Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stroma cells triggers intracellular signals regulating cell-adhesion-mediated drug resistance (CAM-DR). Stromal cell protection of ...ALL cells has been shown to require active AKT. In chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT pathway is reported. A novel FDA-approved PI3Kδ inhibitor, CAL-101/idelalisib, leads to downregulation of p-AKT and increased apoptosis of CLL cells. Recently, two additional PI3K inhibitors have received FDA approval. As the PI3K/AKT pathway is also implicated in adhesion-mediated survival of ALL cells, PI3K inhibitors have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K in normal hematopoietic cells, and in ALL. We focus on summarizing targeting strategies of PI3K in ALL.
Recent investigations of rodent Tmem163 suggest that it binds to and transports zinc as a dimer, and that alanine mutagenesis of its two species-conserved aspartate (D123A/D127A) residues proposed to ...bind zinc, perturbs protein function. Direct corroboration, however, is lacking whether it is an influx or efflux transporter in cells. We hypothesized that human TMEM163 is a zinc effluxer based on its predicted protein characteristics. We used cultured human cell lines that either stably or transiently expressed TMEM163, and pre-loaded the cells with zinc to determine transport activity. We found that TMEM163-expressing cells exhibited significant reduction of intracellular zinc levels as evidenced by two zinc-specific fluorescent dyes and radionuclide zinc-65. The specificity of the fluorescence signal was confirmed upon treatment with TPEN, a high-affinity zinc chelator. Multiple sequence alignment and phylogenetic analyses showed that TMEM163 is related to distinct members of the cation diffusion facilitator (CDF) protein family. To further characterize the efflux function of TMEM163, we substituted alanine in two homologous aspartate residues (D124A/D128A) and performed site-directed mutagenesis of several conserved amino acid residues identified as non-synonymous single nucleotide polymorphism (S61R, S95C, S193P, and E286K). We found a significant reduction of zinc efflux upon cellular expression of D124A/D128A or E286K protein variant when compared with wild-type, suggesting that these particular amino acids are important for normal protein function. Taken together, our findings demonstrate that TMEM163 effluxes zinc, and it should now be designated ZNT11 as a new member of the mammalian CDF family of zinc efflux transporters.
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•Human TMEM163 is a zinc efflux transporter.•Alanine substitution of two conserved aspartic acid residues disrupts zinc transport activity.•Certain non-synonymous single nucleotide polymorphism negatively affects zinc efflux function.•TMEM163 is a distinct member of the CDF family and should now be called ZNT11 protein.
Block and Panel Caving are based on the action of gravity for ore breakage and transport, so that material reaches the drawpoint through gravity flow. The study of caved rock flow is of vital ...importance for defining the design, planning, ore recovery and consequently the profitability of a mining project. This study experimentally investigates the influence of moisture content and fine material on the draw-zone and hang-up frequency. Laboratory experiments were carried out on a physical model (scale 1:75) using a Load Haul Dump system (LHD). The results show that the dimensions, the diameter, and the height of the draw-zone depend on three variables: moisture content, particle size, and accumulated extraction mass. For the case of tests with moisture, the increase in diameter reaches a maximum value and becomes almost constant. The ratio of the flow zone width was found to be in the range of 2.7–3 times the drawpoint width, which is within the range of current block cave design guidelines. Additionally, with moisture contents over 6%, “non-flow” conditions occur due to formation of a cohesive arch. Results of our study were compared with data from the Esmeralda mine where the effects of cohesive arch formation associated with fine material and moisture content were also observed.
This paper presents design and batch manufacturing of a highly stretchable textile‐silicone capacitive sensor to be used in human articulation detection, soft robotics, and exoskeletons. The proposed ...sensor is made of conductive knit fabric as electrode and silicone elastomer as dielectric. The batch manufacturing technology enables production of large sensor mat and arbitrary shaping of sensors, which is precisely achieved via laser cutting of the sensor mat. Individual capacitive sensors exhibit high linearity, low hysteresis, and a gauge factor of 1.23. Compliant, low‐profile, and robust electrical connections are established by fusing filaments of micro coaxial cable to conductive fabric electrodes of the sensor with thermoplastic film. The capacitive sensors are integrated on a reconstructed glove for monitoring finger motions.
The design and batch manufacturing of a stretchable textile‐silicone capacitive sensor is presented. A large sensor mat is created using a scalable, rapid, and reliable batch manufacturing process and laser cutting enables the creation of arbitrary, customizable individual sensors. Compliant and robust connections are created by fusing filaments of coaxial cables to the conductive fabric electrode with thermoplastic film.
Abstract High-temperature superconductor (HTS) cables and magnets are enabling a range of high-current and high-field applications, including compact fusion devices aiming to achieve net energy. ...Defects in HTS pose manufacturing, cost, and operational challenges. A rigorous understanding and predictive capability for defect-induced behavior at relevant scale has not been established. To address this shortcoming, we have developed a cable-level defect characterization experimental platform coupled to high-fidelity computational modeling. The cable ( I c ∼ 438 A at 77.4 K, self-field) comprises a non-twisted 70 cm-long copper former containing a soldered stack of five rare-earth barium copper oxide (REBCO) tapes (each with I c = 115.7 A/4 mm-w at 77.4 K, self-field), which can contain a variety of induced defects. Spatially-resolved electric fields are measured with a high-density voltage tap array and absolute current distribution with six custom-wound embedded Rogowski coils. 3D circuit modeling uses nodal analysis and self-consistently accounts for the magnetic field dependence of critical current. The model successfully predicts the experimentally measured spatial and operating current dependencies of electric field and current distribution with no defects, one defect, and two defects, validating the defect characterization platform as a tool for improving the design, cost, fabrication, and operation of REBCO cables.
In recent years, international organizations, professionals, and representatives of mental health service users have expressed the need to regulate, limit, and even eliminate coercive measures in ...psychiatric treatment. The main objective of the current review is to provide a comprehensive synthesis of existing evidence on coercion in mental health care through a protocol for an umbrella review of systematic reviews. This protocol was designed according to the Joanna Briggs Institute guide for methodological development, conduct, and reporting of umbrella reviews. To minimize bias in the process, two independent reviewers selected the studies to be included, extracted, and synthesized; analyzed the data; and assessed risk of bias of each review. The review protocol was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. This review offers a comprehensive compilation of systematic reviews on coercion developed to date. Coercion causes adverse physical and psychological effects and is an emotional stressor for individuals with psychiatric diagnoses and health care workers. Characterization of coercion across care settings, its impact on clinical outcomes, the perception of those involved, and how coercion could be reduced will also be discussed.
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A Data‐Driven Review of Soft Robotics Jumet, Barclay; Bell, Marquise D.; Sanchez, Vanessa ...
Advanced intelligent systems,
April 2022, Letnik:
4, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The past decade of soft robotics has delivered impactful and promising contributions to society and has seen exponentially increasing interest from scientists and engineers. This interest has ...resulted in growth of the number of researchers participating in the field and the quantity of their resulting contributions, stressing the community's ability to comprehend and build upon the literature. In this work, a data‐driven review is presented that addresses the recent surge of research by providing a quantitative snapshot of the field. Relevant data are catalogued with three levels of analysis. First, publication‐level analysis explores high‐level trends in the field and bibliometric relationships across the more detailed analyses. Second, device‐level analysis examines the tethering of robots and the incorporation of component types (actuators, sensors, controllers, power sources) into each robot. Finally, component‐level analysis investigates the compliances, material compositions, and “function media” (energetic methods by which components operate) of each soft robotic component in the analyzed literature. The reported data indicate a significant reliance on elastomeric materials, electrical and fluidic media, and physical tethering; meanwhile, controllers and power sources remain underdeveloped relative to actuators and sensors. These gaps in the surveyed literature are elaborated upon, and promising future directions for the field of soft robotics are identified.
The field of soft robotics has become challenging to digest due to diverse contributions from a growing spectrum of researchers. This data‐driven review provides a holistic, quantitative snapshot of the field by synthesizing content from hundreds of publications. Highlights include historical trends, rising hot topics, and identification of areas that will further advance the field.
The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs ...tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.
Geographical variations in cancer mortality can be explained, in part, by their association with social inequalities. The objective of our study was to analyse the spatial pattern of mortality in ...relation to the most common causes of cancer in the Spanish autonomous community of Andalusia and its possible association with social inequalities.
A small area cross-sectional study in Andalusia, with census tracts as units of spatial analysis, for the period 2002-2013. Cases and person-years, sex and age group came from the Longitudinal Population Database of Andalusia. Standardized mortality rates and smoothed risk ratios were calculated using the Besag, York and Mollié model for lung, colorectal, breast, prostate, bladder and stomach cancer. In order to evaluate the association with social inequalities we included the deprivation index of the census tract as a covariate.
The results show an East-West mortality pattern with higher risk in the west for lung and bladder cancer among men, and breast cancer among women. For all of Andalusia, the association between deprivation index of the census tract and mortality relative risks is positive and significant for lung, stomach and bladder cancers in men, while in women we observed a negative association for lung cancer and a positive for stomach cancer.
Knowledge regarding the spatial distribution of cancer mortality and the socioeconomic inequalities related should contribute to the design of specific health and social policies-aimed at tackling cancer mortality and social inequalities in areas of high mortality and/or levels of deprivation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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