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

In this study, epoxy/anhydride mixing ratio for the highly silica filled compounds with chromium (III) octoate catalyst was investigated at a low curing temperature (71°C for 40 hr) by evaluating the compressive strength with the weight ratio ranges from 0.3/1.0 to 1.0/1.0 of epoxy part (Part A)/anhydride part (Part B). In case of epoxy/anhydride com- pounds used surface unmodified silica by coupling agent, these compounds need excess anhydride unlike the weight ratio in the conventional epoxy/anhydride compounds. In curing behavior, the epoxy/anhydride compounds containing chromium (III) octoate showed high conversions at 71°C for 40 hr, even if a dipropylene glycol (DPG) was not used as a poly- merization initiator. Also, DPG leads to a poor epoxy network structure. In conclusion, the appropriate weight ratio of Part A/Part B of highly silica filled epoxy/anhydride compounds with chromium (III) octoate catalyst is 0.5/1.0 and the max- imum amounts of silica is 1470 phr of epoxy resin.

Determination of Epoxy/Anhydride Mixing Ratio for the Highly Silica Filled Compounds with Chromium (III) Octoate Catalyst

An integrated magnetic bearing structure can be designed that secures the space inside the rotor core as a space for inserting the magnetic bearing by applying the halva arrangement. In this case, since the bearing exists inside the rotor, the bearing magnetic flux for controlling the rotor position is affected by the magnetic field of the permanent magnet and the rotating magnetic field of the phase winding of the stator. At this time, in a specific combination of the number of pole slots, the arrangement of the windings of the stator facing the bearing teeth appears asymmetrically for each bearing phase. In this paper, for more linear control, the formula for the number of stator pole slots and the number of bearing teeth to eliminate structurally generated force asymmetry was presented, and the formula was verified by comparative analysis of force waveforms for each axis. The validity of the proposed model was verified using the finite element method.

A Study on Combination of Number of Poles and Slots for Uniform Control of Magnetic Bearing

Background/Aims: Positron emission tomography-computed tomography (PET-CT) is a nuclear imaging technique that provides noninvasive, three dimensional, quantitative images. Recently, PET-CT has been shown to be valuable in assessing patients with inflammatory diseases; however, the clinical utility of PET-CT in the evaluation of inflammatory bowel disease (IBD) has not been defined. Thus, the aim of this study was to determine the clinical utility of PET-CT in the evaluation of IBD. Methods: Between November 2006 and September 2010, clinical, endoscopic, and radiological data on 14 patients (6 males and 8 females: age range, 33-79 years) with suspected IBD were collected. The standard work-up method for a definite diagnosis of IBD included ileocolonoscopy. Results: The 14 patients were divided into the following five groups: ulcerative colitis (n=4, 29%), intestinal Behcet’s disease (n=3, 21%), intestinal tuberculosis (n=2, 14%), malignancy (n=2, 14%), and no abnormal findings with colonoscopy (n=3, 21%). A PET-CT based-diagnosis of IBD correlated with a colonoscopic diagnosis in nine cases (64.3%), but the matching ratio of the distribution of lesions between PET-CT findings and colonoscopic findings was only 18.1% (2/11). Conclusions: The utility of PET-CT in the diagnosis of IBD requires further evaluation. (Intest Res 2011;9:97-104) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

/pdf/the-clinical-utility-of-positron-emission-tomography-cqcsvp95zi.pdf

The Clinical Utility of Positron Emission Tomography-computed Tomography in the Evaluation of Inflammatory Bowel Diseases

were the conventional method reported for the determination of DEHPA, while the spectrophotometric analysis of DEHPA in an organic solvent has not been taken into account. Total organic carbon method as a general quantitative determination tool for most organic materials cannot be used in organic media such as hexane. Despite the disadvantages of requiring the time-consuming calibration and validation with plenty of samples as well as a proper understanding of chemometric techniques in near infrared (NIR) technique for industrial applications, practically useful instrumentations such as attractive portable NIR system have been suggested recently. 7 In this study, common glass vial was used for the convenient NIR quantification of DEHPA in the presence of the interference from a solvent absorption by using NIR spectroscopic technique equipped with a user-friendly commercial software for a multivariate calibration. This will be technically useful for various field applications. Simple wavelength selection and effect of pathlength were also investigated.

/pdf/simple-and-rapid-quantitative-determination-of-di-2-47hx85efvu.pdf

Won Ho Kim

Papers

Determination of Epoxy/Anhydride Mixing Ratio for the Highly Silica Filled Compounds with Chromium (III) Octoate Catalyst

A Study on Combination of Number of Poles and Slots for Uniform Control of Magnetic Bearing

The Clinical Utility of Positron Emission Tomography-computed Tomography in the Evaluation of Inflammatory Bowel Diseases

Simple and Rapid Quantitative Determination of Di(2-ethylhexyl)phosphoric Acid Concentration Using Near Infrared Spectroscopy

Sa1226 IDENTIFICATION OF THE POST-TRANSLATIONAL MODIFICATION OF SOX2 DURING PROGRESSION AND REPROGRAMMING OF COLORECTAL CANCER