Light-emitting diodes (LEDs) are a solid-state light source being used in numerous applications, including display, communications, medical services, etc. However, the reliability assessment of LED ...components is still challenging due to the growing up of the LED complexity and/or the miniaturization of assembly technologies. To face this challenge, this paper proposes a novel accelerated degradation testing (ADT) model considering the self-heating impact in the degradation process of a LED component. So, the self-heating impact is first analyzed and modeled. In fact, the junction temperature of a LED component depends not only on the heat generation (e.g., drive current, dispersing heat) but also on the current state (degradation level) of the component. Then, a modified stochastic difference equation is developed for modelling the degradation process by considering the self-heating impact. The LED reliability formulation is finally derived. In addition, an estimation method based on the maximum likelihood is developed to estimate the proposed model's parameters from experimental data. To validate our models, a case study for LED light sources is implemented. The obtained results show that, compared to the TM-21 standard and the conventional ADT methods, our proposed approach achieves better results in the LED reliability assessment.
•A novel ADT model is proposed for LED reliability assessment.•The impact of self-heating in the LED degradation process is analyzed and modeled.•A degradation process and reliability model integrating the self-heating impact are developed.•An experimental platform for ADT of a LED is investigated.•The proposed ADT model is analyzed and validated with experimental dataset.
Targetable kinase fusions are extremely rare (<1%) in colorectal cancers (CRCs), making their diagnosis challenging and often underinvestigated. They have been shown particularly frequently among ...MSI-High, BRAF/KRAS/NRAS wild-type CRCs with MLH1 loss (MLH1loss MSI-High wild-type).
We searched for NTRK1, NTRK2, NTRK3, ALK, ROS1, BRAF, RET, and NRG1 kinase fusions in CRCs using methods easy-to-implement in pathology laboratories: immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and fully automated real-time PCR targeted analyses. RNA-sequencing analyses were used for confirmation.
Among 84 selected MLH1 deficient (IHC) CRCs cases, MLH1loss MSI-High wild-type CRCs consisted first in 19 cases after Idylla™ analyses and finally in 18 cases (21%) after RNA-sequencing (detection of one additional KRASG12D mutation). FISH (and when relevant, IHC) analyses concluded in 5 NTRK1, 3 NTRK3, 1 ALK, 2 BRAF, and 2 RET FISH positive tumors. ALK and NTRK1 rearranged tumors were IHC positive, but pan-TRK IHC was negative in the 3 NTRK3 FISH positive tumors. RNA-sequencing analyses confirmed 12 of 13 fusions with only one false positive RET FISH result. Finally, 12/18 (67%) of MLH1loss MSI-High wild-type CRCs contained targetable kinase fusions.
Our study demonstrates the feasibility, but also the cost-effectiveness, of a multistep but rapid diagnostic strategy based on nonsequencing methods to identify rare and targetable kinase fusions in patients with advanced CRCs, as well as the high prevalence of these kinase fusions in MLH1loss MSI-High wild-type CRCs. Nevertheless, confirmatory RNA-sequencing analyses are necessary in case of low FISH positive nuclei percentage to rule out FISH false-positive results.
•Gene fusions are very rare (<1%) in colorectal cancers (CRCs) but more frequent in MSI-High RAS-BRAF wild-type CRCs.•Among 84 CRCs with MLH1 loss, including 18 RAS-BRAF wild-type cases, we diagnosed 12 (66.7%) gene fusions.•Tumors with MLH1 loss, microsatellite instability and no RAS-BRAF mutation must be tested for targetable gene fusions.•NTRK1, NTRK3, ALK, RET, and BRAF gene fusions diagnosis is attainable in CRCs using fluorescent in situ hybridization (FISH).•Low percentage FISH results must be confirmed using RNA-sequencing analyses.
Abstract
Introduction: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory ...verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. Methods: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). Results: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. Discussion: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.
•Development of intermittent drying models corresponding to two physical situations.•Identification of three regimes in the dynamics of an intermittent drying.•Operational diagram for selecting the ...best parameters for an intermittent drying.•Influence of the mass transfer Biot number on the dynamics of intermittent drying.
Intermittent drying is a promising technique that may improve drying performance, when compared to stationary drying. An intermittent drying is composed of a succession of cycles, each of them consisting in an active drying period followed by a tempering period. It is typically characterized by two parameters: the duration of the cycles tc and the ratio of the duration of the drying period of a cycle to the total duration of the cycle χ. In this work, we derive two general models of the intermittent drying of a solid material, corresponding to different physical situations: a continuous model, to describe a situation where liquid water is continuously distributed through the material, and a shrinking core model, to describe a situation where the material is divided into a humid core and a dry zone. With these models, we provide a thorough analysis of the influence of the parameters characterizing the intermittent drying of a material on the dynamics of this drying, over wide ranges of values of these parameters. The results allows the identification of three possible regimes in the dynamics of an intermittent drying, when it is compared to a stationary one, what is summarized into an operational diagram that could be useful to select the best parameters for an intermittent drying process. Notably, the results show that one of these regions (with small values of tc and χ) corresponds to high energy efficiency, without significantly increasing the total drying time compared to continuous drying, if the external resistance to mass transfer is negligible. The models also exhibit that the external mass transfer Biot number, Bim, has a strong influence on the dynamics of an intermittent drying; the influence of tc and χ on drying performance is mitigated as Bim decreases. Finally, the models are used to shed new light on experimental data from the literature, regarding the intermittent drying of several products, for different operating conditions. The investigation of the influence of the operating conditions and the product properties on the drying performance shows that strategies such as varying the intermittency ratio or using inherently intermittent dryer can enhance the drying kinetics.
This article describes highly luminescent ionic compounds in liquid and crystalline states, where a naphthalene moiety is conjugated to an imidazolium center decorated with alkyl chains of different ...lengths. We have characterized, by X-ray diffraction of a single crystal and the liquid, that these compounds are organized in rod-shaped assemblies. The formation of this molecular architecture is governed by ionic interactions that dominate those of the lesser π-π and van der Waals interactions. Consequently, aromatic naphthalene rings are confined to the environment of alkyl chains (diluted in an apolar solvent), thus avoiding the extinction of luminescence by the formation of chromophore excimers, as shown in photophysical data.
This article describes highly luminescent ionic compounds in liquid and crystalline states, where a naphthalene moiety is conjugated to an imidazolium center decorated with two different lengths of alkyl chains.
AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte hypertrophy without affecting downstream targets ...previously suggested to be involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of activated T cells (NFAT) and extracellular signal-regulated kinases. Instead, cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation, which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in wild-type but not in AMPKα2-deficient mice. Treatment of wild-type mice with O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation, thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O-GlcNAcylation.
Summary
Sickle cell disease (SCD) is characterised by chronic haemolysis and oxidative stress. Herein, we investigated 30 SCD patients and found 40% with elevated mitochondria levels (SS‐mito+) in ...their mature red blood cells, while 60% exhibit similar mitochondria levels compared to the AA group (SS‐mito−). The SS‐mito+ patients are characterised by higher reticulocytosis and total bilirubin levels, lower foetal haemoglobin, and non‐functional mitochondria. Interestingly, we demonstrated decreased levels of mitophagy inducers, PINK1 and NIX, and higher levels of HSP90 chaperone in their red cells. Our results highlighted for the first time an abnormal retention of mitochondria in SCD linked with mitophagy‐related proteins.
The addition of a solid carrier before drying seems a promising way to improve the processability and the drying kinetics of yeast pellets. However, its influence on the quality of the yeasts during ...and at the end of the drying is not yet well understood and is investigated in this communication. A yeast paste was mixed with different amounts of wheat flour, a solid carrier, to obtain pellets with 69, 55, and 40 wt% moisture content. The fermentation activity of the yeasts was measured in samples taken throughout the drying process of these pellets. The experimental results highlight that the addition of a carrier does not significantly alter the quality of the yeasts before drying but has a negative impact on their final quality at the end of the drying process. Moreover, the addition of a solid carrier leads to a continuous decrease in the fermentation activity of the yeasts from the beginning of drying, in contrast to the activity of the yeasts in the absence of a carrier, which remains high during drying, as long as the moisture content of the pellets is larger than about 0.5 (d.b.).
The hallmark of neurofibromatosis type 1 (NF1) is the onset of dermal or plexiform neurofibromas, mainly composed of Schwann cells. Plexiform neurofibromas can transform into malignant peripheral ...nerve sheath tumors (MPNST) that are resistant to therapies.
The aim of this study was to identify an additional pathway in the NF1 tumorigenesis. We focused our work on Wnt signaling that is highly implicated in cancer, mainly in regulating the proliferation of cancer stem cells. We quantified mRNAs of 89 Wnt pathway genes in 57 NF1-associated tumors including dermal and plexiform neurofibromas and MPNSTs. Expression of two major stem cell marker genes and five major epithelial-mesenchymal transition marker genes was also assessed. The expression of significantly deregulated Wnt genes was then studied in normal human Schwann cells, fibroblasts, endothelial cells, and mast cells and in seven MPNST cell lines.
The expression of nine Wnt genes was significantly deregulated in plexiform neurofibromas in comparison with dermal neurofibromas. Twenty Wnt genes showed altered expression in MPNST biopsies and cell lines. Immunohistochemical studies confirmed the Wnt pathway activation in NF1-associated MPNSTs. We then confirmed that the knockdown of NF1 in Schwann cells but not in epithelial cells provoked the activation of Wnt pathway by functional transfection assays. Furthermore, we showed that the protein expression of active β-catenin was increased in NF1-silenced cell lines. Wnt pathway activation was strongly associated to both cancer stem cell reservoir and Schwann-mesenchymal transition.
We highlighted the implication of Wnt pathway in NF1-associated tumorigenesis.
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