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This book provides detailed fundamental theoretical reviews and preparations necessary for developing advanced dynamics modeling and control strategies for various types of robotic systems. This research book specifically addresses and discusses the uniqueness issue of representing orientation or rotation, and further proposes an innovative isometric embedding approach. The novel approach can not only reduce the dynamic formulation for robotic systems into a compact form, but it also offers a new way to realize the orientational trajectory-tracking control procedures. In addition, the book gives a comprehensive introduction to fundamentals of mathematics and physics that are required for modeling robot dynamics and developing effective control algorithms. Many computer simulations and realistic 3D animations to verify the new theories and algorithms are included in the book as well. It also presents and discusses the principle of duality involved in robot kinematics, statics, and dynamics. The duality principle can guide the dynamics modeling and analysis into a right direction for a variety of robotic systems in different types from open serial-chain to closed parallel-chain mechanisms. It intends to serve as a diversified research reference to a wide range of audience, including undergraduate juniors and seniors, graduate students, researchers, and engineers interested in the areas of robotics, control and applications.

The enhancement of the functional properties of materials at reduced dimensions is crucial for continuous advancements in nanoelectronic applications. Here, we report that the scale reduction leads to the emergence of an important functional property, ferroelectricity, challenging the long-standing notion that ferroelectricity is inevitably suppressed at the scale of a few nanometers. A combination of theoretical calculations, electrical measurements, and structural analyses provides evidence of room-temperature ferroelectricity in strain-free epitaxial nanometer-thick films of otherwise nonferroelectric strontium titanate (SrTiO3). We show that electrically induced alignment of naturally existing polar nanoregions is responsible for the appearance of a stable net ferroelectric polarization in these films. This finding can be useful for the development of low-dimensional material systems with enhanced functional properties relevant to emerging nanoelectronic devices.

Determining why hydraulic fracturing (also known as fracking) triggered earthquakes in the Duvernay Formation in Canada is important for future hazard mitigation. Schultz et al. found that injection volume was the key operational parameter correlated with induced earthquakes in the Duvernay. However, geological factors also played a considerable role in determining whether a large injection volume would trigger earthquakes. These findings provide a framework that may lead to better forecasting of induced seismicity. Science , this issue p. 304 Induced seismicity from hydrofracturing in Canada is related to the well fluid injection volumes. A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (10 4 to 10 5 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index–modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive cancer with a poor prognosis. Although microRNA (miRNA) transcripts have a crucial role in carcinogenesis and development, little information is known regarding the aberrant DNA methylation of miRNAs in PDAC. Using methylated DNA immunoprecipitation-chip analysis, we found that miR-615-5p was hypermethylated in its putative promoter region, which silenced its expression in PDAC cell lines. In addition, the overexpression of miR-615-5p in pancreatic cancer cells suppressed cell proliferation, migration and invasion. Insulin-like growth factor 2 (IGF2) is an imprinted gene, and its abnormal expression contributes to tumor growth. Here, we identified IGF2 as a target of miR-615-5p using a luciferase reporter assay. IGF2 upregulation in PDAC tissues was not correlated with a loss of imprinting but was inversely correlated with miR-615-5p downregulation. In addition, miR-615-5p suppressed pancreatic cancer cell proliferation, migration and invasion by directly targeting IGF2, and this effect could be reversed by co-transfection with IGF2. Furthermore, the stable overexpression of miR-615-5p inhibited tumor growth in vivo and was correlated with IGF2 expression. Using RNA sequencing, we further identified miR-615-5p as potentially targeting other genes, such as the proto-oncogene JUNB , and interfering with the insulin signaling pathway. Taken together, our results demonstrate that miR-615-5p was abnormally downregulated in PDAC cells due to promoter hypermethylation, which limited its inhibition of IGF2 and other target genes, thereby contributing to tumor growth, invasion and migration. These data demonstrate a novel and important role of miR-615-5p as a tumor suppressor in PDAC.

Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces. Precisely controlled growth of oxide interfaces at the atomic layer level is critical for device applications but quite challenging. Here Sun et al. show real time monitoring and control of the surface composition of epitaxial strontium titanate perovskite films by analysing the Kikuchi lines.

Polyionic liquid based gels have stimulated significant interest due to their wide applications in flexible electronics, such as wearable electronics, roll-up displays, smart mobile devices and implantable biosensors. Novel supported liquid gel electrolyte using polymerisable ionic liquid and an acrylate monomer, has been developed in this work by entrapping ionic liquid during polymerisation instead of post polymerisation impregnation. The chemically crosslinked polyionic liquid gel electrolyte (PIL) is prepared using 2-hydroxyethylmethacrylate (HEMA) monomer and a polymerisable ionic liquid, 1,4-di(vinylimidazolium)butane bisbromide (DVIMBr) in an ionic liquid (IL- 1-butyl-3 methylimidazolium hexafluorophosphate) as the polymerisation solvent, which resulted in in-situ entrapment of the IL in the gel during polymerisation and crosslinking of the polymer. The supported liquid gel electrolyte (SLG) material was characterised with thermal analysis, infrared spectroscopy, and dynamic mechanical analysis, and was found to be stable with good mechanical properties. The electrochemical analysis showed that these chemically cross-linked PIL gel electrolyte-supported ILs are suitable for solid-state, flexible supercapacitor applications.

The key nuclear export protein CRM1/XPO1 may represent a promising novel therapeutic target in human multiple myeloma (MM). Here we showed that chromosome region maintenance 1 (CRM1) is highly expressed in patients with MM, plasma cell leukemia cells and increased in patient cells resistant to bortezomib treatment. CRM1 expression also correlates with increased lytic bone and shorter survival. Importantly, CRM1 knockdown inhibits MM cell viability. Novel, oral, irreversible selective inhibitors of nuclear export (SINEs) targeting CRM1 (KPT-185, KPT-330) induce cytotoxicity against MM cells (ED 50 <200 n M ), alone and cocultured with bone marrow stromal cells (BMSCs) or osteoclasts (OC). SINEs trigger nuclear accumulation of multiple CRM1 cargo tumor suppressor proteins followed by growth arrest and apoptosis in MM cells. They further block c-myc, Mcl-1, and nuclear factor κB (NF-κB) activity. SINEs induce proteasome-dependent CRM1 protein degradation; concurrently, they upregulate CRM1, p53-targeted, apoptosis-related, anti-inflammatory and stress-related gene transcripts in MM cells. In SCID mice with diffuse human MM bone lesions, SINEs show strong anti-MM activity, inhibit MM-induced bone lysis and prolong survival. Moreover, SINEs directly impair osteoclastogenesis and bone resorption via blockade of RANKL-induced NF-κB and NFATc1, with minimal impact on osteoblasts and BMSCs. These results support clinical development of SINE CRM1 antagonists to improve patient outcome in MM.

IntroductionSchizophrenia is a common chronic disease in psychiatric long-term care institutions. Taipei City Hospital Songde Branch Psychiatric Nursing Home (TCHSBPNH) is the first public psychiatric nursing home in Taipei City. There’s not only a complete interdisciplinary care system, but also detail initial evaluation at admission of residents, including basic demographic information, cognitive assessments, activities of daily living, and so on. It is known that patients with schizophrenia are generally accompanied by cognitive impairments, which further affects their activities of daily living (ADL) performance, but we still don’t know the correlation between of them.ObjectivesThis study aimed to investigate the relationships between cognitive function and ADL function of psychiatric nursing home residents with schizophrenia. The results would promote clinical intervention in ADL training for institutional patients.Methods39 participants with chronic schizophrenia (mean age =63.95±6.59 years) were recruited for the study from 2020 to 2021 in TCHSBPNH. We collected every resident’s assessment data, including Mini-Mental State Examination (MMSE), Barthel Index, Lawton - Brody Instrumental Activities Of Daily Living Scale (Lawton IADL scale) and Composite Physical Function (CPF) Scale. The Pearson correlation coefficient was used to examine the correlation between cognitive function and ADL.ResultsModerate positive correlations were showed between cognitive function and ADL (p<.05). The statistic results as follow, MMSE and Barthel Index (γ=.627, p<.001), Lawton IADL scale (γ=.431, p=.006), and CPF (γ=.341, p=.034) respectively exhibited significant correlations.Image:Image 2:Image 3:ConclusionsThere is a positive correlation between cognitive function and ADL in psychiatric nursing home residents with schizophrenia. The better cognitive function performance becomes, the better independent ADL functions will be. Thus, the psychiatric nursing home residents’ independent ADL training will also vary from person to person.Disclosure of InterestNone Declared

Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16–44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5–32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6–30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9–61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis. AbbVie and Boehringer Ingelheim.

The theory of superconductivity developed by Bardeen, Cooper and Schrieffer (BCS) explains the stabilization of electron pairs into a spin-singlet, even frequency, state by the formation of an energy gap within which the density of states is zero. At a superconductor interface with an inhomogeneous ferromagnet, a gapless odd frequency superconducting state is predicted, in which the Cooper pairs are in a spin-triplet state. Although indirect evidence for such a state has been obtained, the gap structure and pairing symmetry have not so far been determined. Here we report scanning tunnelling spectroscopy of Nb superconducting films proximity coupled to epitaxial Ho. These measurements reveal pronounced changes to the Nb subgap superconducting density of states on driving the Ho through a metamagnetic transition from a helical antiferromagnetic to a homogeneous ferromagnetic state for which a BCS-like gap is recovered. The results prove odd frequency spin-triplet superconductivity at superconductor/inhomogeneous magnet interfaces. In the proximity of noncollinear magnetization, the Cooper-paired electrons of a superconductor may exist in a spin-triplet state. Here, the authors use scanning tunnel methods to directly observe this effect in Niobium as an adjacent film of Holmium is driven between helical and ferromagnetic order.