Here we demonstrate a 3D-printable microvalve that is transparent, built with a biocompatible resin, and has a simple architecture that can be easily scaled up into large arrays. The open-at-rest ...valve design is derived from Quake's PDMS valve design. We used a stereolithographic (SL) 3D printer to print a thin (25 or 10 μm-thick) membrane (1200 or 500 μm-diam.) that is pneumatically pressed (∼3-6 psi) over a bowl-shaped seat to close the valve. We used poly(ethylene diacrylate) (MW = 258) (PEG-DA-258) as the resin because it yields transparent cytocompatible prints. Although the flexibility of PEG-DA-258 is inferior to that of other microvalve fabrication materials such as PDMS, the valve benefits from the bowl design and the membrane's high restoring force since it does not need a negative pressure to re-open. We also 3D-printed a micropump by combining three Quake-style valves in series. The micropump only requires positive pressure for its operation and profits from the fast return to the valves' open states. Moreover, we printed a 64-valve array constructed with 500 μm-diam. valves to demonstrate the reliability and scalability of the valves. Overall, we demonstrate the 3D-printing of compact microvalves and micropumps using a process that precludes the need for specialized, time-consuming labor.
Protoplanets can produce structures in protoplanetary disks via gravitational disk-planet interactions. Once detected, such structures serve as signposts of planet formation. Here we investigate the ...kinematic signatures in disks produced by multi-Jupiter mass (MJ) planets using 3D hydrodynamics and radiative transfer simulations. Such a planet opens a deep gap, and drives transonic vertical motions inside. Such motions include both a bulk motion of the entire half-disk column, and turbulence on scales comparable to and smaller than the scale height. They significantly broaden molecular lines from the gap, producing double-peaked line profiles at certain locations, and a kinematic velocity dispersion comparable to thermal after azimuthal averaging. The same planet does not drive fast vertical motions outside the gap, except at the inner spiral arms and the disk surface. Searching for line broadening induced by multi-MJ planets inside gaps requires an angular resolution comparable to the gap width, an assessment of the gap gas temperature to within a factor of 2, and a high sensitivity needed to detect line emission from the gap.
HH 212 is one of the well-studied protostellar systems, showing the first vertically resolved disk with a warm atmosphere around the central protostar. Here we report a detection of nine organic ...molecules (including newly detected ketene, formic acid, deuterated acetonitrile, methyl formate, and ethanol) in the disk atmosphere, confirming that the disk atmosphere is, for HH 212, the chemically rich component, identified before at a lower resolution as a "hot corino." More importantly, we report the first systematic survey and abundance measurement of organic molecules in the disk atmosphere within ∼40 au of the central protostar. The relative abundances of these molecules are similar to those in the hot corinos around other protostars and in Comet Lovejoy. These molecules can be either (i) originally formed on icy grains and then desorbed into gas phase or (ii) quickly formed in the gas phase using simpler species ejected from the dust mantles. The abundances and spatial distributions of the molecules provide strong constraints on models of their formation and transport in star formation. These molecules are expected to form even more complex organic molecules needed for life and deeper observations are needed to find them.
Globally, the health workforce has long suffered from labour shortages. This has been exacerbated by the workload increase caused by the COVID-19 pandemic. Major collapses in healthcare systems ...across the world during the peak of the pandemic led to calls for strategies to alleviate the increasing job attrition problem within the healthcare sector. This turnover may worsen given the overwhelming pressures experienced by the health workforce during the pandemic, and proactive measures should be taken to retain healthcare workers. This review aims to examine the factors affecting turnover intention among healthcare workers during the COVID-19 pandemic. A mixed studies systematic review was conducted. The PubMed, Embase, Scopus, CINAHL, Web of Science and PsycINFO databases were searched from January 2020 to March 2022. The Joanna Briggs Institute's Critical Appraisal Tools and the Mixed Methods Appraisal Tool version 2018 were applied by two independent researchers to critically appraise the methodological quality. Findings were synthesised using a convergent integrated approach and categorised thematically. Forty-three studies, including 39 quantitative, two qualitative and two mixed methods studies were included in this review. Eighteen were conducted in the Middle East, ten in the Americas, nine in the Asia-Pacific region and six in Europe. Nurses (n = 35) were included in the majority of the studies, while physicians (n = 13), allied health workers (n = 11) and healthcare administrative or management staff (n = 7) were included in a smaller proportion. Five themes emerged from the data synthesis: (1) fear of COVID-19 exposure, (2) psychological responses to stress, (3) socio-demographic characteristics, (4) adverse working conditions, and (5) organisational support. A wide range of factors influence healthcare workers' turnover intention in times of pandemic. Future research should be more focused on specific factors, such as working conditions or burnout, and specific vulnerable groups, including migrant healthcare workers and healthcare profession minorities, to aid policymakers in adopting strategies to support and incentivise them to retain them in their healthcare jobs.
Spatially resolved structures in protoplanetary disks hint at unseen planets. Previous imaging observations of the transitional disk around MWC 758 revealed an inner cavity, a ring-like outer disk, ...emission clumps, and spiral arms, all possibly generated by companions. We present ALMA dust continuum observations of MWC 758 at 0.87 mm wavelength with 43 × 39 mas angular resolution (6.9 × 6.2 au) and 20 Jy beam−1 rms. The central submillimeter emission cavity is revealed to be eccentric; once deprojected, its outer edge can be well fitted by an ellipse with an eccentricity of 0.1 and one focus on the star. The broad ring-like outer disk is resolved into three narrow rings with two gaps in between. The outer two rings tentatively show the same eccentricity and orientation as the innermost ring bounding the inner cavity. The two previously known dust emission clumps are resolved in both the radial and azimuthal directions, with radial widths equal to ∼4× the local scale height. Only one of the two spiral arms previously imaged in near-infrared (NIR) scattered light is revealed in ALMA dust emission, at a slightly larger stellocentric distance owing to projection effects. We also submit evidence of disk truncation at ∼100 au based on comparing NIR imaging observations with models. The spirals, the north clump, and the truncated disk edge are all broadly consistent with the presence of one companion exterior to the spirals at roughly 100 au.
Adaptive networks consist of a collection of nodes with adaptation and learning abilities. The nodes interact with each other on a local level and diffuse information across the network to solve ...estimation and inference tasks in a distributed manner. In this work, we compare the mean-square performance of two main strategies for distributed estimation over networks: consensus strategies and diffusion strategies. The analysis in the paper confirms that under constant step-sizes, diffusion strategies allow information to diffuse more thoroughly through the network and this property has a favorable effect on the evolution of the network: diffusion networks are shown to converge faster and reach lower mean-square deviation than consensus networks, and their mean-square stability is insensitive to the choice of the combination weights. In contrast, and surprisingly, it is shown that consensus networks can become unstable even if all the individual nodes are stable and able to solve the estimation task on their own. When this occurs, cooperation over the network leads to a catastrophic failure of the estimation task. This phenomenon does not occur for diffusion networks: we show that stability of the individual nodes always ensures stability of the diffusion network irrespective of the combination topology. Simulation results support the theoretical findings.
Orbit constraint problems can be encountered in mechanical equipment and amusement equipment. Mechanics exercises generally consider the ideal physical model, and the practical problems also consider ...the influence of friction, which makes the problem more complex and and practical. The problem of the force and oscillation of objects on orbit needs to be deeply discussed. In order to simulate the orbital motion of objects more realistically and help students expand their theoretical mechanics beyond class, we study the orbit constraint of a small bead on a rotating large circular hoop in a horizontal plane about an axis passing through a point on the circumference. The coupling equations followed by the bead on the hoop are derived using Newton's second law in a planar polar coordinate system and solved by numerical methods. We found that under the action of friction, when the initial angular velocity of the bead is greater than the critical angular velocity, the bead will rotate on the ring, and the number of rotations is related to the initial angular velocity and influenced by the friction coefficient. At different initial angular velocities, the number of oscillations of the bead on the hoop is basically the same and ultimately stops near the fixed point.
ObjectiveIn the tumour microenvironment, critical drivers of immune escape include the oncogenic activity of the tumour cell-intrinsic osteopontin (OPN), the expression of programmed death ligand 1 ...(PD-L1) and the expansion of tumour-associated macrophages (TAMs). We investigated the feasibility of targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models.DesignWe analysed the number of tumour-infiltrating immune cells and the inflammatory immune profiles in chemically induced liver tumour isolated from wild-type and OPNknockout (KO) mice. In vitro cell cocultures were further conducted to investigate the crosstalk between TAMs and HCC cells mediated by OPN, colony stimulating factor-1 (CSF1) and CSF1 receptor (CSF1R). The in vivo efficacy of anti-PD-L1 and CSF1/CSF1R inhibition was evaluated in OPN overexpressing subcutaneous or orthotopic mouse model of HCC.ResultsThe numbers of TAMs, as well as the expression levels of M2 macrophage markers and PD-L1 were significantly decreased, but the levels of cytokines produced by T-helper 1 (Th1) cells were upregulated in tumour tissues from OPN KO mice compared with that from the controls. In addition, we observed a positive association between the OPN and PD-L1 expression, and OPN expression and TAM infiltration in tumour tissues from patients with HCC. We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages. Combining anti-PD-L1 and CSF1R inhibition elicited potent antitumour activity and prolonged survival of OPNhigh tumour-bearing mice. Histological, flow cytometric and ELISA revealed increased CD8+ T cell infiltration, reduced TAMs and enhanced Th1/Th2 cytokine balance in multiple mouse models of HCC.ConclusionsOPN/CSF1/CSF1R axis plays a critical role in the immunosuppressive nature of the HCC microenvironment. Blocking CSF1/CSF1R prevents TAM trafficking and thereby enhances the efficacy of immune checkpoint inhibitors for the treatment of HCC.
Many protein‐coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical ...markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein we examined the expression profiles of long noncoding RNAs (lncRNAs) found in fetal and adult liver in mice. Many fetal hepatic lncRNAs were identified; one of these, lncRNA‐mPvt1, is an oncofetal RNA that was found to promote cell proliferation, cell cycling, and the expression of stem cell‐like properties of murine cells. Interestingly, we found that human lncRNA‐hPVT1 was up‐regulated in HCC tissues and that patients with higher lncRNA‐hPVT1 expression had a poor clinical prognosis. The protumorigenic effects of lncRNA‐hPVT1 on cell proliferation, cell cycling, and stem cell‐like properties of HCC cells were confirmed both in vitro and in vivo by gain‐of‐function and loss‐of‐function experiments. Moreover, mRNA expression profile data showed that lncRNA‐hPVT1 up‐regulated a series of cell cycle genes in SMMC‐7721 cells. By RNA pulldown and mass spectrum experiments, we identified NOP2 as an RNA‐binding protein that binds to lncRNA‐hPVT1. We confirmed that lncRNA‐hPVT1 up‐regulated NOP2 by enhancing the stability of NOP2 proteins and that lncRNA‐hPVT1 function depends on the presence of NOP2. Conclusion: Our study demonstrates that the expression of many lncRNAs is up‐regulated in early liver development and that the fetal liver can be used to search for new diagnostic markers for HCC. LncRNA‐hPVT1 promotes cell proliferation, cell cycling, and the acquisition of stem cell‐like properties in HCC cells by stabilizing NOP2 protein. Regulation of the lncRNA‐hPVT1/NOP2 pathway may have beneficial effects on the treatment of HCC. (Hepatology 2014;60:1278–1290)
Tumor cells with stemness (stem‐cell) features contribute to initiation and progression of hepatocellular carcinoma (HCC), but involvement of long noncoding RNAs (lncRNAs) remains largely unclear. ...Genome‐wide analyses were applied to identify tumor‐associated lncRNA‐DANCR. DANCR expression level and prognostic values of DANCR were assayed in two HCC cohorts (China and Korea, n = 135 and 223). Artificial modulation of DANCR (down‐ and overexpression) was done to explore the role of DANCR in tumorigenesis and colonization, and tumor‐bearing mice were used to determine therapeutic effects. We found that lncRNA‐DANCR is overexpressed in stem‐like HCC cells, and this can serve as a prognostic biomarker for HCC patients. Experiments showed that DANCR markedly increased stemness features of HCC cells to promote tumorigenesis and intra‐/extrahepatic tumor colonization. Conversely, DANCR knockdown attenuated the stem‐cell properties and in vivo interference with DANCR action led to decreased tumor cell vitality, tumor shrinkage, and improved mouse survival. Additionally, we found that the role of DANCR relied largely on an association with, and regulation of, CTNNB1. Association of DANCR with CTNNB1 blocked the repressing effect of microRNA (miR)−214, miR‐320a, and miR‐199a on CTNNB1. This observation was confirmed in vivo, suggesting a novel mechanism of tumorigenesis involving lncRNAs, messenger RNAs, and microRNAs. Conclusions: These studies reveal a significance and mechanism of DANCR action in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HCC. (Hepatology 2016;63:499–511)
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