Wet cleaning of Ta-based extreme ultraviolet photomasks at room temperature.

Owing to the wavelength-dependent limits of the deep ultraviolet exposure process, the semiconductor industry introduced extreme ultraviolet (EUV) lithography operating at a 13.5 nm wavelength. Traditional photomasks employ pellicles for protection; however, EUV-specific pellicles are not widely applicable to commercial processes, requiring the development of a EUV photomask cleaning method. In this study, a wet cleaning method for Ta-based EUV photomasks at room temperature was systematically examined in terms of key parameters, including the pattern step height, surface topography, and particulate count, via atomic force microscopy and x-ray reflectivity. Post sulfuric acid-hydrogen peroxide mixture (SPM) treatment, the photomask exhibited a stable step height, indicating minimal pattern degradation. Additionally, discernible alterations in the surface roughness and a decrease in particle count were observed, further indicating to the effectiveness of SPM-mediated cleaning. Conversely, following standard clean-1 (SC-1) treatment, while the pattern step height remained relatively unchanged, a notable increase in surface irregularities and macroscopic particulates was observed, suggesting a suboptimal cleaning efficiency of the SC-1 solution despite its potential for pattern structure preservation. Our room temperature wet cleaning method efficiently reduces wear-out and successfully eliminates contaminants, potentially prolonging the EUV photomask's productivity and durability.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Comparative Sensing and Judgment Control System for Temperature Maintenance for Optimal Treatment in Hyperthermic Intraperitoneal Chemotherapy Surgery.

For tumors wherein cancer cells remain in the tissue after colorectal cancer surgery, a hyperthermic anticancer agent is injected into the abdominal cavity to necrotize the remaining cancer cells with heat using a hyperthermic intraperitoneal chemotherapy system. However, during circulation, the processing temperature is out of range and the processing result is deteriorated. This paper proposes a look-up table (LUT) module design method that can stably maintain the processing temperature range during circulation via feedback. If the temperature decreases or increases, the LUT transmits a command signal to the heat exchanger to reduce or increase heat input, thereby maintaining the treatment temperature range. The command signal for increasing and decreasing heat input is Tp and Ta, respectively. The command signal for the treatment temperature range is Ts. If drug temperatures below 41 and above 43 °C are input to the LUT, it sends a Tp or Ta signal to the heat exchanger to increase or decrease the input heat, respectively. If the drug's temperature is 41-43 °C, the LUT generates a Ts signal and proceeds with the treatment. The proposed system can automatically control drug temperature using temperature feedback to ensure rapid, accurate, and safe treatment.

Full-length nuclear receptor allosteric regulation.

Nuclear receptors are a superfamily of transcription factors regulated by a wide range of lipids that include phospholipids, fatty acids, heme-based metabolites, and cholesterol-based steroids. Encoded as classic two-domain modular transcription factors, nuclear receptors possess a DNA-binding domain (DBD) and a lipid ligand-binding domain (LBD) containing a transcriptional activation function. Decades of structural studies on the isolated LBDs of nuclear receptors established that lipid-ligand binding allosterically regulates the conformation of the LBD, regulating transcriptional coregulator recruitment and thus nuclear receptor function. These structural studies have aided the development of several FDA-approved drugs, highlighting the importance of understanding the structure-function relationships between lipids and nuclear receptors. However, there are few published descriptions of full-length nuclear receptor structure and even fewer descriptions of how lipids might allosterically regulate full-length structure. Here, we examine multidomain interactions based on the published full-length nuclear receptor structures, evaluating the potential of interdomain interfaces within these nuclear receptors to act as inducible sites of allosteric regulation by lipids.

Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Efficacy and safety of cilostazol-based triple antiplatelet therapy compared with clopidogrel-based dual antiplatelet therapy in patients with acute ST-elevation myocardial infarction undergoing percutaneous coronary intervention: A multicenter, randomized, open-label, phase 4 trial.

BACKGROUND: Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. METHODS: In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. RESULTS: The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P = .297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P = .225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P = .029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P = .020). CONCLUSIONS: The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.

Immediate versus staged complete revascularization in patients with ST-segment elevation myocardial infarction and multivessel coronary artery disease: results from a prematurely discontinued randomized multicenter trial.

BACKGROUND: We aimed to compare clinical outcomes between immediate and staged complete revascularization in primary percutaneous coronary intervention (PCI) for treating ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD). METHODS: A total of 248 patients were enrolled in a prospective, randomized, and multicenter registry. Immediate revascularization was defined as one-time PCI of culprit and non-culprit lesions at the initial procedure. Staged revascularization was defined as PCI of non-culprit lesions at a later date (mean, 4.4 days; interquartile range, 1-11.4), following initial culprit revascularization. The end points were major adverse cardiovascular events (MACE; composite of total death, recurrent myocardial infarction, and revascularization), any individual components of MACE, cardiac death, stent thrombosis, and stroke at 12 months. RESULTS: During a follow-up of 1 year, MACE occurred in 12 patients (11.6%) in the immediate revascularization group and in 8 patients (7.5%) in staged revascularization group (hazard ratio [HR] 1.60, 95% confidence interval [CI] 0.65-3.91). The incidence of total death was numerically higher in the immediate group than in the staged group (9.7% vs 2.8%, HR 3.53, 95% CI 0.97-12.84); There were no significant differences between the 2 groups in risks of any individual component of MACE, cardiac death, stroke, and in-hospital complications, such as need for transfusion, bleeding, acute renal failure, and acute heart failure. This study was prematurely terminated due to halt of production of everolimus-eluting stents (manufactured as PROMUS Element by Boston Scientific, Natick, Massachusetts). CONCLUSIONS: Due to its limited power, no definite conclusion can be drawn regarding complete revascularization strategy from the present study. Further large randomized clinical trials would be warranted to confirm optimal timing of complete revascularization for patients with STEMI and MVD.

Assessment of the capacity of ChatGPT as a self-learning tool in medical pharmacology: a study using MCQs.

BACKGROUND: ChatGPT is a large language model developed by OpenAI that exhibits a remarkable ability to simulate human speech. This investigation attempts to evaluate the potential of ChatGPT as a standalone self-learning tool, with specific attention on its efficacy in answering multiple-choice questions (MCQs) and providing credible rationale for its responses. METHODS: The study used 78 test items from the Korean Comprehensive Basic Medical Sciences Examination (K-CBMSE) for years 2019 to 2021. 78 test items translated from Korean to English with four lead-in prompts per item resulted in a total of 312 MCQs. The MCQs were submitted to ChatGPT and the responses were analyzed for correctness, consistency, and relevance. RESULTS: ChatGPT responded with an overall accuracy of 76.0%. Compared to its performance on recall and interpretation questions, the model performed poorly on problem-solving questions. ChatGPT offered correct rationales for 77.8% (182/234) of the responses, with errors primarily arising from faulty information and flawed reasoning. In terms of references, ChatGPT provided incorrect citations for 69.7% (191/274) of the responses. While the veracity of reference paragraphs could not be ascertained, 77.0% (47/61) were deemed pertinent and accurate with respect to the answer key. CONCLUSION: The current version of ChatGPT has limitations in accurately answering MCQs and generating correct and relevant rationales, particularly when it comes to referencing. To avoid possible threats such as spreading inaccuracies and decreasing critical thinking skills, ChatGPT should be used with supervision.

Estimation of One-Repetition Maximum, Type, and Repetition of Resistance Band Exercise Using RGB Camera and Inertial Measurement Unit Sensors.

Resistance bands are widely used nowadays to enhance muscle strength due to their high portability, but the relationship between resistance band workouts and conventional dumbbell weight training is still unclear. Thus, this study suggests a convolutional neural network model that identifies the type of band workout and counts the number of repetitions and a regression model that deduces the band force that corresponds to the one-repetition maximum. Thirty subjects performed five different exercises using resistance bands and dumbbells. Joint movements during each exercise were collected using a camera and an inertial measurement unit. By using different types of input data, several models were created and compared. As a result, the accuracy of the convolutional neural network model using inertial measurement units and joint position is 98.83%. The mean absolute error of the repetition counting algorithm ranges from 0.88 (seated row) to 3.21 (overhead triceps extension). Lastly, the values of adjusted r-square for the 5 exercises are 0.8415 (chest press), 0.9202 (shoulder press), 0.8429 (seated row), 0.8778 (biceps curl), and 0.9232 (overhead triceps extension). In conclusion, the model using 10-channel inertial measurement unit data and joint position data has the best accuracy. However, the model needs to improve the inaccuracies resulting from non-linear movements and one-time performance.

Tunable, stable, and reversible n-type doping of MoS2via thermal treatment in N-methyl-2-pyrrolidone.

Here, we report a highly stable and reversible n-type doping of monolayer MoS2using thermal treatment in N-methyl-2-pyrrolidone (NMP). The Raman and photoluminescence spectroscopic measurements as well as the device performance of the MoS2transistors suggested a stronger n-type doping effect with increasing time and temperature of the thermal treatment in NMP. Within the given time (5-60 min) and temperature (50 °C-110 °C), the surface treatment in NMP provided an electron concentration from 6 × 1010to 2 × 1012cm-2. Owing to the n-type doping effect, the thermal treatment in NMP reduced the contact resistance and enhanced the field-effect mobility of the MoS2transistors. The n-type doping via thermal treatment in NMP remained effective for more than 12 months in ambient air, and could be completely removed after immersion in isopropanol. These results demonstrate that thermal treatment in NMP can be a facile and effective route to achieve stable and reversible doping of two-dimensional materials including MoS2for their applications in high-performance electronics and optoelectronics.

Investigating the Functional Role of the Cysteine Residue in Dehydrin from the Arctic Mouse-Ear Chickweed Cerastium arcticum.

The stress-responsive, SK5 subclass, dehydrin gene, CaDHN, has been identified from the Arctic mouse-ear chickweed Cerastium arcticum. CaDHN contains an unusual single cysteine residue (Cys143), which can form intermolecular disulfide bonds. Mutational analysis and a redox experiment confirmed that the dimerization of CaDHN was the result of an intermolecular disulfide bond between the cysteine residues. The biochemical and physiological functions of the mutant C143A were also investigated by in vitro and in vivo assays using yeast cells, where it enhanced the scavenging of reactive oxygen species (ROS) by neutralizing hydrogen peroxide. Our results show that the cysteine residue in CaDHN helps to enhance C. arcticum tolerance to abiotic stress by regulating the dimerization of the intrinsically disordered CaDHN protein, which acts as a defense mechanism against extreme polar environments.

Enhanced performance of multilayer MoS2transistors encapsulated with a photoresist.

We report the enhanced performance of multilayer MoS2transistors by AZ®5214E photoresist encapsulation. The MoS2transistors with SiO2bottom-gate dielectrics exhibited an average increase of 4× in the on/off-current ratio and a 50% increase in the field-effect mobility after photoresist encapsulation. The Y-function method further showed a decrease of 87% in the contact resistance and a 30% increase in the intrinsic carrier mobility, suggesting that photoresist encapsulation provides not only n-type doping but also dielectric screening. The Raman spectra of the photoresist-encapsulated MoS2also suggest n-type doping, which may be due to the electropositive hydroxyl groups in the photoresist. The operation of the photoresist-encapsulated MoS2transistors remained stable in ambient air for at least one month. These results demonstrate that simple photoresist encapsulation can be an effective performance booster of MoS2and other transition metal dichalcogenides transistors.

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. CONCLUSIONS: Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.

Impact of chronic outward force on arterial responses of proximal and distal of long superficial femoral artery stent.

BACKGROUND: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA. METHODS: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis. RESULTS: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm2 vs. 8.53 ± 5.18 mm2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001). CONCLUSIONS: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

Analysis of Visuo Motor Control between Dominant Hand and Non-Dominant Hand for Effective Human-Robot Collaboration.

The human-in-the-loop technology requires studies on sensory-motor characteristics of each hand for an effective human-robot collaboration. This study aims to investigate the differences in visuomotor control between the dominant (DH) and non-dominant hands in tracking a target in the three-dimensional space. We compared the circular tracking performances of the hands on the frontal plane of the virtual reality space in terms of radial position error (ΔR), phase error (Δθ), acceleration error (Δa), and dimensionless squared jerk (DSJ) at four different speeds for 30 subjects. ΔR and Δθ significantly differed at relatively high speeds (ΔR: 0.5 Hz; Δθ: 0.5, 0.75 Hz), with maximum values of ≤1% compared to the target trajectory radius. DSJ significantly differed only at low speeds (0.125, 0.25 Hz), whereas Δa significantly differed at all speeds. In summary, the feedback-control mechanism of the DH has a wider range of speed control capability and is efficient according to an energy saving model. The central nervous system (CNS) uses different models for the two hands, which react dissimilarly. Despite the precise control of the DH, both hands exhibited dependences on limb kinematic properties at high speeds (0.75 Hz). Thus, the CNS uses a different strategy according to the model for optimal results.

Analysis of Control Characteristics between Dominant and Non-Dominant Hands by Transient Responses of Circular Tracking Movements in 3D Virtual Reality Space.

Human movement is a controlled result of the sensory-motor system, and the motor control mechanism has been studied through diverse movements. The present study examined control characteristics of dominant and non-dominant hands by analyzing the transient responses of circular tracking movements in 3D virtual reality space. A visual target rotated in a circular trajectory at four different speeds, and 29 participants tracked the target with their hands. The position of each subject's hand was measured, and the following three parameters were investigated: normalized initial peak velocity (IPV2), initial peak time (IPT2), and time delay (TD2). The IPV2 of both hands decreased as target speed increased. The results of IPT2 revealed that the dominant hand reached its peak velocity 0.0423 s earlier than the non-dominant hand, regardless of target speed. The TD2 of the hands diminished by 0.0218 s on average as target speed increased, but the dominant hand statistically revealed a 0.0417-s shorter TD2 than the non-dominant hand. Velocity-control performances from the IPV2 and IPT2 suggested that an identical internal model controls movement in both hands, whereas the dominant hand is likely more experienced than the non-dominant hand in reacting to neural commands, resulting in better reactivity in the movement task.

Intricacies of Upper Blepharoplasty in Asian Burden Lids.

Differences between Oriental and Caucasian eyelids have been explained in great detail in several reports in the past. The purpose of this article is to discuss the functional aspects of Asian double fold upper blepharoplasty and to present techniques that help to improve both the functional and cosmetic outcomes and satisfaction after surgery. The eyes of Asians are relatively small with thick skin in the eyelids and periorbital area. They typically lack the upper eyelid crease (creating the so-called double eyelid) due to burden factors like thick skin, hypertrophied orbicularis oculi muscle (OOM), submuscular fibroadipose tissue, thick orbital septum, abundant preaponeurotic fat, and lower positioned transverse ligament. Asian eyes may also have a superior visual field defect due to skin overriding the upper lid margin (skin-OOM-fat complex slide down). These burden factors result in the eyelashes appearing short and becoming misdirected and pressed toward the globe, causing functional discomfort. As a compensatory mechanism, Asian people tend to engage the frontalis muscle to lift the eyebrow to help them open their eyes. Along with aesthetic enhancement, double-eyelid surgery in Asian burden lids can improve the functional deficiencies helping the patients to open the eyes more easily. In addition, treatment of the Mongolian fold (medial epicanthal fold), caused by medial hypertrophy of preseptal OOM, augments the surgical results. In this report, we present the appropriate preoperative assessment, surgical technique, and postoperative care that should be employed to achieve consistently good functional and aesthetic outcomes in these patients.

Branched Copper Oxide Nanoparticles Induce Highly Selective Ethylene Production by Electrochemical Carbon Dioxide Reduction.

For long-term storage of renewable energy, the electrochemical carbon dioxide reduction reaction (CO2RR) offers a promising option for converting electricity to permanent forms of chemical energy. In this work, we present highly selective ethylene production dependent upon the catalyst morphology using copper oxide nanoparticles. The branched CuO nanoparticles were synthesized and then deposited on conductive carbon materials. After activation, the major copper species changed to Cu+, and the resulting electrocatalyst exhibited a high Faradaic efficiency (FE) of ethylene reaching over 70% and a hydrogen FE of 30% without any byproducts in a neutral aqueous solution. The catalyst also showed high durability (up to 12 h) with the ethylene FE over 65%. Compared to cubic morphology, the initial branched copper oxide structure formed highly active domains with interfaces and junctions in-between during activation, which caused large surface area with high local pH leading to high selectivity and activity for ethylene production.

Fragile X Mental Retardation Protein positively regulates PKA anchor Rugose and PKA activity to control actin assembly in learning/memory circuitry.

Recent work shows Fragile X Mental Retardation Protein (FMRP) drives the translation of very large proteins (>2000 aa) mediating neurodevelopment. Loss of function results in Fragile X syndrome (FXS), the leading heritable cause of intellectual disability (ID) and autism spectrum disorder (ASD). Using the Drosophila FXS disease model, we discover FMRP positively regulates the translation of the very large A-Kinase Anchor Protein (AKAP) Rugose (>3000 aa), homolog of ASD-associated human Neurobeachin (NBEA). In the central brain Mushroom Body (MB) circuit, where Protein Kinase A (PKA) signaling is necessary for learning/memory, FMRP loss reduces Rugose levels and targeted FMRP overexpression elevates Rugose levels. Using a new in vivo transgenic PKA activity reporter (PKA-SPARK), we find FMRP loss reduces PKA activity in MB Kenyon cells whereas FMRP overexpression elevates PKA activity. Consistently, loss of Rugose reduces PKA activity, but Rugose overexpression has no independent effect. A well-established PKA output is regulation of F-actin cytoskeleton dynamics. In the FXS disease model, F-actin is aberrantly accumulated in MB lobes and single MB Kenyon cells. Consistently, Rugose loss results in similar F-actin accumulation. Moreover, targeted FMRP, Rugose and PKA overexpression all result in increased F-actin accumulation in the MB circuit. These findings uncover a FMRP-Rugose-PKA mechanism regulating actin cytoskeleton. This study reveals a novel FMRP mechanism controlling neuronal PKA activity, and demonstrates a shared mechanistic connection between FXS and NBEA associated ASD disease states, with a common link to PKA and F-actin misregulation in brain neural circuits. SIGNIFICANCE STATEMENT: Autism spectrum disorder (ASD) arises from a wide array of genetic lesions, and it is therefore critical to identify common underlying molecular mechanisms. Here, we link two ASD states; Neurobeachin (NBEA) associated ASD and Fragile X syndrome (FXS), the most common inherited ASD. Using established Drosophila disease models, we find Fragile X Mental Retardation Protein (FMRP) positively regulates translation of NBEA homolog Rugose, consistent with a recent advance showing FMRP promotes translation of very large proteins associated with ASD. FXS exhibits reduced cAMP induction, a potent activator of PKA, and Rugose/NBEA is a PKA anchor. Consistently, we find brain PKA activity strikingly reduced in both ASD models. We discover this pathway regulation controls actin cytoskeleton dynamics in brain neural circuits.

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

BACKGROUND: Current guidelines recommend dual antiplatelet therapy (DAPT) of aspirin plus a P2Y12 inhibitor for at least 12 months after implantation of drug-eluting stents (DES) in patients with acute coronary syndrome. However, available data about the optimal duration of DAPT in patients with acute coronary syndrome undergoing percutaneous coronary intervention are scant. We aimed to investigate whether a 6-month duration of DAPT would be non-inferior to the conventional 12-month or longer duration of DAPT in this population. METHODS: We did a randomised, open-label, non-inferiority trial at 31 centres in South Korea. Patients were eligible if they had unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, and underwent percutaneous coronary intervention. Enrolled patients were randomly assigned, via a web-based system by computer-generated block randomisation, to either the 6-month DAPT group or to the 12-month or longer DAPT group, with stratification by site, clinical presentation, and diabetes. Assessors were masked to treatment allocation. The primary endpoint was a composite of all-cause death, myocardial infarction, or stroke at 18 months after the index procedure in the intention-to-treat population. Secondary endpoints were the individual components of the primary endpoint; definite or probable stent thrombosis as defined by the Academic Research Consortium; and Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 18 months after the index procedure. The primary endpoint was also analysed per protocol. This trial is registered with ClinicalTrials.gov, number NCT01701453. FINDINGS: Between Sept 5, 2012, and Dec 31, 2015, we randomly assigned 2712 patients; 1357 to the 6-month DAPT group and 1355 to the 12-month or longer DAPT group. Clopidogrel was used as a P2Y12 inhibitor for DAPT in 1082 (79·7%) patients in the 6-month DAPT group and in 1109 (81·8%) patients in the 12-month or longer DAPT group. The primary endpoint occurred in 63 patients in the 6-month DAPT group and in 56 patients in the 12-month or longer DAPT group (cumulative event rate 4·7% vs 4·2%; absolute risk difference 0·5%; upper limit of one-sided 95% CI 1·8%; pnon-inferiority=0·03 with a predefined non-inferiority margin of 2·0%). Although all-cause mortality did not differ significantly between the 6-month DAPT group and the 12-month or longer DAPT group (35 [2·6%] patients vs 39 [2·9%]; hazard ratio [HR] 0·90 [95% CI 0·57-1·42]; p=0·90) and neither did stroke (11 [0·8%] patients vs 12 [0·9%]; 0·92 [0·41-2·08]; p=0·84), myocardial infarction occurred more frequently in the 6-month DAPT group than in the 12-month or longer DAPT group (24 [1·8%] patients vs ten [0·8%]; 2·41 [1·15-5·05]; p=0·02). 15 (1·1%) patients had stent thrombosis in the 6-month DAPT group compared with ten (0·7%) in the 12-month or longer DAPT group (HR 1·50 [95% CI 0·68-3·35]; p=0·32). The rate of BARC type 2-5 bleeding was 2·7% (35 patients) in the 6-month DAPT group and 3·9% (51 patients) in the 12-month or longer DAPT group (HR 0·69 [95% CI 0·45-1·05]; p=0·09). Results from the per-protocol analysis were similar to those from the intention-to-treat analysis. INTERPRETATION: The increased risk of myocardial infarction with 6-month DAPT and the wide non-inferiority margin prevent us from concluding that short-term DAPT is safe in patients with acute coronary syndrome undergoing percutaneous coronary intervention with current-generation DES. Prolonged DAPT in patients with acute coronary syndrome without excessive risk of bleeding should remain the standard of care. FUNDING: Abbott Vascular Korea, Medtronic Vascular Korea, Biosensors Inc, and Dong-A ST.