egg stage. RNA interference (RNAi)-mediated silencing showed that knockdown of NlNF-YA, NlNF-YB, or NlNF-YC in third-instar nymphs significantly extended the fifth-instar duration, and decreased nymph-adult molting rate. The addition of 20-hydroxyecdysone could specifically rescue the defect in adult molting caused by NlNF-YARNAi, indicating that NlNF-Y might modulate the ecdysone signaling pathway in the BPH. In addition, NlNF-YARNAi, NlNF-YBRNAi, or NlNF-YCRNAi led to small and moderately malformed forewings and hindwings, and impaired the normal assembly of indirect flight muscles. Adult BPHs treated with NlNF-YARNAi, NlNF-YBRNAi, or NlNF-YCRNAi produced fewer eggs, and eggs laid by these BPHs had arrested embryogenesis. These findings deepen our understanding of NF-Y function in hemipteran insects.
A robust sequencing assay of a thousand amplicons for the high‐throughput population monitoring of Alpine ibex immunogenetics

Genetic variation is a major factor determining susceptibility to diseases. Polymorphism at the major histocompatibility complex (MHC) and other immune function loci can underlie health and reproductive success of individuals. Endangered species of low population size could be severely compromised to evolve disease resistance due to reduced adaptive variation. A major impediment to screen adaptive genetic variation in wild species is the difficulty to comprehensively genotype immune-related loci based on low input material. Here, we design and validate a targeted amplicon sequencing assay to parallelize the analysis of a thousand loci of the MHC, other immunity-related genes, and genome-wide markers for the assessment of population structure. We apply the approach to Alpine ibex, one of the most successful examples of restoration of a large mammal in Europe. We used 51 whole genome sequenced individuals to select representative target SNPs. We integrated SNP call data from four related species for amplification robustness and genotyped 158 Alpine ibex individuals for validation. We show that the genome-wide markers perform equally well at resolving population structure as RAD-seq or low-coverage genome sequencing datasets with orders of magnitude more markers. The targeted amplicon sequencing assay is robust to >100-fold variation in input DNA quantity and generates useful genotype information from fecal samples. The amplicon marker set also identified recent species hybridization events with domestic goats. The immune loci show unexpectedly high degrees of differentiation within the species. Our assay strategy can realistically be implemented into population genetic surveys of a large range of species.
Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans

Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, thus enabling the activation of the mTOR pathway. These findings further link lamin to metabolic regulation.
DNA methylation directs nucleosome positioning in RNA-mediated transcriptional silencing

Repressive chromatin modifications are instrumental in regulation of gene expression and transposon silencing. In Arabidopsis thaliana, transcriptional silencing is performed by the RNA-directed DNA methylation (RdDM) pathway. In this process, two specialized RNA polymerases, Pol IV and Pol V, produce non-coding RNAs, which recruit several RNA-binding proteins and lead to the establishment of repressive chromatin marks. An important feature of chromatin is nucleosome positioning, which has also been implicated in RdDM. We show that RdDM affects nucleosomes via the SWI/SNF chromatin remodeling complex. This leads to the establishment of nucleosomes on methylated regions, which counteracts the general depletion of DNA methylation on nucleosomal regions. Nucleosome placement by RdDM has no detectable effects on the pattern of DNA methylation. Instead, DNA methylation by RdDM and other pathways affects nucleosome positioning. We propose a model where DNA methylation serves as one of the determinants of nucleosome positioning.
The Regulatory Evolution of the Primate Fine-Motor System

In mammals, fine motor control is essential for skilled behavior, and is subserved by specialized subdivisions of the primary motor cortex (M1) and other components of the brain’s motor circuitry. We profiled the epigenomic state of several components of the Rhesus macaque motor system, including subdivisions of M1 corresponding to hand and orofacial control. We compared this to open chromatin data from M1 in rat, mouse, and human. We found broad similarities as well as unique specializations in open chromatin regions (OCRs) between M1 subdivisions and other brain regions, as well as species- and lineage-specific differences reflecting their evolutionary histories. By distinguishing shared mammalian M1 OCRs from primate- and human-specific specializations, we highlight gene regulatory programs that could subserve the evolution of skilled motor behaviors such as speech and tool use.
Active palpation underlying shape perception is shaped by physiological thresholds and experience

Hand movements are essential for tactile perception of objects. However, why different individuals converge on specific movement patterns is not yet clear. Focusing on planar shape perception, we tracked the hands of 11 participants while they practiced shape recognition. Our results show that planar shape perception is mediated by contour-following movements, either tangential to the contour or spatially-oscillating perpendicular to it, and by scanning movements, crossing between distant parts of the shapes’ contour. Both strategies exhibited non-uniform coverage of the shapes’ contours. We found that choice of strategy during the first experimental session was strongly correlated with two idiosyncratic parameters: participants with lower tactile resolution tended to move faster; and faster-adapting participants tended to employ oscillatory movements more often. In addition, practicing on isolated geometric features increased the tendency to use the contour-following strategy. These results provide insights into the processes of strategy selection in tactile perception. SIGNIFICANCE STATMENT Hand movements are integral components of tactile perception. Yet, the specific motion strategies used to perceive specific objects and features, and their dependence on physiological features and on experience, are understudied. Focusing on planar shape perception and using high-speed hand tracking we show that human participants employ two basic palpation strategies: Contour-following and scanning. We further show that the strategy chosen by each participant and its kinematics depend strongly on the participant’s physiological thresholds – indicative of spatial resolution and temporal adaptation - and on their perceptual experience.
Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva

Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues due to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2/ACVR1. From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2 compared with other receptors of the BMP/TGFβ signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducible ACVR1Q207D transgenic mouse line, which provides a model of heterotopic ossification, as well as an inducible ACVR1R206H knock-in, which serves as a genetically and physiologically faithful model of FOP. In both models, saracatinib was well tolerated and potently inhibited the development of heterotopic ossification even when administered transiently following soft tissue injury. Together, these data suggest that saracatinib is an efficacious clinical candidate for repositioning in the treatment of FOP, offering an accelerated path to clinical proof of efficacy studies and potentially significant benefits to individuals with this devastating condition.
Repression of lysosomal transcription factors Tfeb and Tfe3 is essential for the migration and function of microglia

As the primary phagocytic cells of the central nervous system, microglia exquisitely regulate their lysosomal activity to facilitate brain development and homeostasis. However, mechanisms that coordinate lysosomal activity with microglia development, migration, and function remain unclear. Here we show that embryonic macrophages require the lysosomal GTPase RagA and the GTPase-activating protein Folliculin to colonize the brain in zebrafish. We demonstrate that embryonic macrophages in rraga mutants show increased expression of lysosomal genes but display significant downregulation of immune and migration-related genes. Furthermore, we find that RagA and Folliculin repress the key lysosomal transcription factor Tfeb, and its homologs Tfe3a and Tfe3b, in the macrophage lineage. Using RNA-Sequencing, we establish that Tfeb and Tfe3 are required for activation of lysosomal target genes under conditions of stress but not for basal expression of lysosomal pathways. Collectively, our data define a lysosomal regulatory circuit essential for macrophage development and function in vivo. Teaser The degradation machinery of the cell must be carefully controlled for the normal formation and function of key immune cells called microglia.
Cell size is a determinant of stem cell potential during aging

Stem cells are remarkably small in size. Whether small size is important for stem cell function is unknown. We find that murine hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. Preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing large HSCs size by shortening G1 averts the loss of stem cell potential under conditions causing stem cell exhaustion. Finally, we show that a fraction of murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function in vivo and propose that stem cell enlargement contributes to their functional decline during aging. One Sentence Summary Size increase drives stem cell aging.