Development of Wafer-Type Plasma Monitoring Sensor with Automated Robot Arm Transfer Capability for Two-Dimensional In Situ Processing Plasma Diagnosis.

In this work, we propose our newly developed wafer-type plasma monitoring sensor based on a floating-type double probe method that can be useful for two-dimensional (2D) in situ plasma diagnosis within a semiconductor processing chamber. A key achievement of this work is the first realization of an ultra-thin plasma monitoring sensor with a system thickness of ~1.4 mm, which supports a fully automated robot arm transfer capability for in situ plasma diagnosis. To the best of our knowledge, it is the thinnest accomplishment among all wafer-type plasma monitoring sensors. Our proposed sensor is assembled with two Si wafers and SiO2-based probes; accordingly, it makes it possible to monitor the actual dynamics of processing plasmas under electrostatic chucking (ESC) conditions. Also, it allows for the prevention of chamber contamination issues after continuously exposing the radio frequency (RF) to various processing gases. Using a test-bed chamber, we successfully demonstrated the feasibility and system performance of the proposed sensor, including robot arm transfer capability, vacuum and thermal stress durability, and data integrity and reproducibility. Consequently, compared with the conventional plasma diagnostic tools, we expect that our proposed sensor will be highly beneficial for tool-to-tool matching (TTTM) and/or for studying various plasma-related items by more accurately providing the parameters of processing plasmas, further saving both time and manpower resources required for preventive maintenance (PM) routines as well.

Spatially targeted brain cancer immunotherapy with closed-loop controlled focused ultrasound and immune checkpoint blockade.

Despite the challenges in treating glioblastomas (GBMs) with immune adjuvants, increasing evidence suggests that targeting the immune cells within the tumor microenvironment (TME) can lead to improved responses. Here, we present a closed-loop controlled, microbubble-enhanced focused ultrasound (MB-FUS) system and test its abilities to safely and effectively treat GBMs using immune checkpoint blockade. The proposed system can fine-tune the exposure settings to promote MB acoustic emission-dependent expression of the proinflammatory marker ICAM-1 and delivery of anti-PD1 in a mouse model of GBM. In addition to enhanced interaction of proinflammatory macrophages within the PD1-expressing TME and significant improvement in survival (P < 0.05), the combined treatment induced long-lived memory T cell formation within the brain that supported tumor rejection in rechallenge experiments. Collectively, our findings demonstrate the ability of MB-FUS to augment the therapeutic impact of immune checkpoint blockade in GBMs and reinforce the notion of spatially tumor-targeted (loco-regional) brain cancer immunotherapy.

Oncology Trainee Perceptions of the Prior Authorization Process: A National Survey.

PURPOSE: The medical trainee perspective regarding the prior authorization process has not been previously assessed. Here we evaluate the perceptions of radiation and medical oncology trainees regarding the prior authorization process and its effect on their training and patient care. METHODS AND MATERIALS: A 12-question, nonincentivized, electronic national survey of radiation and medical oncology trainees at all Accreditation Council for Graduate Medical Education accredited oncology programs was conducted. Participation, perspectives, and experiences with the prior authorization process were assessed by Likert scale, free response, and multiple response selection. RESULTS: Between January and March of 2019, the survey was distributed to 1505 trainees at 76 institutions with responses from 174/616 radiation (28.2%) and 139/889 medical oncology trainees (15.6%). The majority (69.2%) reported participating in the prior authorization process (radiation: 78.2% vs medical: 57.6%; P < .01). Most trainees (71%) reported concern for decline in the quality of patient care due to the prior authorization process. The majority of trainees (77.1%) reported decreased enthusiasm for work and choice of profession, with a higher incidence in medical oncology trainees (83.1% vs 73.7%, P = .04). The most commonly recommended modifications by trainees included that the insurance reviewer be in the same specialty as the ordering provider (87.7%), providers be compensated for participation (82.7%), and turnaround time be more rapid (74.3%). CONCLUSIONS: These data indicate that trainees in US oncology programs are active participants in the prior authorization process and report that prior authorization approvals negatively influence their medical training and the quality of patient care. Additional efforts to revise the insurance approval process are warranted.

Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound.

Brain tumors are particularly challenging malignancies, due to their location in a structurally and functionally distinct part of the human body - the central nervous system (CNS). The CNS is separated and protected by a unique system of brain and blood vessel cells which together prevent most bloodborne therapeutics from entering the brain tumor microenvironment (TME). Recently, great strides have been made through microbubble (MB) ultrasound contrast agents in conjunction with ultrasound energy to locally increase the permeability of brain vessels and modulate the brain TME. As we elaborate in this review, this physical method can effectively deliver a wide range of anticancer agents, including chemotherapeutics, antibodies, and nanoparticle drug conjugates across a range of preclinical brain tumors, including high grade glioma (glioblastoma), diffuse intrinsic pontine gliomas, and brain metastasis. Moreover, recent evidence suggests that this technology can promote the effective delivery of novel immunotherapeutic agents, including immune check-point inhibitors and chimeric antigen receptor T cells, among others. With early clinical studies demonstrating safety, and several Phase I/II trials testing the preclinical findings underway, this technology is making firm steps towards shaping the future treatments of primary and metastatic brain cancer. By elaborating on its key components, including ultrasound systems and MB technology, along with methods for closed-loop spatial and temporal control of MB activity, we highlight how this technology can be tuned to enable new, personalized treatment strategies for primary brain malignancies and brain metastases.

Improvement of Automatic Measurement Evaluation System for Subway Structures by Adjacent Excavation.

This study evaluated the structural stability of subway structures based on adjacent excavations by comparing automatically measured and numerically analyzed data. The reliability of the automated measurement methodology was evaluated by first applying probability statistical analysis to the measured results and then comparing these results with the numerically analyzed results. An improvement in the calculation method evaluation system, including the method of processing and analysis of the automatically measured data of subway structures through the average value of probability density, was proposed. As a result of the field measurement and numerical analysis, the measured results of tunnel displacement and track deformation exhibited some differences. However, it was determined that the construction stage and location where the maximum values of the tunnel displacement and track deformation occurred had similarities.

Single-cell analysis reveals effective siRNA delivery in brain tumors with microbubble-enhanced ultrasound and cationic nanoparticles.

RNA-based therapies offer unique advantages for treating brain tumors. However, tumor penetrance and uptake are hampered by RNA therapeutic size, charge, and need to be "packaged" in large carriers to improve bioavailability. Here, we have examined delivery of siRNA, packaged in 50-nm cationic lipid-polymer hybrid nanoparticles (LPHs:siRNA), combined with microbubble-enhanced focused ultrasound (MB-FUS) in pediatric and adult preclinical brain tumor models. Using single-cell image analysis, we show that MB-FUS in combination with LPHs:siRNA leads to more than 10-fold improvement in siRNA delivery into brain tumor microenvironments of the two models. MB-FUS delivery of Smoothened (SMO) targeting siRNAs reduces SMO protein production and markedly increases tumor cell death in the SMO-activated medulloblastoma model. Moreover, our analysis reveals that MB-FUS and nanoparticle properties can be optimized to maximize delivery in the brain tumor microenvironment, thereby serving as a platform for developing next-generation tunable delivery systems for RNA-based therapy in brain tumors.

Chemical and physical reinforcement behavior of dialdehyde nanocellulose in PVA composite film: A comparison of nanofiber and nanocrystal.

Nanocellulose can be categorized into cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs). CNFs and CNCs are oxidized by periodate oxidation to introduce dialdehyde groups, which can act as a crosslinking agent. Polyvinyl alcohol (PVA) is widely used in food packaging, however, it is vulnerable to aqueous environments. In this study, dialdehyde nanocellulose-reinforced PVA nanocomposite films were fabricated to enhance the water resistance. CNF and CNC were oxidized using varying amounts of sodium periodate and the selected fillers were designated as DCNF and DCNC, respectively. In the case of DCNF, physicochemical networking effect was induced to PVA, while DCNC showed only chemical network reinforcement effect. However, both PVA/DCNF and PVA/DCNC composite films have significantly improved vulnerabilities in moisture environment compared to PVA films. These results indicate that while physical network structures are important, the chemically formed network structures can play a crucial role in enhancing the water resistance of PVA films.

Chemical and physical reinforcement of hydrophilic gelatin film with di-aldehyde nanocellulose.

Gelatin is a representative hydrophilic protein material with remarkable biocompatibility and biodegradability. From the aspect of materials processing, gelatin also has the advantage that its entire fabrication process can be performed in an aqueous solution. However, practical application of various gelatin materials-in particular gelatin films-has thus far been limited because of their weak mechanical properties and vulnerability under aqueous environments. To overcome these disadvantages, both physical reinforcement approaches and chemical cross-linking agents have been tested. However, little research has been done to make these two roles work at the same time. In this study, cellulose nanocrystals containing aldehyde groups were prepared via a periodate oxidation process and used for cross-linkable reinforcement of gelatin-based bio-composite films. The results revealed that the di-aldehyde cellulose nanocrystal (D-CNC) could react and covalently cross-link with the amine group of the gelatin molecules via Schiff base formation and compared with neat CNC. The gelatin bio-composite film reinforced with the prepared D-CNC exhibited excellent tensile properties and water resistance, and its mechanical and hydrophilic properties could be easily controlled by adjusting the D-CNC content and was greater than addition of same amount in CNC. Therefore, D-CNC will facilitate the widespread use of existing water-soluble polymers, especially natural hydrophilic proteins and can be used in conventional application fields such as the food, pharmaceutical, and biomedical industries.

Retinoic Acid Receptor-Related Receptor Alpha Ameliorates Autoimmune Arthritis via Inhibiting of Th17 Cells and Osteoclastogenesis.

Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis characterized by progressive joint destruction. IL-17-producing CD4+ T (Th17) cells play pivotal roles in RA development and progression. Retinoic acid receptor-related orphan receptor alpha (RORα) is a negative regulator of inflammatory responses, whereas RORγt, another member of the ROR family, is a Th17 lineage-specific transcription factor. Here, we investigated the immunoregulatory potential of RORα in collagen-induced arthritis (CIA) mice, an experimental model of RA. Cholesterol sulfate (CS) or SR1078, a ligand of RORα, inhibited RORγt expression and Th17 differentiation in vitro. In addition, fortification of RORα in T cells inhibited the expression levels of glycolysis-associated genes. We found that RORα overexpression in CIA mice attenuated the clinical and histological severities of inflammatory arthritis. The anti-arthritic effect of RORα was associated with suppressed Th17 differentiation and attenuated mTOR-STAT3 signaling in T cells. Furthermore, altered RORα activity could directly affect osteoclastogenesis implicated in progressive bone destruction in human RA. Our findings defined a critical role of RORα in the pathogenesis of RA. These data suggest that RORα may have novel therapeutic uses in the treatment of RA.

Congenital lobar emphysema concurrent with pneumothorax and pneumomediastinum in a dog.

A two-year-old castrated male Pomeranian dog was referred with the chief complaints of coughing and subcutaneous emphysema. On physical examination, the crepitant areas were palpable. When auscultated, the right chest was absent of respiratory sound, while the sound of the opposite side was enhanced. Radiographs presented pneumothorax and pneumomediastinum. On computed tomography, hypoattenuated bulla-like lesion at right middle lung lobe and trapped air in mediastinum were shown. After patient stabilization, surgery for excision of affected lobe was performed. During follow-up period, there were no recurrence and complication on radiographic examination. Based on clinical and pathological findings, the dog was diagnosed as congenital lobar emphysema.

An Ultrasonic Multi-Beam Concentration Meter with a Neuro-Fuzzy Algorithm for Water Treatment Plants.

Ultrasonic concentration meters have widely been used at water purification, sewage treatment and waste water treatment plants to sort and transfer high concentration sludges and to control the amount of chemical dosage. When an unusual substance is contained in the sludge, however, the attenuation of ultrasonic waves could be increased or not be transmitted to the receiver. In this case, the value measured by a concentration meter is higher than the actual density value or vibration. As well, it is difficult to automate the residuals treatment process according to the various problems such as sludge attachment or sensor failure. An ultrasonic multi-beam concentration sensor was considered to solve these problems, but an abnormal concentration value of a specific ultrasonic beam degrades the accuracy of the entire measurement in case of using a conventional arithmetic mean for all measurement values, so this paper proposes a method to improve the accuracy of the sludge concentration determination by choosing reliable sensor values and applying a neuro-fuzzy learning algorithm. The newly developed meter is proven to render useful results from a variety of experiments on a real water treatment plant.

Experimental Investigation of Mechanical and Thermal Properties of Silica Nanoparticle-Reinforced Poly(acrylamide) Nanocomposite Hydrogels.

Current studies investigating properties of nanoparticle-reinforced polymers have shown that nanocomposites often exhibit improved properties compared to neat polymers. However, over two decades of research, using both experimental studies and modeling analyses, has not fully elucidated the mechanistic underpinnings behind these enhancements. Moreover, few studies have focused on developing an understanding among two or more polymer properties affected by incorporation of nanomaterials. In our study, we investigated the elastic and thermal properties of poly(acrylamide) hydrogels containing silica nanoparticles. Both nanoparticle concentration and size affected hydrogel properties, with similar trends in enhancements observed for elastic modulus and thermal diffusivity. We also observed significantly lower swellability for hydrogel nanocomposites relative to neat hydrogels, consistent with previous work suggesting that nanoparticles can mediate pseudo crosslinking within polymer networks. Collectively, these results indicate the ability to develop next-generation composite materials with enhanced mechanical and thermal properties by increasing the average crosslinking density using nanoparticles.

In vivo and in vitro application of black soybean peptides in the amelioration of endoplasmic reticulum stress and improvement of insulin resistance.

AIMS: Hepatic endoplasmic reticulum (ER) stress plays a key role in the development of obesity-induced insulin resistance. This study evaluated the effects of peptides from black soybean (BSP) on ER stress and insulin signaling in vitro and in vivo. MAIN METHODS: Using C2C12 myotubes or HepG2 cells, we evaluated the effects of BSP on the expression of proteins involved in insulin signaling and in the ER stress response in insulin-sensitive or insulin-resistant cells. BSP was given orally to db/db mice for 5weeks to investigate its antidiabetic effects in vivo and the underlying mechanisms. KEY FINDINGS: BSP increased GLUT4 translocation and glucose transport in myotubes and stimulated Akt-mediated glycogen synthase kinase-3beta (GSK-3beta) and Foxo1 phosphorylation in HepG2 cells. BSP significantly restored the suppression of insulin-mediated Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the activation of ER stress-responsive proteins by thapsigargin. BSP also significantly reduced blood glucose and improved glucose tolerance in db/db mice. The serum lipid profile (triglyceride and high-density lipoprotein concentrations) improved concomitantly with the BSP-induced downregulation of hepatic fatty acid synthase expression in db/db mice. Consistent with the results observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress response in diabetic mice concomitantly with an increased expression of phospho-Foxo1. SIGNIFICANCE: A peptide mixture, BSP, showed beneficial effects through multiple mechanisms involving the suppression of hepatic ER stress and restoration of insulin resistance, suggesting that it has potential as an antidiabetic agent.

Enhanced thermoelectric figure-of-merit in nanostructured p-type silicon germanium bulk alloys.

A dimensionless thermoelectric figure-of-merit (ZT) of 0.95 in p-type nanostructured bulk silicon germanium (SiGe) alloys is achieved, which is about 90% higher than what is currently used in space flight missions, and 50% higher than the reported record in p-type SiGe alloys. These nanostructured bulk materials were made by using a direct current-induced hot press of mechanically alloyed nanopowders that were initially synthesized by ball milling of commercial grade Si and Ge chunks with boron powder. The enhancement of ZT is due to a large reduction of thermal conductivity caused by the increased phonon scattering at the grain boundaries of the nanostructures combined with an increased power factor at high temperatures.

Stress-induced cardiomyopathy presenting as acute myocardial infarction.

Stress-induced cardiomyopathy is described as an acute cardiomyopathy that occurs under the influence of an excessive level of catecholamine related to intense emotional stress. A 64-year-old woman presented with symptoms of acute myocardial infarction after emotional upset, but her coronary angiographic findings were revealed to be normal. Diffuse T wave inversions were observed in her electrocardiograms with akinetic wall motions sparing the basal segments in her left ventriculography. After four months, her electrocardiogram and echocardiogram findings had completely returned to normal. The precise diagnosis of this acute cardiomyopathy must be emphasized because it can initially be misdiagnosed as acute coronary syndromes. However in complete contrast to acute myocardial infarction, it has a rapid and favorable recovery with hardly any sequelae after a few months.