Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of ATG4C function in vivo

ABSTRACT Despite the great advances in macroautophagy/autophagy research in the last years, the in vivo role of the different members of the four mammalian orthologs of yeast Atg4 protease (ATG4A-D) remain unclear. To gain further insights into the functional relevance of Atg4 orthologs, we have generated mutant mice deficient in Atg4c. These mice are viable and fertile, and do not display any obvious abnormalities, indicating that they are able to develop the autophagic response required during the early neonatal period. However, they show tissue-specific autophagy alterations, including reduced autophagic flux in diaphragm and show decreased breathing and locomotor activity after fasting. In addition, atg4c -/- mice show reduced number of circulating T and B lymphocytes, which is associated with accumulation of apoptotic cells in the spleen and an increased susceptibility to develop chemically-induced fibrosarcomas. Moreover, through the analysis of cells and mice simultaneously deficient for ATG4C and ATG4D proteases we also reveal a role for ATG4C in mATG8 proteins delipidation. Abbreviations ATG4 (autophagy related 4 cysteine peptidase); ATG4A (autophagy related 4A cysteine peptidase); ATG4B (autophagy related 4B cysteine peptidase); ATG4C (autophagy related 4C cysteine peptidase); ATG4D (autophagy related 4D cysteine peptidase); Atg8 (autophagy related 8); GABARAP (GABA type A receptor-associated protein); GABARAPL1(GABA type A receptor-associated protein like 1); GABARAPL2 (GABA type A receptor-associated protein like 2); MAP1LC3A/LC3A (microtubule associated protein 1 light chain 3 alpha); MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta); mATG8 (mammalian Atg8); PE (phosphatidylethanolamine); PS (phosphatydylserine); SQSTM1/p62 (sequestosome 1).
Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery

Abstract Background The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics of the tumour microenvironment (TME). Recent studies have confirmed the presence and potential influence of the microbiome in TME on cancer progression. Elucidating the relationship between microbes in the TME and cancer could provide valuable insights into novel diagnostic markers and therapeutic strategies for HCC and thus warrants a closer investigation of the role of intratumoural microbiome in the HCC TME. Methods We determined the presence of intratumoural microbiome using fluorescence in situ hybridisation, and explored the microbial community profiles in the HCC TME in paired tumour and adjacent normal tissues using 16S rDNA sequencing. Microbial signatures were characterised in the paired group, and their correlation with clinical characteristics was further investigated. We clustered the microbial signatures of tumour tissues by hepatotypes, and further analysis was performed to elucidate the independent prognostic value of the hepatotypes. Results This study revealed that microbial profiles and community networks differed notably between tumours and adjacent normal tissues. Proteobacteria and Actinobacteria were the most abundant phyla in the HCC TME. The TME microbial profiles also revealed heterogeneities between individuals and between multiple tumour lesions. Clustering of the microbial profiles into two hepatotypes revealed different microbial network patterns. Additionally, the hepatotypes were revealed to be independent prognostic factors in patients with resected HCC. Conclusions Our study illuminates the microbial profiles in the TME of HCC and presents the hepatotype as a potential independent biomarker for the prognostic prediction of HCC after surgery.
Measuring the Polarization of the Cosmic Microwave Background with BICEP3

Inflation, a period of accelerated expansion in the early Universe, is postulated to answer the horizon, flatness and monopole problems in the standard model of the Universe. This inflationary scenario generically predicts the existence of primordial gravitational waves, which would leave an unique B-mode polarization pattern in the Cosmic Microwave Background. Detection of the primordial B modes at degree angular scales would be a direct evidence for inflation; and the amplitude, parametrized by the tensor-to-scalar ratio r, would allow us to probe the energy scale at 10-35 second after the Big Bang. The Bicep/Keck Array experiment is a series of telescopes located at the Amundsen-Scott South Pole Station designed to measure the CMB polarization at degree angular scales. The latest result in Bicep/Keck Array, using data collected up to 2015, and combined with other external data, set upper limits on r This dissertation provides an overview of the Bicep3 instrument design. In particular, the performance of the sub-Kelvin focal plane structure, antenna-coupled transition edge sensor and time domain multiplexing SQUID readout system. We discuss various calibration methods used to probe instrument sensitivity and systematics. Finally, we review the analysis pipeline, and some preliminary results from Bicep3.
Utility of Minimal Physiologically Based Pharmacokinetic Models for Assessing Fractional Distribution, Oral Absorption, and Series-Compartment Models of Hepatic Clearance

Minimal physiologically based pharmacokinetic (mPBPK) models are physiologically relevant, require less information than full PBPK models, and offer flexibility in pharmacokinetics (PK). The well-stirred hepatic model (WSM) is commonly used in PBPK, whereas the more plausible dispersion model (DM) poses computational complexities. The series-compartment model (SCM) mimics the DM but is easier to operate. This work implements the SCM and mPBPK models for assessing fractional tissue distribution, oral absorption, and hepatic clearance using literature-reported blood and liver concentration-time data in rats for compounds mainly cleared by the liver. Further handled were various complexities, including nonlinear hepatic binding and metabolism, differing absorption kinetics, and sites of administration. The SCM containing one to five (n) liver subcompartments yields similar fittings and provides comparable estimates for hepatic extraction ratio (ER), prehepatic availability (Fg), and first-order absorption rate constants (ka). However, they produce decreased intrinsic clearances (CLint) and liver-to-plasma partition coefficients (Kph) with increasing n as expected. Model simulations demonstrated changes in intravenous and oral PK profiles with alterations in Kph and ka and with hepatic metabolic zonation. The permeability (PAMPA P) of the various compounds well explained the fitted fractional distribution (fd) parameters. The SCM and mPBPK models offer advantages in distinguishing systemic, extrahepatic, and hepatic clearances. The SCM allows for incorporation of liver zonation and is useful in assessing changes in internal concentration gradients potentially masked by similar blood PK profiles. Improved assessment of intraorgan drug concentrations may offer insights into active moieties driving metabolism, biliary excretion, pharmacodynamics, and hepatic toxicity. SIGNIFICANCE STATEMENT The minimal physiologically based pharmacokinetic model and the series-compartment model are useful in assessing oral absorption and hepatic clearance. They add flexibility in accounting for various drug- or system-specific complexities, including fractional distribution, nonlinear binding and saturable hepatic metabolism, and hepatic zonation. These models can offer improved insights into the intraorgan concentrations that reflect physiologically active moieties often driving disposition, pharmacodynamics, and toxicity.
Dogs’ expectations about occlusion events: from expectancy violation to exploration

Previous research on human infants has shown that violations of basic physical regularities can stimulate exploration, which may represent a type of hypothesis testing aimed at acquiring knowledge about new causal relationships. In this study, we examined whether a similar connection between expectancy violation and exploration exists in nonhuman animals. Specifically, we investigated how dogs react to expectancy violations in the context of occlusion events. Throughout three experiments, dogs exhibited longer looking times at expectancy-inconsistent events than at consistent ones. This finding was further supported by pupil size analyses in the first two eye-tracking experiments. Our results suggest that dogs expect objects to reappear when they are not obstructed by a screen and consider the size of the occluding screen in relation to the occluded object. In Experiment 3, expectancy violations increased the dogs' exploration of the target object, similar to the findings with human infants. We conclude that expectancy violations can provide learning opportunities for nonhuman animals as well.
The reliability of the serial reaction time task: meta-analysis of test–retest correlations

The Serial Reaction Time task, one of the most widely used tasks to index procedural memory, has been increasingly employed in individual differences research examining the role of procedural memory in language and other cognitive abilities. Yet, despite consistently producing robust procedural learning effects at the group level (i.e. faster responses to sequenced/probable trials versus random/improbable trials), these effects have recently been found to have poor reliability. In this meta-analysis (N = 7), comprising 719 participants (M = 20.81, s.d. = 7.13), we confirm this ‘reliability paradox’. The overall retest reliability of the robust procedural learning effect elicited by the SRTT was found to be well below acceptable psychometric standards (r < 0.40). However, split-half reliability within a session is better, with an overall estimate of 0.66. There were no significant effects of sampling (participants' age), methodology (e.g. number of trials, sequence type) and analytical decisions (whether all trials were included when computing the procedural learning scores; using different indexes of procedural learning). Thus, despite producing robust effects at the group-level, until we have a better understanding of the factors that improve the reliability of this task using the SRTT for individual differences research should be done with caution.
High physiological function for corals with thermally tolerant, host-adapted symbionts

The flexibility to associate with more than one symbiont may considerably expand a host's niche breadth. Coral animals and dinoflagellate micro-algae represent one of the most functionally integrated and widespread mutualisms between two eukaryotic partners. Symbiont identity greatly affects a coral's ability to cope with extremes in temperature and light. Over its broad distribution across the Eastern Pacific, the ecologically dominant branching coral, Pocillopora grandis, depends on mutualisms with the dinoflagellates Durusdinium glynnii and Cladocopium latusorum. Measurements of skeletal growth, calcification rates, total mass increase, calyx dimensions, reproductive output and response to thermal stress were used to assess the functional performance of these partner combinations. The results show both host–symbiont combinations displayed similar phenotypes; however, significant functional differences emerged when exposed to increased temperatures. Negligible physiological differences in colonies hosting the more thermally tolerant D. glynnii refute the prevailing view that these mutualisms have considerable growth tradeoffs. Well beyond the Eastern Pacific, pocilloporid colonies with D. glynnii are found across the Pacific in warm, environmentally variable, near shore lagoonal habitats. While rising ocean temperatures threaten the persistence of contemporary coral reefs, lessons from the Eastern Pacific indicate that co-evolved thermally tolerant host–symbiont combinations are likely to expand ecologically and spread geographically to dominate reef ecosystems in the future.
Phosphorus storage and utilization strategies of two bloom-forming freshwater cyanobacteria

The inter-relationships between cellular phosphorus (P) storage, dissolved inorganic P (DIP) uptake affinity, alkaline phosphatase activity (APA) and dissolved inorganic nitrogen (DIN) concentrations were studied in two ubiquitous diazotrophic freshwater cyanobacteria, Raphidiopsis raciborskii (six strains) and Chrysosporum ovalisporum (two strains). DIP uptake kinetics were measured using rates of incorporation of the radio-isotope, 33P and APA as a proxy for DOP-ester utilization. The study showed that DIP uptake of individual strains followed Michaelis–Menten kinetics (modified in our study to incorporate cellular P quotas), but differed with DIN and P availability, and between growth stages. High-affinity DIP uptake and APA were activated below a P quota threshold of approximately 0.01 µg P µg−1 C across the species and strains. C. ovalisporum had significantly higher APA and P quotas (per unit C and cell) but lower uptake affinity than R. raciborskii. Demand for DIP by C. ovalisporum increased when N fixation occurred, but typically not for R. raciborskii. Our results indicate that cyanobacterial species and strains differ in their strategies to P limiting conditions, and highlight the interplay between N and P. Physiological adaptations like APA and diazotrophy of cyanobacteria adapting to low DIP and/or DIN conditions may occur simultaneously and drive species dominance in oligotrophic environments.
Parkinson’s disease: symptoms and medications at the end of life

Objectives People with Parkinson’s disease (PwP) have a high palliative symptom burden throughout their disease course, equivalent to advanced malignancy. We aim to establish trends in symptom frequency and prescribing in the 72 hours prior to death for PwP. Methods Retrospective case note review of PwP who died between February 2019 and September 2020. Results 51 patients were included. 60.78% of patients (n=31) had agitation and 58.82% (n=30) had pain in the final 72 hours. Patients with cognitive impairment were 4.67 times more likely to experience agitation (p=0.035) compared with those without, with higher total midazolam doses (29.18 mg vs 11.4 mg, p=0.21). Terminal motor symptoms were recorded in three patients. 28.57% of patients received the recommended dose of rotigotine for dopaminergic therapy. Conclusions PwP have a significant symptom burden at the end of life (EOL) with levels of terminal agitation at the higher end of those expected in the general population. There was a trend towards higher doses of sedation, rather than analgesia, in people with coexistent cognitive impairment. Terminal stiffness, despite being seldom documented in the literature, is an important although infrequent symptom. Rotigotine use at EOL remains commonplace and better understanding of its effect and dosing is required.
Simpler is Much Faster: Fair and Independent Inner Product Search

The problem of inner product search (IPS) is important in many fields. Although maximum inner product search (MIPS) is often considered, its result is usually skewed and static. Users are hence hard to obtain diverse and/or new items by using the MIPS problem. Motivated by this, we formulate a new problem, namely the fair and independent IPS problem. Given a query, a threshold, and an output size k, this problem randomly samples k items from a set of items such that the inner product of the query and item is not less than the threshold. For each item that satisfies the threshold, this problem is fair, because the probability that such an item is outputted is equal to that for each other item. This fairness can yield diversity and novelty, but this problem faces a computational challenge. Some existing (M)IPS techniques can be employed in this problem, but they require O(n) or o(n) time, where n is the dataset size. To scale well to large datasets, we propose a simple yet efficient algorithm that runs in O(log n + k) expected time. We conduct experiments using real datasets, and the results demonstrate that our algorithm is up to 330 times faster than baselines.
How Significant Attributes are in the Community Detection of Attributed Multiplex Networks

Existing community detection methods for attributed multiplex networks focus on exploiting the complementary information from different topologies, while they are paying little attention to the role of attributes. However, we observe that real attributed multiplex networks exhibit two unique features, namely, consistency and homogeneity of node attributes. Therefore, in this paper, we propose a novel method, called ACDM, which is based on these two characteristics of attributes, to detect communities on attributed multiplex networks. Specifically, we extract commonality representation of nodes through the consistency of attributes. The collaboration between the homogeneity of attributes and topology information reveals the particularity representation of nodes. The comprehensive experimental results on real attributed multiplex networks well validate that our method outperforms state-of-the-art methods in most networks.
Embedding Based Retrieval in Friend Recommendation

Friend recommendation systems in online social and professional networks such as Snapchat helps users find friends and build connections, leading to better user engagement and retention. Traditional friend recommendation systems take advantage of the principle of locality and use graph traversal to retrieve friend candidates, e.g. Friends-of-Friends (FoF). While this approach has been adopted and shown efficacy in companies with large online networks such as Linkedin and Facebook, it suffers several challenges: (i) discrete graph traversal offers limited reach in cold-start settings, (ii) it is expensive and infeasible in realtime settings beyond 1 or 2 hop requests owing to latency constraints, and (iii) it cannot well-capture the complexity of graph topology or connection strengths, forcing one to resort to other mechanisms to rank and find top-K candidates. In this paper, we proposed a new Embedding Based Retrieval (EBR) system for retrieving friend candidates, which complements the traditional FoF retrieval by retrieving candidates beyond 2-hop, and providing a natural way to rank FoF candidates. Through online A/B test, we observe statistically significant improvements in the number of friendships made with EBR as an additional retrieval source in both low- and high-density network markets. Our contributions in this work include deploying a novel retrieval system to a large-scale friend recommendation system at Snapchat, generating embeddings for billions of users using Graph Neural Networks, and building EBR infrastructure in production to support Snapchat scale.
Static Prediction of Parallel Computation Graphs (Abstract)

Many results in the theory of parallel scheduling, dating back to Brent's Theorem, are expressed in terms of the parallel dependency structure of a program as represented by a Directed Acyclic Graph (DAG). In the world of parallel and concurrent program analysis, such DAG models are also used to study deadlock, data races, and priority inversions, to name just a few examples. In all of these cases, it tends to be convenient to think of the DAG as a model of the program itself-we might say, for example, that the time to run a parallel program on P processors depends on the work and span of the program's DAG. This assumes that the DAG is a static, predictable property of the program. In reality, however, a DAG typically models the runtime relationships between threads during a particular execution of a program. To obtain the DAG, one might simulate an execution (or all possible executions) using some form of cost semantics, a dynamic semantics that produces the DAG as it executes the program. In fine-grained parallel programs, such as those that result from constructs such as fork/join, spawn/sync, async/finish, and futures, these DAGs tend to be especially dynamic and dependent on the features of a particular execution. For example, a divide-and-conquer algorithm implemented using fork/join parallelism may divide a certain number of times depending on the input size, and a program written with futures can choose to wait on threads or not wait on threads depending on conditions available only at runtime. Such programs are best represented by a (possibly infinite) family of DAGs, representing all possible executions of the program.
Pre-Semester Predictors of Course Retention in a Large Online Graduate CS Program

Online education is convenient and accessible, but also brings new challenges to retention. Prior research has found that students in online programs---including CS programs---are more likely to withdraw both from individual classes as well as the program as a whole than students in traditional programs. In this study, we delve deeper into retention at the level of individual courses. We analyze three courses offered as part of a large online CS graduate degree program taught at a major research university in the United States. We obtained voluntary data from students across 12 semesters---including gender, prior CS experience, and anticipated workload for the course---and analyzed these variables in the context of course retention. While the average course drop rate for the examined courses in the program was 7%, variations in this rate could be predicted by a number of different attributes: for instance, we observed that women, native English speakers, and students with less prior education were allmore likely to complete a course that they had started. Importantly, these predictors can be measured before the class begins, supporting early intervention.
Subpaving-Map: Fast Terrain Mapping for Outdoor Scenes based on Set-membership Theory

Three-dimension terrain modeling of outdoor scenes mostly relies on probability theory. However, the lack of inherent robustness in probability methods can lead to the coupling and accumulation of uncertainties from multiple sources, making it difficult to ensure the reliability of the constructed terrain model. In order to build an accurate and highly robust dense terrain map, three-dimension terrain mapping based on set-membership theory is studied. Subpaving-Map, a fast terrain mapping method for outdoor scenes is proposed, which includes three modules: measurement modeling, feature association and terrain map update. Subpaving-Map fully considers the strict constraint boundary of terrain uncertainty during the process of mapping. Subpaving-Map is compared with Octomap on the KITTI dataset, and it is demonstrated that Subpaving-Map achieves a balance in accuracy, real-time performance and robustness.
LightGT: A Light Graph Transformer for Multimedia Recommendation

Multimedia recommendation methods aim to discover the user preference on the multi-modal information to enhance the collaborative filtering (CF) based recommender system. Nevertheless, they seldom consider the impact of feature extraction on the user preference modeling and prediction of the user-item interaction, as the extracted features contain excessive information irrelevant to the recommendation. To capture the informative features from the extracted ones, we resort to Transformer model to establish the correlation between the items historically interacted by the same user. Considering its challenges in effectiveness and efficiency, we propose a novel Transformer-based recommendation model, termed as Light Graph Transformer model (LightGT). Therein, we develop a modal-specific embedding and a layer-wise position encoder for the effective similarity measurement, and present a light self-attention block to improve the efficiency of self-attention scoring. Based on these designs, we can effectively and efficiently learn the user preference from the off-the-shelf items' features to predict the user-item interactions. Conducting extensive experiments on Movielens, Tiktok and Kwai datasets, we demonstrate that LigthGT significantly outperforms the state-of-the-art baselines with less time. Our code is publicly available at: https://github.com/Liuwq-bit/LightGT.