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1.
Nanotechnology ; 35(12)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38061057

ABSTRACT

In this article, a 0.7 nm thick monolayer MoS2nanosheet gate-all-around field effect transistors (NS-GAAFETs) with conformal high-κmetal gate deposition are demonstrated. The device with 40 nm channel length exhibits a high on-state current density of ~410µAµm-1with a large on/off ratio of 6 × 108at drain voltage = 1 V. The extracted contact resistance is 0.48 ± 0.1 kΩµm in monolayer MoS2NS-GAAFETs, thereby showing the channel-dominated performance with the channel length scaling from 80 to 40 nm. The successful demonstration of device performance in this work verifies the integration potential of transition metal dichalcogenides for future logic transistor applications.

2.
Urology ; 183: 264-273, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37839472

ABSTRACT

The objective of this scoping review is to provide a summary of the current literature regarding adolescents and young adults with histories of cloacal anomalies. Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews were used. Data were categorized into four domains-urologic, colorectal, gynecologic/obstetric, and sexual/psychosocial. The current literature has poor study quality and mostly consists of retrospective studies of small cohorts with varying definitions of outcomes. Women with cloacal anomalies are at high risk for urologic dysfunction but can maintain kidney health and achieve social continence with medical and surgical management. Sexual function and adult healthcare transition are areas ripe for improved future research.


Subject(s)
Colon , Psychosocial Support Systems , Rectum , Transition to Adult Care , Urogenital Abnormalities , Adolescent , Female , Humans , Young Adult , Colon/abnormalities , Kidney/abnormalities , Rectum/abnormalities , Retrospective Studies , Urogenital Abnormalities/psychology
4.
Nat Mater ; 22(5): 591-598, 2023 May.
Article in English | MEDLINE | ID: mdl-37012436

ABSTRACT

Large spin-orbit torques (SOTs) generated by topological materials and heavy metals interfaced with ferromagnets are promising for next-generation magnetic memory and logic devices. SOTs generated from y spin originating from spin Hall and Edelstein effects can realize field-free magnetization switching only when the magnetization and spin are collinear. Here we circumvent the above limitation by utilizing unconventional spins generated in a MnPd3 thin film grown on an oxidized silicon substrate. We observe conventional SOT due to y spin, and out-of-plane and in-plane anti-damping-like torques originated from z spin and x spin, respectively, in MnPd3/CoFeB heterostructures. Notably, we have demonstrated complete field-free switching of perpendicular cobalt via out-of-plane anti-damping-like SOT. Density functional theory calculations show that the observed unconventional torques are due to the low symmetry of the (114)-oriented MnPd3 films. Altogether our results provide a path toward realization of a practical spin channel in ultrafast magnetic memory and logic devices.

5.
Cancers (Basel) ; 15(4)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36831600

ABSTRACT

Malignant melanoma is the deadliest form of skin cancer. Despite significant efforts in sun protection education, melanoma incidence is still rising globally, drawing attention to other socioenvironmental risk factors for melanoma. Ethanol and acetaldehyde (AcAH) are ubiquitous in our diets, medicines, alcoholic beverages, and the environment. In the liver, ethanol is primarily oxidized to AcAH, a toxic intermediate capable of inducing tumors by forming adducts with proteins and DNA. Once in the blood, ethanol and AcAH can reach the skin. Although, like the liver, the skin has metabolic mechanisms to detoxify ethanol and AcAH, the risk of ethanol/AcAH-associated skin diseases increases when the metabolic enzymes become dysfunctional in the skin. This review highlights the evidence linking cutaneous ethanol metabolism and melanoma. We summarize various sources of skin ethanol and AcAH and describe how the reduced activity of each alcohol metabolizing enzyme affects the sensitivity threshold to ethanol/AcAH toxicity. Data from the Gene Expression Omnibus database also show that three ethanol metabolizing enzymes (alcohol dehydrogenase 1B, P450 2E1, and catalase) and an AcAH metabolizing enzyme (aldehyde dehydrogenase 2) are significantly reduced in melanoma tissues.

6.
Int J Pediatr Otorhinolaryngol ; 166: 111460, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36764079

ABSTRACT

OBJECTIVES: Cochlear implantation is indicated for pediatric patients with bilateral severe to profound sensorineural hearing loss. The literature reports large variability in cochlear implant (CI) device survival and rates of explantation and reimplantation. This retrospective chart review summarizes CI survival and rates of explantation and reimplantation in pediatric CI recipients at a Canadian tertiary pediatric hospital over 32 years. METHODS: A retrospective chart review of all pediatric patients who received a Cochlear Corporation® CI between April 1988 and June 2020 was undertaken. Rates of explantation/reimplantation were collected and categorized based on device type and reason for failure (medical, device, and inconclusive failure). Device survival analysis based on implant model was also completed utilizing Kaplan-Meier curves. RESULTS: 512 CIs were implanted over the 32-year period by four surgeons (77.1%, 18.16%, 4.49%, and 0.20%, respectively). Patient age ranged from seven months to 20.4 years. The overall explantation and reimplantation rate was 3.32% (17/512 implants), with seven as a result of device failure (1.37%), nine events of medical failure (1.76%), and one inconclusive failure (0.20%). Cumulative CI survival rates at 5, 10, 15, and 20 years were 98.15%, 96.33%, 95.53%, and 94.39%. CONCLUSION: The overall institutional CI failure, explantation, and reimplantation rates are lower than the average reported rates in the literature.


Subject(s)
Cochlear Implantation , Cochlear Implants , Child , Humans , Infant , Retrospective Studies , Reoperation , Canada , Replantation , Prosthesis Failure
7.
Can Geriatr J ; 25(4): 390-403, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36505918

ABSTRACT

Sarcopenia, an age-associated skeletal muscle disorder characterized by muscle loss, is associated with disability in elderly populations. This literature review summarizes the impact of protein intake and supplementation on the indicators of severe sarcopenia-muscle mass, muscle strength, and physical function in community-dwelling older adults. We performed a literature search on PubMed, EMBASE, and MedLine, and included studies that evaluated the effects of protein intake with or without exercise intervention and on sarcopenia in community-dwelling older adults. Information regarding study participants, protein intervention, and sarcopenia-related outcomes were collected. Protein supplementation with or without exercise positively improves muscle mass, and aspects of muscle strength and physical function in sarcopenic and pre-frail older adults, while it elicited inconclusive effects in healthy populations. Greater dietary animal-based and soy-based protein diets can improve muscle mass in older adults. In conclusion, protein supplementation can improve muscle mass and reduce the risk of sarcopenia in sarcopenia and pre-frail older adults, while future studies should continue to investigate the effects of protein supplementation on indicators of sarcopenia in healthy older adults.

8.
PLoS One ; 17(3): e0265007, 2022.
Article in English | MEDLINE | ID: mdl-35259201

ABSTRACT

While fatty acid metabolism is altered under physiological conditions, alterations can also be maladaptive in diseases such as diabetes and heart failure. Peroxisome Proliferator Activated Receptor α (PPARα) is a transcription factor that regulates fat metabolism but its role in regulating lipid storage in the heart is unclear. The aim of this study is to improve our understanding of how cardiac PPARα regulates cardiac health and lipid accumulation. To study the role of cardiac PPARα, tamoxifen inducible cardiac-specific PPARα knockout mouse (cPPAR-/-) were treated for 5 days with tamoxifen and then studied after 1-2 months. Under baseline conditions, cPPAR-/- mice appear healthy with normal body weight and mortality is not altered. Importantly, cardiac hypertrophy or reduced cardiac function was also not observed at baseline. Mice were fasted to elevate circulating fatty acids and induce cardiac lipid accumulation. After fasting, cPPAR-/- mice had dramatically lower cardiac triglyceride levels than control mice. Interestingly, cPPAR-/- hearts also had reduced Plin2, a key protein involved in lipid accumulation and lipid droplet regulation, which may contribute to the reduction in cardiac lipid accumulation. Overall, this suggests that a decline in cardiac PPARα may blunt cardiac lipid accumulation by decreasing Plin2 and that independent of differences in systemic metabolism a decline in cardiac PPARα does not seem to drive pathological changes in the heart.


Subject(s)
Fasting , PPAR alpha , Animals , Fatty Acids/metabolism , Lipid Metabolism/physiology , Liver/metabolism , Mice , Mice, Knockout , PPAR alpha/genetics , PPAR alpha/metabolism , Perilipin-2/metabolism , Tamoxifen/metabolism
9.
Respir Res ; 22(1): 266, 2021 Oct 19.
Article in English | MEDLINE | ID: mdl-34666750

ABSTRACT

INTRODUCTION: Over 300 million people in the world live with asthma, resulting in 500,000 annual global deaths with future increases expected. It is estimated that around 50-80% of asthma exacerbations are due to viral infections. Currently, a combination of long-acting beta agonists (LABA) for bronchodilation and glucocorticoids (GCS) to control lung inflammation represent the dominant strategy for the management of asthma, however, it is still sub-optimal in 35-50% of moderate-severe asthmatics resulting in persistent lung inflammation, impairment of lung function, and risk of mortality. Mechanistically, LABA/GCS combination therapy results in synergistic efficacy mediated by intracellular cyclic adenosine monophosphate (cAMP). HYPOTHESIS: Increasing intracellular cAMP during LABA/GCS combination therapy via inhibiting phosphodiesterase 4 (PDE4) and/or blocking the export of cAMP by ATP Binding Cassette Transporter C4 (ABCC4), will potentiate anti-inflammatory responses of mainstay LABA/GCS therapy. METHODS: Expression and localization experiments were performed using in situ hybridization and immunohistochemistry in human lung tissue from healthy subjects, while confirmatory transcript and protein expression analyses were performed in primary human airway epithelial cells and cell lines. Intervention experiments were performed on the human airway epithelial cell line, HBEC-6KT, by pre-treatment with combinations of LABA/GCS with PDE4 and/or ABCC4 inhibitors followed by Poly I:C or imiquimod challenge as a model for viral stimuli. Cytokine readouts for IL-6, IL-8, CXCL10/IP-10, and CCL5/RANTES were quantified by ELISA. RESULTS: Using archived human lung and human airway epithelial cells, ABCC4 gene and protein expression were confirmed in vitro and in situ. LABA/GCS attenuation of Poly I:C or imiquimod-induced IL-6 and IL-8 were potentiated with ABCC4 and PDE4 inhibition, which was greater when ABCC4 and PDE4 inhibition was combined. Modulation of cAMP levels had no impact on LABA/GCS modulation of Poly I:C-induced CXCL10/IP-10 or CCL5/RANTES. CONCLUSION: Modulation of intracellular cAMP levels by PDE4 or ABCC4 inhibition potentiates LABA/GCS efficacy in human airway epithelial cells challenged with viral stimuli. The data suggest further exploration of the value of adding cAMP modulators to mainstay LABA/GCS therapy in asthma for potentiated anti-inflammatory efficacy.


Subject(s)
Adrenergic beta-2 Receptor Agonists/pharmacology , Budesonide/pharmacology , Cyclic AMP/metabolism , Epithelial Cells/drug effects , Formoterol Fumarate/pharmacology , Glucocorticoids/pharmacology , Lung/drug effects , Aminopyridines/pharmacology , Benzamides/pharmacology , Benzothiazoles/pharmacology , Cell Line , Chemokines/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cyclohexanecarboxylic Acids/pharmacology , Cyclopropanes/pharmacology , Drug Synergism , Drug Therapy, Combination , Epithelial Cells/metabolism , Humans , Lung/metabolism , Multidrug Resistance-Associated Proteins/antagonists & inhibitors , Multidrug Resistance-Associated Proteins/metabolism , Nitriles/pharmacology , Phosphodiesterase 4 Inhibitors/pharmacology , Rolipram/pharmacology , Second Messenger Systems , Triazoles/pharmacology
10.
Head Neck ; 41(8): 2625-2635, 2019 08.
Article in English | MEDLINE | ID: mdl-30905082

ABSTRACT

BACKGROUND: We aimed to investigate the prognostic role of examined (dissected) lymph nodes (ELNs), negative LNs (NLNs), and positive (metastatic) LNs (PLNs) counts and LN ratio (LNR = PLNs/ELNs×100) in patients with major salivary gland cancer (SGC). METHODS: Data were retrieved for major SGC patients diagnosed between 1988 and 2011 from Surveillance, Epidemiology, and End Results program. RESULTS: We have included 5446 patients with major SGC. Most patients had parotid gland cancer (84.61%). Patients having >18 ELNs, >4 PLNs, and >33.33% LNR were associated with a worse survival. Moreover, older age, male patients, grade IV, distant stage, unmarried patients, submandibular gland cancer, and received chemotherapy but not received surgery were significantly associated with a worse survival. CONCLUSIONS: We demonstrated that patients with >18 ELNs and >4 PLNs counts, and >33.33% LNR were high-risk group patients. We strongly suggest adding the ELNs and PLNs counts and/or LNR into the current staging system.


Subject(s)
Lymph Nodes/pathology , Lymphatic Metastasis , Neoplasm Staging/methods , Salivary Gland Neoplasms/pathology , Adult , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Salivary Gland Neoplasms/mortality
11.
ACS Appl Mater Interfaces ; 10(36): 30794-30802, 2018 Sep 12.
Article in English | MEDLINE | ID: mdl-30073827

ABSTRACT

The superior carrier mobility of SiGe alloys make them a highly desirable channel material in complementary metal-oxide-semiconductor (CMOS) transistors. Passivation of the SiGe surface and the associated minimization of interface defects between SiGe channels and high- k dielectrics continues to be a challenge for fabrication of high-performance SiGe CMOS. A primary source of interface defects is interfacial GeO x. This interfacial oxide can be decomposed using an oxygen-scavenging reactive gate metal, which nearly eliminates the interfacial oxides, thereby decreasing the amount of GeO x at the interface; the remaining ultrathin interlayer is consistent with a SiO x-rich interface. Density functional theory simulations demonstrate that a sub-0.5 nm thick SiO x-rich surface layer can produce an electrically passivated HfO2/SiGe interface. To form this SiO x-rich interlayer, metal gate stack designs including Al/HfO2/SiGe and Pd/Ti/TiN/nanolaminate (NL)/SiGe (NL: HfO2-Al2O3) were investigated. As compared to the control Ni-gated devices, those with Al/HfO2/SiGe gate stacks demonstrated more than an order of magnitude reduction in interface defect density with a sub-0.5 nm SiO x-rich interfacial layer. To further increase the oxide capacitance, the devices were fabricated with a Ti oxygen scavenging layer separated from the HfO2 by a conductive TiN diffusion barrier (remote scavenging). The Pd/Ti/TiN/NL/SiGe structures exhibited significant capacitance enhancement along with a reduction in interface defect density.

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