Miracle-dz/UniFAR-FTUs huggingface dataset:
Formal Links between Feature Diversity and Phylogenetic Diversity

The extent to which phylogenetic diversity (PD) captures feature diversity (FD) is a topical and controversial question in biodiversity conservation. In this short paper, we formalise this question and establish a precise mathematical condition for FD (based on discrete characters) to coincide with PD. In this way, we make explicit the two main reasons why the two diversity measures might disagree for given data; namely, the presence of certain patterns of feature evolution and loss, and using temporal branch lengths for PD in settings that may not be appropriate (e.g. due to rapid evolution of certain features over short periods of time). Our paper also explores the relationship between the ‘Fair Proportion’ index of PD and a simple index of FD (both of which correspond to Shapley values in cooperative game theory). In a second mathematical result, we show that the two indices can take identical values for any phylogenetic tree, provided the branch lengths in the tree are chosen appropriately.
Distance-based metrics for comparing conformational ensembles of intrinsically disordered proteins

Intrinsically disordered proteins (IDPs) are proteins whose native functional states represent ensembles of highly diverse conformations. Such ensembles are a challenge for quantitative structure comparisons as their conformational diversity precludes optimal superimposition of the atomic coordinates, necessary for deriving common similarity measures such as the root-mean-square deviation (RMSD) of these coordinates. Here we introduce superimposition-free metrics, which are based on computing matrices of Cα-Cα distance distributions within ensembles and comparing these matrices between ensembles. Differences between two matrices yield information on the similarity between specific regions of the polypeptide, whereas the global structural similarity is captured by the ens_dRMS, defined as the root-mean-square difference between the medians of the Cα-Cαdistance distributions of two ensembles. Together, our metrics enable rigorous investigations of structure-function relationships in conformational ensembles of IDPs derived using experimental restraints or by molecular simulations, and for proteins containing both structured and disordered regions. Statement of Significance Important biological insight is obtained from comparing the high-resolution structures of proteins. Such comparisons commonly involve superimposing two protein structures and computing the residual root-mean-square deviation of the atomic positions. This approach cannot be applied to intrinsically disordered proteins (IDPs) because IDPs do not adopt well-defined 3D structures, rather, their native functional state is defined by ensembles of heterogeneous conformations that cannot be meaningfully superimposed. We report new measures that quantify the local and global similarity between different conformational ensembles by evaluating differences between the distributions of residue-residue distances and their statistical significance. Applying these measures to IDP ensembles and to a protein containing both structured and intrinsically disordered domains provides deeper insights into how structural features relate to function.
Iterative community-driven development of a SARS-CoV-2 tissue simulator

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.
Nucleus

Heterogeneous multi-processors are designed to bridge the gap between performance and energy efficiency in modern embedded systems. This is achieved by pairing Out-of-Order (OoO) cores, yielding performance through aggressive speculation and latency masking, with In-Order (InO) cores, that preserve energy through simpler design. By leveraging migrations between them, workloads can therefore select the best setting for any given energy/delay envelope. However, migrations introduce execution overheads that can hurt performance if they happen too frequently. Finding the optimal migration frequency is critical to maximize energy savings while maintaining acceptable performance. We develop a simulation methodology that can 1) isolate the hardware effects of migrations from the software, 2) directly compare the performance of different core types, 3) quantify the performance degradation and 4) calculate the cost of migrations for each case. To showcase our methodology we run mibench, a microbenchmark suite, and show that migrations can happen as fast as every 100k instructions with little performance loss. We also show that, contrary to numerous recent studies, hypothetical designs do not need to share all of their internal components to be able to migrate at that frequency. Instead, we propose a feasible system that shares level 2 caches and a translation lookaside buffer that matches performance and efficiency. Our results show that there are phases comprising up to 10% that a migration to the OoO core leads to performance benefits without any additional energy cost when running on the InO core, and up to 6% of phases where a migration to the InO core can save energy without affecting performance. When considering a policy that focuses on improving the energy-delay product, results show that on average 66% of the phases can be migrated to deliver equal or better system operation without having to aggressively share the entire memory system or to revert to migration periods finer than 100k instructions.
Intrinsically-typed definitional interpreters for imperative languages

A definitional interpreter defines the semantics of an object language in terms of the (well-known) semantics of a host language, enabling understanding and validation of the semantics through execution. Combining a definitional interpreter with a separate type system requires a separate type safety proof. An alternative approach, at least for pure object languages, is to use a dependently-typed language to encode the object language type system in the definition of the abstract syntax. Using such intrinsically-typed abstract syntax definitions allows the host language type checker to verify automatically that the interpreter satisfies type safety. Does this approach scale to larger and more realistic object languages, and in particular to languages with mutable state and objects? In this paper, we describe and demonstrate techniques and libraries in Agda that successfully scale up intrinsically-typed definitional interpreters to handle rich object languages with non-trivial binding structures and mutable state. While the resulting interpreters are certainly more complex than the simply-typed λ-calculus interpreter we start with, we claim that they still meet the goals of being concise, comprehensible, and executable, while guaranteeing type safety for more elaborate object languages. We make the following contributions: (1) A dependent-passing style technique for hiding the weakening of indexed values as they propagate through monadic code. (2) An Agda library for programming with scope graphs and frames, which provides a uniform approach to dealing with name binding in intrinsically-typed interpreters. (3) Case studies of intrinsically-typed definitional interpreters for the simply-typed λ-calculus with references (STLC+Ref) and for a large subset of Middleweight Java (MJ).
EMODA: a tutor oriented multimodal and contextual emotional dashboard

Learners' emotional state has proven to be a key factor for successful learning. Visualizing learners' emotions during synchronous on-line learning activities can help tutors in creating and maintaining socio-affective relationships with their learners. However, few dashboards offer emotional information on the learning activity. The current study focuses on synchronous interactions via a videoconferencing tool dedicated to foreign language training. We collected data on learners' emotions in real conditions during ten sessions (five sessions for two learners). We propose to adopt and combine different models of emotions (discrete and dimensional) and to use heterogeneous APIs for measuring learners' emotions from different data sources (audio, video, self-reporting and interaction traces). Based on a thorough data analysis, we propose an approach to combine different cues to infer information on learners' emotional states. We finally present the EMODA dashboard, an affective multimodal and contextual visual analytics dashboard, which allows the tutor to monitor learners' emotions and better understand their evolution during the synchronous learning activity.
Low-discrepancy blue noise sampling

We present a novel technique that produces two-dimensional low-discrepancy (LD) blue noise point sets for sampling. Using one-dimensional binary van der Corput sequences, we construct two-dimensional LD point sets, and rearrange them to match a target spectral profile while preserving their low discrepancy. We store the rearrangement information in a compact lookup table that can be used to produce arbitrarily large point sets. We evaluate our technique and compare it to the state-of-the-art sampling approaches.
A prospective study of functional outcome of posteromedial plating in the management of complex tibial plateau fractures

Tibial plateau fractures have a complicated intra articular fracture pattern, representing approximately 1.2% of all fractures. The occurrence of posteromedial fragment is relatively common in high energy tibial plateau fractures Aims and Objectives: To study the role of posteromedial plating in management of complex tibial plateau fractures with a posteromedial fragment. Materials and methods: 26 cases above 25 years of age, from the patient admitted to Rajah Muthaiah Medical College and Hospital, Annamalai University, Chidambaram with posteromedial fragment in tibial plateau fractures that were operated between May 2016 to May 2018 were undertaken for the study. Reduction can be maintained with a Kirchner wire and a pointed reduction clamp. The plate is placed directly over the area of maximal displacement at the apex of the fracture. Results: Of the 26 patients with type IV, V and VI Schatzker’s tibial plateau fractures from x ray and CT scan of knee joint, 24 had pre contoured posteromedial plate and 2 patients had recon plate where the fragment was comparatively small and comminuted. We analysed patients with Rasmussen scoring postoperatively. In our analysis among 26 patients, functional score were excellent in 20, Good in 3, Fair in two and poor in one patient. There was one patient with grade I compound injury who had developed infection that later resolved after wound wash and resuturing on the 5th postoperative day with judicial use of antibiotics. One patient had collapse due to premature weight bearing. Two patients had transient paraesthesia of the saphenous nerve; both resolved completely.
Sero-Prevalence of Hepatitis B Virus and Associated Factors Among Pregnant Mothers Attending Antenatal Care in Public Health Facilities, Dire Dawa

Background: According to the WHO report, Ethiopia is regarded as a country with intermediate to hyperendemic viral hepatitis infections, though it has no national strategy for surveillance, prevention and control of viral hepatitis. Without intervention, a mother who is positive for HBsAg and HBeAg has as high as 90% risk of passing the infection to her offspring. Therefore, this study tried to assess the seroprevalence and associated factors of HBV infection among pregnant women attending antenatal care in public health facilities of Dire-Dawa, Eastern Ethiopia.Materials and methods: A facility based cross-sectional study was conducted from January to March 2018 among 334 pregnant mothers. After obtaining a consent forms, data were collected by face to face interview and blood samples were collected to test for HBsAg. Logistic regression analysis was employed to identify factors significantly associated with HBV infection. A p value <0.05 was considered as level of significance.Results: The mean age of participated pregnant mothers was 24.93 years (+2 SD 5.21). The prevalence of HBV infection found to be 8.4% in the study area. On multivariate analysis, being single pregnant mothers (p-0.002), having nose/ear pierce (p-0.018), history of blood transfusion (p-0.008), circumcision (p-0.004), and HIV coinfection (p-0.032)} were factors significantly associated with HBV infection.Conclusion: To halt spread of this virus, increasing awareness on modes of transmission should be considered. Screening all pregnant women for HBV should be made as part of routine antenatal care service. Interventions should be targeted on reduction of circumcision by all concerned bodies.
Rescue the child or treat the adult? Understandings among professionals in dual treatment of substance-use disorders and parenting

Aims: Dual treatment of parents with substance-use disorders (SUD) is an approach which aims to meet the needs of both SUD patients and their children. Whereas the parents need to learn to live without substances, the children need a predictable and structured environment with parents who are sensitive and psychologically available. In this study we explore the possibilities and challenges of this joint approach from the perspectives of professionals employed in an in-patient facility for families with parental SUD. Methods: A qualitative design was used comprising three focus-group interviews with 15 professionals: two groups with ward staff and one with therapists, all working at a family ward for parents with SUD and their children. Data were analysed using thematic analysis. Results: Professionals faced difficulties combining the needs of parents and children and seemed to choose to prioritise either the adult with SUD or the wellbeing of the child. However, some professionals described what might be a third and alternative solution by supporting the mothers in everyday life, routines, and care, through exploring present moment situations. This approach seemed to help parents become more conscious of the child, their interaction with the child, and their own feelings. Professionals described working at the family ward as emotionally challenging. Conclusion: Combining treatment of parental SUD, interventions to improve parenting roles and practice, and at the same time focusing on the developmental needs of children, is experienced as a complex and demanding task. Different priorities and treatment aims may enhance tensions between professionals. Even though professionals experience in-patient dual treatment as challenging, they believe this approach facilitates positive development in substance dependent parents and their children.
Korean-Vietnamese Neural Machine Translation with Named Entity Recognition and Part-of-Speech Tags

SUMMARY Since deep learning was introduced, a series of achievements has been published in the ﬁeld of automatic machine translation (MT). However, Korean-Vietnamese MT systems face many challenges because of a lack of data, multiple meanings of individual words, and grammatical diversity that depends on context. Therefore, the quality of Korean-Vietnamese MT systems is still sub-optimal. This paper discusses a method for applying Named Entity Recognition (NER) and Part-of-Speech (POS) tagging to Vietnamese sentences to improve the performance of Korean-Vietnamese MT systems. In terms of implementation, we used a tool to tag NER and POS in Vietnamese sentences. In addition, we had access to a Korean-Vietnamese parallel corpus with more than 450K paired sentences from our previous research paper. The experimental results indicate that tagging NER and POS in Vietnamese sentences can improve the quality of Korean-Vietnamese Neural MT (NMT) in terms of the Bi-Lingual Evaluation Understudy (BLEU) and Translation Error Rate (TER) score. On average, our MT system improved by 1.21 BLEU points or 2.33 TER scores after applying both NER and POS tagging to the Vietnamese corpus. Due to the structural features of language, the MT systems in the Korean to Vietnamese direction always give better BLEU and TER results than translation machines in the reverse direction.
Master-Slave FF Using DICE Capable of Tolerating Soft Errors Occurring Around Clock Edge

SUMMARY This letter reveals that an edge-triggered master-slave ﬂip-ﬂop (FF) using well-known soft error tolerant DICE (dual interlocked storage cell) is vulnerable to soft errors occurring around clock edge. This letter presents a design of a soft error tolerant FF based on the master-slave FF using DICE. The proposed design modiﬁes the connection between the master and slave latches to make the FF not vulnerable to these errors. The hardware overhead is almost the same as that for the original edge-triggered FF using the DICE.
The circulatory physiopathology of human red blood cells investigated with a multiplatform model of cellular homeostasis. II. Capillary transits and the role of PIEZO1

In this and the next paper of this series we apply the red cell model introduced in the previous paper to investigate the changes in RBC homeostasis during capillary transits and over the full circulatory lifespan of the cells. These are topics inaccessible to direct experimentation but rendered mature for a modelling approach by recent findings and by a large body of apparently unrelated early results which robustly constrain the parameter space offering the opportunity for an in depth study of the mechanisms involved. Capillary transit times vary between 0.5 and 1.5s during which the red blood cells squeeze and deform in the capillary stream transiently opening stress-gated PIEZO1 channels, creating minuscule quantal changes in RBC ion contents and volume. Widely accepted early views originally based on results from experimentally shear-stressed red cells suggested that quantal changes generated during capillary transits add up over time to generate the documented changes in RBC density during their long circulatory lifespan, the quantal hypothesis. Applying the new PIEZO1 extension of the RBC model (RCM) introduced in the previous paper we investigated in detail the changes in homeostatic variables that may be expected during single capillary transits resulting from transient PIEZO1 channel activation. The predicted quantal volume changes were infinitesimal in magnitude, biphasic in nature, and essentially irreversible within inter-transit periods. A sub-second transient PIEZO1 activation triggered a sharp swelling peak followed by a much slower recovery period towards lower-than-baseline volumes. The peak response was caused by net CaCl2and fluid gain via PIEZO1 channels driven by the steep electrochemical inward Ca2+gradient. The ensuing dehydration followed a complex time-course with sequential, but partially overlapping contributions by KCl loss via Ca2+-activated Gardos channels, PMCA mediated calcium extrusion and chloride efflux by the Jacobs-Steward mechanism. The change in relative cell volume predicted for single capillary transits was below 10−4, an infinitesimal volume change incompatible with a functional role in capillary flow. The biphasic response predicted by the RCM appears to conform to the quantal hypothesis, but whether its cumulative effects could account for the documented changes in density during RBC senescence required an investigation of the effects of myriad transits over the full period of circulatory lifespan, the subject of the next paper of this series.
A series of molecular modeling techniques to reveal selective mechanisms of inhibitors to β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) and β-site amyloid precursor protein cleaving enzyme 2 (BACE2)

Abstract Inhibition of β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) has been shown to be an effective treatment for Alzheimer’s disease. A wealth of research has focused on finding highly selective small-molecule inhibitors targeting the BACE1 over its close homologue BACE2 to avoid potential side effects. However, given the highly structural similarities of BACE1 and BACE2, designing highly selective BACE1 inhibitors remains a huge challenge. Recently, it has been reported that a potential BACE1 inhibitor named C28 (∼52-fold selectivity) exhibited greater selectivity to BACE1 over BACE2 than the previously reported inhibitors AZD3293 and AZD3839 (∼1.5-fold and 14-fold selectivity). However, few computational studies have been performed to reveal its underlying mechanisms. In this study, a series of molecular modeling techniques were performed to reveal the selective mechanisms. Classical molecular dynamics (cMD) simulations indicated that the major variations appeared to be controlled by overall protein dynamics. Free energy calculations further suggested that the binding affinities of AZD3293 to BACE1 and BACE2 are similar, but the binding affinity of AZD3839 and C28 to BACE1 is much higher than to BACE2, and that the major variations are electrostatic interactions. The protein dynamics and energy differences were further observed in accelerated molecular dynamics (aMD) simulations. In addition, the umbrella sampling simulations revealed the inhibitors’ different patterns of dissociation from the binding pockets of BACE1 and BACE2, and that different energy barriers were responsible for the selectivity. The physical principles revealed by this study may facilitate the rational design of more potent BACE1 selective inhibitors. Communicated by Ramaswamy H. Sarma