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As semiconductor chips have been integrated to enhance their performance, a low-dielectric-constant material, SiCOH, with a relative dielectric constant k ≤ 3.5 has been widely used as an intermetal dielectric (IMD) material in multilevel interconnects to reduce the resistance-capacitance delay. Plasma-polymerized tetrakis(trimethylsilyoxy)silane (ppTTMSS) films were created using capacitively coupled plasma-enhanced chemical vapor deposition with deposition plasma powers ranging from 20 to 60 W and then etched in CF4/O2 plasma using reactive ion etching. No significant changes were observed in the Fourier-transform infrared spectroscopy (FTIR) spectra of the ppTTMSS films after etching. The refractive index and dielectric constant were also maintained. As the deposition plasma power increased, the hardness and elastic modulus increased with increasing ppTTMSS film density. The X-ray photoelectron spectroscopy (XPS) spectra analysis showed that the oxygen concentration increased but the carbon concentration decreased after etching owing to the reaction between the plasma and film surface. With an increase in the deposition plasma power, the hardness and elastic modulus increased from 1.06 to 8.56 GPa and from 6.16 to 52.45 GPa. This result satisfies the hardness and elastic modulus exceeding 0.7 and 5.0 GPa, which are required for the chemical-mechanical polishing process in semiconductor multilevel interconnects. Furthermore, all leakage-current densities of the as-deposited and etched ppTTMSS films were measured below 10-6 A/cm2 at 1 MV/cm, which is generally acceptable for IMD materials.
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The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.
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Complexo de Golgi , Processamento de Proteína Pós-Traducional , Humanos , Complexo de Golgi/metabolismo , Transporte Proteico , Transdução de Sinais , Proteínas de Membrana/metabolismoRESUMO
Oxidative stress resulting from reactive oxygen species and other toxic metabolites is involved in human diseases, and it plays an important role in aging. In Caenorhabditis elegans, SKN-1 is required for protection against oxidative stress and aging. As p38 mitogen-activated protein kinase signaling is activated in response to oxidative stress, SKN-1 accumulates in intestinal nuclei and induces phase II detoxification genes. However, NSY-1, a well-known mitogen-activated protein kinase kinase kinase (MAPKKK) of C. elegans, acts as a partial regulator of the SKN-1-induced oxidative stress signaling pathway, suggesting that the regulator for optimal activation of SKN-1 remains unknown. Here, we report a MAPKKK, MEKK-3, as a new regulator required for full activation of SKN-1-mediated resistance against oxidative stress and aging. In RNA-interference-based screening, we found that the simultaneous knockdown of mekk-3 and nsy-1 significantly decreased the oxidative stress resistance and survival of SKN-1 transgenic worms. MEKK-3 was induced in response to oxidative stress. Mechanistic analysis revealed that double knockdown of mekk-3 and nsy-1 completely suppressed the nuclear localization of SKN-1. These results were reproduced in mutant worms in which SKN-1 is constitutively localized to intestinal nuclei. In addition, mekk-3 and nsy-1 were required for optimal induction of SKN-1 target genes such as gcs-1 and trx-1. These data indicate that MEKK-3 plays an essential role in the SKN-1-dependent signaling pathway involved in oxidative stress resistance and longevity by cooperating with NSY-1.
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The Golgi apparatus is an essential cellular organelle that mediates homeostatic functions, including vesicle trafficking and the post-translational modification of macromolecules. Its unique stacked structure and dynamic functions are tightly regulated, and several Golgi proteins play key roles in the functioning of unconventional protein secretory pathways triggered by cellular stress responses. Recently, an increasing number of studies have implicated defects in Golgi functioning in human diseases such as cancer, neurodegenerative, and immunological disorders. Understanding the extraordinary characteristics of Golgi proteins is important for elucidating its associated intracellular signaling mechanisms and has important ramifications for human health. Therefore, analyzing the mechanisms by which the Golgi participates in disease pathogenesis may be useful for developing novel therapeutic strategies. This review articulates the structural features and abnormalities of the Golgi apparatus reported in various diseases and the suspected mechanisms underlying the Golgi-associated pathologies. Furthermore, we review the potential therapeutic strategies based on Golgi function.
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Complexo de Golgi , Proteínas , Humanos , Complexo de Golgi/metabolismo , Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , HomeostaseRESUMO
InGaAs-based photodetectors have been generally used for detection in the short-wave infrared (SWIR) region. However, the epitaxial process used to grow these materials is expensive; therefore, InGaAs-based photodetectors are limited to space exploration and military applications. Many researchers have expended considerable efforts to address the problem of SWIR photodetector development using lead sulfide (PbS) quantum dots (QDs). Along with their cost-efficient solution processability and flexible substrate compatibility, PbS QDs are highly interesting for the quantum-size-effect tunability of their bandgaps, spectral sensitivities, and wide absorption ranges. However, the performance of PbS QD-based SWIR photodetectors is limited owing to inefficient carrier transfer and low photo and thermal stabilities. In this study, a simple method is proposed to overcome these problems by incorporating CdS in PbS QD shells to provide efficient carrier transfer and enhance the long-term stability of SWIR photodetectors against oxidation. The SWIR photodetectors fabricated using thick-shell PbS/CdS QDs exhibited a high on/off (light/dark) ratio of 11.25 and a high detectivity of 4.0 × 1012 Jones, which represents a greater than 10 times improvement in these properties relative to those of PbS QDs. Moreover, the lifetimes of thick-shell PbS/CdS QD-based SWIR photodetectors were significantly improved owing to the self-passivation of QD surfaces.
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Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic treatment with clozapine can induce obsessive compulsive disorder (OCD)-like behavior in mice. We injected mice with long-term continuous release pellets embedded with clozapine four times at 60-day intervals and then monitored the mice for signs of OCD-like behavior up to 40 wk. of age. We found clozapine increases grooming behavior as early as 30 wk. of age. We also investigated the effect clozapine on grooming behavior in Sapap3 knockout (KO) mice, which are a well-known animal model of OCD. In Sapap3 heterozygous KO mice, clozapine increases grooming behavior much earlier than in wild-type mice, suggesting a clozapine-OCD gene interaction. Fluoxetine, which is often used in the treatment of OCS and OCD, reduced the grooming behavior induced by clozapine. These data demonstrate that chronic clozapine treatment can generate OCD-like behavior in mice and support the hypothesis that clozapine produces de novo OCS regardless of schizophrenia status.
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Comportamento Animal , Clozapina/efeitos adversos , Transtorno Obsessivo-Compulsivo/induzido quimicamente , Animais , Asseio Animal , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/deficiência , Transtorno Obsessivo-Compulsivo/genéticaRESUMO
The proposed study describes the development of a carbon nanotube (CNT)-based gas sensor capable of detecting the presence of hydrogen (H2) gas at room temperature. CNT yarn used in the proposed sensor was fabricated from synthesized CNT arrays. Subsequently, the yarn was treated by means of a simple one-step procedure, called acid treatment, to facilitate removal of impurities from the yarn surface and forming functional species. To verify the proposed sensor's effectiveness with regard to detection of H2 gas at room temperature, acid-treated CNT and pure yarns were fabricated and tested under identical conditions. Corresponding results demonstrate that compared to the untreated CNT yarn, the acid-treated CNT yarn exhibits higher sensitivity to the presence of H2 gas at room temperature. Additionally, the acid-treated CNT yarn was observed to demonstrate excellent selectivity pertaining to H2 gas.
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Palladium-coated multi-walled carbon nanotube (Pd-MWCNT) nanocomposites have been experimentally proven to show highly improved hydrogen (H2) gas detection characteristics at room temperature when compared with single MWCNTs. In this context, we develop an efficient and convenient method for forming nanocomposites by coating Pd nanoparticles on an MWCNT film. Furthermore, we test the applicability of the nanocomposites as sensing materials in detecting H2 gas at room temperature in a reliable and sensitive manner in contrast with ordinary metal-oxidebased gas sensors that operate at high temperatures. We first study the detection efficacy of the Pd-MWCNT film relative to pure MWCNT film. Subsequently, we investigate the Pd-MWCNT sensor's sensitivity over time for different gas concentrations, the sensor response time, and sensor reproducibility and reliability under various conditions including bending tests. Our sensor exhibits stable reliable detection characteristics and excellent structural flexibility.
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Mutations in protocadherin 19 (PCDH19), which is on the X-chromosome, cause the brain disease Epilepsy in Females with Mental Retardation (EFMR). EFMR is also often associated with autism-like symptoms. In mice and humans, epilepsy occurs only in heterozygous females who have a mixture of PCDH19 wild-type (WT) and mutant cells caused by random X-inactivation; it does not occur in hemizygous PCDH19 mutant males. This unique inheritance pattern strongly suggests the underlying disease mechanism operates via interference between WT and mutant cells rather than being a result of complete loss of PCDH19 functions. Although it remains unclear whether the other symptoms of EFMR also conform to this unique genotype-phenotype relationship, PCDH19 mutant males were recently reported to demonstrate autism-like symptoms. We, therefore, used a Pcdh19 knockout (KO) mouse model to ask whether a complete lack of PCDH19 causes autism-like behaviors. Consistent with the autism observed in EFMR females, we found Pcdh19 heterozygous KO female mice (with mosaic expression of PCDH19) show defects in sociability in the 3-chamber test. Surprisingly, hemizygous Pcdh19 KO male mice (without any PCDH19 expression) exhibit impaired sociability in the 3-chamber test and reduced social interactions in the reciprocal social interaction test. We also observed that, compared to WT mice, mutant mice display more repetitive behaviors, including self-grooming and rearing. These findings indicate that hemizygous Pcdh19 KO male mice show autism-like phenotypes.
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Transtorno Autístico/genética , Comportamento Animal , Caderinas/genética , Deleção de Genes , Animais , Feminino , Masculino , Camundongos Knockout , Protocaderinas , Comportamento SocialRESUMO
We attempted surface modification in ZnO nanoparticles (NPs) synthesized by the sol-gel process with polyvinyl pyrrolidone (PVP) applied to bulk-heterojunction polymer solar cells (PSCs) as an electron transport layer (ETL). In general, ZnO NPs have trap sites due to oxygen vacancies which capture electrons and degrade the performance of the PSCs. Devices with six different PVP:Zn ratios (0.615 g, 1.230 g, 1.846 g, 2.460 g, 3.075 g, and 3.690 g) were fabricated for surface modification, and the optimized PVP:Zn ratio (2.460 g) was found for PSCs based on P3HT/PCBM. The power conversion efficiency (PCE) of the fabricated PSCs with PVP-capped ZnO exhibited a significant increase of approximately 21% in PCE and excellent air-stability as compared with the uncapped ZnO-based PSCs.
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A body pressure relief system was newly developed with optical pressure sensors for pressure ulcer prevention. Unlike a conventional alternating pressure air mattress (APAM), this system automatically regulates air flow into a body supporting mattress with adaptive inflation (or deflation) duration in response to the pressure level in order to reduce skin stress due to prolonged high pressures. The system continuously quantifies the body pressure distribution using time-of-flight (ToF) optical sensors. The proposed pressure sensor, a ToF optical sensor in the air-filled cell, measures changes in surface height of mattress when pressed under body weight, thereby indirectly indicating the interface pressure. Non-contact measurement of optical sensor usually improves the durability and repeatability of the system. The pressure sensor was successfully identified the 4 different-predefined postures, and quantitatively measured the body pressure distribution of them. Duty cycle of switches in solenoid valves was adjusted to 0-50% for pressure relief, which shows that the interface pressure was lower than 32 mmHg for pressure ulcer prevention.
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A compatible low-bandgap donor polymer (poly[N-90-heptadecanyl-2,7carbazole-alt-3,6-bis(thiophen-5-yl)-2,5-dioctyl-2,5-dihydropyrrolo [3,4] pyrrole-1,4-dione], PCBTDPP) was judicially introduced into the archetypal poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PC61BM) photoactive system to fabricate highly efficient ternary based bulk heterojunction polymer solar cells (PSCs). The PCBTDPP ternary-based PSC with optimal loading (0.2 wt.%) displayed outstanding performance with a champion power conversion efficiency (PCE) of 5.28% as compared to the PCE (4.67%) for P3HT:PC61BM-based PSC (reference). The improved PCE for PCBTDPP ternary-based PSC can be mainly attributed to the incorporation of PCBTDPP into P3HT:PC61BM that beneficially improved the optical, morphological, electronic, and photovoltaic (PV) performance. This work instills a rational strategy for identifying components (donor/acceptor (D/A) molecules) with complementary beneficial properties toward fabricating efficient ternary PSCs.
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Shortwave infrared (SWIR) sensors have attracted interest due to their usefulness in applications like military and medical equipment. SWIR sensors based on various materials are currently being studied. However, most SWIR detectors need additional optical filters and cooling systems to detect specific wavelengths. In order to overcome these limitations, we proposed a solution processed SWIR sensor that can operate at room temperature using lead chloride (PbS) QDs as a photoactive layer. Additionally, we adapted zinc oxide (ZnO) nanoparticles (NPs) as an electron transport layer (ETL) to improve the sensitivity of a PbS SWIR sensor. In this study, PbS SWIR sensors with and without a ZnO NPs layer were fabricated and their current-voltage (I-V) characteristics were measured. The on/off ratio of the PbS SWIR sensor with ZnO NPs was 2.87 times higher than that of the PbS SWIR sensor without ZnO NPs at the maximum current difference. The PbS SWIR sensor with ZnO NPs showed more stable current characteristics than that without ZnO NPs because of the ZnO NPs' high electron mobility and proper lowest unoccupied molecular orbital (LUMO) level.
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Genetic and pharmacological manipulations targeting metabotropic glutamate receptor 5 (mGluR5) affect performance in behavioural paradigms that depend on cognitive flexibility. Many of these studies involved exposing mice to highly stressful conditions including electric foot shocks or water immersion and forced swimming. Because mGluR5 is also implicated in resilience and stress responses, however, apparent impairments in inhibitory learning may have been an artifact of manipulation-induced changes in affective state. To address this, we present here a characterization of cognitive flexibility in mGluR5 knockout (KO) mice conducted with a rodent touchscreen cognitive assessment apparatus in which the animals experience significantly less stress.Our results indicate a significant reversal learning impairment relative to wild-type (WT) controls in the two-choice Visual Discrimination-Reversal (VDR) paradigm. Upon further analysis, we found that this deficit is primarily driven by a prolonged period of perseveration in the early phase of reversal. We also observed a similar perseveration phenotype in the KO mice in the Extinction (EXT) paradigm. In addition, mGluR5 KO mice show higher breakpoints in the touchscreen Progressive Ratio (PR) and altered decision making in the Effort-related Choice (ERC) tasks. Interestingly, this impairment in PR is an additional manifestation of an increased propensity to perseverate on the emission of relatively simplistic behavioural outputs.Together, these findings suggest that under conditions of low stress, mGluR5 KO mice exhibit a pronounced perseverative phenotype that blunts cognitive flexibility.
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Comportamento Animal , Receptor de Glutamato Metabotrópico 5/deficiência , Estresse Psicológico/patologia , Animais , Comportamento de Escolha , Tomada de Decisões , Discriminação Psicológica , Extinção Psicológica , Comportamento Alimentar , Deleção de Genes , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Glutamato Metabotrópico 5/antagonistas & inibidores , Receptor de Glutamato Metabotrópico 5/metabolismo , Análise e Desempenho de Tarefas , Percepção VisualRESUMO
Quantum-dot (QD) light-emitting devices (QLEDs) have been attracting considerable attention owing to the unique properties of process, which can control the emission wavelength by controlling the particle size, narrow emission bandwidth, and high brightness. Although there have been rapid advances in terms of luminance and efficiency improvements, the long-term device stability is limited by the low chemical stability and photostability of the QDs against moisture and air. In this study, we report a simple method, which can for enhance the long-term stability of QLEDs against oxidation by inserting Al into the shells of CdSe/ZnS QDs. The Al coated on the ZnS shell of QDs act as a protective layer with Al2O3 owing to photo-oxidation, which can prevents the photodegradation of QD with prolonged irradiation and stabilize the device during a long-term operation. The QLEDs fabricated using CdSe/ZnS/Al QDs exhibited a maximum luminance of 57,580 cd/m2 and current efficiency of 5.8 cd/A, which are significantly more than 1.6 times greater than that of CdSe/ZnS QDs. Moreover, the lifetimes of the CdSe/ZnS/Al-QD-based QLEDs were significantly improved owing to the self-passivation at the QD surfaces.
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Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gutâ»brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.
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A thermal convection-based accelerometer was fabricated, and its characteristics were analyzed in this study. To understand the thermal convection of the accelerometer, the Grashof and Prandtl number equations were analyzed. This study conducted experiments to improve not only the sensitivity, but also the frequency band. An accelerometer with a more voluminous cavity showed better sensitivity. In addition, when the accelerometer used a gas medium with a large density and small viscosity, its sensitivity also improved. On the other hand, the accelerometer with a narrow volume cavity that used a gas medium with a small density and large thermal diffusivity displayed a larger frequency band. In particular, this paper focused on a Z-axis response to extend the performance of the accelerometer.
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In bulk heterojunction polymer solar cells (BHJ-PSCs), poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) is the most commonly used hole selective interlayer (HSIL). However, its acidity, hygroscopic nature, and the use of indium tin oxide (ITO) etching can degrade the overall photovoltaic performance and the air-stability of BHJ-PSCs. Solvent engineering is considered as a facile approach to overcome these issues. In this work, we engineered the HSIL using ethanol (ET) treated PEDOT:PSS to simultaneously enhance the photovoltaic performance properties and air-stability of the fabricated devices. We systematically investigated the influence of ET on the microstructural, morphological, interfacial characteristics of modified HSIL and photovoltaic characteristics of BHJ-PSCs. Compared with the BHJ-PSC with pristine PEDOT:PSS, a significant enhancement of power conversion efficiency (~17%) was witnessed for the BHJ-PSC with PEDOT:PSS-ET (v/v, 1:0.5). Consequently, the BHJ-PSC with PEDOT:PSS-ET (v/v, 1:0.5) as HSIL exhibited remarkably improved air-stability.
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We investigated the role of a functional solid additive, 2,3-dihydroxypyridine (DHP), in influencing the optoelectronic, morphological, structural and photovoltaic properties of bulk-heterojunction-based polymer solar cells (BHJ PSCs) fabricated using poly(3-hexylthiophene): indene-C60 bisadduct (P3HT:IC60BA) photoactive medium. A dramatic increase in the power conversion efficiency (~20%) was witnessed for the BHJ PSCs treated with DHP compared to the pristine devices. A plausible explanation describing the alignment of pyridine moieties of DHP with the indene side groups of IC60BA is presented with a view to improving the performance of the BHJ PSCs via improved crystalline order and hydrophobicity changes.
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Detecting heterogenic tumor cells that are traveling in our body through blood stream for the tumor metastasis is one way for cancer prognosis. Due to the heterogeneity of circulating tumor cells (CTCs), further identification of tumor cell types should be accompanied with CTCs isolation from blood cells in peripheral blood sample. Both negative enrichment and recollection of isolated CTCs are required in the downstream analysis, which are time-consuming, labor-intensive, and massive equipment required. To solve these limitations, we have developed a simple and disposable spiral shape microfluidic channel that can separate all CTCs from blood cells, and at the same time, can identify the types of CTCs based on epithelial cell adhesion molecule (EpCAM) expression level. Two different types of tumor cells, MCF-7 and MDA-MB-231, both from the same origin of breast carcinoma cells, were used to demonstrate the functionality of the developed system. The spiral channel system could capture the EpCAM positive and negative CTCs with 96.3% and 81.2% purity, respectively, while both EpCAM positive and negative CTCs were differently positioned along the microfluidic channel. The average selectivity of EpCAM positive and negative CTCs is 6.1:4.8. In addition, the throughput of the system was optimized at a sample flow rate of 150µl/min. The developed system successfully demonstrated its potential to identify biomarkers, including EpCAM, for detecting the heterogenic CTCs.