Miracle-dz/UniFAR-FTUs huggingface dataset:
Reorganization of inter‐chromosomal interactions in the 2q37‐deletion syndrome

Chromosomes occupy distinct interphase territories in the three‐dimensional nucleus. However, how these chromosome territories are arranged relative to one another is poorly understood. Here, we investigated the inter‐chromosomal interactions between chromosomes 2q, 12, and 17 in human mesenchymal stem cells (MSCs) and MSC‐derived cell types by DNA‐FISH. We compared our findings in normal karyotypes with a three‐generation family harboring a 2q37‐deletion syndrome, featuring a heterozygous partial deletion of histone deacetylase 4 (HDAC4) on chr2q37. In normal karyotypes, we detected stable, recurring arrangements and interactions between the three chromosomal territories with a tissue‐specific interaction bias at certain loci. These inter‐chromosomal interactions were confirmed by Hi‐C. Interestingly, the disease‐related HDAC4 deletion resulted in displaced inter‐chromosomal arrangements and altered interactions between the deletion‐affected chromosome 2 and chromosome 12 and/or 17 in 2q37‐deletion syndrome patients. Our findings provide evidence for a direct link between a structural chromosomal aberration and altered interphase architecture that results in a nuclear configuration, supporting a possible molecular pathogenesis.
Learning to Update for Object Tracking

Model update lies at the heart of object tracking.Generally, model update is formulated as an online learning problem where a target model is learned over the online training dataset. Our key innovation is to \emph{learn the online learning algorithm itself using large number of offline videos}, i.e., \emph{learning to update}. The learned updater takes as input the online training dataset and outputs an updated target model. As a first attempt, we design the learned updater based on recurrent neural networks (RNNs) and demonstrate its application in a template-based tracker and a correlation filter-based tracker. Our learned updater consistently improves the base trackers and runs faster than realtime on GPU while requiring small memory footprint during testing. Experiments on standard benchmarks demonstrate that our learned updater outperforms commonly used update baselines including the efficient exponential moving average (EMA)-based update and the well-designed stochastic gradient descent (SGD)-based update. Equipped with our learned updater, the template-based tracker achieves state-of-the-art performance among realtime trackers on GPU.
Automatic Speech Recognition and Topic Identification for Almost-Zero-Resource Languages

Automatic speech recognition (ASR) systems often need to be developed for extremely low-resource languages to serve end-uses such as audio content categorization and search. While universal phone recognition is natural to consider when no transcribed speech is available to train an ASR system in a language, adapting universal phone models using very small amounts (minutes rather than hours) of transcribed speech also needs to be studied, particularly with state-of-the-art DNN-based acoustic models. The DARPA LORELEI program provides a framework for such very-low-resource ASR studies, and provides an extrinsic metric for evaluating ASR performance in a humanitarian assistance, disaster relief setting. This paper presents our Kaldi-based systems for the program, which employ a universal phone modeling approach to ASR, and describes recipes for very rapid adaptation of this universal ASR system. The results we obtain significantly outperform results obtained by many competing approaches on the NIST LoReHLT 2017 Evaluation datasets.
The influence of bilateral sagittal split ramus osteotomy on the stress distributions in the temporomandibular joints of the patients with facial asymmetry under symmetric occlusions

Abstract The aim of this study is to compare the differences in the stress distributions in the temporomandibular joints (TMJs) of the patients with facial asymmetry before and after bilateral sagittal split ramus osteotomy (BSSRO) under the symmetric occlusions using the three-dimensional (3D) finite element method. Ten facial asymmetry patients (Preoperative group, age 24.6 ± 4.8 years) and 10 asymptomatic subjects (Control group, age 26.8 ± 4.9 years) were recruited. After the patients underwent BSSRO, they were further assigned as the Postoperative group. 3D geometries of the finite element models of the mandible, disc, maxilla, and teeth were reconstructed according to cone-beam computed tomography (CBCT) image data. Contact elements were used to simulate the interaction of the disc-condyle, disc-temporal bone, and upper-lower dentition. The muscle forces and boundary conditions corresponding to the central and anterior occlusions were applied on the models of the 3 groups. The finite element models were validated with experimental data showing the accuracy of the simulation results. The simulation predicted preoperative significant differences of stresses between non-deviated sides and deviated sides were disappeared after the surgery under the central and anterior occlusions (P < .05). Almost all stresses in the patient models had significantly decreased after BSSRO, leveling it to the stress values of the normal subjects. Moreover, the simulation results coincided with the clinical cases which showed that BSSRO had helped to release or remove the signs and symptoms of temporomandibular disorders (TMD). In conclusion, BSSRO could correct the asymmetric stress distributions of TMJs and decrease the magnitude of the stresses for the patients with facial asymmetry. Those decreases also associated with the recovery of TMD.
Aquaporin 4 Silencing Aggravates Hydrocephalus Induced by Injection of Autologous Blood in Rats

Background Aquaporin 4 (AQP4), the most abundant aquaporin in the brain, is a type of bidirectional water channel controlling the brain-water balance and plays a critical role in physiologic and pathologic water balance in the brain. AQP4 was reported to be elevated in hydrocephalus; therefore, we hypothesized that AQP4 contributes to hydrocephalus. In this study, the role of AQP4 in hydrocephalus was explored. Material/Methods The hydrocephalus rat model was established by injection of autologous blood. On Day 1 and Day 3 after injection of autologous blood, magnetic resonance imaging (MRI) and hematoxylin-eosin (HE) staining were performed to detect the changes in ventricles, and quantitative real-time PCR (qRT-PCR) and immunohistochemistry were carried out to detect the changes in AQP4 level. Thereafter, an AQP4-specific siRNA was used to downregulate AQP4. Then, on Day 3 after injection of autologous blood, the levels of AQP4 and connexin-43 were detected by qRT-PCR, immunohistochemistry, immunofluorescence, or Western blot analysis. MRI and HE staining were performed to detect the changes in ventricles, and Evans blue extravasation assay was used to assess blood-brain barrier integrity. Results The hydrocephalus rat model was established successfully, and hydrocephalus rats showed a higher AQP4 level. Silencing AQP4 aggravated the hydrocephalus, with enlarged lateral ventricles and destruction of ependymal integrity and blood-brain barrier. Conclusions Our study demonstrates that silencing AQP4 aggravates hydrocephalus, indicating that AQP4 protects against hydrocephalus.
Influence of vitamin E on organic matter fermentation, ruminal protein and fatty acid metabolism, protozoa concentrations and transfer of fatty acids

Vitamin E (Vit. E) is discussed to influence ruminal biohydrogenation. The objective of this study was to investigate the influence of a Vit. E supplementation on rumen fermentation characteristics, ruminal microbial protein synthesis as well as ruminal organic matter fermentation. Furthermore, we aimed to investigate the influence of Vit. E supplementation on short-chain fatty acids (SCFA) and protozoa concentrations in the rumen and, in addition, on transfer rates of middle-chain and long-chain fatty acids into the duodenum in lactating dairy cows. Eight rumen and duodenum fistulated German Holstein cows were assigned to either a group receiving 2,327 IU/d Vit. E (138.6 IU/kg DM DL-α-tocopherylacetate; n = 4) or a control group (23.1 IU/kg DM; n = 4). Neither ruminal protein synthesis nor organic matter fermentation was influenced by treatment. Vit. E did not act on the concentrations of short-chain fatty acids and protozoa in rumen fluid. Duodenal flow of C13:0 (1.3 versus 0.2 g/d, p = 0.014) and iso-C14:0 (1.0 versus 0.5 g/d, p = 0.050) was higher in the Vit. E group. We observed a trend for higher duodenal flows for C12:0 (1.6 versus 0.9 g/d, p = 0.095) and anteiso-C15:0 (12.2 versus 8.9 g/d, p = 0.084). Transfer rate of C12:0 tended to be higher in the Vit. E group (125.61 versus 73.96, p = 0.082). No other transfer rates were affected by treatment. Further studies are necessary to investigate the influence of Vit. E on rumen microbiota and their fatty acid production as well as on the impact of different doses of Vit. E supplementation on variables of protein synthesis efficiency.
Exploring Cultural Differences in the Extent to Which People Perceive and Desire Control

In a seminal theory piece, Weisz and colleagues argued that control over one’s environment was less attainable and desirable in Japan than in America. Subsequently, many scholars have extrapolated from this argument to claim broad-based cultural differences in control: that Western/individualist cultures perceive and desire more personal control over their environment than do Eastern/collectivist cultures. Yet surprisingly little empirical research has put this claim to the test. To test this notion, in Study 1 we examined perceived control over one’s life in 38 nationally representative samples (N = 48,951). In Study 2, we measured desire for control in community samples across 27 nations (N = 4,726). Together, the studies show lower levels of perceived and desired control in Japan than in any other nation. Over and above the Japan effect, there was no evidence for differences in perceived or desired control between individualist and collectivist nations, or between holistic and nonholistic nations.
Complete Substrate Inhibition of Cytochrome P450 2C8 by AZD9496, an Oral Selective Estrogen Receptor Degrader

AZD9496 ((E)-3-(3,5-difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic acid) is an oral selective estrogen receptor degrader currently in clinical development for treatment of estrogen receptor–positive breast cancer. In a first-in-human phase 1 study, AZD9496 exhibited dose nonlinear pharmacokinetics, the mechanistic basis of which was investigated in this study. The metabolism kinetics of AZD9496 were studied using human liver microsomes (HLMs), recombinant cytochrome P450s (rP450s), and hepatocytes. In addition, modeling approaches were used to gain further mechanistic insights. CYP2C8 was predominantly responsible for biotransformation of AZD9496 to its two main metabolites whose rate of formation with increasing AZD9496 concentrations exhibited complete substrate inhibition in HLM, rCYP2C8, and hepatocytes. Total inhibition by AZD9496 of amodiaquine N-deethylation, a specific probe of CYP2C8 activity, confirmed the completeness of this inhibition. The commonly used substrate inhibition model analogous to uncompetitive inhibition fit poorly to the data. However, using the same model but without constraints on the number of molecules occupying the inhibitory binding site (i.e., nS1ES) provided a significantly better fit (F test, P < 0.005). With the improved model, up to three AZD9496 molecules were predicted to bind the inhibitory site of CYP2C8. In contrast to previous studies showing substrate inhibition of P450s to be partial, our results demonstrate complete substrate inhibition of CYP2C8 via binding of more than one molecule of AZD9496 to the inhibitory site. As CYP2C8 appears to be the sole isoform catalyzing formation of the main metabolites, the substrate inhibition might explain the observed dose nonlinearity in the clinic at higher doses.
Impact of European vaccination policies on seasonal influenza vaccination coverage rates: An update seven years later

ABSTRACT Seasonal influenza can have serious morbid consequences and can even result in death, particularly in at-risk populations, including healthcare professionals (HCPs), elderly and those living with a medical risk condition. Although in Europe recommendations exist for annual influenza vaccination in these populations in most countries, the vaccination coverage rate (VCR) is often well below the World Health Organization target of 75% coverage. In our previous survey in 2009 we showed that some elements of national vaccination policies, e.g. reminder systems, strong official recommendation, and easy access, seemed to contribute to achieving higher influenza VCRs among elderly. We repeated the survey in 2016, using the same methodology to assess changes in influenza VCRs among the elderly and in the impact of policy elements on these VCRs. In addition, we collected information about VCRs among HCPs, and those living with a medical risk condition. The median VCR in the 21 countries that had recommendations for influenza vaccination in the elderly was 35.3%, ranging from 1.1% in Estonia to 74.5% in Scotland. The average VCRs for HCPs and those living with medical risk conditions, available in 17 and 10 countries, respectively, were 28.3% (range 7% in Czech Republic to 59.1% in Portugal) and 32.2% (range from 20.0% in the Czech Republic and Hungary to 59.6% in Portugal), respectively. Fewer countries were able to provide data from HCP and those living with medical risk conditions. Since the initial survey during the 2007–2008 influenza season, VCRs have decreased in the elderly in the majority of countries, thus, achieving high VCRs in the elderly and the other target groups is still a major public health challenge in Europe. This could be addressed by the identification, assessment and sharing of best practice for influenza vaccination policies.
Muscular weakness in adolescence is associated with disability 30 years later: a population-based cohort study of 1.2 million men

Objective To investigate the associations of muscular strength in adolescence with later disability pension (DP), across different body mass index (BMI) categories and in combination with aerobic fitness. Method This prospective cohort study consisted of males aged 16–19 years, recruited from the Swedish military conscription register between 1969 and 1994. A total of 1 212 503 adolescents met all the inclusion criteria and were therefore included in the analyses. Knee extension, handgrip and elbow flexion strength and aerobic fitness (bicycle ergometer test) were measured during conscription. Causes of DP were retrieved from the Social Insurance Office between years 1971 and 2012 (average follow-up time: 29.6 years). Results Knee extension strength in adolescence was inversely associated with men’s risk of obtaining DP due to all causes (HR 1.40, 95% CI 1.36 to 1.44 for lowest vs highest strength quintile). Thus, muscular weakness was associated with DP. The risk associated with low muscular strength differed between specific causes of DP and the strongest associations were found for psychiatric, nervous system and other causes (HRs between 1.47 and 1.90 for lowest vs highest quintile). Being strong was associated with lower DP risk across BMI categories and being unfit, weak and obese was associated with the highest DP risk (HR 3.70, 95% CI 2.99 to 4.58). Conclusion There was a strong association between muscular weakness and disability. A combination of muscular weakness and low aerobic fitness was an especially important risk factor for disability. This adds weight to call for muscular strength and fitness enhancing exercise for adolescents in all BMI categories.
Qualitative Measurements of Policy Discrepancy for Return-Based Deep Q-Network

The deep Q-network (DQN) and return-based reinforcement learning are two promising algorithms proposed in recent years. The DQN brings advances to complex sequential decision problems, while return-based algorithms have advantages in making use of sample trajectories. In this brief, we propose a general framework to combine the DQN and most of the return-based reinforcement learning algorithms, named R-DQN. We show that the performance of the traditional DQN can be significantly improved by introducing return-based algorithms. In order to further improve the R-DQN, we design a strategy with two measurements to qualitatively measure the policy discrepancy. We conduct experiments on several representative tasks from the OpenAI Gym and Atari games. The state-of-the-art performance achieved by our method with this proposed strategy validates its effectiveness.
Canonical Tensor Decomposition for Knowledge Base Completion

The problem of Knowledge Base Completion can be framed as a 3rd-order binary tensor completion problem. In this light, the Canonical Tensor Decomposition (CP) (Hitchcock, 1927) seems like a natural solution; however, current implementations of CP on standard Knowledge Base Completion benchmarks are lagging behind their competitors. In this work, we attempt to understand the limits of CP for knowledge base completion. First, we motivate and test a novel regularizer, based on tensor nuclear $p$-norms. Then, we present a reformulation of the problem that makes it invariant to arbitrary choices in the inclusion of predicates or their reciprocals in the dataset. These two methods combined allow us to beat the current state of the art on several datasets with a CP decomposition, and obtain even better results using the more advanced ComplEx model.
Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes.

Background Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. Objective We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. Methods We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Results Mean ± SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 ± 28.9 and 138.7 ± 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of β-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. Conclusions These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.
EGFL7: Master regulator of cancer pathogenesis, angiogenesis and an emerging mediator of bone homeostasis

Epidermal growth factor‐like domain‐containing protein 7 (EGFL7), a member of the epidermal growth factor (EGF)‐like protein family, is a potent angiogenic factor expressed in many different cell types. EGFL7 plays a vital role in controlling vascular angiogenesis during embryogenesis, organogenesis, and maintaining skeletal homeostasis. It regulates cellular functions by mediating the main signaling pathways (Notch, integrin) and EGF receptor cascades. Accumulating evidence suggests that Egfl7 plays a crucial role in cancer biology by modulating tumor angiogenesis, metastasis, and invasion. Dysregulation of Egfl7 has been frequently found in several types of cancers, such as malignant glioma, colorectal carcinoma, oral and oesophageal cancers, gastric cancer, hepatocellular carcinoma, pancreatic cancer, breast cancer, lung cancer, osteosarcoma, and acute myeloid leukemia. In addition, altered expression of miR‐126, a microRNA associated with Egfl7, was found to play an important role in oncogenesis. More recently, our study has shown that EGFL7 is expressed in both the osteoclast and osteoblast lineages and promotes endothelial cell activities via extracellular signal‐regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), and integrin signaling cascades, indicative of its angiogenic regulation in the bone microenvironment. Thus, understanding the role of EGFL7 may provide novel insights into the development of improved diagnostics and therapeutic treatment for cancers and skeletal pathological disorders, such as ischemic osteonecrosis and bone fracture healing.
Molecular Mechanisms for the Adaptive Switching Between the OAS/RNase L and OASL/RIG-I Pathways in Birds and Mammals

Host cells develop the OAS/RNase L [2′–5′–oligoadenylate synthetase (OAS)/ribonuclease L] system to degrade cellular and viral RNA, and/or the OASL/RIG-I (2′–5′–OAS like/retinoic acid inducible protein I) system to enhance RIG-I-mediated IFN induction, thus providing the first line of defense against viral infection. The 2′–5′–OAS-like (OASL) protein may activate the OAS/RNase L system using its typical OAS-like domain (OLD) or mimic the K63-linked pUb to enhance antiviral activity of the OASL/RIG-I system using its two tandem ubiquitin-like domains (UBLs). We first describe that divergent avian (duck and ostrich) OASL inhibit the replication of a broad range of RNA viruses by activating and magnifying the OAS/RNase L pathway in a UBL-dependent manner. This is in sharp contrast to mammalian enzymatic OASL, which activates and magnifies the OAS/RNase L pathway in a UBL-independent manner, similar to 2′–5′–oligoadenylate synthetase 1 (OAS1). We further show that both avian and mammalian OASL can reversibly exchange to activate and magnify the OAS/RNase L and OASL/RIG-I system by introducing only three key residues, suggesting that ancient OASL possess 2–5A [px5′A(2′p5′A)n; x = 1-3; n ≥ 2] activity and has functionally switched to the OASL/RIG-I pathway recently. Our findings indicate the molecular mechanisms involved in the switching of avian and mammalian OASL molecules to activate and enhance the OAS/RNase L and OASL/RIG-I pathways in response to infection by RNA viruses.