EMMA-X: An EM-like Multilingual Pre-training Algorithm for Cross-lingual Representation Learning

Expressing universal semantics common to all languages is helpful in understanding the meanings of complex and culture-specific sentences. The research theme underlying this scenario focuses on learning universal representations across languages with the usage of massive parallel corpora. However, due to the sparsity and scarcity of parallel data, there is still a big challenge in learning authentic ``universals'' for any two languages. In this paper, we propose EMMA-X: an EM-like Multilingual pre-training Algorithm, to learn (X)Cross-lingual universals with the aid of excessive multilingual non-parallel data. EMMA-X unifies the cross-lingual representation learning task and an extra semantic relation prediction task within an EM framework. Both the extra semantic classifier and the cross-lingual sentence encoder approximate the semantic relation of two sentences, and supervise each other until convergence. To evaluate EMMA-X, we conduct experiments on XRETE, a newly introduced benchmark containing 12 widely studied cross-lingual tasks that fully depend on sentence-level representations. Results reveal that EMMA-X achieves state-of-the-art performance. Further geometric analysis of the built representation space with three requirements demonstrates the superiority of EMMA-X over advanced models.Comment: Accepted by NeurIPS 202

A Surgeon\u27s handedness in direct anterior approach-hip replacement.

BACKGROUND: The impact of handedness on clinical outcomes was easily overlooked in hip replacement. This study aimed to find whether the component positioning and hip function were affected by the handedness in total hip arthroplasty (THA) through direct anterior approach (DAA). METHODS: Total 102 patients who underwent bilateral DAA-THAs simultaneously between May 2016 and November 2018 in our institute were reviewed. All surgeries were operated by one right-handed surgeon. Their demographic, cup positioning, stem alignment, femoral stem fit, Harris hip score (HHS), intraoperative and postoperative complications were used to evaluate the role of handedness in DAA. RESULTS: The inclination of left cups was significantly larger than that of right cups (42.61 ± 7.32 vs 39.42 ± 7.19, p = 0.000). The stem fit of left femur was significantly larger than that of right femur (84.34 ± 4.83 vs 82.81 ± 6.07, p = 0.043). No significant differences in safe zone ratio, HHS and complications between bilateral hips were found. CONCLUSIONS: A surgeon\u27s handedness had significant impact on cup\u27s inclination and femoral stem fit in DAA-THA. However, there were no significant differences of cup malpositioning, stem alignment, hip function scores and complications between bilateral DAA-THAs

Cullin 3SPOP ubiquitin E3 ligase promotes the poly-ubiquitination and degradation of HDAC6

The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines. Furthermore, we demonstrated that Cullin 3-based ubiquitin E3 ligase(s) primarily reduced the stability of HDAC6. Importantly, we identified SPOP, an adaptor protein of Cullin 3 family E3 ligases, specifically interacted with HDAC6, and promoted its poly-ubiquitination and subsequent degradation in cells. Notably, cancer-derived SPOP mutants disrupted their binding with HDAC6 and thereby failed to promote HDAC6 degradation. More importantly, increased cellular proliferation and migration in SPOP-depleted HCT116 colon cancer cells could be partly reversed by additional depletion of HDAC6, suggesting that HDAC6 is a key downstream effector for SPOP tumor suppressor function. Together, our data identify the tumor suppressor SPOP as an upstream negative regulator for HDAC6 stability, and SPOP loss-of-function mutations might lead to elevated levels of the HDAC6 oncoprotein to facilitate tumorigenesis and metastasis in various human cancers

Mapping the Distribution of Water Resource Security in the Beijing-Tianjin-Hebei Region at the County Level under a Changing Context

The Beijing-Tianjin-Hebei (Jingjinji) region is the most densely populated region in China and suffers from severe water resource shortage, with considerable water-related issues emerging under a changing context such as construction of water diversion projects (WDP), regional synergistic development, and climate change. To this end, this paper develops a framework to examine the water resource security for 200 counties in the Jingjinji region under these changes. Thus, county-level water resource security is assessed in terms of the long-term annual mean and selected typical years (i.e., dry, normal, and wet years), with and without the WDP, and under the current and projected future (i.e., regional synergistic development and climate change). The outcomes of such scenarios are assessed based on two water-crowding indicators, two use-to-availability indicators, and one composite indicator. Results indicate first that the water resources are distributed unevenly, relatively more abundant in the northeastern counties and extremely limited in the other counties. The water resources are very limited at the regional level, with the water availability per capita and per unit gross domestic product (GDP) being only 279/290 m3 and 46/18 m3 in the current and projected future scenarios, respectively, even when considering the WDP. Second, the population carrying capacity is currently the dominant influence, while economic development will be the controlling factor in the future for most middle and southern counties. This suggests that significant improvement in water-saving technologies, vigorous replacement of industries from high to low water consumption, as well as water from other supplies for large-scale applications are greatly needed. Third, the research identifies those counties most at risk to water scarcity and shows that most of them can be greatly relieved after supplementation by the planned WDP. Finally, more attention should be paid to the southern counties because their water resources are not only limited but also much more sensitive and vulnerable to climate change. This work should benefit water resource management and allocation decisions in the Jingjinji region, and the proposed assessment framework can be applied to other similar problems.This study is supported by the National Key Research and Development Program of China (2016YFC0401401) and the National Natural Science Foundation of China (51609256, 51609122, 51522907, 51739011, and 51569026). Partial support is also from the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2017QNRC001

Critical current density: Measurements vs. reality

Different experimental techniques are employed to evaluate the critical current density (Jc), namely transport current measurements and two different magnetisation measurements forming quasi-equilibrium and dynamic critical states. Our technique-dependent results for superconducting YBa 2Cu3O7 (YBCO) film and MgB2 bulk samples show an extremely high sensitivity of Jc and associated interpretations, such as irreversibility fields and Kramer plots, which lose meaning without a universal approach. We propose such approach for YBCO films based on their unique pinning features. This approach allows us to accurately recalculate the magnetic-field-dependent Jc obtained by any technique into the Jc behaviour, which would have been measured by any other method without performing the corresponding experiments. We also discovered low-frequency-dependent phenomena, governing flux dynamics, but contradicting the considered ones in the literature. The understanding of these phenomena, relevant to applications with moving superconductors, can clarify their dramatic impact on the electric-field criterion through flux diffusivity and corresponding measurements. © Copyright EPLA, 2013

Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4

The bromodomain and extra-terminal (BET) family of proteins, comprised of four members including BRD2, BRD3, BRD4 and the testis-specific isoform BRDT, largely function as transcriptional co-activators 1–3 and play critical roles in various cellular processes, including cell cycle, apoptosis, migration and invasion 4,5. As such, BET proteins enhance the oncogenic functions of major cancer drivers by either elevating their expression such as c-Myc in leukemia 6,7 or by promoting transcriptional activities of oncogenic factors such as AR and ERG in the prostate cancer setting 8. Pathologically, BET proteins are frequently overexpressed and clinically linked to various types of human cancers 5,9,10, therefore pursued as attractive therapeutic targets for selective inhibition in patients. To this end, a number of bromodomain inhibitors, including JQ1 and I-BET, have been developed 11,12 and shown promising outcomes in early clinical trials. Despite resistance to BET inhibitor has been documented in pre-clinical models 13–15 the molecular mechanisms underlying acquired resistance are largely unknown. Here, we report that Cullin 3SPOP earmarks BET proteins including BRD2, BRD3 and BRD4 for ubiquitination-mediated degradation. Pathologically, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of BET proteins, leading to their elevated abundance in SPOP-deficient prostate cancer. As a result, prostate cancer cells and prostate cancer patient-derived organoids harboring SPOP mutations are more resistant to BET inhibitor-induced cell growth arrest and apoptosis. Therefore, our results elucidate the tumor suppressor role of SPOP in prostate cancer by negatively controlling BET protein stability, and also provide a molecular mechanism for BET inhibitor resistance in prostate cancer patients bearing SPOP mutations

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Potential threat of SARS-CoV-2 in coastal waters

A novel coronavirus (SARS-CoV-2) has caused more than 150 million confirmed infections worldwide, while it is not clear whether it affects the coastal waters. This paper proposed a biophysical model based on 16 scenarios with different virus half-life parameters to assess potential viral contamination from 25 municipal sewage outfalls into the Bohai Sea. Viral concentration maps showing spatial and temporal changes are provided based on a biophysical model under multiple scenarios. Results demonstrate that adjacent sea areas can become exposed to SARS-CoV-2 via water-borne transport from outfalls, with a higher risk in winter, because SARS-CoV-2 can be highly stable at low temperature. As coastal waters are the ultimate sink for wastewater and the epidemic will last for long time, this work is of great importance to raise awareness, identify vulnerable areas for marine mammals, and avoid the risk of exposure of tourists at bathing beach

Epigenetic reprogramming during the maternal‐to‐zygotic transition

Abstract After fertilization, sperm and oocyte fused and gave rise to a zygote which is the beginning of a new life. Then the embryonic development is monitored and regulated precisely from the transition of oocyte to the embryo at the early stage of embryogenesis, and this process is termed maternal‐to‐zygotic transition (MZT). MZT involves two major events that are maternal components degradation and zygotic genome activation. The epigenetic reprogramming plays crucial roles in regulating the process of MZT and supervising the normal development of early development of embryos. In recent years, benefited from the rapid development of low‐input epigenome profiling technologies, new epigenetic modifications are found to be reprogrammed dramatically and may play different roles during MZT whose dysregulation will cause an abnormal development of embryos even abortion at various stages. In this review, we summarized and discussed the important novel findings on epigenetic reprogramming and the underlying molecular mechanisms regulating MZT in mammalian embryos. Our work provided comprehensive and detailed references for the in deep understanding of epigenetic regulatory network in this key biological process and also shed light on the critical roles for epigenetic reprogramming on embryonic failure during artificial reproductive technology and nature fertilization