Gyeongsang National University

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. \n \nFor 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. \n \nHere, 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.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Rapid Prototyping (RP) technologies provide the ability to fabricate initial prototypes from various model materials. Stratasys Fused Deposition Modeling (FDM) is a typical RP process that can fabricate prototypes out of ABS plastic. To predict the mechanical behavior of FDM parts, it is critical to understand the material properties of the raw FDM process material, and the effect that FDM build parameters have on anisotropic material properties. This paper characterizes the properties of ABS parts fabricated by the FDM 1650. Using a Design of Experiment (DOE) approach, the process parameters of FDM, such as raster orientation, air gap, bead width, color, and model temperature were examined. Tensile strengths and compressive strengths of directionally fabricated specimens were measured and compared with injection molded FDM ABS P400 material. For the FDM parts made with a 0.003 inch overlap between roads, the typical tensile strength ranged between 65 and 72 percent of the strength of injection molded ABS P400. The compressive strength ranged from 80 to 90 percent of the injection molded FDM ABS. Several build rules for designing FDM parts were formulated based on experimental results.

We report the observation of a narrow charmoniumlike state produced in the exclusive decay process ${B}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\rightarrow}{K}^{\ifmmode\pm\else\textpm\fi{}}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$. This state, which decays into ${\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$, has a mass of $3872.0\ifmmode\pm\else\textpm\fi{}0.6\mathrm{(}\mathrm{s}\mathrm{t}\mathrm{a}\mathrm{t}\mathrm{)}\ifmmode\pm\else\textpm\fi{}0.5\mathrm{(}\mathrm{s}\mathrm{y}\mathrm{s}\mathrm{t}\mathrm{)}\text{ }\text{ }\mathrm{M}\mathrm{e}\mathrm{V}$, a value that is very near the ${M}_{{D}^{0}}+{M}_{{D}^{*0}}$ mass threshold. The results are based on an analysis of 152M $B$-$\overline{B}$ events collected at the $\ensuremath{\Upsilon}(4S)$ resonance in the Belle detector at the KEKB collider. The signal has a statistical significance that is in excess of $10\ensuremath{\sigma}$.

A new class of organic nanoparticles (CN-MBE nanoparticles) with a mean diameter of ca. 30-40 nm, which exhibit a strongly enhanced fluorescence emission, were prepared by a simple reprecipitation method. CN-MBE (1-cyano-trans-1,2-bis-(4'-methylbiphenyl)ethylene) is very weakly fluorescent in solution, but the intensity is increased by almost 700 times in the nanoparticles. Enhanced emission in CN-MBE nanoparticles is attributed to the synergetic effect of intramolecular planarization and J-type aggregate formation (restricted excimer formation) in nanopaticles. On/off fluorescence switching for organic vapor was demonstrated with CN-MBE nanoparticles.

The RENO experiment has observed the disappearance of reactor electron antineutrinos, consistent with neutrino oscillations, with a significance of 4.9 standard deviations. Antineutrinos from six $2.8\text{ }\text{ }{\mathrm{GW}}_{\mathrm{th}}$ reactors at the Yonggwang Nuclear Power Plant in Korea, are detected by two identical detectors located at 294 and 1383 m, respectively, from the reactor array center. In the 229 d data-taking period between 11 August 2011 and 26 March 2012, the far (near) detector observed 17102 (154088) electron antineutrino candidate events with a background fraction of 5.5% (2.7%). The ratio of observed to expected numbers of antineutrinos in the far detector is $0.920\ifmmode\pm\else\textpm\fi{}0.009(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}0.014(\mathrm{syst})$. From this deficit, we determine ${sin}^{2}2{\ensuremath{\theta}}_{13}=0.113\ifmmode\pm\else\textpm\fi{}0.013(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}0.019(\mathrm{syst})$ based on a rate-only analysis.

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model. This study presents the assembly and analysis of the genome sequence of a female domestic Duroc pig and a comparison with the genomes of wild and domestic pigs from Europe and Asia; the results shed light on the evolutionary relationship between European and Asian wild boars. The domestic pig (Sus scrofa) is an important livestock species, its genome shaped by thousands of years of domestication and, latterly, sophisticated breeding practices. A high-quality draft genome sequence for a female domestic Duroc pig is published in this issue of Nature, under the auspices of the Swine Genome Sequencing Consortium. Comparisons of the genomes of wild and domestic pigs shed light on the evolutionary relationship between European and Asian wild boars, and reveal the rapid evolution of genes involved in the immune response and in olfaction. The authors identify many possible disease-causing gene variants, increasing the potential of the pig as a biomedical model, and present a detailed analysis of endogenous porcine retroviruses, knowledge of which is important for the possible use of pigs in xenotransplantation.

Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials.

Soft and conformable wearable electronics require stretchable semiconductors, but existing ones typically sacrifice charge transport mobility to achieve stretchability. We explore a concept based on the nanoconfinement of polymers to substantially improve the stretchability of polymer semiconductors, without affecting charge transport mobility. The increased polymer chain dynamics under nanoconfinement significantly reduces the modulus of the conjugated polymer and largely delays the onset of crack formation under strain. As a result, our fabricated semiconducting film can be stretched up to 100% strain without affecting mobility, retaining values comparable to that of amorphous silicon. The fully stretchable transistors exhibit high biaxial stretchability with minimal change in on current even when poked with a sharp object. We demonstrate a skinlike finger-wearable driver for a light-emitting diode.

The analysis and design of the phase-locked loop (PLL) system is presented for the phase tracking system of the three phase utility interface inverters. The dynamic behavior of the closed loop PLL system is investigated in both continuous and discrete-time domains, and the optimization method is considered for the second order PLL system. In particular, the performance of the three phase PLL system is analyzed in the distorted utility conditions such as the phase unbalancing, harmonics, and offset caused by the nonlinear load conditions and measurement errors. The tracking errors under these distorted utility conditions are also derived. The phase tracking system is implemented in a digital manner using a digital signal processor (DSP) to verify the analytic results. The design considerations for the phase tracking system are deduced from the analytic and experimental results.

10.1021/cr100160e

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for the sequential activation of downstream targets, such as MEK and the transcription factor ERK, which control numerous cellular and physiological processes, including organism development, cell cycle control, cell proliferation and differentiation, cell survival, and death. Defects in this signaling cascade are associated with diseases such as cancer. RAF inhibitors (RAFi) combined with MEK blockers represent an FDA-approved therapeutic strategy for numerous RAF-mutant cancers, including melanoma, non-small cell lung carcinoma, and thyroid cancer. However, the development of therapy resistance by cancer cells remains an important barrier. Autophagy, an intracellular lysosome-dependent catabolic recycling process, plays a critical role in the development of RAFi resistance in cancer. Thus, targeting RAF and autophagy could be novel treatment strategies for RAF-mutant cancers. In this review, we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and RAFi-resistance. Furthermore, we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic profiles. Additionally, this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

Charge carrier mobility is still the most challenging issue that should be overcome to realize everyday organic electronics in the near future. In this Communication, we show that introducing smart side-chain engineering to polymer semiconductors can facilitate intermolecular electronic communication. Two new polymers, P-29-DPPDBTE and P-29-DPPDTSE, which consist of a highly conductive diketopyrrolopyrrole backbone and an extended branching-position-adjusted side chain, showed unprecedented record high hole mobility of 12 cm(2)/(V·s). From photophysical and structural studies, we found that moving the branching position of the side chain away from the backbone of these polymers resulted in increased intermolecular interactions with extremely short π-π stacking distances, without compromising solubility of the polymers. As a result, high hole mobility could be achieved even in devices fabricated using the polymers at room temperature.

SIZ1 is a SUMO E3 ligase that facilitates conjugation of SUMO to protein substrates. siz1-2 and siz1-3 T-DNA insertion alleles that caused freezing and chilling sensitivities were complemented genetically by expressing SIZ1, indicating that the SIZ1 is a controller of low temperature adaptation in plants. Cold-induced expression of CBF/DREB1, particularly of CBF3/DREB1A, and of the regulon genes was repressed by siz1. siz1 did not affect expression of ICE1, which encodes a MYC transcription factor that is a controller of CBF3/DREB1A. A K393R substitution in ICE1 [ICE1(K393R)] blocked SIZ1-mediated sumoylation in vitro and in protoplasts identifying the K393 residue as the principal site of SUMO conjugation. SIZ1-dependent sumoylation of ICE1 in protoplasts was moderately induced by cold. Sumoylation of recombinant ICE1 reduced polyubiquitination of the protein in vitro. ICE1(K393R) expression in wild-type plants repressed cold-induced CBF3/DREB1A expression and increased freezing sensitivity. Furthermore, expression of ICE1(K393R) induced transcript accumulation of MYB15, which encodes a MYB transcription factor that is a negative regulator of CBF/DREB1. SIZ1-dependent sumoylation of ICE1 may activate and/or stabilize the protein, facilitating expression of CBF3/DREB1A and repression of MYB15, leading to low temperature tolerance.

Many signaling, cytoskeletal, and transport proteins have to be localized to the plasma membrane (PM) in order to carry out their function. We surveyed PM-targeting mechanisms by imaging the subcellular localization of 125 fluorescent protein-conjugated Ras, Rab, Arf, and Rho proteins. Out of 48 proteins that were PM-localized, 37 contained clusters of positively charged amino acids. To test whether these polybasic clusters bind negatively charged phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipids, we developed a chemical phosphatase activation method to deplete PM PI(4,5)P2. Unexpectedly, proteins with polybasic clusters dissociated from the PM only when both PI(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] were depleted, arguing that both lipid second messengers jointly regulate PM targeting.

Artificial skin that simultaneously mimics sensory feedback and mechanical properties of natural skin holds substantial promise for next-generation robotic and medical devices. However, achieving such a biomimetic system that can seamlessly integrate with the human body remains a challenge. Through rational design and engineering of material properties, device structures, and system architectures, we realized a monolithic soft prosthetic electronic skin (e-skin). It is capable of multimodal perception, neuromorphic pulse-train signal generation, and closed-loop actuation. With a trilayer, high-permittivity elastomeric dielectric, we achieved a low subthreshold swing comparable to that of polycrystalline silicon transistors, a low operation voltage, low power consumption, and medium-scale circuit integration complexity for stretchable organic devices. Our e-skin mimics the biological sensorimotor loop, whereby a solid-state synaptic transistor elicits stronger actuation when a stimulus of increasing pressure is applied.

The cross section for ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$ between 3.8 and 5.5 GeV is measured with a $967\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ data sample collected by the Belle detector at or near the $\ensuremath{\Upsilon}(nS)$ ($n=1,2,\dots{},5$) resonances. The $Y(4260)$ state is observed, and its resonance parameters are determined. In addition, an excess of ${\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$ production around 4 GeV is observed. This feature can be described by a Breit-Wigner parametrization with properties that are consistent with the $Y(4008)$ state that was previously reported by Belle. In a study of $Y(4260)\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$ decays, a structure is observed in the $M({\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}J/\ensuremath{\psi})$ mass spectrum with $5.2\ensuremath{\sigma}$ significance, with mass $M=(3894.5\ifmmode\pm\else\textpm\fi{}6.6\ifmmode\pm\else\textpm\fi{}4.5)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and width $\ensuremath{\Gamma}=(63\ifmmode\pm\else\textpm\fi{}24\ifmmode\pm\else\textpm\fi{}26)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$, where the errors are statistical and systematic, respectively. This structure can be interpreted as a new charged charmoniumlike state.

The teacher's use of motivational strategies is generally believed to enhance student motivation, yet the literature has little empirical evidence to support this claim. Based on a large‐scale investigation of 40 ESOL classrooms in South Korea involving 27 teachers and more than 1,300 learners, this study examined the link between the teachers' motivational teaching practice and their students' language learning motivation. The students' motivation was measured by a self‐report questionnaire and a classroom observation instrument specifically developed for this investigation, the motivation orientation of language teaching (MOLT). The MOLT observation scheme was also used to assess the teachers' use of motivational strategies, along with a posthoc rating scale filled in by the observer. The MOLT follows the real‐time coding principle of Spada and Fröhlich's (1995) communication orientation of language teaching (COLT) scheme but uses categories of observable teacher behaviors derived from Dörnyei's (2001) motivational strategies framework for foreign language classrooms. The results indicate that the language teachers' motivational practice is linked to increased levels of the learners' motivated learning behavior as well as their motivational state.

Serious climate changes and energy-related environmental problems are currently critical issues in the world. In order to reduce carbon emissions and save our environment, renewable energy harvesting technologies will serve as a key solution in the near future. Among them, triboelectric nanogenerators (TENGs), which is one of the most promising mechanical energy harvesters by means of contact electrification phenomenon, are explosively developing due to abundant wasting mechanical energy sources and a number of superior advantages in a wide availability and selection of materials, relatively simple device configurations, and low-cost processing. Significant experimental and theoretical efforts have been achieved toward understanding fundamental behaviors and a wide range of demonstrations since its report in 2012. As a result, considerable technological advancement has been exhibited and it advances the timeline of achievement in the proposed roadmap. Now, the technology has reached the stage of prototype development with verification of performance beyond the lab scale environment toward its commercialization. In this review, distinguished authors in the world worked together to summarize the state of the art in theory, materials, devices, systems, circuits, and applications in TENG fields. The great research achievements of researchers in this field around the world over the past decade are expected to play a major role in coming to fruition of unexpectedly accelerated technological advances over the next decade.

Yogurt gels are a type of soft solid, and these networks are relatively dynamic systems that are prone to structural rearrangements. The physical properties of yogurt gels can be qualitatively explained using a model for casein interactions that emphasizes a balance between attractive (e.g., hydrophobic attractions, casein cross-links contributed by calcium phosphate nanoclusters and covalent disulfide cross-links between caseins and denatured whey proteins) and repulsive (e.g., electrostatic or charge repulsions, mostly negative at the start of fermentation) forces. Various methods are discussed to investigate the physical and structural attributes of yogurts. Various processing variables are discussed which influence the textural properties of yogurts, such as total solids content, heat treatment, and incubation temperatures. A better understanding of factors contributing to the physical and structural attributes may allow manufacturers to improve the quality of yogurt.