BackgroundPembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non–small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). MethodsIn this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator’s choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety. ResultsMedi...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_protocol.pdf

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61121-X.pdf

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

The Internet has led to the creation of a digital society, where (almost) everything is connected and is accessible from anywhere. However, despite their widespread adoption, traditional IP networks are complex and very hard to manage. It is both difficult to configure the network according to predefined policies, and to reconfigure it to respond to faults, load, and changes. To make matters even more difficult, current networks are also vertically integrated: the control and data planes are bundled together. Software-defined networking (SDN) is an emerging paradigm that promises to change this state of affairs, by breaking vertical integration, separating the network's control logic from the underlying routers and switches, promoting (logical) centralization of network control, and introducing the ability to program the network. The separation of concerns, introduced between the definition of network policies, their implementation in switching hardware, and the forwarding of traffic, is key to the desired flexibility: by breaking the network control problem into tractable pieces, SDN makes it easier to create and introduce new abstractions in networking, simplifying network management and facilitating network evolution. In this paper, we present a comprehensive survey on SDN. We start by introducing the motivation for SDN, explain its main concepts and how it differs from traditional networking, its roots, and the standardization activities regarding this novel paradigm. Next, we present the key building blocks of an SDN infrastructure using a bottom-up, layered approach. We provide an in-depth analysis of the hardware infrastructure, southbound and northbound application programming interfaces (APIs), network virtualization layers, network operating systems (SDN controllers), network programming languages, and network applications. We also look at cross-layer problems such as debugging and troubleshooting. In an effort to anticipate the future evolution of this new paradigm, we discuss the main ongoing research efforts and challenges of SDN. In particular, we address the design of switches and control platforms—with a focus on aspects such as resiliency, scalability, performance, security, and dependability—as well as new opportunities for carrier transport networks and cloud providers. Last but not least, we analyze the position of SDN as a key enabler of a software-defined environment.

https://publications.uni.lu/bitstream/10993/20596/1/survey_on_SDN.pdf

Software-Defined Networking: A Comprehensive Survey

Recently, high-speed motors are receiving a lot of attention in the industrial field. When driving a motor at high speed, the advantages include high power density, high efficiency, and miniaturization. However, the disadvantages of the high-speed operation of motors are mechanical and structural safety. This is because the bearings used in high-speed motors require characteristics such as precision and low friction. There are two prominent types of bearings mainly used in high-speed motors: rolling bearings and magnetic bearings. A feature of rolling bearings is that they reduce frictional resistance by contacting points or lines between the shaft and the bearing. However, the disadvantages of rolling bearings are high mechanical friction losses due to the need for contact with the lubrication system. Maintenance costs are high. For this reason, a lot of research on bearings is being conducted to reduce the frictional loss of bearings and increase their efficiency and reliability. Bearings that are advantageous for high-speed operation are magnetic bearings that do not require lubricants, have no friction loss, and have low maintenance. However, magnetic bearings have disadvantages such as high cost and difficulty in miniaturization. In this paper, a stator with a separated teeth structure was used to compensate for these disadvantages. Using this, a model with miniaturization, light weight, and high manufacturability was proposed. The model name proposed in this study is called the STMB (separated teeth magnetic bearing). There are also disadvantages of the STMB model proposed in this paper. A model that compensates for this drawback is called the HSTMB (hybrid separated teeth magnetic bearing). The HSTMB reduces the weight by removing the back yoke of the stator and has advantages of a high filling rate and high productivity in the form of a module. As a result, high productivity, light weight, and high performance are possible when the HSTMB is applied, which was proven through FEA (finite element analysis).

/pdf/a-study-on-weight-reduction-and-high-performance-in-1nq4tnvt.pdf

A Study on Weight Reduction and High Performance in Separated Magnetic Bearings

Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis and is associated with increased circulating glucocorticoid levels. Salvia plebeia R.Br. (SPR) has been used as herbal remedy for a variety of inflammatory diseases and has various biological actions such as antioxidant and anti-inflammatory activities. However, there are no reports on the effects of SPR and its bioactive components on muscle atrophy. Herein, we investigated the anti-atrophic effect of SPR and rosmarinic acid (RosA), a major compound of SPR, on dexamethasone (DEX)-induced skeletal muscle atrophy in C2C12 myotubes. Myotubes were treated with 10 μM DEX in the presence or absence of SPR or RosA at different concentrations for 24 h and subjected to immunocytochemistry, western blot, and measurements of ROS and ATP levels. SPR and RosA increased viability and inhibited protein degradation in DEX-treated C2C12 myotubes. In addition, RosA promoted the Akt/p70S6K/mTOR pathway and reduced ROS production, and apoptosis. Furthermore, the treatment of RosA significantly recovered SOD activity, autophagy activity, mitochondrial contents, and APT levels in DEX-treated myotubes. These findings suggest that SPR and RosA may provide protective effects against DEX-induced muscle atrophy and have promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.

/pdf/salvia-plebeia-r-br-and-rosmarinic-acid-attenuate-219ey1m7.pdf

Salvia plebeia R.Br. and Rosmarinic Acid Attenuate Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes

Nowadays, in wind power generator systems, the use of a permanent magnet synchronous generator with high output density per unit volume is increasing. Among them, the magnetization performance of the spoke-type permanent magnet synchronous generator (PMSG) is low compared to that of the other types of permanent magnet synchronous generators owing to its structural characteristics. Magnetization performance is critical because it is directly related to demagnetization and mass productivity of permanent magnets, and it can cause a reduction in the load performance when non-magnetization occurs owing to low magnetization performance. In addition, an important parameter in the wind turbine is the starting performance, which is affected by the cogging torque of the permanent magnet synchronous generator. Therefore, in this study, we propose a spoke-type PMSG rotor shape design that considers magnetization and cogging torque. The magnetization principle and factors affecting the magnetization performance were analyzed, and a rotor shape with improved magnetization performance was designed. In addition, the rotor barrier asymmetric structure for reducing cogging torque was applied and the performance of the final model was analyzed through finite element analysis (FEA). The feasibility was verified through production and testing of prototypes.

Spoke type Permanent Magnet Synchronous Generator Design considering Magnetizing and Cogging Torque

Permanent magnet synchronous generators (PMSGs) with high output density per unit volume are becoming widespread in wind-power generation systems. Among them, spoke-type PMSGs are more challenging to magnetize than other PMSGs, owing to their structural characteristics. Magnetization performance is critical because it is directly related to the demagnetization and mass productivity of permanent magnets, and load performance is reduced when non-magnetization occurs due to the low magnetization performance. Additionally, the starting performance is crucial in wind turbines and is influenced by the cogging torque of the PMSG. This is because starting a wind turbine with a large cogging torque is more challenging. Therefore, this study proposes a spoke-type PMSG rotor shape design for low capacity wind turbines that considers magnetization and cogging torques. We analyzed the principle of magnetization and the factors influencing magnetization performance, and designed a rotor shape with improved magnetization performance. Additionally, we applied an asymmetric rotor barrier structure to reduce the cogging torque and analyze the performance of the final model using finite element analysis. We analyzed the temperature saturation during the operation of the final model using a thermal network method and validated the irreversible demagnetization accordingly.

/pdf/design-of-spoke-type-permanent-magnet-synchronous-generator-26y1d0zv.pdf

Design of Spoke-Type Permanent Magnet Synchronous Generator for Low Capacity Wind Turbine Considering Magnetization and Cogging Torques

Concentrated IPMSM has advantages in various aspects, such as space ratio, mass productivity, and copper loss, but concentrated winding has a limitation that the eddy current loss of permanent magnets is quite large compared to distributed winding. Eddy current loss means the heat of the rotor and becomes larger during high-speed operation. Therefore, in the concentrated IPMSM that requires high-speed operation, it is essential to design to reduce eddy current loss. In this paper, in order to reduce the eddy current loss of the IPMSM, a shape that increases the reluctance of the q-axis was applied to the rotor, and each was designed by dividing into concentrated winding and distributed winding. The number of pole slots of concentrated winding was selected as 6 poles and 9 slots, and the number of pole slots of distributed winding was selected as 6 poles and 27 slots. Through FEA, the voltammetry limit circle and T-N curve were compared according to each winding method. By comparing the d-axis inductance and q-axis inductance, a model that is advantageous at high speed was confirmed, and the no-load and load characteristics according to the operating speed were compared in detail. 

Won Ho Kim

Papers

A Study on Weight Reduction and High Performance in Separated Magnetic Bearings

Salvia plebeia R.Br. and Rosmarinic Acid Attenuate Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes

Spoke type Permanent Magnet Synchronous Generator Design considering Magnetizing and Cogging Torque

Design of Spoke-Type Permanent Magnet Synchronous Generator for Low Capacity Wind Turbine Considering Magnetization and Cogging Torques

A Study On the Operational Characteristics and Eddy Current Loss Reduction of IPMSM According to Winding Method