Superhydrophobic and superoleophobic surfaces have so far been made by roughening a hydrophobic material. However, no surfaces were able to repel extremely-low-energy liquids such as fluorinated ...solvents, which completely wet even the most hydrophobic material. We show how roughness alone, if made of a specific doubly reentrant structure that enables very low liquid-solid contact fraction, can render the surface of any material superrepellent. Starting from a completely wettable material (silica), we micro- and nanostructure its surface to make it superomniphobic and bounce off all available liquids, including perfluorohexane. The same superomniphobicity is further confirmed with identical surfaces of a metal and a polymer. Free of any hydrophobic coating, the superomniphobic silica surface also withstands temperatures over 1000°C and resists biofouling.
Magnetic torques generated through spin-orbit coupling
promise energy-efficient spintronic devices. For applications, it is important that these torques switch films with perpendicular magnetizations ...without an external magnetic field
. One suggested approach
to enable such switching uses magnetic trilayers in which the torque on the top magnetic layer can be manipulated by changing the magnetization of the bottom layer. Spin currents generated in the bottom magnetic layer or its interfaces transit the spacer layer and exert a torque on the top magnetization. Here we demonstrate field-free switching in such structures and show that its dependence on the bottom-layer magnetization is not consistent with the anticipated bulk effects
. We describe a mechanism for spin-current generation
at the interface between the bottom layer and the spacer layer, which gives torques that are consistent with the measured magnetization dependence. This other-layer-generated spin-orbit torque is relevant to energy-efficient control of spintronic devices.
The ability to manipulate droplets on a substrate using electric signals
-known as digital microfluidics-is used in optical
, biomedical
, thermal
and electronic
applications and has led to ...commercially available liquid lenses
and diagnostics kits
. Such electrical actuation is mainly achieved by electrowetting, with droplets attracted towards and spreading on a conductive substrate in response to an applied voltage. To ensure strong and practical actuation, the substrate is covered with a dielectric layer and a hydrophobic topcoat for electrowetting-on-dielectric (EWOD)
; this increases the actuation voltage (to about 100 volts) and can compromise reliability owing to dielectric breakdown
, electric charging
and biofouling
. Here we demonstrate droplet manipulation that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive substrate without the need for added layers. In this electrodewetting mechanism, which is phenomenologically opposite to electrowetting, the liquid-substrate interaction is not controlled directly by electric field but instead by field-induced attachment and detachment of ionic surfactants to the substrate. We show that this actuation mechanism can perform all the basic fluidic operations of digital microfluidics using water on doped silicon wafers in air, with only ±2.5 volts of driving voltage, a few microamperes of current and about 0.015 times the critical micelle concentration of an ionic surfactant. The system can also handle common buffers and organic solvents, promising a simple and reliable microfluidic platform for a broad range of applications.
Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We ...previously showed that β1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph nodes and bone. However, how β1 integrins are activated in PCa cells is unknown. In this study, we identified a novel mechanism of β1 integrin activation. Using knockdown experiments, we first demonstrated that talin1, but not talin2, is important in β1 integrin activation. We next showed that talin1 S425 phosphorylation, but not total talin1 expression, correlates with metastatic potential of PCa cells. Expressing a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 and C4-2B4 PCa cells, decreased activation of β1 integrins, integrin-mediated adhesion, motility and increased the sensitivity of the cells to anoikis. In contrast, reexpression of the phosphorylation-mimicking mutant talin1(S425D) led to increased β1 integrin activation and generated biologic effects opposite to talin1(S425A) expression. In the highly metastatic PC3-MM2 cells, expression of a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 cells, abolished their ability to colonize in the bone following intracardiac injection, while reexpression of phosphorylation-mimicking mutant talin1(S425D) restored their ability to metastasize to bone. Immunohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in human bone metastases when compared with normal tissues, primary tumors or lymph node metastases. We further showed that p35 expression, an activator of Cdk5, and Cdk5 activity were increased in metastatic tumor cells, and that Cdk5 kinase activity is responsible for talin1 phosphorylation and subsequent β1 integrin activation. Together, our study reveals Cdk5-mediated phosphorylation of talin1 leading to β1 integrin activation is a novel mechanism that increases metastatic potential of PCa cells.
The emergence of electrowetting-on-dielectric (EWOD) in the early 2000s made the once-obscure electrowetting phenomenon practical and led to numerous activities over the last two decades. As an ...eloquent microscale liquid handling technology that gave birth to digital microfluidics, EWOD has served as the basis for many commercial products over two major application areas: optical, such as liquid lenses and reflective displays, and biomedical, such as DNA library preparation and molecular diagnostics. A number of research or start-up companies (
e.g.
, Phillips Research, Varioptic, Liquavista, and Advanced Liquid Logic) led the early commercialization efforts and eventually attracted major companies from various industry sectors (
e.g.
, Corning, Amazon, and Illumina). Although not all of the pioneering products became an instant success, the persistent growth of liquid lenses and the recent FDA approvals of biomedical analyzers proved that EWOD is a powerful tool that deserves a wider recognition and more aggressive exploration. This review presents the history around major EWOD products that hit the market to show their winding paths to commercialization and summarizes the current state of product development to peek into the future. In providing the readers with a big picture of commercializing EWOD and digital microfluidics technology, our goal is to inspire further research exploration and new entrepreneurial adventures.
Electrowetting on EWOD surface: a droplet beading or spreading (left) or translating (right) by electric signals. The EWOD technology made the once-obscure electrowetting phenomenon practical, leading to the host of commercial products today.
To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders.
Data were from the World Health Organization (WHO) World Mental Health ...(WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 63,678) and analyzed at different levels of clinical severity.
Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders).
Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.
Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the ...lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary tumor cells undergoing epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β1) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during inflammation. EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of TGF-β1 to promote CCR7/CCL21-mediated crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF-β1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated activation of the JunB transcription factor. Blockade of CCR7, or treatment with a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic mice. On the other hand, TGF-β1 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify TGF-β1-induced EMT as a mechanism, which activates tumor cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of tumor cells.
Abstract Background Dedicated intensive care unit (ICU) physician staffing is associated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data are ...available on the role of a cardiac intensivist in the cardiac intensive care unit (CICU). Objectives This study investigated the association of cardiac intensivist–directed care with clinical outcomes in adult patients admitted to the CICU. Methods This study analyzed 2,431 patients admitted to the CICU at Samsung Medical Center in Seoul, South Korea, from January 2012 to December 2015. In January 2013 the CICU was changed from a low-intensity staffing model to a high-intensity staffing model managed by a dedicated cardiac intensivist. Eligible patients were divided into either a low-intensity management group (n = 616) or a high-intensity management group (n = 1,815). One-to-many (1:N) propensity score matching with variable matching ratios was also performed. The primary outcome was death in the CICU. Results Death in the CICU occurred in 55 patients (8.9%) in the low-intensity group versus 74 patients (4.1%) in the high-intensity group (p < 0.001). Of 135 patients who underwent extracorporeal membrane oxygenation, the CICU mortality rate in the high-intensity group was also lower than that in the low-intensity group (54.5% vs. 22.5%; p = 0.001). On propensity score matching, high-intensity staffing was found associated with a lower CICU mortality rate in the matched cohort of patients (7.5% vs. 3.7%; adjusted odds ratio: 0.53; 95% confidence interval: 0.32 to 0.86; p = 0.010). In overall and propensity-matched patients, there were no substantive differences in either median length of CICU stay or readmission rates between the 2 groups. Conclusions The presence of a dedicated cardiac intensivist was associated with a reduction in CICU mortality rates in patients with cardiovascular disease who required critical care.
We calculate the spin-independent scattering cross section for direct detection that results from the electromagnetic polarizability of a composite scalar "stealth baryon" dark matter candidate, ...arising from a dark SU(4) confining gauge theory-"stealth dark matter." In the nonrelativistic limit, electromagnetic polarizability proceeds through a dimension-7 interaction leading to a very small scattering cross section for dark matter with weak-scale masses. This represents a lower bound on the scattering cross section for composite dark matter theories with electromagnetically charged constituents. We carry out lattice calculations of the polarizability for the lightest "baryon" states in SU(3) and SU(4) gauge theories using the background field method on quenched configurations. We find the polarizabilities of SU(3) and SU(4) to be comparable (within about 50%) normalized to the stealth baryon mass, which is suggestive for extensions to larger SU(N) groups. The resulting scattering cross sections with a xenon target are shown to be potentially detectable in the dark matter mass range of about 200-700 GeV, where the lower bound is from the existing LUX constraint while the upper bound is the coherent neutrino background. Significant uncertainties in the cross section remain due to the more complicated interaction of the polarizablity operator with nuclear structure; however, the steep dependence on the dark matter mass, 1/m(B)(6), suggests the observable dark matter mass range is not appreciably modified. We briefly highlight collider searches for the mesons in the theory as well as the indirect astrophysical effects that may also provide excellent probes of stealth dark matter.
In Alzheimer's disease (AD), memory impairment is the most prominent feature that afflicts patients and their families. Although reactive astrocytes have been observed around amyloid plaques since ...the disease was first described, their role in memory impairment has been poorly understood. Here, we show that reactive astrocytes aberrantly and abundantly produce the inhibitory gliotransmitter GABA by monoamine oxidase-B (Maob) and abnormally release GABA through the bestrophin 1 channel. In the dentate gyrus of mouse models of AD, the released GABA reduces spike probability of granule cells by acting on presynaptic GABA receptors. Suppressing GABA production or release from reactive astrocytes fully restores the impaired spike probability, synaptic plasticity, and learning and memory in the mice. In the postmortem brain of individuals with AD, astrocytic GABA and MAOB are significantly upregulated. We propose that selective inhibition of astrocytic GABA synthesis or release may serve as an effective therapeutic strategy for treating memory impairment in AD.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK