Learning multi-stage tasks with one demonstration via self-replay

In this work, we introduce a novel method to learn everyday-like multistage tasks from a single human demonstration, without requiring any prior object knowledge. Inspired by the recent Coarse-to-Fine Imitation Learning method, we model imitation learning as a learned object reaching phase followed by an openloop replay of the demonstrator’s actions. We build upon this for multi-stage tasks where, following the human demonstration, the robot can autonomously collect image data for the entire multi-stage task, by reaching the next object in the sequence and then replaying the demonstration, and then repeating in a loop for all stages of the task. We evaluate with real-world experiments on a set of everydaylike multi-stage tasks, which we show that our method can solve from a single demonstration. Videos and supplementary material can be found at this webpage

The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation

Non‐coding RNAs (ncRNAs) constitute the majority of the transcriptome, as the result of pervasive transcription of the mammalian genome. Different RNA species, such as lncRNAs, miRNAs, circRNA, mRNAs, engage in regulatory networks based on their reciprocal interactions, often in a competitive manner, in a way denominated “competing endogenous RNA (ceRNA) networks” (“ceRNET”): miRNAs and other ncRNAs modulate each other, since miRNAs can regulate the expression of lncRNAs, which in turn regulate miRNAs, titrating their availability and thus competing with the binding to other RNA targets. The unbalancing of any network component can derail the entire regulatory circuit acting as a driving force for human diseases, thus assigning “new” functions to “old” molecules. This is the case of XIST, the lncRNA characterized in the early 1990s and well known as the essential molecule for X chromosome inactivation in mammalian females, thus preventing an imbalance of X‐linked gene expression between females and males. Currently, literature concerning XIST biology is becoming dominated by miRNA associations and they are also gaining prominence for other lncRNAs produced by the X‐inactivation center. This review discusses the available literature to explore possible novel functions related to ceRNA activity of lncRNAs produced by the X‐inactivation center, beyond their role in dosage compensation, with prospective implications for emerging gender‐biased functions and pathological mechanisms

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing a form of acute pulmonary respiratory disorder named COVID-19, declared a pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in the interplay between viruses and host cells. Although the impact of host miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started by a bioinformatics prediction of cellular miRNAs potentially targeting viral RNAs; then, a number of criteria also based on experimental evidence and virus biology were applied, giving rise to eight promising binding miRNAs. Their interaction with viral sequences was experimentally validated by transfecting luciferase-based reporter plasmids carrying viral target sequences or their inverted sequences into the lung A549 cell line. Transfection of the reporter plasmids resulted in a reduction of luciferase activity for five out of the eight potential binding sites, suggesting responsiveness to endogenously expressed miRNAs. Co-transfection of the reporter plasmids along with miRNA mimics led to a further and strong reduction of luciferase activity, validating the interaction between miR-219a-2-3p, miR-30c-5p, miR-378d, miR-29a-3p, miR-15b-5p, and viral sequences. miR-15b was also able to repress plasmid-driven Spike expression. Intriguingly, the viral target sequences are fully conserved in more recent variants such as United Kingdom variant B.1.1.7 and South Africa 501Y.V2. Overall, this study provides a first experimental evidence of the interaction between specific cellular miRNAs and SARS-CoV-2 sequences, thus contributing to understanding the molecular mechanisms underlying virus infection and pathogenesis to envisage innovative therapeutic interventions and diagnostic tools

A novel ceRNA regulatory network involving the long non-coding antisense RNA SPACA6P-AS, miR-125a and its mRNA targets in hepatocarcinoma cells

MicroRNAs (miRNA), and more recently long non-coding RNAs (lncRNA), are emerging as a driving force for hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death. In this work, we investigated a possible RNA regulatory network involving two oncosuppressive miRNAs, miR-125a and let-7e, and a long non-coding antisense RNA, SPACA6P-AS (SP-AS), all transcribed from the same locus, with SP-AS in the opposite direction and thus carrying complementary sequences to the miRNAs. In vitro experiments validated the binding of the miRNAs to SP-AS. Then, the boosting of either the miRNAs or SP-AS levels demonstrated their reciprocal inhibition. In addition, overexpression of SP-AS resulted in a reduced silencing activity of miR-125a and let-7e toward their key oncogenic targets, i.e., Lin28b, MMP11, SIRT7, Zbtb7a, Cyclin D1, CDC25B, HMGA2, that resulted significantly upregulated. Finally, the analysis of 374 HCC samples in comparison to 50 normal liver tissues showed an upregulation of SP-AS and a reverse expression of miR-125a, not observed for let-7e; consistently, miR-125a oncogenic targets were upregulated. Overall, the data depict a novel competing endogenous RNA (ceRNA) network, ceRNET, whereby miR-125a can regulate the expression of SP-AS, which in turn regulates the miRNA by competing with the binding to the mRNA targets. We speculate that the unbalancing of any network component may contribute to hepatocarcinogenesis

microRNA-377-3p downregulates the oncosuppressor T-cadherin in colorectal adenocarcinoma cells

Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for the adiponectin-receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of the T-cadherin receptor. In addition, the loss of T-cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this study explores their possible contribution to the downregulation of T-cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target miRNA sites within the 3ʹ UTR of T-cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the T-cadherin sequence, and thus downregulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of T-cadherin in CRC, the regulatory circuit highlighted in this study may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets

Effective action for Superconductors and BCS-Bose crossover

A standard perturbative expansion around the mean-field solution is used to derive the low-energy effective action for superconductors at T=0. Taking into account the density fluctuations at the outset we get the effective action where the density $\rho$ is the conjugated momentum to the phase $\theta$ of the order parameter. In the hydrodynamic regime, the dynamics of the superconductor is described by a time dependent non-linear Schr\"odinger equation (TDNLS) for the field $\Psi(x)=\sqrt{\rho/2} e^{i\theta}$. The evolution of the density fluctuations in the crossover from weak-coupling (BCS) to strong-coupling (Bose condensation of localized pairs) superconductivity is discussed for the attractive Hubbard model. In the bosonic limit, the TDNLS equation reduces to the the Gross-Pitaevskii equation for the order parameter, as in the standard description of superfluidity. The conditions under which a phase-only action can be derived in the presence of a long-range interaction to describe the physics of the superconductivity of ``bad metals'' are discussed.Comment: 13 pages, accepted for publication on Phys. Rev.

Publisher's Note: “Attosecond state-resolved carrier motion in quantum materials probed by soft x-ray XANES” [Appl. Phys Rev. 8, 011408 (2021)]

Recent developments in attosecond technology led to table-top x-ray spectroscopy in the soft x-ray range, thus uniting the element- and state-specificity of core-level x-ray absorption spectroscopy with the time resolution to follow electronic dynamics in real-time. We describe recent work in attosecond technology and investigations into materials such as Si, SiO2, GaN, Al2O3, Ti, and TiO2, enabled by the convergence of these two capabilities. We showcase the state-of-the-art on isolated attosecond soft x-ray pulses for x-ray absorption near-edge spectroscopy to observe the 3d-state dynamics of the semi-metal TiS2 with attosecond resolution at the Ti L-edge (460 eV). We describe how the element- and state-specificity at the transition metal L-edge of the quantum material allows us to unambiguously identify how and where the optical field influences charge carriers. This precision elucidates that the Ti:3d conduction band states are efficiently photo-doped to a density of 1.9 × 1021 cm−3. The light-field induces coherent motion of intra-band carriers across 38% of the first Brillouin zone. Lastly, we describe the prospects with such unambiguous real-time observation of carrier dynamics in specific bonding or anti-bonding states and speculate that such capability will bring unprecedented opportunities toward an engineered approach for designer materials with pre-defined properties and efficiency. Examples are composites of semiconductors and insulators like Si, Ge, SiO2, GaN, BN, and quantum materials like graphene, transition metal dichalcogens, or high-Tc superconductors like NbN or LaBaCuO. Exiting are prospects to scrutinize canonical questions in multi-body physics, such as whether the electrons or lattice trigger phase transitions

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding