bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Mitochondrial Apoptosis to Overcome Treatment Resistance in Cancer
Authors: Ngoi Natalie Yan Li , Choong Clarice , Lee Joanne , Bellot Gregory , Wong Andrea LA , Goh Boon Cher , Pervaiz Shazib
Published: March 2020

Deregulated cellular apoptosis is a hallmark of cancer and chemotherapy resistance. The B-cell lymphoma 2 (BCL-2) protein family members are sentinel molecules that regulate the mitochondrial apoptosis machinery and arbitrate cell fate through a delicate balance between pro- and anti-apoptotic factors. The recognition of the anti-apoptotic BCL2 gene as an oncogenic driver in hematological malignancies has directed attention toward unraveling the biological significance of each of the BCL-2 superfamily members in cancer progression and garnered interest in the targeting of apoptosis in cancer therapy. Accordingly, the approval of venetoclax (ABT-199), a small molecule BCL-2 inhibitor, in patients with chronic lymphocytic leukemia and acute myeloid leukemia has become the proverbial torchbearer for novel candidate drug approaches selectively targeting the BCL-2 superfamily. Despite the inspiring advances in this field, much remains to be learned regarding the optimal therapeutic context for BCL-2 targeting. Functional assays, such as through BH3 profiling, may facilitate prediction of treatment response, development of drug resistance and shed light on rational combinations of BCL-2 inhibitors with other branches of cancer therapy. This review summarizes the pathological roles of the BCL-2 family members in cancer, discusses the current landscape of their targeting in clinical practice, and highlights the potential for future therapeutic inroads in this important area.
WNK1 Kinase Stimulates Angiogenesis to Promote Tumor Growth and Metastasis
Authors: Sie Zong-Lin , Li Ruei-Yang , Sampurna Bonifasius Putera , Hsu Po-Jui , Liu Shu-Chen , Wang Horng-Dar , Huang Chou-Long , Yuh Chiou-Hwa
Published: March 2020

With-no-lysine (K)-1 (WNK1) is the founding member of family of four protein kinases with atypical placement of catalytic lysine that play important roles in regulating epithelial ion transport. Gain-of-function mutations of WNK1 and WNK4 cause a mendelian hypertension and hyperkalemic disease. WNK1 is ubiquitously expressed and essential for embryonic angiogenesis in mice. Increasing evidence indicates the role of WNK kinases in tumorigenesis at least partly by stimulating tumor cell proliferation. Here, we show that human hepatoma cells xenotransplanted into zebrafish produced high levels of vascular endothelial growth factor (VEGF) and WNK1, and induced expression of zebrafish wnk1. Knockdown of wnk1 in zebrafish decreased tumor-induced ectopic vessel formation and inhibited tumor proliferation. Inhibition of WNK1 or its downstream kinases OSR1 (oxidative stress responsive kinase 1)/SPAK (Ste20-related proline alanine rich kinase) using chemical inhibitors decreased ectopic vessel formation as well as proliferation of xenotransplanted hepatoma cells. The effect of WNK and OSR1 inhibitors is greater than that achieved by inhibitor of VEGF signaling cascade. These inhibitors also effectively inhibited tumorigenesis in two separate transgenic zebrafish models of intestinal and hepatocellular carcinomas. Endothelial-specific overexpression of wnk1 enhanced tumorigenesis in transgenic carcinogenic fish, supporting endothelial cell-autonomous effect of WNK1 in tumor promotion. Thus, WNK1 can promote tumorigenesis by multiple effects that include stimulating tumor angiogenesis. Inhibition of WNK1 may be a potent anti-cancer therapy.
Modifying the Surface Structure of Perovskite-Based Catalysts by Nanoparticle Exsolution
Authors: Lindenthal Lorenz , Rameshan Raffael , Summerer Harald , Ruh Thomas , Popovic Janko , Nenning Andreas , Löffler Stefan , Opitz Alexander Karl , Blaha Peter , Rameshan Christoph
Published: March 2020

In heterogeneous catalysis, surfaces decorated with uniformly dispersed, catalytically-active (nano)particles are a key requirement for excellent performance. Beside standard catalyst preparation routines—with limitations in controlling catalyst surface structure (i.e., particle size distribution or dispersion)—we present here a novel time efficient route to precisely tailor catalyst surface morphology and composition of perovskites. Perovskite-type oxides of nominal composition ABO3 with transition metal cations on the B-site can exsolve the B-site transition metal upon controlled reduction. In this exsolution process, the transition metal emerges from the oxide lattice and migrates to the surface where it forms catalytically active nanoparticles. Doping the B-site with reducible and catalytically highly active elements, offers the opportunity of tailoring properties of exsolution catalysts. Here, we present the synthesis of two novel perovskite catalysts Nd0.6Ca0.4FeO3-δ and Nd0.6Ca0.4Fe0.9Co0.1O3-δ with characterisation by (in situ) XRD, SEM/TEM and XPS, supported by theory (DFT+U). Fe nanoparticle formation was observed for Nd0.6Ca0.4FeO3-δ. In comparison, B site cobalt doping leads, already at lower reduction temperatures, to formation of finely dispersed Co nanoparticles on the surface. These novel perovskite-type catalysts are highly promising for applications in chemical energy conversion. First measurements revealed that exsolved Co nanoparticles significantly improve the catalytic activity for CO2 activation via reverse water gas shift reaction.
Radical C–H 18F-Difluoromethylation of Heteroarenes with [18F]Difluoromethyl Heteroaryl-Sulfones by Visible Light Photoredox Catalysis
Authors: Lemos Agostinho Luís Pereira , Trump Laura , Lallemand Bénédicte , Pasau Patrick , Mercier Joël , Lemaire Christian , Monbaliu Jean-Christophe , Genicot Christophe , Luxen André
Published: March 2020

The 18F-labeling of CF2H groups has been recently studied in radiopharmaceutical chemistry owing to the favorable nuclear and physical characteristics of the radioisotope 18F for positron emission tomography (PET). Following up on the reported efficiency of the [18F]difluoromethyl benzothiazolyl-sulfone ([18F]1) as a 18F-difluoromethylating reagent, we investigated the influence of structurally-related [18F]difluoromethyl heteroaryl-sulfones in the reactivity toward the photoredox C–H 18F-difluoromethylation of heteroarenes under continuous-flow conditions. In the present work, six new [18F]difluoromethyl heteroaryl-sulfones [18F]5a–[18F]5f were prepared and, based on the overall radiochemical yields (RCYs), three of these reagents ([18F]5a, [18F]5c, and [18F]5f) were selected for the fully automated radiosynthesis on a FASTlabTM synthesizer (GE Healthcare) at high level of starting radioactivity. Subsequently, their efficiency as 18F-difluoromethylating reagents was evaluated using the antiherpetic drug acyclovir as a model substrate. Our results showed that the introduction of molecular modifications in the structure of [18F]1 influenced the amount of fac-IrIII(ppy)3 and the residence time needed to ensure a complete C–H 18F-difluoromethylation process. The photocatalytic C–H 18F-difluoromethylation reaction with the reagents [18F]5a, [18F]5c, and [18F]5f was extended to other heteroarenes. Radical-trapping experiments demonstrated the likely involvement of radical species in the C–H 18F-difluoromethylation process.
Identification of a Reaction Intermediate and Mechanism of Action of Intermediary Enzymes in Plumbagin Biosynthetic Pathway Using Molecular Dynamics Simulation
Authors: K S Muralidharan , Lalitha Roopa , Girija Shanmugam , Kumar R Pravin , P S Akshai , N Swamy Meghana , M Nayana , Jayanthi Malaiyandi
Published: March 2020

The biosynthesis of plumbagin is known to occur via the acetate polymalonate pathway; however there are several intermediary steps that remain unidentified that leads to its synthesis. The study identifies enzyme naphthoate synthase to catalyze the cyclization of O-malonyl benzoyl CoA to form an intermediate that is acted upon by thioesterase before the reaction proceeds to form plumbagin. Two possible structures were predicted for this intermediate using quantum mechanics studies. A total of 60 ns molecular dynamics simulations revealed the most probable intermediate structure of the predicted two.
Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN)
Authors: Zhao Yin , Lei Yuan , He Shi-Wei , Li Ying-Qin , Wang Ya-Qin , Hong Xiao-Hong , Liang Ye-Lin , Li Jun-Yan , Chen Yang , Luo Wei-Jie , Zhang Pan-Pan , Yang Xiao-Jing , He Qing-Mei , Ma Jun , Liu Na , Tang Ling-Long
Published: March 2020

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.
Relationship between Heart Disease and Liver Disease: A Two-Way Street
Authors: El Hadi Hamza , Di Vincenzo Angelo , Vettor Roberto , Rossato Marco
Published: March 2020

In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.
Lactobacillus fermentum CECT5716 Supplementation in Rats during Pregnancy and Lactation Impacts Maternal and Offspring Lipid Profile, Immune System and Microbiota
Authors: Azagra-Boronat Ignasi , Tres Alba , Massot-Cladera Malén , Franch Àngels , Castell Margarida , Guardiola Francesc , Pérez-Cano Francisco J. , Rodríguez-Lagunas Maria J.
Published: March 2020

Probiotics have shown potential for their use in early life. This study aimed to investigate whether the administration of Lactobacillus fermentum CECT5716 during pregnancy and lactation periods impacts maternal and offspring plasma lipid profile, immune system and microbiota. Rats were supplemented with the probiotic during gestation and two weeks of lactation. After supplementation, although the microbiota composition was not affected, the probiotic strain was detected in all cecal contents of dams and in some of their pups. Dams showed reduced proportion of T cytotoxic cells in the mesenteric lymph nodes, modulation of intestinal cytokines (IL-10 and IL-12) and changes in plasma fatty acids (20:0, 22:0, 20:5 n-3, and 18:3 n-6). Pups showed changes in immunoglobulins (intestinal IgA and plasmatic IgG2a and IgG2c) and fatty acid profile (17:0, 22:0, and 18:2 n-6). Overall, Lactobacillus fermentum CECT5716 supplementation contributed to beneficially modulating the immune system of the mother and its offspring.
Clozapine Prevents Poly (I:C) Induced Inflammation by Modulating NLRP3 Pathway in Microglial Cells
Authors: V. Giridharan Vijayasree , Scaini Giselli , Colpo Gabriela D. , Doifode Tejaswini , F. Pinjari Omar , Teixeira Antônio L. , Petronilho Fabricia , Macêdo Danielle , Quevedo João , Barichello Tatiana
Published: March 2020

Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have suggested the presence of neuroinflammation in schizophrenia. In the present study, the effect of antipsychotic drugs, including clozapine, risperidone, and haloperidol (10, 20 and 20 μM, respectively), on the production of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-18, INF-γ, and TNF-α was investigated in the unstimulated and polyriboinosinic-polyribocytidilic acid [poly (I:C)]-stimulated primary microglial cell cultures. In the unstimulated cultures, clozapine, risperidone, and haloperidol did not influence the cytokine levels. Nevertheless, in cell cultures under strong inflammatory activation by poly (I:C), clozapine reduced the levels of IL-1α, IL-1β, IL-2, and IL-17. Risperidone and haloperidol both reduced the levels of IL-1α, IL-1β, IL-2, and IL-17, and increased the levels of IL-6, IL-10, INF-γ, and TNF-α. Based on the results that were obtained with the antipsychotic drugs and observing that clozapine presented with a more significant anti-inflammatory effect, clozapine was selected for the subsequent experiments. We compared the profile of cytokine suppression obtained with the use of NLRP3 inflammasome inhibitor, CRID3 to that obtained with clozapine, to test our hypothesis that clozapine inhibits the NLRP3 inflammasome. Clozapine and CRID3 both reduced the IL-1α, IL-1β, IL-2, and IL-17 levels. Clozapine reduced the level of poly (I:C)-activated NLRP3 expression by 57%, which was higher than the reduction thay was seen with CRID3 treatment (45%). These results suggest that clozapine might exhibit anti-inflammatory effects by inhibiting NLRP3 inflammasome and this activity is not typical with the use of other antipsychotic drugs under the conditions of strong microglial activation.
Job Opening for Nucleosome Mechanic: Flexibility Required
Authors: Pitman Mary , Melters Daniël P. , Dalal Yamini
Published: March 2020

The nucleus has been studied for well over 100 years, and chromatin has been the intense focus of experiments for decades. In this review, we focus on an understudied aspect of chromatin biology, namely the chromatin fiber polymer’s mechanical properties. In recent years, innovative work deploying interdisciplinary approaches including computational modeling, in vitro manipulations of purified and native chromatin have resulted in deep mechanistic insights into how the mechanics of chromatin might contribute to its function. The picture that emerges is one of a nucleus that is shaped as much by external forces pressing down upon it, as internal forces pushing outwards from the chromatin. These properties may have evolved to afford the cell a dynamic and reversible force-induced communication highway which allows rapid coordination between external cues and internal genomic function.
Sensitivity Improvement of Quantum Dot-Blended Hybrid Detector for X-ray Imaging
Authors: Kim Seahong , Lee Jehoon , Kang Jungwon
Published: March 2020

This study investigated the characteristics of an indirect-type hybrid X-ray detector with a conjugated polymer poly(3-hexylthiophene) (P3HT) and CdSe quantum dot (QD) blended active layer. To improve detection sensitivity, the optimal blending ratio of P3HT:CdSe QDs, ligand exchange effect, and optimal process condition of the active layer were examined. The detector with a P3HT:CdSe QDs = 1:5 blended active layer showed the highest collected charge density (CCD) and highest sensitivity under X-ray irradiation. The replacement of a trioctylphosphine (TOP) ligand by a pyridine ligand effectively assisted the charge transport and reduced the QD aggregation, increasing the detection sensitivity of the detector by 75% after the ligand exchange. To further improve the sensitivity of the proposed detector, the optimized process conditions of the active layer were studied. The sensitivity of the detector with an active layer of about 80 nm thickness formed by a double-coating method showed the highest CCD of 62.5 nA/cm2, and the highest sensitivity of 0.14 mA/Gy∙cm2. Due to additional pyridine treatment between the double-coating processes, the surface roughness of the active layer decreased, and the CCD and sensitivity subsequently increased.
Determination of Modules in Pleasurable Design to Fulfil Customer Requirements and Provide a Customized Product in the Food Industry
Authors: Wedowati Endang Retno , Singgih Moses Laksono , Gunarta I Ketut
Published: March 2020

Customers’ needs and wants with regard to dairy products are increasingly diverse, and companies must be able to produce a variety of products. This study aimed to obtain alternative product configurations in accordance with customer requirements and to determine the types of modules required to realize the product by synergizing conjoint analysis and the decision-making trial and evaluation laboratory (DEMATEL) method. The product configuration was based on pleasurable design consisting of three aspects, namely functionality, usability, and pleasure. Pleasurable design was chosen because it involves the human in the product design as a product user so that the product design is in accordance with customer expectations. The research used the survey method with consumers of ice cream. Descriptive analysis was used to describe the product attributes desired by consumers. Orthogonal design was used to construct alternative product configurations, while the product configuration rank was determined using conjoint analysis. Based on the results of the research, the selected attributes for the functionality aspects were taste and texture, the selected attributes for the usability aspects were shape and packaging materials, and the selected attributes for the pleasure aspects were health benefits and appearance. The orthogonal design results led to 25 alternative product configurations, followed by determination of the ranking of alternative product configurations. Then the DEMATEL method was applied to analyse the relationship between the product configuration attributes to determine the types of modules that must be provided.
A Two-Stage Framework for Automated Malignant Pulmonary Nodule Detection in CT Scans
Authors: EL-Bana Shimaa , Al-Kabbany Ahmad , Sharkas Maha
Published: March 2020

This research is concerned with malignant pulmonary nodule detection (PND) in low-dose CT scans. Due to its crucial role in the early diagnosis of lung cancer, PND has considerable potential in improving the survival rate of patients. We propose a two-stage framework that exploits the ever-growing advances in deep neural network models, and that is comprised of a semantic segmentation stage followed by localization and classification. We employ the recently published DeepLab model for semantic segmentation, and we show that it significantly improves the accuracy of nodule detection compared to the classical U-Net model and its most recent variants. Using the widely adopted Lung Nodule Analysis dataset (LUNA16), we evaluate the performance of the semantic segmentation stage by adopting two network backbones, namely, MobileNet-V2 and Xception. We present the impact of various model training parameters and the computational time on the detection accuracy, featuring a 79.1% mean intersection-over-union (mIoU) and an 88.34% dice coefficient. This represents a mIoU increase of 60% and a dice coefficient increase of 30% compared to U-Net. The second stage involves feeding the output of the DeepLab-based semantic segmentation to a localization-then-classification stage. The second stage is realized using Faster RCNN and SSD, with an Inception-V2 as a backbone. On LUNA16, the two-stage framework attained a sensitivity of 96.4%, outperforming other recent models in the literature, including deep models. Finally, we show that adopting a transfer learning approach, particularly, the DeepLab model weights of the first stage of the framework, to infer binary (malignant-benign) labels on the Kaggle dataset for pulmonary nodules achieves a classification accuracy of 95.66%, which represents approximately 4% improvement over the recent literature.
Thermodynamic Limits and Optimality of Microbial Growth
Authors: Saadat Nima , Nies Tim , Rousset Yvan , Ebenhöh Oliver
Published: March 2020

Understanding microbial growth with the use of mathematical models has a long history that dates back to the pioneering work of Jacques Monod in the 1940s. Monod’s famous growth law expressed microbial growth rate as a simple function of the limiting nutrient concentration. However, to explain growth laws from underlying principles is extremely challenging. In the second half of the 20th century, numerous experimental approaches aimed at precisely measuring heat production during microbial growth to determine the entropy balance in a growing cell and to quantify the exported entropy. This has led to the development of thermodynamic theories of microbial growth, which have generated fundamental understanding and identified the principal limitations of the growth process. Although these approaches ignored metabolic details and instead considered microbial metabolism as a black box, modern theories heavily rely on genomic resources to describe and model metabolism in great detail to explain microbial growth. Interestingly, however, thermodynamic constraints are often included in modern modeling approaches only in a rather superficial fashion, and it appears that recent modeling approaches and classical theories are rather disconnected fields. To stimulate a closer interaction between these fields, we here review various theoretical approaches that aim at describing microbial growth based on thermodynamics and outline the resulting thermodynamic limits and optimality principles. We start with classical black box models of cellular growth, and continue with recent metabolic modeling approaches that include thermodynamics, before we place these models in the context of fundamental considerations based on non-equilibrium statistical mechanics. We conclude by identifying conceptual overlaps between the fields and suggest how the various types of theories and models can be integrated. We outline how concepts from one approach may help to inform or constrain another, and we demonstrate how genome-scale models can be used to infer key black box parameters, such as the energy of formation or the degree of reduction of biomass. Such integration will allow understanding to what extent microbes can be viewed as thermodynamic machines, and how close they operate to theoretical optima.
Human Creativity and Consciousness: Unintended Consequences of the Brain’s Extraordinary Energy Efficiency?
Authors: Palmer Tim
Published: March 2020

It is proposed that both human creativity and human consciousness are (unintended) consequences of the human brain’s extraordinary energy efficiency. The topics of creativity and consciousness are treated separately, though have a common sub-structure. It is argued that creativity arises from a synergy between two cognitive modes of the human brain (which broadly coincide with Kahneman’s Systems 1 and 2). In the first, available energy is spread across a relatively large network of neurons, many of which are small enough to be susceptible to thermal (ultimately quantum decoherent) noise. In the second, available energy is focussed on a smaller subset of larger neurons whose action is deterministic. Possible implications for creative computing in silicon are discussed. Starting with a discussion of the concept of free will, the notion of consciousness is defined in terms of an awareness of what are perceived to be nearby counterfactual worlds in state space. It is argued that such awareness arises from an interplay between memories on the one hand, and quantum physical mechanisms (where, unlike in classical physics, nearby counterfactual worlds play an indispensable dynamical role) in the ion channels of neural networks, on the other. As with the brain’s susceptibility to noise, it is argued that in situations where quantum physics plays a role in the brain, it does so for reasons of energy efficiency. As an illustration of this definition of consciousness, a novel proposal is outlined as to why quantum entanglement appears to be so counter-intuitive.
The Triangle Wave Versus the Cosine: How Classical Systems Can Optimally Approximate EPR-B Correlations
Authors: Gill Richard David
Published: March 2020

The famous singlet correlations of a composite quantum system consisting of two two-level components in the singlet state exhibit notable features of two kinds. One kind are striking certainty relations: perfect anti-correlation, and perfect correlation, under certain joint settings. The other kind are a number of symmetries, namely invariance under a common rotation of the settings, invariance under exchange of components, and invariance under exchange of both measurement outcomes. One might like to restrict attention to rotations in the plane since those are the ones most commonly investigated experimentally. One can then also further distinguish between the case of discrete rotations (e.g., only settings which are a whole number of degrees are allowed) and continuous rotations. We study the class of classical correlation functions, i.e., generated by classical physical systems, satisfying all these symmetries, in the continuous, planar, case. We call such correlation functions classical EPR-B correlations. It turns out that if the certainty relations and rotational symmetry holds at the level of the correlations, then rotational symmetry can be imposed “for free” on the underlying classical physical model by adding an extra randomisation level. The other binary symmetries are obtained “for free”. This leads to a simple heuristic description of all possible classical EPR-B correlations in terms of a “spinning bi-coloured disk” model. We deliberately use the word “heuristic” because technical mathematical problems remain wide open concerning the transition from finite or discrete to continuous. The main purpose of this paper is to bring this situation to the attention of the mathematical community. We do show that the widespread idea that “quantum correlations are more extreme than classical physics would allow” is at best highly inaccurate, through giving a concrete example of a classical correlation which satisfies all the symmetries and all the certainty relations and which exceeds the quantum correlations over a whole range of settings. It is found by a search procedure in which we randomly generate classical physical models and, for each generated model, evaluate its properties in a further Monte-Carlo simulation of the model itself.
Role of Waste Cost in Thermoeconomic Analysis
Authors: Uysal Cuneyt , Kwak Ho-Young
Published: March 2020

Power plants or thermal systems wherein products such as electricity and steam are generated affect the natural environment, as well as human society, through the discharging of wastes. The wastes from such plants may include ashes, flue gases, and hot water streams. The waste cost is of primary importance in plant operation and industrial ecology. Therefore, an appropriate approach for including waste cost in a thermoeconomic analysis is essential. In this study, a method to take waste cost into account in thermoeconomics to determine the production cost of products via thermoeconomic analysis is proposed. The calculation of the waste cost flow rates at the dissipative units and their allocation to system components are important to obtain the production cost of a plant.
Exploring the Impact of Variability in Resistance Distributions of RRAM on the Prediction Accuracy of Deep Learning Neural Networks
Authors: Prabhu Nagaraj , Loy Jia Jun Desmond , Dananjaya Putu , Lew Wen , Toh Eng , Raghavan Nagarajan
Published: March 2020

In this work, we explore the use of the resistive random access memory (RRAM) device as a synapse for mimicking the trained weights linking neurons in a deep learning neural network (DNN) (AlexNet). The RRAM devices were fabricated in-house and subjected to 1000 bipolar read-write cycles to measure the resistances recorded for Logic-0 and Logic-1 (we demonstrate the feasibility of achieving eight discrete resistance states in the same device depending on the RESET stop voltage). DNN simulations have been performed to compare the relative error between the output of AlexNet Layer 1 (Convolution) implemented with the standard backpropagation (BP) algorithm trained weights versus the weights that are encoded using the measured resistance distributions from RRAM. The IMAGENET dataset is used for classification purpose here. We focus only on the Layer 1 weights in the AlexNet framework with 11 × 11 × 96 filters values coded into a binary floating point and substituted with the RRAM resistance values corresponding to Logic-0 and Logic-1. The impact of variability in the resistance states of RRAM for the low and high resistance states on the accuracy of image classification is studied by formulating a look-up table (LUT) for the RRAM (from measured I-V data) and comparing the convolution computation output of AlexNet Layer 1 with the standard outputs from the BP-based pre-trained weights. This is one of the first studies dedicated to exploring the impact of RRAM device resistance variability on the prediction accuracy of a convolutional neural network (CNN) on an AlexNet platform through a framework that requires limited actual device switching test data.
Study on Two Component Gas Transport in Nanopores for Enhanced Shale Gas Recovery by Using Carbon Dioxide Injection
Authors: Guo Chaohua , Li Rongji , Wang Xin , Liu Hongji
Published: March 2020

Injecting carbon dioxide to enhance shale gas recovery (CO2-EGR) is a useful technique that has raised great research interests. Clear understanding of the two-component gas transport mechanisms in shale nanopores is the foundation for the efficient development of shale gas reservoir (SGR) and also the long-term geological storage of CO2. Although extensive studies on single-component gas transport and corresponding models in shale nanopores have been carried out in recent years, limited studies have been conducted on two-component or even multi-component gas transport models in shale nanopores. In this work, the shale nanopores were classified into inorganic and organic nanopores. The corresponding models for two-component gas transport were constructed. Mechanisms including Knudsen diffusion, slip flow, viscous flow, and molecular diffusion are considered in the inorganic pores. In the organic pores, due to existence of adsorption gas, surface diffusion is further considered besides the aforementioned mechanisms. Effects of pressure, temperature, fraction of organic nanopores, and gas concentration were analyzed. Results show that gas apparent permeability is negatively correlated with pressure, and positively correlated with temperature and organic nanopore fraction. As the concentration of CH4 decreases, the apparent permeability of CH4 increases continuously, while the apparent permeability of CO2 decreases. The permeability ratio of CH4 in the total permeability is negatively correlated with pressure and gas concentration ratio. Additionally, the contribution of transport mechanisms to the total gas apparent permeability has been analyzed. It is found that the surface diffusion contributes up to 5.68% to gas apparent permeability under high pressure. The contribution of molecular diffusion can reach up to 88.83% in mesopores under low pressure. Under high pressure and macropores, it contributes less than 1.41%. For all situations, the contribution of viscous flow is more than 46.36%, and its contribution can reach up to 86.07%. Results of this study not only can improve the understanding of two-component gas transport in nanochannels, but also can lay the foundation for more reliable reservoir simulation of CO2-EGR.
The Impacts of Calamity Logging on the Development of Spruce Wood Prices in Czech Forestry
Authors: Toth Daniel , Maitah Mansoor , Maitah Kamil , Jarolínová Veronika
Published: March 2020

Currently, the decline in spruce wood prices is a serious problem for the forestry sector in the Czech Republic. We estimate that the fall in wood prices in European markets causes losses not only to the forestry companies producing, harvesting, and processing the wood, but also to the workers in the sector. These losses are mainly caused by a combination of several natural factors: drought, climate change, and the effects of bark beetles. In particular, spruce bark beetles cause the greatest damage. Due to this bark beetle calamity, unplanned logging has increased. In 2019, these damages have culminated. Almost 100 million m3 of wood has been harvested over the last decade due to the bark beetle and more than half of this volume has been mined in the last four years. Therefore, the losses in the forestry sector are around EUR 1.12 billion. The aim of this study is an analysis of the relationship between the volume of incidental logging and the decline in the price of spruce wood. These results show the strong correlation between the measure of unplanned wood harvesting and the decrease in wood prices, as well as an estimate of price development if the upward trend of incidental mining continues. The average price of wood in the Czech Republic could thus reach a historical minimum of EUR 79.39 per m3 of spruce and category SM/JE II (spruce/fir). In addition, the decline in wood prices will be reflected in the management of forestry and timber businesses, including stagnant wages for forestry workers. The socio-economic impact of the bark beetle calamity is high and is most affected by the decline in spruce timber prices.
Soil Functional Responses to Natural Ecosystem Restoration of a Pine Forest Peucedano-Pinetum after a Fire
Authors: Hewelke Edyta , Górska Ewa Beata , Gozdowski Dariusz , Korc Marian , Olejniczak Izabella , Prędecka Anna
Published: March 2020

Progressing climate change increases the frequency of droughts and the risk of the occurrence of forest fires with an increasing range and a dramatic course. The availability of water and its movement within an ecosystem is a fundamental control of biological activity and physical properties, influencing many climatic processes, whereas soil water repellency (SWR) is a key phenomenon affecting water infiltration into the soil system. Focusing on wide-spectrum effects of fire on the soil system, the research was conducted on a pine stand (Peucedano-Pinetum W. Mat. (1962) 1973) in Kampinos National Park located in central Poland, affected by severe and weak fires, as well as control plots. The main aim of the study was to examine the regeneration of the ecosystem 28 months after the occurrence of a fire. The effect of SWR and soil moisture content, total organic carbon, nitrogen and pH, and gain an understanding of the environmental conditions and processes that shaped the evolution of the species structure of soil microorganism communities (fungal vs. bacterial) have been examined. The Water Drop Penetration Time (WDPT) test was used to assess spatial variability of SWR in 28 plots. Soil bacterial and fungal communities were analysed by Illumina’MISeq using 16S rRNA and Internal Transcribed Spacers 1 (ITS1) regions in six selected plots. After a relatively wet summer, elevated hydrophobicity occurred in areas affected by a weak fire as much as 20 cm into the soil depth. The severe fire and subsequent increase in the richness of the succession of non-forest species contributed to the elimination of hydrophobicity. SWR was more closely linked to the structure and diversity of soil microbial communities than soil physicochemical properties that took place in response to the fire. A statistically significant relationship between the relative occurrence of microorganisms (≥ 1.0% in at least one of the samples) and SWR was established for the following fungi and bacteria species: Archaeorhizomyces sp., Leotiomycetes sp., Byssonectria fusispora, Russula vesca, Geminibasidium sp., family Isosphaeraceae and Cyanobacteria (class 4C0d-2, order MLE1-12). Insight into the functional roles of the individual identified microbial taxa that may be responsible for the occurrence of hydrophobicity was also presented.
Transcriptomic Analysis Reveals Hormonal Control of Shoot Branching in Salix matsudana
Authors: Liu Juanjuan , Ni Bingbing , Zeng Yanfei , He Caiyun , Zhang Jianguo
Published: March 2020

Shoot branching is regulated by axillary bud activities, which subsequently grow into branches. Phytohormones play a central role in shoot branching control, particularly with regard to auxin, cytokinins (CKs), strigolactones (SLs), and gibberellins (GAs). To further study the molecular basis for the shoot branching in Salix matsudana, how shoot branching responds to hormones and regulatory pathways was investigated, and potential genes involved in the regulation of shoot branching were identified. However, how these positive and inhibitory processes work on the molecular level remains unknown. RNA-Seq transcriptome expression analysis was used to elucidate the mechanisms underlying shoot branching. In total, 102 genes related to auxin, CKs, SLs, and GAs were differentially expressed in willow development. A majority of the potential genes associated with branching were differentially expressed at the time of shoot branching in S. matsudana, which have more number of branching. These findings are consistent with the growth and physiological results. A regulatory network model was proposed to explain the interaction between the four hormones that control shoot branching. Collectively, the results presented here contribute to a more comprehensive understanding of the hormonal effects on shoot branching in S. matsudana. In the future, these findings will help uncover the interactions among auxin, SLs, CKs, and GAs that control shoot branching in willow, which could help improve plant structures through the implementation of molecular techniques in targeted breeding.
Magic on the Menu: Where Are All the Magical Food and Beverage Experiences?
Authors: Spence Charles , Youssef Jozef , Kuhn Gustav
Published: March 2020

Magic and dining have long been popular forms of entertainment. What is more, both involve some kind of transformation, and yet while the more theatrical aspects of dining have grown in popularity in recent decades, there is a surprising paucity of magical food and beverage experiences out there. In this article, we trace the historical appearance of food and drink and culinary items in the performance of magic. We also review some of the more magical elements of food design that have appeared on menus in bars and restaurants in recent years. We introduce the edible lightbulb dish from the menu at Kitchen Theory Chef’s Table and link it to the stage magic of Derren Brown. We also discuss some of the reasons as to why magical food experiences might be rare in the context of dining. In so doing, our hope is to highlight an intriguing area for future research and innovation. Along the way, we identify some possible candidate approaches for the introduction of edible magic onto the menu in the context of modernist cuisine.
Luminous Blue Variables
Authors: Weis Kerstin , Bomans Dominik J.
Published: March 2020

Luminous Blue Variables are massive evolved stars, here we introduce this outstanding class of objects. Described are the specific characteristics, the evolutionary state and what they are connected to other phases and types of massive stars. Our current knowledge of LBVs is limited by the fact that in comparison to other stellar classes and phases only a few “true” LBVs are known. This results from the lack of a unique, fast and always reliable identification scheme for LBVs. It literally takes time to get a true classification of a LBV. In addition the short duration of the LBV phase makes it even harder to catch and identify a star as LBV. We summarize here what is known so far, give an overview of the LBV population and the list of LBV host galaxies. LBV are clearly an important and still not fully understood phase in the live of (very) massive stars, especially due to the large and time variable mass loss during the LBV phase. We like to emphasize again the problem how to clearly identify LBV and that there are more than just one type of LBVs: The giant eruption LBVs or η Car analogs and the S Dor cycle LBVs.
Supercoiling, R-Loops, Replication and the Functions of Bacterial Type 1A Topoisomerases
Authors: Brochu Julien , Breton Émilie-Vlachos , Drolet Marc
Published: March 2020

Type 1A topoisomerases (topos) are the only topos that bind single-stranded DNA and the only ones found in all cells of the three domains of life. Two subfamilies, topo I and topo III, are present in bacteria. Topo I, found in all of them, relaxes negative supercoiling, while topo III acts as a decatenase in replication. However, recent results suggest that they can also act as back-up for each other. Because they are ubiquitous, type 1A enzymes are expected to be essential for cell viability. Single topA (topo I) and topB (topo III) null mutants of Escherichia coli are viable, but for topA only with compensatory mutations. Double topA topB null mutants were initially believed to be non-viable. However, in two independent studies, results of next generation sequencing (NGS) have recently shown that double topA topB null mutants of Bacillus subtilis and E. coli are viable when they carry parC parE gene amplifications. These genes encode the two subunits of topo IV, the main cellular decatenase. Here, we discuss the essential functions of bacterial type 1A topos in the context of this observation and new results showing their involvement in preventing unregulated replication from R-loops.
Clinical Observations and Treatment Approaches for Scoliosis in Prader–Willi Syndrome
Authors: van Bosse Harold J.P. , Butler Merlin G.
Published: March 2020

Prader–Willi syndrome (PWS) is recognized as the first example of genomic imprinting, generally due to a de novo paternal 15q11-q13 deletion. PWS is considered the most common genetic cause of marked obesity in humans. Scoliosis, kyphosis, and kyphoscoliosis are commonly seen in children and adolescents with PWS with a prevalence of spinal deformities cited between 15% to 86%. Childhood risk is 70% or higher, until skeletal maturity, with a bimodal age distribution with one peak before 4 years of age and the other nearing adolescence. As few reports are available on treating scoliosis in PWS, we described clinical observations, risk factors, therapeutic approaches and opinions regarding orthopedic care based on 20 years of clinical experience. Treatments include diligent radiographic screening, starting once a child can sit independently, ongoing physical therapy, and options for spine casting, bracing and surgery, depending on the size of the curve, and the child’s age. Similarly, there are different surgical choices including a spinal fusion at or near skeletal maturity, versus a construct that allows continued growth while controlling the curve for younger patients. A clear understanding of the risks involved in surgically treating children with PWS is important and will be discussed.
Phylogeography and the Evolutionary History of Sunflower (Helianthus annuus L.): Wild Diversity and the Dynamics of Domestication
Authors: Park Brian , Burke John M.
Published: March 2020

Patterns of genetic variation in crops are the result of selection and demographic changes that occurred during their domestication and improvement. In many cases, we have an incomplete picture of the origin of crops in the context of their wild progenitors, particularly with regard to the processes producing observed levels of standing genetic variation. Here, we analyzed sequence diversity in cultivated sunflower (Helianthus annuus L.) and its wild progenitor (common sunflower, also H. annuus) to reconstruct phylogeographic relationships and population genetic/demographic patterns across sunflower. In common sunflower, south-north patterns in the distribution of nucleotide diversity and lineage splitting indicate a history of rapid postglacial range expansion from southern refugia. Cultivated sunflower accessions formed a clade, nested among wild populations from the Great Plains, confirming a single domestication event in central North America. Furthermore, cultivated accessions sorted by market type (i.e., oilseed vs. confectionery) rather than breeding pool, recapitulating the secondary development of oil-rich cultivars during its breeding history. Across sunflower, estimates of nucleotide diversity and effective population sizes suggest that cultivated sunflower underwent significant population bottlenecks following its establishment ~5000 years ago. The patterns inferred here corroborate those from previous studies of sunflower domestication, and provide a comprehensive overview of its evolutionary history.
A Comprehensive Transcriptomics Analysis Reveals Long Non-Coding RNA to Be Involved in the Key Metabolic Pathway in Response to Waterlogging Stress in Maize
Authors: Yu Feng , Tan Zengdong , Fang Tian , Tang Kaiyuan , Liang Kun , Qiu Fazhan
Published: March 2020

Waterlogging stress (WS) in a dynamic environment seriously limits plant growth, development, and yield. The regulatory mechanism underlying WS conditions at an early stage in maize seedlings is largely unknown. In the present study, the primary root tips of B73 seedlings were sampled before (0 h) and after (2 h, 4 h, 6 h, 8 h, 10 h, and 12 h) WS and then subjected to transcriptome sequencing, resulting in the identification of differentially expressed protein-coding genes (DEpcGs) and long non-coding RNAs (DElncRs) in response to WS. These DEpcGs were classified into nine clusters, which were significantly enriched in several metabolic pathways, such as glycolysis and methionine metabolism. Several transcription factor families, including AP2-EREBP, bZIP, NAC, bHLH, and MYB, were also significantly enriched. In total, 6099 lncRNAs were identified, of which 3190 were DElncRs. A co-expression analysis revealed lncRNAs to be involved in 11 transcription modules, 10 of which were significantly associated with WS. The DEpcGs in the four modules were enriched in the hypoxia response pathways, including phenylpropanoid biosynthesis, MAPK signaling, and carotenoid biosynthesis, in which 137 DElncRs were also co-expressed. Most of the co-expressed DElncRs were co-localized with previously identified quantitative trait loci associated with waterlogging tolerance. A quantitative reverse transcription-polymerase chain reaction analysis of DEpcG and DElncR expression among the 32 maize genotypes after 4 h of WS verified significant expression correlations between them as well as significant correlation with the phenotype of waterlogging tolerance. Moreover, the high proportion of hypoxia response elements in the promoter region increased the reliability of the DElncRs identified in this study. These results provide a comprehensive transcriptome in response to WS at an early stage of maize seedlings and expand our understanding of the regulatory network involved in hypoxia in plants.