Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation

Significance The Mre11–Rad50–Nbs1 (MRN) complex is well known for participating in DNA damage response pathways and mediating the ATM-dependent phosphorylation signaling cascade. Hypomorphic mutations in the human MRN complex have been identified in autosomal recessive genetic diseases, ataxia-telangiectasia–like disorder, and Nijmegen breakage syndrome. Here, we show that MRN forms a mitosis-specific complex with a protein, MMAP, which mediates a mitotic signaling cascade between PLK1 and KIF2A. We demonstrate that the assembly of this complex is crucial for normal spindle dynamics during mitosis. Thus, our study describes a signaling cascade in which PLK1-dependent phosphorylation promotes the assembly of the MRN–MMAP–PLK1–KIF2A complex, leading to mitotic spindle turnover and chromosome alignment. The MRE11–RAD50–NBS1 (MRN) complex is well known for participating in DNA damage response pathways in all phases of cell cycle. Here, we show that MRN constitutes a mitosis-specific complex, named mMRN, with a protein, MMAP. MMAP directly interacts with MRE11 and is required for optimal stability of the MRN complex during mitosis. MMAP colocalizes with MRN in mitotic spindles, and MMAP-deficient cells display abnormal spindle dynamics and chromosome segregation similar to MRN-deficient cells. Mechanistically, both MMAP and MRE11 are hyperphosphorylated by the mitotic kinase, PLK1; and the phosphorylation is required for assembly of the mMRN complex. The assembled mMRN complex enables PLK1 to interact with and activate the microtubule depolymerase, KIF2A, leading to spindle turnover and chromosome segregation. Our study identifies a mitosis-specific version of the MRN complex that acts in the PLK1–KIF2A signaling cascade to regulate spindle dynamics and chromosome distribution.
The reality editor : an open and universal tool for understanding and controlling the physical world

In a future where every physical object has the ability to compute and connect with other physical things, we have to rethink our present user interfaces and interaction metaphors. The desktop metaphor used in personal computers and smartphones was invented for data organization and is not well suited for interaction with things in the physical world. As a result, the growing number of interconnected things (or Internet of Things devices) surrounding us are becoming hard to operate. Each IoT device requires a different app to control it and forces the user to memorize a unique connection and interface. In addition, connected things made by different companies cannot easily be connected to one another. This thesis introduces a novel, directly mapped user interface for connected things built upon World Wide Web technology, a decentralized networking infrastructure for connected things to talk to each other, and a simple, visual user interface for understanding and controlling the connected things around us. The overall system is called the Reality Editor, an open-source, freely and publicly available tool for creating ecosystems of interconnected things. The thesis discusses the design of the Reality Editor, its core ideas and implementation details and a series of real world prototypes that were built to evaluate and improve the tool. Thesis Supervisor: Pattie Maes Title: Professor of Media Arts and Sciences, Program in Media Arts and Sciences The Reality Editor: An Open and Universal Tool for Understanding and Controlling the Physical World by Valentin Heun The following people served as readers for this thesis:
Look to Go: An Empirical Evaluation of Eye-Based Travel in Virtual Reality

We present two experiments evaluating the effectiveness of the eye as a controller for travel in virtual reality (VR). We used the FOVE head-mounted display (HMD), which includes an eye tracker. The first experiment compared seven different travel techniques to control movement direction while flying through target rings. The second experiment involved travel on a terrain: moving to waypoints while avoiding obstacles with three travel techniques. Results of the first experiment indicate that performance of the eye tracker with head-tracking was close to head motion alone, and better than eye-tracking alone. The second experiment revealed that completion times of all three techniques were very close. Overall, eye-based travel suffered from calibration issues and yielded much higher cybersickness than head-based approaches.
The RNA-Recognition Motifs of TAR DNA-Binding Protein 43 May Play a Role in the Aberrant Self-Assembly of the Protein

The TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein implicated in gene regulation and RNA processing and shuffling. It is a ribonuclear protein that carries out most of its functions by binding specific nucleic acid sequences with its two RNA-recognition motifs, RRM1 and RRM2. TDP-43 has been identified in toxic cytosolic inclusions in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). The unstructured C-terminus has prion-like behavior and has been considered the driver of the aberrant self-assembly of TDP-43. In this work, we set out to test the hypothesis that the RNA-binding domains could also play a role in protein aggregation. This knowledge could be of important value for understanding TDP-43 aberrant, disease-leading behavior and, in the future, inform the design of small molecules that could prevent or slow down protein aggregation by exploiting the RNA-binding properties of the protein. We investigated the behavior of the two tandem RRM domains separately and linked together and studied their self-assembly properties and RNA-binding ability with a number of biophysical techniques. The picture that emerges from our study suggests that this region of the protein plays an important and so far unexplored role in the aggregation of this protein.
Probabilistic Argumentation and Information Algebras of Probability Potentials on Families of Compatible Frames

Probabilistic argumentation is an alternative to causal modeling with Bayesian networks. Probabilistic argumentation structures (PAS) are defined on families of compatible frames (f.c.f). This is a generalization of the usual multivariate models based on families of variables. The crucial relation of conditional independence between frames of a f.c. f is introduced and shown to form a quasi-separoid, a weakening of the well-known structure of a separoid. It is shown that PAS generate probability potentials on the frames of the f.c. f. The operations of aggregating different PAS and of transport of a PAS from one frame to another induce an algebraic structure on the family of potentials on the f.c. f, an algebraic structure which is similar to valuation algebras related to Bayesian networks, but more general. As a consequence the well-known local computation architectures of Bayesian networks for inference apply also for the potentials on f.c. f. Conditioning and conditionals can be defined for potentials and it is shown that these concepts satisfy similar properties as conditional probability distributions. Finally a max/prod algebra between potentials is defined and applied to find most probable configurations for a factorization of potentials.
Towards a Language Server Protocol Infrastructure for Graphical Modeling

The development of modern IDEs is still a challenging and time-consuming task, which requires implementing the support for language-specific features such as syntax highlighting or validation. When the IDE targets a graphical language, its development becomes even more complex due to the rendering and manipulation of the graphical notation symbols. To simplify the development of IDEs, the Language Server Protocol (LSP) proposes a decoupled approach based on language-agnostic clients and language-specific servers. LSP clients communicate changes to LSP servers, which validate and store language instances. However, LSP only addresses textual languages (i.e., character as atomic unit) and neglects the support for graphical ones (i.e., nodes/edges as atomic units). In this paper, we present our vision to decouple graphical language IDEs discussing the alternatives for integrating LSP's ideas in their development. Moreover, we propose a novel LSP infrastructure to simplify the development of new graphical modeling tools, in which Web technologies may be used for editor front-ends while leveraging existing modeling frameworks to build language servers.
Using Time to Break Symmetry: Universal Deterministic Anonymous Rendezvous

Two anonymous mobile agents navigate synchronously in an anonymous graph and have to meet at a node, using a deterministic algorithm. This is a symmetry breaking task called rendezvous, equivalent to the fundamental task of leader election between the agents. When is this feasible in a completely anonymous environment? It is known that agents can always meet if their initial positions are nonsymmetric, and that if they are symmetric and agents start simultaneously then rendezvous is impossible. What happens for symmetric initial positions with non-simultaneous start? Can symmetry between the agents be broken by the delay between their starting times? In order to answer these questions, we consider space-time initial configurations (abbreviated by STIC). A STIC is formalized as [(u,v),δ], where u and v are initial nodes of the agents in some graph and δ is a non-negative integer that represents the difference between their starting times. A STIC is feasible if there exists a deterministic algorithm, even dedicated to this particular STIC, which accomplishes rendezvous for it. Our main result is a characterization of all feasible STICs and the design of a universal deterministic algorithm that accomplishes rendezvous for all of them without any a priori knowledge of the agents. Thus, as far as feasibility is concerned, we completely solve the problem of symmetry breaking between two anonymous agents in anonymous graphs. Moreover, we show that such a universal algorithm cannot work for all feasible STICs in time polynomial in the initial distance between the agents.
The Surgical Apgar Score and frailty as outcome predictors in short- and long-term evaluation of fit and frail older patients undergoing elective laparoscopic cholecystectomy – a prospective cohort study

Introduction Frailty increases the risk of poor surgical outcomes in the older population. Some intraoperative factors may also influence the final result and can be evaluated. The Surgical Apgar Score (SAS) is a simple system predicting postoperative mortality and morbidity. However, the utility of the SAS remains unknown in fit and frail older patients undergoing elective laparoscopic cholecystectomy due to benign gallbladder diseases. Aim To evaluate the usefulness of the SAS in predicting 30-day morbidity and 1-year mortality in older fit and frail patients undergoing elective laparoscopic cholecystectomy. Material and methods Consecutive patients (≥ 70 years) were enrolled in the prospective study. The Comprehensive Geriatric Assessment (CGA) was used to diagnose frailty. Logistic regression was conducted to investigate the association between the scores and the outcomes. Results The study included 144 consecutive older patients with a median age of 76 (range: 70–91) years. The prevalence of frailty was 44.4%. The 30-day mortality and morbidity were 0% and 11.8%, respectively. The 1-year mortality was 6.3% and 7 out of 9 occurred in the frail group. SAS < 7 points was identified as an independent predictor of 30-day postoperative morbidity (OR = 5.1; 95% CI: 1.5–18.1). Age > 85 years (OR = 1.9; 95% CI: 1.2–16.4) and frailty (OR = 3.4; 95% CI: 1.1–19.3) were predictors of 1-year mortality. Conclusions Laparoscopic cholecystectomy can be safely performed in older fit and frail patients. The SAS, not age, turned out to be the most important predictor of 30-day morbidity. Frailty and age > 85 years were predictors of 1-year mortality. Older patients with SAS < 7 points should be followed meticulously in order to diagnose and treat potential complications early on.
Combinatorial Approach for Complex Disorder Prediction: Case Study of Neurodevelopmental Disorders

Early prediction of complex disorders (e.g., autism and other neurodevelopmental disorders) is one of the fundamental goals of precision medicine and personalized genomics. An early prediction of complex disorders can improve the prognosis, increase the effectiveness of interventions and treatments, and enhance the life quality of affected patients. Considering the genetic heritability of neurodevelopmental disorders, we are proposing a novel framework for utilizing rare coding variation for early prediction of these disorders in subset of affected samples. We provide a combinatorial framework for addressing this problem, denoted as Odin (Oracle for DIsorder predictioN), to make a prediction for a small, yet significant, subset of affected cases while having very low false positive rate (FPR) prediction for unaffected samples. Odin also takes advantage of the available functional information (e.g., pairwise coexpression of genes during brain development) to increase the prediction power beyond genes with recurrent variants. Application of our method accurately recovers an additional 8% of autism cases without any severe variant in known recurrent mutated genes with a <1% FPR. Furthermore, Odin predicted a set of 391 genes that severe variants in these genes can cause autism or other developmental delay disorders. Approaches such as the one presented in this paper are needed to translate the biomedical discoveries into actionable items by clinicians. Odin is publicly available at https://github.com/HormozdiariLab/Odin.
HITECS: A UML Profile and Analysis Framework for Hardware-in-the-Loop Testing of Cyber Physical Systems

Hardware-in-the-loop (HiL) testing is an important step in the development of cyber physical systems (CPS). CPS HiL test cases manipulate hardware components, are time-consuming and their behaviors are impacted by the uncertainties in the CPS environment. To mitigate the risks associated with HiL testing, engineers have to ensure that (1) HiL test cases are well-behaved, i.e., they implement valid test scenarios and do not accidentally damage hardware, and (2) HiL test cases can execute within the time budget allotted to HiL testing. This paper proposes an approach to help engineers systematically specify and analyze CPS HiL test cases. Leveraging the UML profile mechanism, we develop an executable domain-specific language, HITECS, for HiL test case specification. HITECS builds on the UML Testing Profile (UTP) and the UML action language (Alf). Using HITECS, we provide analysis methods to check whether HiL test cases are well-behaved, and to estimate the execution times of these test cases before the actual HiL testing stage. We apply HITECS to an industrial case study from the satellite domain. Our results show that: (1) HITECS is feasible to use in practice; (2) HITECS helps engineers define more complete and effective well-behavedness assertions for HiL test cases, compared to when these assertions are defined without systematic guidance; (3) HITECS verifies in practical time that HiL test cases are well-behaved; and (4) HITECS accurately estimates HiL test case execution times.
Association of thyroid status prior to transition to end-stage renal disease with early dialysis mortality.

Background Advanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation. Methods Among US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation. Results Among 15 335 patients in the 1-year prelude cohort, TSH levels >5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH >5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels >5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels >5.0-10.0 mIU/L and >10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH >10.0 mIU/L, particularly after laboratory covariate adjustment. Conclusions Among new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels >5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.
Fine-Grained Quality Assessment for Compressed Images

Image quality assessment (IQA) has attracted more and more attention due to the urgent demand in image services. The perceptual-based image compression is one of the most prominent applications that require IQA metrics to be highly correlated with human vision. To explore IQA algorithms that are more consistent with human vision, several calibrated databases have been constructed. However, the distorted images in the existing databases are usually generated by corrupting the pristine images with various distortions in coarse levels, such that the IQA algorithms validated on them may be inefficient to optimize the perceptual-based image compression with fine-grained quality differences. In this paper, we construct a large-scale image database which can be used for fine-grained quality assessment of compressed images. In the proposed database, reference images are compressed at constant bitrate levels by JPEG encoders with different optimization methods. To distinguish subtle differences, the pair-wise comparison method is utilized to rank them in subjective experiments. We select 100 reference images for the proposed database, and each image is compressed into three target bitrates by four different JPEG optimization methods, such that 1200 distorted images are generated in total. Sixteen well-known IQA algorithms are evaluated and analyzed on the proposed database. With the devised fine-grained IQA database, we expect to further promote image quality assessment by shifting it from a coarse-grained stage to a fine-grained stage. The database is available at: https://sites.google. com/site/zhangxinf07/fg-iqa.
Facilitating Pretend Play in Autistic Children: Results from an Augmented Reality App Evaluation

Autistic children find pretend play difficult. Previous work suggests Augmented Reality (AR) has potential in eliciting pretend play in children with autism. This paper presents the evaluation of an Augmented Reality app to help autistic children engage in solitary pretend play. We followed a user-centred design process, involving various techniques and stakeholders. Results from a pre-post study design suggest the AR system is promising in facilitating quantitative aspects of pretend play in autistic children.
Estimating interviewee's willingness in multimodal human robot interview interaction

This study presents a prediction model of a speaker's willingness level in human-robot interview interaction by using multimodal features (i.e., verbal, audio, and visual). We collected a novel multimodal interaction corpus, including two types of annotation data sets of willingness. A binary classification task of the willingness level (high or low) was implemented to evaluate the proposed multimodal prediction model. We obtained the best classification accuracy (i.e., 0.6) using the random forest model with audio and motion features. The difference between best accuracy (i.e., 0.6) and coder's recognition accuracy (i.e., 0.73) was 0.13.
Exogenous Nicotinamide Adenine Dinucleotide Induces Resistance to Citrus Canker in Citrus

Nicotinamide adenine dinucleotide (NAD) is a universal electron carrier that participates in important intracellular metabolic reactions and signaling events. Interestingly, emerging evidence in animals indicates that cellular NAD can be actively or passively released into the extracellular space, where it is processed or perceived by ectoenzymes or cell-surface receptors. We have recently shown in Arabidopsis thaliana that exogenous NAD induces defense responses, that pathogen infection leads to release of NAD into the extracellular space at concentrations sufficient for defense activation, and that depletion of extracellular NAD (eNAD) by transgenic expression of the human NAD-hydrolyzing ectoenzyme CD38 inhibits plant immunity. We therefore hypothesize that, during plant–microbe interactions, NAD is released from dead or dying cells into the extracellular space where it interacts with adjacent naïve cells’ surface receptors, which in turn activate downstream immune signaling. However, it is currently unknown whether eNAD signaling is unique to Arabidopsis or the Brassicaceae family. In this study, we treated citrus plants with exogenous NAD+ and tested NAD+-induced transcriptional changes and disease resistance. Our results show that NAD+ induces profound transcriptome changes and strong resistance to citrus canker, a serious citrus disease caused by the bacterial pathogen Xanthomonas citri subsp. citri (Xcc). Furthermore, NAD+-induced resistance persists in new flushes emerging after removal of the tissues previously treated with NAD+. Finally, NAD+ treatment primes citrus tissues, resulting in a faster and stronger induction of multiple salicylic acid pathway genes upon subsequent Xcc infection. Taken together, these results indicate that exogenous NAD+ is able to induce immune responses in citrus and suggest that eNAD may also be an elicitor in this woody plant species.
Prevalence of sicca syndrome in the Peruvian population.

OBJECTIVES Sjögren's syndrome is a complex and heterogeneous autoimmune disease characterised by ocular and oral dryness (1), which mainly affects the exocrine glands. The objective of this study was to determine the prevalence of sicca syndrome (SS) in the Peruvian population. The age and gender of patients with SS and their national prevalence and in each of the departments were defined. METHODS Cross-sectional prevalence study. All the people that the Ministry of Health (MINSA) in Peru covered health treatments from January to December 2016 were taken into account. The patients with SS were newly or previously diagnosed with sicca syndrome (Sjögren's) according to the international classification of diseases version 10 (ICD-10) of the World Health Organization (WHO). The prevalence was determined considering the number of cases of SS in the total population registered by the Ministry of Health (MINSA). RESULTS 1,301 cases of SS were observed in a total population of 15,417,345 people served in 25 territories. The prevalence of SS in this population was 0.0084%, the prevalence rate was 8.4 cases per 100,000 persons (95% CI: 7.99-8.91). The prevalence of SS was higher in the territories of Tacna, Lima, La Libertad, Arequipa, Callao, and Apurímac. CONCLUSIONS The results of this study show the prevalence of SS in the Peruvian population and serve to strengthen the health strategies of rheumatology, ophthalmology, and oral health to improve the diagnosis, treatment, follow-up of the disease, and the quality of life of patients with SS.