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

Adsorpdon behaviors ofNi(II), Co(II), Sr(II), and(I) ions were nvestigated on amorphous alumina with varying pH at three different etalion concentrations under the condition of 0.I M ionlc strength.With increasingmctalion concentration, the percentage of adsorption decreased and the adsorption edge was shifted to a higher pH value. The adsorption data obtained usingthe metal ion concentration of 1.0 M were quantitatively analyzed by surfacecomplexation modelingof Ni(Ⅱ) and Co(Ⅱ) ions adsorbed at high pH (>8)were found to be in hydrolyzed forms.

Surface Complexation Modeling of Ni(II), Co(II), and Sr(II) Adsorption on Amorphous Alumina

We applied a polymer-based surface modification technique to the surface treatment of a microporous activated carbon. We used a new chelating polymer, carboxymethylated polyethyleneimine (CM-PEI), as a functional polymer to modify the carbon surface. In this study, we examined the adsorption phenomena of the CM-PEI on an activated carbon with a nanopore less than 2 nm in diameter and evaluated the adsorption mechanism using three kinds of models; Langmuir, Freundlich, and Redlich-Peterson isotherm. It was found that the adsorption of CM-PEI on the F400 follows the Freundlich isotherm model. Furthermore, desorption experiments of the CM-PEI were carried out to examine the stability of the CM-PEI adsorption on the F400 and to estimate the applicability of the CM-PEI-coated F400 to the adsorbents. It was observed that most of the CM-PEI remains on the F400 for 7 days in the pH range of 3 to 7. Especially, the adsorption amount of CM-PEI on the F400 did not change after 3 days at the pH range of 5 to 7, indicating that the CM-PEI strongly adheres to the F400.

Adsorption of Carboxymethylated Polyethyleneimine (CM-PEI) on a Microporous Activated Carbon

The cure kinetics of blends of epoxy resin (4,4'-tetraglycidyl diaminodiphenyl methane; TGDDM)/ curing agent (diaminodiphenyl sulfone; DDS) with ATPEI-CTBN-ATPEI triblock copolymer (ABA type) were studied using differential scanning calorimetry under isothermal conditions to determine the reaction parameters such as activation energy and reaction constants. By increasing the amount of ABA in the blends, the final cure conversion was decreased. Lower values of the final cure conversions in the epoxy/ABA blends indicated that ABA hinders the cure reaction between the epoxy and the curing agent. The value of the reaction order m for the initial autocatalytic reaction was not affected by blending ABA with epoxy resin, i.e., the value was approximately 1.0. The value of n for the n-th order component in the autocatalytic analysis was increased from 2.0 to 3.4 by increasing the amount of ABA in the blends. A diffusion controlled reaction was observed as the cure conversion increased and the curing reaction was successfully analyzed by incorporating the diffusion control term in the rate equation for the epoxy/ DDS/ABA blends. The glass transition temperature of the cured blend was improved from 187 to 205°C and the value of the fracture toughness was also improved by about 400% compared to that of the unmodified resin at 30 wt% of ABA triblock copolymer. This is attributed to the formation of co-continuous morphology between the epoxy phase and ABA triblock copolymer phase. By increasing the amount of ABA, compressive strain, tensile stress and strain of the cured blends were increased, but the compressive stress was reduced due to the presence of CTBN rubbery phases.

Cure Kinetics and Mechanical Properties of New Polyetherimide Toughened Epoxy Resin

The diagnosis of gastric varices may be difficult due to their anatomic location and morphology. In this abstract we describe a case of gastric varices, of which a duplex Doppler sonography was useful in the diagnosis, that was initially suggested as submucosal tumor of the stomach by barium studies and endoscopy.

Gastric varices: diagnosis with duplex Doppler ultrasonography--a case report.

PMardran;Report NAS-NS 3058, 1%5.3. Mitchell, W. G.; Spaletto, M. I.; Lewis, K,; Sa@no, M.D.; Smith, M. M. ﬁThe.E~ect”of Ion+kdrange Purtf-cation on the Detetntination of Plutonium at the NewBrunswick hboratory Report NBL-323, 1990.4. Cleveland, J. M. Z?re Chemistry of Plutoniarn, Am.Nucl. Sot.: lWX pp.11-159.5. Sub, M. Y.; be, C. H.; Sohn, S. C.; ~ J. S.; Kim,W. H.; Eom, T. 1™.Ball. Konzm Chern

Won Ho Kim

Papers

Surface Complexation Modeling of Ni(II), Co(II), and Sr(II) Adsorption on Amorphous Alumina

Adsorption of Carboxymethylated Polyethyleneimine (CM-PEI) on a Microporous Activated Carbon

Cure Kinetics and Mechanical Properties of New Polyetherimide Toughened Epoxy Resin

Gastric varices: diagnosis with duplex Doppler ultrasonography--a case report.

Ion Exchange Separation of Plutonium for the Characterization of the Spent Nuclear Fuels