By analyzing gene expression data in glioblastoma in combination with matched microRNA profiles, we have uncovered a posttranscriptional regulation layer of surprising magnitude, comprising more than ...248,000 microRNA (miR)-mediated interactions. These include ∼7,000 genes whose transcripts act as miR “sponges” and 148 genes that act through alternative, nonsponge interactions. Biochemical analyses in cell lines confirmed that this network regulates established drivers of tumor initiation and subtype implementation, including PTEN, PDGFRA, RB1, VEGFA, STAT3, and RUNX1, suggesting that these interactions mediate crosstalk between canonical oncogenic pathways. siRNA silencing of 13 miR-mediated PTEN regulators, whose locus deletions are predictive of PTEN expression variability, was sufficient to downregulate PTEN in a 3′UTR-dependent manner and to increase tumor cell growth rates. Thus, miR-mediated interactions provide a mechanistic, experimentally validated rationale for the loss of PTEN expression in a large number of glioma samples with an intact PTEN locus.
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► Computational inference reveals a network of miR-mediated interactions in glioblastoma ► These interactions regulate thousands of genes, including oncogenes and tumor suppressors ► These interactions regulate miR targets without affecting miR expression ► These interactions enable crosstalk between established oncogenic pathways
Computational inference uncovers a massive RNA-RNA interaction network in glioblastoma, which is shown to regulate established tumor drivers, such as PTEN, by modulating microRNA availability.
In recent years, techniques of using system disturbance data to validate generator models have been widely discussed. Dynamic model validation and calibration is becoming one of the important ...applications to smart grid initiative. As this kind of technique is utilized to validate generator model, procedures of data screening and reprocessing are essential because raw data obtained from measurement is not always satisfactory. Regarding model parameter calibration, system model is usually quite complicated with various parameters interacting with each other. Artificial intelligent tool is the prior option to save the laborious tuning process and enhance the parameter accuracy. This paper presents a guideline to validate and calibrate parameters of generating units using the record data from phasor measurement unit. Associated procedures for signal filtering on the measurement data, key parameters screening, intelligent search of model parameters, and cross check of legitimate parameters will be discussed in detail. Finally, two historical disturbance cases that happened in the Taiwan power (Taipower) system are applied in accordance with the proposed guideline to demonstrate its effectiveness on generator parameter validation and calibration.
With the advancements in wind turbine technologies, the cost of wind energy has become competitive with other fuel-based generation resources. Due to the price hike of fossil fuel and the concern of ...global warming, the development of wind power has rapidly progressed over the last decade. The annual growth rate has exceeded 26% since the 1990s. Many countries have set a goal for high penetration levels of wind generation. Recently, several large-scale wind generation projects have been implemented all over the world. It is economically beneficial to integrate very large amounts of wind capacity in power systems. Unlike other traditional generation facilities, using wind turbines presents technical challenges in producing continuous and controllable electric power. A distinct feature of wind energy is its nature of being ldquointermittent.rdquo Since it is difficult to predict and control the output of wind generation, its potential impacts on the electric grid are different from the traditional energy sources. At a high penetration level, an extrafast response reserve capacity is needed to cover the shortfall of generation when a sudden deficit of wind takes place. To enable a proper management of the uncertainty, this paper presents an approach to make wind power become a more reliable source on both energy and capacity by using energy storage devices. Combining the wind power generation system with energy storage will reduce fluctuation of wind power. Since it requires capital investment for the storage system, it is important to estimate the reasonable storage capacities for the desired applications. In addition, an energy storage application for reducing the output variation during the gust wind is also studied.
To examine the association between health literacy, level of disease knowledge, and adherence behavior among patients with type 2 diabetes.
A cross-sectional survey study of 1059 Mandarin- and ...Taiwanese-speaking patients aged 20 years or older with type 2 diabetes was conducted. The demographic profiles of the sample strata were determined by analyzing the Taiwanese National Health Insurance Database. Participants were enrolled and completed questionnaires between April and November of 2015. The patients were assessed using a self-developed questionnaire with high internal consistency (KR-20 = .84).
Construct validity was supported by Confirmatory Factor Analysis. Respondents scored lowest in diet-related knowledge. Health literacy and diabetes knowledge were significantly greater when patients cared for themselves with additional caretaker assistance. Patient age, gender, and educational attainment were associated with adherence behavior.
This study conducted a nation-wide survey of patients with diabetes and the results showed that respondents possessed fairly strong diabetes-specific health literacy and knowledge. However, health literacy shouldn't be assessed as an isolated concept. Instead, it should be assessed in conjunction with adherence behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mirtrons are alternative precursors for microRNA biogenesis that were recently described in invertebrates. These short hairpin introns use splicing to bypass Drosha cleavage, which is otherwise ...essential for the generation of canonical animal microRNAs. Using computational and experimental strategies, we now establish that mammals have mirtrons as well. We identified 3 mirtrons that are well conserved and expressed in diverse mammals, 16 primate-specific mirtrons, and 46 candidates supported by limited cloning evidence in primates. As with some fly and worm mirtrons, the existence of well-conserved mammalian mirtrons indicates their relatively ancient incorporation into endogenous regulatory pathways. However, as worms, flies, and mammals each have different sets of mirtrons, we hypothesize that different animals may have independently evolved the capacity for this hybrid small RNA pathway. This notion is supported by our observation of several clade-specific features of mammalian and invertebrate mirtrons.
The AKT kinases have emerged as promising therapeutic targets in oncology and both allosteric and ATP-competitive AKT inhibitors have entered clinical investigation. However, long-term efficacy of ...such inhibitors will likely be challenged by the development of resistance. We have established prostate cancer models of acquired resistance to the allosteric inhibitor MK-2206 or the ATP-competitive inhibitor ipatasertib following prolonged exposure. While alterations in AKT are associated with acquired resistance to MK-2206, ipatasertib resistance is driven by rewired compensatory activity of parallel signaling pathways. Importantly, MK-2206 resistance can be overcome by treatment with ipatasertib, while ipatasertib resistance can be reversed by co-treatment with inhibitors of pathways including PIM signaling. These findings demonstrate that distinct resistance mechanisms arise to the two classes of AKT inhibitors and that combination approaches may reverse resistance to ATP-competitive inhibition.
Without demosaicing processing, this paper first proposes a new approach to extract more accurate gradient/edge information on mosaic images directly. Next, based on spectral-spatial correlation, a ...novel adaptive heterogeneity-projection with proper mask size for each pixel is presented. Combining the extracted gradient/edge information and the adaptive heterogeneity-projection values, a new edge-sensing demosaicing algorithm is presented. Based on 24 popular testing images, experimental results demonstrated that our proposed high-quality demosaicing algorithm has the best image quality performance when compared with several recently published algorithms.
Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the ...inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.
This article presents a low-complexity digital low-dropout regulator (DLDO) design featuring a novel voltage regulation and transient enhancement scheme, and a charge-redistribution-based ripple ...suppression (CRRS) technique that smooths output by redistribution of excessive energy via a small capacitor. Also proposed is a fast-turnaround general DLDO design approach comprising a hybrid discrete-continuous DLDO model and techniques for modeling nonlinear performance enhancement techniques, with which a DLDO's performances for given specifications can be evaluated in the early design stage to shorten the development time. A DLDO test chip fabricated using 110 nm CMOS technology shows a fast settling time of 67 and 250 ns for light-to-heavy (i.e., 2.5 and 50 mA) and heavy-to-light transient, and an output voltage ripple as low as 3 mV with proposed CRRS. The core occupies only 0.022 mm 2 , thanks to the resource-sharing architecture of a proposed digital controller and hardware simplicity. With an input voltage of 1 V and output voltage of 0.85 V, proposed design achieves a peak current efficiency of 99.6% with a 100 MHz operating clock frequency.
This study focuses on the interaction between the oxide layer area of a transistor and its ferroelectric layer area. An experimental comparison of transistor oxide layer area demonstrates that the ...larger the ratio of oxide to ferroelectric layers, the larger the on/off ratio, thus improving performance. A subsequent experiment aimed to further demonstrate this in different sized devices, and changing the ratio of <inline-formula> <tex-math notation="LaTeX">\text{A}_{\text {HZO}}/\text{A}_{\text {SiO2}} </tex-math></inline-formula> (the area of HfZrO x divided by oxide layer) showed the same tendency as above, but also produced an unexpected finding in that a comparison of on/off ratio exhibits an abnormal electric characteristic. This study discusses this abnormal electric characteristic and proposes an explanatory physical model.
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