Special Target Research Articles

A label-free AuNP bioprobe-assisted CRISPR/Cas12a colorimetric platform for high-throughput detection of Staphylococcus aureus ST398

Rapid and accurate screening of foodborne pathogens in contaminated food is with great significance for food safety. AuNPs-based colorimetric assay is an attractive strategy in the field of food safety inspection, but is limited by tedious probe preparation, low color rendering resolution, and narrow color gamut. Herein, we proposed an e nhanced c olorimetric p latform based on the C RISPR/Cas12a system and label-free D NA-AuNP p robe (CDP-ECP) for high-throughput detection of Staphylococcus aureus ST398. In this strategy, a novel and specific gene targeting S. aureus ST398 was identified and efficient AuNP-bioprobe was successfully prepared. Through a PCR/RAA amplification, the trans -ssDNA cleavage ability induced by target DNA product triggered an aggregation performance for the prepared AuNP-bioprobe pairs, which could realize target colorimetric detection within 50 min. Under optimal conditions, the colorimetric assay could detect as low as 6.4 × 10 2 cfu/mL of S. aureus ST398 in pure culture. Specific gene mining and target-induced trans -cleavage character gave this method a superior specificity and anti-interference. More importantly, this colorimetric method can be extended to a high-throughput platform for rapid detection of spiked and natural sample by using a common microplate reader. Since it is simple to operate, low cost, high sensitivity and specificity, this new platform is fully qualified for clinical diagnosis, environmental monitoring onsite testing requirements. • This efficient colorimetric assay based CRISPR/Cas12a system and novel special target enables highly specific and sensitive detection of Staphylococcus aureus ST398. • The improved, instantaneous deep-freezing method was proposed to achieve low cost and high efficiency preparation of DNA-AuNP probes. • The clever combination with enhanced hybridisation buffer and low-speed centrifugation can significantly improve the signal-to-noise ratio of colorimetric assay. • The visual platform shows excellent high-throughput performance for S. aureus ST398 detection in natural food samples.

A Switching Mode Control Scheme for the Hovering Control of Quadrotor Unmanned Aerial Vehicles

This paper presents a novel switching mode control scheme for the six-DOF hovering control of underactuated quadrotor unmanned aerial vehicles (QUAVs) with strong coupling. Through this paper, the full six states of the position and attitude of the QUAV can be controlled to the special target configuration in a fixed time. First, a continuously differentiable fixed time controller with a state constraint was designed for the position system. Second, a fixed-time integral sliding mode controller was designed for the attitude subsystem. Thirdly, a switching law was designed to switch the above two types of controllers a limited number of times during hovering control. Additionally, the crash problem is fully discussed during the entire control process. In summary, the full-state hover mission was completed. The simulation experiments verify the effectiveness of the control algorithm.

Periodic flank modifications for optimal excitation behavior of practical gear geometries

The design of modern transmissions faces new challenges regarding the main design principles efficiency, service life and noise emissions. These challenges are further intensified by the progressing electrification of vehicle drive systems and the associated trend towards higher rotational speeds. In order to achieve the design objectives at the level of flank modifications, the microgeometry has to satisfy partially competing requirements. Most present gears are designed with combinations of standard modifications to obtain the best possible compromise between the competing goals. The application of periodic modifications provides a possibility to avoid particularly the trade-off between the two design principles load carrying capacity and excitation. The periodic modifications directly compensate the alternating part of the elastic deformations in the mesh without changing the load distribution. They can be used to optimize the excitation behavior independently of the load carrying capacity. Theoretical studies show the potential of periodic modifications to optimize the excitation behavior for a special target load or even for broad load ranges. Experimental investigations at two test rigs of the Gear Research Center (FZG) verify the effectiveness of these flank forms to optimize the excitation behavior for different practical gear main geometries.

Lokakarya Satuan Pendidikan Aman Bencana (SPAB) dan Psychological First Aid (PFA)

One of the FPRB volunteers' tasks is to strengthen the capacity of schools in Kabupaten Bandung for the government-initiated program, namely socializing the SPAB (Satuan Pendidikan Aman Bencana). Given that a disaster situation is one that puts survivors in a state of crisis, the survivors (disaster victims) are likely to have emotional reactions in various ways. The FPRB Volunteers of Kabupaten Bandung are the PKM's special target for the 2020-2022 period. The reason for the FPRB Volunteers of Kabupaten Bandung being the subject of the PKM is due to the needs of the organization, which will soon be implemented in 41 schools in 31 sub-districts throughout Kabupaten Bandung as the beneficiaries of the SPAB carried out by the FPRB Volunteers of Kabupaten Bandung as participants. The research method used in the PKM is the experimental research method. The researcher conducted quantitative research using a pre-experimental design, type 1 group, pre-test-post-test (pre-test, single-group final test), called quasi-experimental. The result of the service is that the workshop that has been given has led to an increase in SPAB and PFA facilitation skills among FPRB volunteers.

Technical Readiness and Stereotypes in Hospital Nursing-A Question of Gender and Age?

(1) Background: The nursing profession is associated with various stereotypes. These social images or prejudices against specific groups can inhibit the personal growth of individuals, e.g., sociodemographic characteristics influence the social image of nurses. Based on the forward-looking topic digitization, we examined and discussed the influences of sociodemographic characteristics and motives of hospital nurses on technical readiness to gain insights into the digitization process in hospital nursing. (2) Methods: As part of an online survey on technical readiness among German hospital nurses, we particularly examined sociodemographic influences on technical readiness and the relationship between sociodemographic characteristics and professional motives. Furthermore, we included a qualitative analysis of optional comment fields. (3) Results: The analysis included 295 responses. Age and gender had a significant influence on technical readiness. Furthermore, the importance of motives differed between gender and age. The analysis of the comments produced three categories specifying our results: beneficial experiences, obstructive experiences and further conditions. (4) Conclusions: In general, the nurses showed high technical readiness. In order to gain high motivation for digitization and promote personal growth, special targeting and cooperation between gender and age groups can be beneficial. However, there are more sites at system level, such as funding, cooperation and consistence.

Nanospheres of Near-Infrared Aggregation-Induced Emission Probes to Target Mitochondria to Ablate Tumors with Reactive Oxygen Species Generation under Hypoxia

Severe aggregation-caused quenching and the lack of special organelle targeting in conventional photosensitizers (PSs) have limited their advantages in terms of their accurate spatial–temporal control and noninvasive features. Furthermore, severe tumor hypoxia equally diminished the effectiveness of treatment. Herein, a series of aggregation-induced emission (AIE) PSs with precise targeting of organelles are synthesized by simply regulating the molecular structure. The rotation of the donor in the molecule was optimized by altering the tail chain of the triphenylamine derivative, which inhibited nonradiative internal conversion and promoted intersystem crossing to facilitate the free radical generation, and the production efficiency of the type I reactive oxygen species exceeds that of the commercial indicator rose bengal (3-fold). The optimal AIE PS named BETTP can specifically target mitochondria and recognize cancer cells. Simultaneously, live/dead cell costaining assays and flow cytometry validated that BETTP nanoparticles (NPs) have the ability to efficaciously ablate cancer cells in hypoxic conditions after encapsulating BETTP into carriers as nanoparticles. In addition, BETTP NPs also manifest superior performance during near-infrared imaging-guided type I photodynamic therapy in solid tumors. Such BETTP NPs demonstrate the critical feasibility of achieving precise delivery of drugs and targeting of organelles for precise therapy in hypoxic environments, providing a reliable reference for tumor hypoxia challenges.

Profissionais de apoio à inclusão escolar: quem são e o que fazem esses novos atores no cenário educacional?

ABSTRACT The study is a part of the dissertation published by the author, whose general objective was to describe and analyze the profile and performance of school inclusion support professionals in different municipal contexts, involving five municipalities, three in the state of Bahia and two in the state of São Paulo. Thirty school inclusion support professionals participated in the study, through focus groups. The objective of this article was to analyze administrative aspects and functions performed by these school inclusion support professionals in the school context. Despite gaps in the literature, the theoretical framework used was sufficient to support the research. The results showed: precariousness in the profile and performance of professionals, support service adopted indiscriminately, bad working conditions, function deviation, professional without an adequate profile, precariousness, and privatization of support for school inclusion. In addition to pointing out that school inclusion support professionals are, in some situations, the only professionals, when they should be part of a support network, the importance of this professional is pointed out for a portion of students from the special education target audience. However, there is a need for: definition of guidelines, improvement of working conditions, definition of job attributions, continuing education, and supervision.

Stabilization mechanism of Pb with an amino- and mercapto-polymer to assist phytoremediation.

An important concern during phytoremediation of heavy metal contamination in soils is the risk of leaching of heavy metals before they can be taken up by plants. The most effective method is to use heavy metal stabilizers. However, the stabilization without selectivity will greatly inhibit the phytoremediation effect of all heavy metals. A novel polymer with amino and mercapto groups named as AMP has been prepared as a new exclusive soil stabilizer for Pb. The adsorption of AMP toward Pb belonged to a monolayer adsorption and chemical process. The adsorption capacity of Pb increased with the increase of pH and initial Pb concentration, and obeyed the Langmuir model and pseudo-second-order model, respectively. An amazing maximum adsorption capacity of 588mg Pb g-1 was reached for AMP when initial concentration was 300mg Pb L-1, while K2 of 0.594gmg-1 min-1 was obtained when the initial Pb concentration was 2.0mgL-1. The distribution coefficient of AMP to Pb in the mixture of five heavy metals was as high as 3110mLg-1, which was at least 7-fold greater than those of other heavy metals, exhibiting high selective to Pb. AMP showed a fast, large adsorption capacity and good selectivity due to the abundance of sulfhydryl and amino functional groups in the polymer and their interaction with metal ions. The effects of AMP in soil remediation were further tested by a soil column leaching experiment and a pot experiment, and the good stabilization effect of AMP on Pb and the less effect on bioavailability of other heavy metals at recommended doses were verified. This study was expected to solve the problem of leaching risk of the target metal such as Pb in sludge during land use. It provided a new idea of exclusive stabilization to assist phytoremediation of non-target heavy metals by reducing the leaching risk of some special target metal.

Discrimination leading to social intolerance in senior high school “case study in Manado, Indonesia”

Discrimination behaviours frequently occur in a school setting. The establishment of discriminatory behaviours is due to a variety of factors, including those present in educational settings. Using a descriptive qualitative method, the researcher finds out the discrimination sample as the impact of class differences between special target classes and regular classes at Senior High School Manado. Researchers analysed the psychological and social impact of these differences, especially concentrating on how these differences can lead to discrimination and social intolerance among students. The environment of school, teachers, and the influence of social stratification cannot be separated from the existence of discrimination that breeds social intolerance. Researchers explain how inequality in access to quality education, differences in learning approaches, and social norms applied in the classroom can lead to misunderstanding, stereotypes, and conflicts among students. In addition, this article emphasizes the importance of inclusive education as a solution to overcome differences and reduce the harmful effects of class differences in schools. This research provides a recommendation to the government in education to understand this phenomenon that will enable us to create a more just and inclusive educational environment, and encourage students to be tolerant, which will help achieve for equal education for all.

RESEARCH OF DEVELOPMENT AND INNOVATION OF CYBER PROTECTION AT CRITICAL INFRASTRUCTURE FACILITIES

Critical infrastructure objects — infrastructure objects, systems, their parts and their totality, which are important for the economy, national security and defense, the malfunctioning of which can harm vital national interests. Classification of objects as critical infrastructure is carried out in accordance with the procedure established by the Cabinet of Ministers of Ukraine. The assignment of banks, other entities operating in the financial services markets, state regulation and supervision of the activities of which is carried out by the National Bank of Ukraine, payment organizations, participants of payment systems, operators of payment infrastructure services is carried out in accordance with the procedure established by the National Bank of Ukraine. Classification of objects to critical infrastructure, which carry out activities on the service markets, state regulation and supervision of the activities of which are carried out by state bodies, is carried out in accordance with the procedure established by such state bodies. Given the importance of cyber security in today's world, critical infrastructure objects are becoming a special target for cyber criminals and cyber threats. These facilities include energy systems, transportation, communication networks, medical facilities and other important sectors that ensure the necessary functioning of society. This article aims to analyze and review modern approaches used to ensure cyber security at critical infrastructure facilities. Research and implementation of the latest strategies and approaches in this area can help increase the level of protection of important systems, as well as detect and respond to new cyber threats, maintaining the reliability and functioning of society as a whole. The main aspects that should be considered when developing innovative approaches to protecting critical infrastructure objects from cyber threats: predictive threat analysis: Understanding potential cyber threats and their impact on critical infrastructure facilities. Detection of new attack vectors and vulnerabilities; development and implementation of the latest technologies: Use of artificial intelligence, machine learning, blockchain and other innovative technologies in the field of cyber defense to prevent attacks and detect security breaches; creation of integrated protection strategies, development of flexible and comprehensive cyber protection strategies that take into account the specifics of each sector of critical infrastructure objects and its needs; introduction of international standards and regulations, cooperation at the international level to establish a unified system of cyber protection standards and rules for critical infrastructure facilities. Cyber defense is constantly evolving, given the constant growth in the number and complexity of cyber threats. To increase the security of critical infrastructure facilities, it is important to consider a number of modern technological trends in cyber protection, namely: artificial intelligence and machine learning; blockchain and cryptography; Internet of Things (IoT) and protection of embedded systems; threat analytics and attack detection; automated means of protection; protection at the level of data processing. The study and implementation of these technological trends in the critical infrastructure sector allows to respond to the complexity of modern cyber threats and provides an increase in the security of systems in real time.

Pelatihan Manajemen Keuangan Sebagai Peningkatan Daya saing bagi Pelaku Usaha Mikro di Kelurahan Sampangan

The purpose of the community service program (PKM) is to provide knowledge and skillsregarding financial management to MSME players in the Sampangan area, especially MSME in RT05 RW VI, A special Target to provide training and guidance in improving financial managementand competitiveness. The majority of participants in community service activities are housewiveswho have businesses in order to increase family income . MSME development prospects are assessedbased on financial analysis. This PKM program activity disseminates to MSME actors, preparesequipment that supports the success of PKM, guides MSME actors in preparing financial statements,conducts training to improve knowledge, monitor and evaluate activities to support the success andsustainability of the business.

Downregulation of miR-125a-5p Leads to STAT3 Increased Expression in Breast Cancer Patients.

Breast cancer (BC) is one of the main causes of cancer-related death in women worldwide. It is necessary to find methods for prognosis and early detection of BC. MicroRNAs inhibit the expression of special target genes at the post-transcriptional stage and have a fundamental role in various cancers. They function as oncogenes or tumor suppressors. MiR-125a- 5p acts as a tumor suppressor in some cancers through a signal transducer and activator of transcription 3 (STAT3) suppression. STAT3 is activated in response to cytokines and growth factors, affecting the transcription of target genes. We examined the association between miR-125a-5p and STAT3 expression levels in breast cancer patients for the first time through a case-control study on an Iranian population. Total RNAs were extracted from breast cancer and healthy tissues using TRIzol Reagent. Complementary DNA synthesis was performed, and Real-time PCR was done using miR-125a and STAT3-specific primers. GAPDH and U48 genes were used as internal controls. Statistical analysis of the results was conducted by SPSS v.19.0 software. We obtained a significant association between miR-125a-5p down-regulation and breast cancer disease (0.4333 in patients vs. 1.656 in controls, p-value = 0.009). STAT3 expression was significantly up-regulated in BC samples relative to healthy subjects (1.324 vs. 0.6557, respectively) and p-value <0.0001. We investigated that decreased miR-125a-5p expression levels were significantly associated with increased STAT3 expression in BC tissues. Therefore, the expression changes of miR- 125a-5p can be an important potential biomarker for early diagnosis of breast cancer. Also, the miRNA molecule may have serious therapeutic potential.

Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives.

Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30-100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes.

Bacterium-Sculpted Porphyrin-Protein-Iron Sulfide Clusters for Distinction and Inhibition of Staphylococcus aureus.

Microbe-catalyzed surface modification is a promising method for the production of special targeting nanomaterials. A bacterium-selective material can be obtained by investigating the microbe-catalyzed mineralization of proteins. Herein, a novel method was fabricated for the biosynthesis of FeS-decorated porphyrin-protein clusters (P-CA@BE) via E. coli (Escherichia coli)-catalyzed bio-Fe(III) reduction and bio-sulfidation of porphyrin (P), caffeic acid (CA), and protein [bovine serum albumin (BSA)] assemblies. The assembly (P-CA@BSA) was identified by spectroscopic methods. Next, the P-CA@BSA assembly was transferred into FeS-decorated porphyrin-protein clusters (P-CA@BE) catalyzed by E. coli. There are partial β-folding proteins in P-CA@BE, which selectively recognize S. aureus (Staphylococcus aureus) and show different antibacterial properties against E. coli and S. aureus. Results demonstrate that the E. coli-catalyzed mineralization of the porphyrin-protein assembly is an effective method for the biosynthesis of S. aureus-sensitive metal-protein clusters.

Calibration of Radar RCS Measurement Errors by Observing the Luneburg Lens Onboard the LEO Satellite.

Accurate radar RCS measurements are critical to the feature recognition of spatial targets. A calibration method for radar RCS measurement errors is proposed for the first time in the context of special target tracking by observing the Luneburg Lens onboard the LEO satellite. The Luneburg Lens has favorable RCS scattering properties for the radar microwave. Thus, the laboratory RCS measurements of the Luneburg Lens, with some fixed incident frequency and with different incident orientations for the radar microwave, will be implemented in order to build a database. The incident orientation for the radar microwave in the satellite body frame will be calculated by taking advantage of the precise orbit parameters, with errors only at the magnitude of several centimeters and within the actual satellite attitude parameters. According to the incident orientation, the referenced RCS measurements can be effectively obtained by the bilinear interpolation in the database. The errors of actual RCS measurements can thus be calibrated by comparing the referenced and the actual RCS measurements. In the RCS measurement experiment, which lasts less than 400 s, the actual RCS measurement errors of the Luneburg Lens are nearly less than 0 dBsm, which indicates that the RCS measurement errors of the spatial targets can be effectively calculated by the proposed calibration method. After the elaborated calibration, the RCS measurements of the spatial targets can be accurately obtained by radar tracking.

Biosensor for a Rapid and Sensitive Detection and Quantification of Nuclease Activity

Nucleases are family of hydrolytic enzymes which cleave the phosphodiesteric bonds between the nucleotides producing 3'-phospho or 5'-phospho end products. These enzymes can be classified as endo- and exo-nucleases, cleaving inside of a polynucleotide chain or at the ends respectively, however, some enzymes may have both activities. Typically, some nucleases prefer double-stranded nucleic acid (e.g. DNase I), while other cleave single-stranded (e.g. Nuclease P1) or RNA-DNA hybrid (RNase H) polynucleotides. Deoxyribonucleases (DNases) are important objects in biotechnology presenting both as tools for manipulations with DNA1 as well as contaminants where nuclease-like activity is undesired.2 In addition, data emerges indicating the importance of DNase activity detection for medical applications, i.e., DNases may be related with various diseases and could be used to monitor the progress of various cancers3 , 4 as well as could be a rapid and fast biomarker of bacterial infections.5 Typically, DNases are being detected and quantified using classical approach: fluorescence detection or gel electrophoresis techniques. Though those methods are highly sensitive and reliable, they are costly, time-consuming as well as require toxic markers such as ethidium bromide or radiolabeled molecules. As alternative methods novel detection techniques for DNase detection were reported, mostly based on fluorescence or chemiluminescence detection incorporating nanomaterials for signal enhancement.6 In addition, electrochemical biosensors, provide simple and inexpensive platform for biomolecule detection while maintaining a high degree of accuracy and sensitivity. However, to this day the absolute majority of electrochemical biosensors are being developed from small biomolecules, e.g., glucose, glycerol, lactate while the development of large marcomolecules, i.e., proteins or enzymes is still lagging. In a case of DNase detection, a few biosensors have been reported. Sato et al. reported electrochemical biosensor for DNase I detection based on ferrocene-modified DNA immobilized on the electrode surface with the detection limit (LOD) up to 10–2 U mL–1. Ding and Qin have reported a potentiometric biosensor for the detection of DNAses based on polycation-sensitive membrane, and for DNase I the LOD was 0.45 U mL–1.7 Despite advances, the developed electrochemical biosensors for DNase detection still lack sensitivities comparable to fluorescence- or radiolabeling-based detection methods and reliability required for the analysis of real samples.In this work we present a rapid and sensitive bioelectrochemical device for the determination of nuclease activity in various fluids. The device system consists of a sensor electrode, a special design DNA target to maximize the nuclease cleavage rate, signal analysis algorithm and the supporting electronics. The developed sensor allows to determine DNase activity in range 0.0003–0.03 U mL–1 with the limit of detection up to 0.00034 U mL–1 over 15 min measurement (calibrated against DNase I standard) as well as has a high storage stability. The system was also implemented using inexpensive single-used electrodes. Moreover, the sensor was tested measuring nuclease activity in real unmodified human saliva samples and demonstrated high accuracy compared to the industry standard DNaseAlert™ QC System. The developed technology could significantly improve nuclease quality control processes in pharma/biotech industry and give new insights into nuclease importance for medical applications. References (1) Pan, Y.; Xiao, L.; Li, A. S. S.; Zhang, X.; Sirois, P.; Zhang, J.; Li, K. Mol Biotechnol 2013, 55 (1), 54–62.(2) Senavirathne, G.; Liu, J.; Lopez, M. A.; Hanne, J.; Martin-Lopez, J.; Lee, J.-B.; Yoder, K. E.; Fishel, R. Nat Methods 2015, 12 (10), 901–902.(3) Patel, P. S.; Patel, B. P.; Rawal, R. M.; Raval, G. N.; Patel, M. M.; Patel, J. B.; Jha, F. P.; Patel, D. D. Tumor Biol 2000, 21(2), 82–89.(4) Balian, A.; Hernandez, F. J. Biomark Res 2021, 9 (1), 86.(5) Flenker, K. S.; Burghardt, E. L.; Dutta, N.; Burns, W. J.; Grover, J. M.; Kenkel, E. J.; Weaver, T. M.; Mills, J.; Kim, H.; Huang, L.; Owczarzy, R.; Musselman, C. A.; Behlke, M. A.; Ford, B.; McNamara, J. O. Molecular Therapy 2017, 25 (6), 1353–1362.(6) Mozioğlu, E.; Akgoz, M.; Kocagöz, T.; Tamerler, C. Anal. Methods 2016, 8 (20), 4017–4021.(7) Ding, J.; Qin, W. Biosensors and Bioelectronics 2013, 47, 559–565. Figure. The general operation scheme of nuclease biosensor. (A) In a case a sample does not contain nuclease the Target nucleotide is not cleaved and its hybridization rate is high. (B) In a case sample contains nucleases the Target nucleotide is cleaved and its hybridization rate is lower and relates to the nuclease activity. Figure 1

Feasibility of inpatient cardiac rehabilitation after percutaneous mitral valve reconstruction using clipping procedures: a retrospective analysis

BackgroundTo date, no studies on the feasibility or outcomes of cardiac rehabilitation (CR) after percutaneous mitral valve reconstruction using clipping procedures have been published. The aim of this study was to report on our first experiences with this special target group.MethodsMonocentric retrospective analysis of 27 patients (72 ± 12 years old, 52% female) who underwent multimodal inpatient CR in the first 2 month after MitraClip™ implantation. A six-minute-walking-test, a handgrip-strength-test and the Berg-Balance-Scale was conducted at the beginning and end of CR. Echocardiography was performed to rule out device-related complications.ResultsAdapted inpatient CR started 16 ± 13 days after clipping intervention and lasted 22 ± 4 days. In 4 patients (15%) CR had to be interrupted or aborted prematurely due to cardiac decompensations. All other patients (85%) completed CR period without complications. Six-minute-walking-distance improved from 272 ± 97 to 304 ± 111 m (p < .05) and dependence on rollator walker or walking aids was significantly reduced (p < .05). Results of handgrip-strength-test and Berg-Balance-Scale increased (p < .05). Overall, social-medical and psychological consultations were well received by the patients and no device-related complications occurred during rehabilitation treatments.ConclusionsThe results indicate that an adapted inpatient CR in selected patients after MitraClip™ implantation is feasible. Patients benefited from treatments both at functional and social-medical level and no device-related complications occurred. Larger controlled studies are needed.

Structure and Anti-Inflammatory Activity Relationship of Ergostanes and Lanostanes in Antrodia cinnamomea.

Antrodia cinnamomea is a precious edible mushroom originating from Taiwan that has been popularly used for adjuvant hepatoprotection and anti-inflammation; however, the chemical principle for its anti-inflammatory activity has not been elucidated, which prevents the quality control of related products. Using the RAW264.7 model for the anti-inflammatory activity assay as a guide, we reported the isolation and structural elucidation of three potent anti-inflammatory compounds from isolated ergostanes (16) and lanostanes (6). Their structures were elucidated on the basis of spectroscopic data analysis including NMR and HR-QTOF-MS. Particularly, the absolute configurations of (25R)-antcin K, (25R)-antcin A, versisponic acid D, and (25R)-antcin C were determined by single crystal X-ray diffraction (XRD). The representative and most promising compound antcin A was shown to suppress pro-inflammatory biomolecule release via the down-regulation of iNOS and COX-2 expression through the NF-κB pathway while the mRNA levels of IL-1β, TNF-α and IL-6 were also decreased. The high dependency on structural variation and activity suggests that there might be special biological targets for antcin A. Our work makes it possible to develop evidence-based dietary supplements from Antrodia cinnamomea based on anti-inflammatory constituents.

Phenylboronic acid modified hydrogel materials and their potential for use in contact lens based drug delivery

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

CU.POKer: Placing DNNs on WSE With Optimal Kernel Sizing and Efficient Protocol Optimization

The tremendous growth in deep learning (DL) applications has created an exponential demand for computing power, which leads to the rise of AI-specific hardware. Targeted toward accelerating computation-intensive DL applications, AI hardware, including but not limited to GPGPU, TPU, ASICs, etc., have been adopted ubiquitously. As a result, domain-specific CAD tools play more and more important roles and have been deeply involved in both the design and compilation stages of modern AI hardware. Recently, ISPD 2020 contest introduced a special challenge targeting at the physical mapping of neural network workloads onto the largest commercial DL accelerator, CS-1 wafer-scale engine (WSE). In this article, we proposed CU.POKer, a high-performance engine fully customized for WSE&#x2019;s deep neural network workload placement challenge. A provably optimal placeable kernel candidate searching scheme and a data-flow-aware placement tool are developed accordingly to ensure the state-of-the-art (SOTA) quality on the real industrial benchmarks. Experimental results on ISPD 2020 contest evaluation suites demonstrated the superiority of our proposed framework over not only the SOTA placer but also the conventional heuristics used in general floorplanning.