bluuebunny/crossref_metadata_2025 huggingface dataset:
Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet?
Authors: Sharma Ruchi , Bose Devika , Maminishkis Arvydas , Bharti Kapil
Published: January 2020

Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD.
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels as Drug Targets for Neurological Disorders
Authors: Santoro Bina , Shah Mala M.
Published: January 2020

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that critically modulate neuronal activity. Four HCN subunits ( HCN1–4) have been cloned, each having a unique expression profile and distinctive effects on neuronal excitability within the brain. Consistent with this, the expression and function of these subunits are altered in diverse ways in neurological disorders. Here, we review current knowledge on the structure and distribution of the individual HCN channel isoforms, their effects on neuronal activity under physiological conditions, and how their expression and function are altered in neurological disorders, particularly epilepsy, neuropathic pain, and affective disorders. We discuss the suitability of HCN channels as therapeutic targets and how drugs might be strategically designed to specifically act on particular isoforms. We conclude that medicines that target individual HCN isoforms and/or their auxiliary subunit, TRIP8b, may provide valuable means of treating distinct neurological conditions.
Neurons, Receptors, and Channels
Authors: Brown David A.
Published: January 2020

Here, I recount some adventures that I and my colleagues have had over some 60 years since 1957 studying the effects of drugs and neurotransmitters on neuronal excitability and ion channel function, largely, but not exclusively, using sympathetic neurons as test objects. Studies include effects of centrally active drugs on sympathetic transmission; neuronal action and neuroglial uptake of GABA in the ganglia and brain; the action of muscarinic agonists on sympathetic neurons; the action of bradykinin on neuroblastoma-derived cells; and the identification of M-current as a target for muscarinic action, including experiments to determine its distribution, molecular composition, neurotransmitter sensitivity, and intracellular regulation by phospholipids and their hydrolysis products. Techniques used include electrophysiological recording (extracellular, intracellular microelectrode, whole-cell, and single-channel patch-clamp), autoradiography, messenger RNA and complementary DNA expression, antibody injection, antisense knockdown, and membrane-targeted lipidated peptides. I finish with some recollections about my scientific career, funding, and changes in laboratory life and pharmacology research over the past 60 years.
Transition Metal—Carbon Bond Enthalpies as Descriptor for the Electrochemical Stability of Transition Metal Carbides in Electrocatalytic Applications
Authors: Göhl Daniel , Rueß Holger , Pander Marc , Zeradjanin Aleksandar R. , Mayrhofer Karl J. J. , Schneider Jochen M. , Erbe Andreas , Ledendecker Marc
Published: January 2020

Transition metal carbides are used for various applications such as hard coating, heterogeneous catalysis, catalyst support material or coatings in fuel cell applications. However, little is known about the stability of their electrochemically active surface in aqueous electrolytes. Herein, the transition metal—carbon bond enthalpy is proposed as stability criterion for various transition metal carbides. The basis is an oxidation mechanism where the rate determining step is the metal—carbon bond cleavage under acidic conditions which was supported by a detailed corrosion study on hexagonal tungsten carbide. In situ flow cell measurements that were coupled to an inductively coupled plasma mass spectrometer corroborated experimentally the linear dependency of the oxidation overpotential on the transition metal—carbon bond enthalpy. The proposed model allows the estimation of the activation overpotential for electrochemical carbide oxidation resulting in a maximized stabilization for carbides in the 4th group (Ti, Zr, Hf). Together with the calculated thermodynamic oxidation potentials, TiC and VC exhibit the highest experimental oxidation potentials (0.85 VRHE). The model can be used for preselecting possible carbide materials for various electrochemical reactions.
Elucidating the Electrochemical Mechanism of NG-Hydroxy-L-Arginine
Authors: Arral Mariah L. , Tooley Christian , Ziino Emily , Halpern Jeffrey Mark
Published: January 2020

NG-Hydroxy-L-arginine (NOHA) is a stable intermediate product in the urea cycle that can be used to monitor the consumption of L-arginine by nitrous oxide synthase (NOS) to produce nitric oxide (NO) and L-citrulline. Research has implicated the urea cycle in many diseases and NO has cultivated interest as a potential biomarker for neural health. Electrochemical detection is an established, cost-effective method that can successfully detect low levels of analyte concentrations. As one of the few electrochemically active species in the urea cycle, NOHA shows promise as a biomarker for monitoring disruptions in this biochemical process. In this study, we show that NOHA has an oxidation peak at +355 mV vs Ag/AgCl at a glassy carbon electrode. In addition, cyclic voltammetry studies with structural analogs—alanine and N-hydroxyguanidine—allowed us to approximate the oxidation wave at +355 mV vs Ag/AgCl to be a one electron process. Diffusivity of NOHA was found using linear scan voltammetry with a rotating disk electrode and approximated at 5.50 × 10−5 cm2 s−1. Ample work is still needed to make a robust biosensor, but the results here characterize the electrochemical activity and represent principle steps in making a NOHA biosensor.
Are We Meeting the Promise of Endotypes and Precision Medicine in Asthma?
Authors: Ray Anuradha , Camiolo Matthew , Fitzpatrick Anne , Gauthier Marc , Wenzel Sally E.
Published: January 2020

While the term asthma has long been known to describe heterogeneous groupings of patients, only recently have data evolved which enable a molecular understanding of the clinical differences. The evolution of transcriptomics (and other ‘omics platforms) and improved statistical analyses in combination with large clinical cohorts opened the door for molecular characterization of pathobiologic processes associated with a range of asthma patients. When linked with data from animal models and clinical trials of targeted biologic therapies, emerging distinctions arose between patients with and without elevations in type 2 immune and inflammatory pathways, leading to the confirmation of a broad categorization of type 2-Hi asthma. Differences in the ratios, sources, and location of type 2 cytokines and their relation to additional immune pathway activation appear to distinguish several different (sub)molecular phenotypes, and perhaps endotypes of type 2-Hi asthma, which respond differently to broad and targeted anti-inflammatory therapies. Asthma in the absence of type 2 inflammation is much less well defined, without clear biomarkers, but is generally linked with poor responses to corticosteroids. Integration of “big data” from large cohorts, over time, using machine learning approaches, combined with validation and iterative learning in animal (and human) model systems is needed to identify the biomarkers and tightly defined molecular phenotypes/endotypes required to fulfill the promise of precision medicine.
A Review of the Application of Biopolymers on Geotechnical Engineering and the Strengthening Mechanisms between Typical Biopolymers and Soils
Authors: Jang Jungyeon
Published: January 2020

The use of admixtures in soils to improve their properties has been implemented since ancient times. Diverse conventional admixtures such as lime, fly ash, and cement have been added to soils. Also, petrochemicals and bacteria are increasingly used for soil improvement and soil stabilization both mechanically and chemically. However, the conventional admixtures for soils cause significant environmental problems (e.g., CO2 emission). Biopolymers can increasingly replace the conventional admixtures for the application of soil improvement and soil stabilization. Numerous studies have been conducted in the past decades to investigate the suitability and efficiency of various biopolymers for soil improvement. This paper focuses on the properties of the most common biopolymers (xanthan gum, gellan gum, agar, polyacrylamide, and guar gum) and gives the mechanism of biopolymer‐treated soils for soil improvements proposed by researchers.
Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review
Authors: Zwolak Iwona
Published: January 2020

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.
Efficacy of Curcumin on Aortic Atherosclerosis: A Systematic Review and Meta-Analysis in Mouse Studies and Insights into Possible Mechanisms
Authors: Lin Ke , Chen Huaijun , Chen Xiaojun , Qian Jinfu , Huang Shushi , Huang Weijian
Published: January 2020

Since the first report in 2005, accumulating interests have been focused on the effect of curcumin in atherosclerosis with discrepancies. Therefore, we conducted a systematic review and meta-analysis to comprehensively estimate its effect against atherosclerosis. Literature search was performed on the database of PubMed, EMBASE, and Cochrane Library to identify relevant studies which estimated the effect of curcumin in atherosclerosis. Reporting effects on aortic lesion area was the primary outcome while effects on serum lipid profiles and circulating inflammatory markers were the secondary outcome. A total of 10 studies including 14 independent pairwise experiments were included in our analysis. We clarified that curcumin could significantly reduce aortic atherosclerotic lesion area (SMD=‐0.89, 95% CI: -1.36 to -0.41, P=0.0003), decrease serum lipid profiles (Tc, MD=‐1.005, 95% CI: -1.885 to -0.124, P=0.025; TG, MD=‐0.045, 95% CI: -0.088 to -0.002, P=0.042; LDL-c, MD=‐0.523, 95% CI: -0.896 to -0.149, P=0.006) as well as plasma inflammatory indicators (TNF-α, MD=‐56.641, 95% CI: -86.848 to -26.433, P<0.001; IL-1β, MD=‐5.089, 95% CI: -8.559 to -1.619, P=0.004). Dose-response meta-analysis predicted effective dosage of curcumin between 0 and 347 mg/kg BW per day, which was safe and nontoxic according to the existing publications. The underlying mechanisms were also discussed and might be associated with the modulation of lipid transport and inflammation in cells within artery walls as well as indirect modulations in other tissues. Clinical evidence from nonatherosclerosis populations revealed that curcumin would lower the lipid profiles and inflammatory responses as it has in a mouse model. However, standard preclinical animal trial designs are still needed; further studies focusing on the optimal dose of curcumin against atherosclerosis and RCTs directly in atherosclerosis patients are also warranted.
On Providing Differentiated Service Exploiting Multi-Instance RPL for Industrial Low-Power and Lossy Networks
Authors: Monowar Muhammad Mostafa , Basheri Mohammed
Published: January 2020

The rapid proliferation of low-power wireless devices enables the industrial users to improve the productivity and safety of the plants as well as efficient management of the system. This can be achieved through significant increase in data collection, remote monitoring, and control of the plants and promoting the development of industrial Internet of Things (IoT) applications. However, the industrial environment is typically harsh causing high link quality variations and topology changes. The wireless devices used in this environment are also resource constrained in terms of energy, memory, and processing power. In spite of their low-power and lossy nature, these networks demand provisioning of differentiated services for various industrial applications having diverse quality of service (QoS) requirements. Considering the unique characteristics of low-power and lossy networks (LLN), routing for low-power and lossy networks (RPL) is devised which was standardized by IETF in 2012. To meet the demand of diverse traffic, RPL supports multiple instances in a single network. This paper proposes MI-RPL, a multi-instance solution of RPL for industrial low-power and lossy networks (LLNs). MI-RPL defines four instances for four distinct traffic classes of industrial monitoring applications in terms of delay and reliability. MI-RPL also introduces composite routing metrics and proposes an objective function (OF) to compute the most suitable path for each instance. The performance of MI-RPL is investigated through simulations that exhibit MI-RPL has better delay and packet delivery performance for delay- and reliability-constrained traffic along with lower energy consumption compared to the standard RPL.
Exploration Entropy for Reinforcement Learning
Authors: Xin Bo , Yu Haixu , Qin You , Tang Qing , Zhu Zhangqing
Published: January 2020

The training process analysis and termination condition of the training process of a Reinforcement Learning (RL) system have always been the key issues to train an RL agent. In this paper, a new approach based on State Entropy and Exploration Entropy is proposed to analyse the training process. The concept of State Entropy is used to denote the uncertainty for an RL agent to select the action at every state that the agent will traverse, while the Exploration Entropy denotes the action selection uncertainty of the whole system. Actually, the action selection uncertainty of a certain state or the whole system reflects the degree of exploration and the stage of the learning process for an agent. The Exploration Entropy is a new criterion to analyse and manage the training process of RL. The theoretical analysis and experiment results illustrate that the curve of Exploration Entropy contains more information than the existing analytical methods.
Multi-Rule Based Ensemble Feature Selection Model for Sarcasm Type Detection in Twitter
Authors: Sundararajan Karthik , Palanisamy Anandhakumar
Published: January 2020

Sentimental analysis aims at inferring how people express their opinion over any piece of text or topic of interest. This article deals with detection of an implicit form of the sentiment, referred to as sarcasm. Sarcasm conveys the opposite of what people try to convey in order to criticize or ridicule in a humorous way. It plays a vital role in social networks since most of the tweets or posts contain sarcastic nuances. Existing approaches towards the study of sarcasm deals only with the detection of sarcasm. In this paper, in addition to detecting sarcasm from text, an approach has been proposed to identify the type of sarcasm. The main motivation behind determining the types of sarcasm is to identify the level of hurt or the true intent behind the sarcastic text. The proposed work aims to improve upon the existing approaches by incorporating a new perspective which classifies the sarcasm based on the level of harshness employed. The major application of the proposed work would be relating the emotional state of a person to the type of sarcasm exhibited by him/her which could provide major insights about the emotional behavior of a person. An ensemble-based feature selection method has been proposed for identifying the optimal set of features needed to detect sarcasm from tweets. This optimal set of features was employed to detect whether the tweet is sarcastic or not. After detecting sarcastic sentences, a multi-rule based approach has been proposed to determine the type of sarcasm. As an initial attempt, sarcasm has been classified into four types, namely, polite sarcasm, rude sarcasm, raging sarcasm, and deadpan sarcasm. The performance and efficiency of the proposed approach has been experimentally analyzed, and change in mood of a person for each sarcastic type has been modelled. The overall accuracy of the proposed ensemble feature selection algorithm for sarcasm detection is around 92.7%, and the proposed multi-rule approach for sarcastic type identification achieves an accuracy of 95.98%, 96.20%, 99.79%, and 86.61% for polite, rude, raging, and deadpan types of sarcasm, respectively.
The Effects of Strength Training Combined with Vitamin C and E Supplementation on Skeletal Muscle Mass and Strength: A Systematic Review and Meta-Analysis
Authors: Dutra Maurilio T. , Martins Wagner Rodrigues , Ribeiro Alexandre L. A. , Bottaro Martim
Published: January 2020

Intense muscle contractile activity can result in reactive oxygen species production in humans. Thus, supplementation of antioxidant vitamins has been used to prevent oxidative stress, enhance performance, and improve muscle mass. In this sense, randomized controlled studies on the effect of vitamin C and E supplementation combined with strength training (ST) on skeletal muscle mass and strength have been conducted. As these studies have come to ambiguous findings, a better understanding of this topic has yet to emerge. The purpose of the present review is to discuss the current knowledge about the effect of vitamin C and E supplementation on muscle mass and strength gains induced by ST. Search for articles was conducted in the following databases: PubMed/Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Google Scholar. This work is in line with the recommendations of the PRISMA statement. Eligible studies were placebo-controlled trials with a minimum of four weeks of ST combined with vitamin C and E supplementation. The quality of each included study was evaluated using the Physiotherapy Evidence Database Scale (PEDro). 134 studies were found to be potentially eligible, but only seven were selected to be included in the qualitative synthesis. A meta-analysis of muscle strength was conducted with 3 studies. Findings from these studies indicate that vitamins C and E has no effect on muscle force production after chronic ST. Most of the evidence suggests that this kind of supplementation does not potentiate muscle growth and could possibly attenuate hypertrophy over time.
Medication Consumption Patterns and Polypharmacy among Community-Dwelling Elderly in Lomé (Togo) in 2017
Authors: Gbeasor-Komlanvi Fifonsi A. , Zida-Compaore Wendpouiré I. C. , Dare Ikpindi H. , Diallo Aboudoulatif , Darre Tchin P. , Potchoo Yao , Belo Mofou , Ekouevi Didier K.
Published: January 2020

Background. In the sub-Saharan African, region of the world with a fast growing aging population and where the use of herbal products is very common, there is a paucity of data on medication consumption patterns among elderly people. The objective of this study was to assess the prevalence of polypharmacy and its associated factors among community-dwelling elderly in Lomé, Togo, in 2017. Methods. A cross-sectional study was conducted from March to June 2017 in Lomé, Togo among people aged 60 years and older. The Respondent Driven Sampling method was used to recruit participants. Data on socio-demographic characteristics and medication consumption patterns, including the use of medicinal plants and dietary supplements, were collected using a standardized questionnaire during a face-to-face interview at participants’ home. Descriptive and binary logistic regression analyses were performed. Results. A total of 370 participants with median age 65 years, (IQR: 62–71) were enrolled in the study. Almost three elderly in five (57.6%) were multimorbid (had two or more chronic diseases). Conventional drugs (78.4%), medicinal plants (14.3%) and other dietary supplements (9.5%) were used by participants. The prevalence of polypharmacy was 22.7% (95% CI: 18.5–27.3%). Concurrent use of conventional drugs and medicinal plants or other dietary supplements was observed among 17.0% of participants and 67.3% reported self-medication. Multimorbidity (aOR = 4.55; 95% CI: [2.42–8.54]) and female sex (aOR = 1.86; 95% CI: [1.00–3.47]) were associated with polypharmacy. Conclusion. One elderly in five uses five or more medications in Togo. Further studies are needed to assess drug-drug interactions and herb-drug interactions among this population.
Effect of Integrated Technologies on Production and Productivity of Pearl Millet in the Dryland Areas of Wag Himira Administrative Zone, Eastern Amhara, Ethiopia
Authors: Berhanu Tafere , Beshir Wubshet , Lakew Alemu
Published: January 2020

Production of pearl millet with yield improvement would have a direct impact on the drought-prone areas of Ethiopia since pearl millet is drought tolerant and early maturing with high water use efficiency. An experiment was conducted to study the performance of pearl millet under different technologies in 2013 and 2014 main cropping seasons at the main site of the research center, Aybra, with the objective of evaluating and identifying appropriate combinations of technologies that enhance the production of pearl millet in the study area. About fourteen integrated technologies were applied in a randomized complete block design with three replications. The analysis was done by using SAS software version 9.1, and means were separated through the Duncan multiple range test. Results of analysis of variance showed that yield-related traits of pearl millet were significantly influenced by the integration of technologies in the 2013 cropping season. According to the results, the maximum yield (3084 kg ha−1) was recorded with the application of the treatment combination of recommended fertilizer application + seed primming + tie ridging, while the minimum was recorded (919 kg ha−1) in the treatment combination of microdose application of fertilizer + primed seed + intercropping of pearl millet with mung bean. In the case of the 2014 cropping season, the highest grain yield (3687 kg ha−1) was recorded with the treatment combination of microdose fertilizer application + primed seed + tie ridging + intercropping of pearl millet with mung bean, whereas the lowest grain yield (2115 kg ha−1) was recorded in the treatment combination of no fertilizer application + primed seed + flat bed. Based on the results of the current investigation, it could be recommended that using technology integration of microdose, tied ridge, primed seed, and intercropping of pearl millet with mung bean is better to attain maximum yield in the study area and similar agroecologies.
Evolution of Dynamic Recrystallization in 5CrNiMoV Steel during Hot Forming
Authors: Hu Zhiqiang , Wang Kaikun
Published: January 2020

The dynamic recrystallization (DRX) behavior of 5CrNiMoV steel was investigated through hot compression at temperatures of 830–1230°C and strain rates of 0.001–10 s−1. From the experimental results, most true stress‐strain curves showed the typical nature of DRX that a single peak was reached at low strains followed by a decrease of stress and a steady state finally at relatively high strains. The constitutive behavior of 5CrNiMoV steel was analyzed to deduce the operative deformation mechanisms, and the correlation between flow stress, temperature, and strain rate was expressed as a sine hyperbolic type constitutive equation. Based on the study of characteristic stresses and strains on the true stress‐strain curves, a DRX kinetics model was constructed to characterize the influence of true strain, temperature, and strain rate on DRX evolution, which revealed that higher temperatures and lower strain rates had a favorable influence on improving the DRX volume fraction at the same true strain. Microstructure observations indicated that DRX was the main mechanism and austenite grains could be greatly refined by reducing the temperature of hot deformation or increasing the strain rate when complete recrystallization occurred. Furthermore, a DRX grain size model of 5CrNiMoV was obtained to predict the average DRX grain size during hot forming.
Light Particle and Quark Chemical Potentials from Negatively to Positively Charged Particle Yield Ratios Corrected by Removing Strong and Weak Decays
Authors: Lao Hai-Ling , Gao Ya-Qin , Liu Fu-Hu
Published: January 2020

The yield ratios of negatively to positively charged pions (π−/π+), negatively to positively charged kaons (K−/K+), and anti-protons to protons (p¯/p) produced in mid-rapidity interval in central gold-gold (Au-Au) collisions, central lead-lead (Pb-Pb) collisions, and inelastic (INEL) or non-single-diffractive (NSD) proton-proton (pp) collisions, as well as in forward rapidity region in INEL pp collisions are analyzed in the present work. Over an energy range from a few GeV to above 10 TeV, the chemical potentials of light flavor particles (pion, kaon, and proton) and quarks (up, down, and strange quarks) are extracted from the mentioned yield ratios in which the contributions of strong decay from high-mass resonance and weak decay from heavy flavor hadrons are removed. Most energy dependent chemical potentials show the maximum at about 4 GeV, while the energy dependent yield ratios do not show such an extremum.
Conditions for Vacuum Instability in Holographic Theories with Dilaton Field
Authors: Tahery Sara , Nair Sreeraj , Zhang Pengming
Published: January 2020

We investigate the vacuum instability in the presence of dilaton field in a holographic setup. Although the dilaton is a bulk field, it leads to the vacuum instability on the boundary. We show that the whole process crucially depends on the probe brane position and as well on the radial coordinate so that the effects of dilaton scale parameter in different regions of the bulk or for different probe brane positions are different. We also observe that in our study, the temperature can strengthen the effect of scale parameter in reducing the potential barrier. Finally, we show that this Schwinger-like effect, although is interesting by itself, does not produce a considerable pair production rate.
Recent Findings in the Posttranslational Modifications of PD-L1
Authors: Li Shu-Man , Zhou Jie , Wang Yun , Nie Run-Cong , Chen Jie-Wei , Xie Dan
Published: January 2020

Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.
Optimized Configuration of Manufacturing Resources for Middle and Lower Batch Customization Enterprises in Cloud Manufacturing Environment
Authors: Yu Yinyun , Xu Wei
Published: January 2020

The optimal configuration of manufacturing resources in the cloud manufacturing environment has always been the focus of research on various advanced manufacturing systems. Aiming at the problem of manufacturing resources optimization configuration for middle and lower batch customization enterprises in cloud manufacturing environment, this paper gives a bi-level programming model for manufacturing resources optimization configuration in cloud manufacturing environment which fully considers customer satisfaction and enterprise customization economic benefits. The method firstly identifies the relationship between customer demands and customer satisfaction through questionnaires and quantifies the Kano model effectively. Then, it uses Quality Function Deployment (QFD) to transform customer demand characteristics into engineering characteristics and integrates the qualitative and quantitative results of the Kano model. Next, the method establishes enterprise economic benefits function according to the factors of order quantity and input cost. Furthermore, a comprehensive nonlinear bi-level programming model is established based on cost, time, and quality constraints. The model is solved by intelligent algorithm. Finally, the validity and feasibility of the model are verified by model simulation of actual orders of an enterprise. This method effectively realizes the optimal configuration of manufacturing resources in the cloud manufacturing environment, while maximizing the interests of both suppliers and demanders.
Successful Treatment of Adenovirus Infection with Brincidofovir in an Immunocompromised Patient after Hematological Stem Cell Transplantation
Authors: Van Genechten T. , van Heerden J. , Bauters T. , Dhooge C.
Published: January 2020

Immunocompromised patients, including hematopoietic stem cell transplantation (HSCT), HIV, and malnourished patients, are at increased risk for viral infections with high incidences of morbidity and mortality. In HSCT patients, the infection risk is increased until immune reconstitution is re-established. Therapy with standard of care antiviral drugs, for example Cidofovir, is expensive, requires prolonged administration, and has unfavorable toxicity profiles. Our case describes the successful use of Brincidofovir (CMX001), a lipid-conjugate of the nucleotide analog Cidofovir, in a 9-year-old post-HSCT girl with disseminated adenovirus infection. The increased efficacy of Brincidofovir (BCV) against multiple viral infections, limited toxicity, and oral-administered schedule opens options in different resource settings.
In Vitro Cytotoxicity and Antitumor Activity of Dual-Targeting Drug Delivery System Based on Modified Magnetic Carbon by Folate
Authors: Du Jinglei , Li Qiang , Chen Lin , Wang Shicai , Zhang Li , Yu Shiping , Yang Yongzhen , Liu Xuguang
Published: January 2020

A dual-targeting drug delivery system (DTDDS) with magnetic targeting and active targeting was obtained to improve the targeting and drug-loading capacity of magnetic drug nanocarriers. An ultraviolet-visible spectrophotometer and flow cytometry were used to investigate the drug-loading and release capacity, cytotoxicity, and inhibition of tumor cell proliferation, separately. Results show that DTDDS has obvious magnetic characteristics, on which the modification amount of folic acid is 64.82 mg g-1. Doxorubicin was taken as a template drug to evaluate its drug-loading capacity, which was as high as 577.12 mg g-1. Good biocompatibility and low cytotoxicity of DTDDS were further confirmed. Moreover, DTDDS can target the folate receptor on the surface of HeLa cells and deliver doxorubicin into HeLa cells, thereby increasing the proliferation inhibition for cancer cells. Therefore, this new dual-targeting drug delivery system shows potential in significantly reducing the toxic side effects of chemotherapy and improving chemotherapy efficiency.
High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats
Authors: Hong Yu-pu , Yu Jia , Su Ying-ru , Mei Fang-chao , Li Man , Zhao Kai-liang , Zhao Liang , Deng Wen-hong , Chen Chen , Wang Wei-xing
Published: January 2020

High-fat diet (HFD) often increases oxidative stress and enhances inflammatory status in the body. Toll-like receptor 4 (TLR4) is widely expressed in the pancreatic tissues and plays an important role in pancreatitis. This study is aimed at investigating the effect of HFD on acute pancreatitis (AP) and the role of TLR4-mediated necroptosis and inflammation in this disease. Weight-matched rats were allocated for an 8-week feeding on the standard chow diet (SCD) or HFD, and then, the AP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at an indicated time point after modeling. Additionally, inhibition of TLR4 signaling by TAK-242 in HFD rats with AP was conducted in vivo. The results showed that the levels of serum free fatty acid (FFA) in HFD rats were higher than those in SCD rats. Moreover, HFD rats were more vulnerable to AP injury than SCD rats, as indicated by more serious pathological damage and much higher pancreatic malondialdehyde (MDA) and lipid peroxidation (LPO) levels as well as lower pancreatic superoxide dismutase (SOD) activities and reduced glutathione (GSH) contents and more intense infiltration of MPO-positive neutrophils and CD68-positive macrophages. In addition, HFD markedly increased the expressions of TLR4 and necroptosis marker (RIP3) and aggravated the activation of NF-κB p65 and the expression of TNF-α in the pancreas of AP rats at indicated time points. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in HFD rats, as indicated by improvement of the above indexes. Taken together, these findings suggest that HFD exacerbated the extent and severity of AP via oxidative stress, inflammatory response, and necroptosis. Inhibition of TLR4 signaling by TAK-242 alleviated oxidative stress and decreased inflammatory reaction and necroptosis, exerting a protective effect during AP in HFD rats.
Rib Exostoses Presenting as Mediastinal Masses: A Rare Presentation and Minireview of the Literature
Authors: Butcovan Doina , Mocanu Veronica , Haliga Raluca Ecaterina , Baran Dana , Ungureanu Carmen , Carp Ştefana , Tinică Grigore
Published: January 2020

Costal osteocartilaginous exostoses, also known as osteochondromas, are the most common neoplasms of the long bones but are rare tumors of the ribs. Osteochondroma is often asymptomatic and incidentally observed. Tumors typically begin to grow before puberty and continue until bone maturation is reached. Our paper presents the case of a 16-year-old young male who was admitted to the hospital with nonspecific symptoms and having a family history of exostosis. Chest X-ray and computed tomography imaging revealed multiple costosternal exostoses, manifested as mediastinal masses, with protrusion into the thoracic cavity, exerting compressive effects on the ascending aorta and pulmonary parenchyma. Surgery is required in childhood if lesions are painful. But if tumor formation occurs in adulthood, such pathological bony outgrowths should always be resected for avoiding further complications. In this patient, surgical intervention removed the tumoral masses and improved the symptoms. Subsequently, histological exam confirmed the diagnosis of osteocartilaginous exostoses and showed the lack of dysplastic changes.
Combined Cerebellar and Spinal Cord Deficits Caused by an Underlying Gynecologic Malignancy
Authors: Othman Tamer , Hendizadeh Moshe-Samuel , Vankina Ritika , Park Susan , Kim Phyllis
Published: January 2020

Paraneoplastic cerebellar degeneration (PCD) is an uncommon autoimmune disorder targeting antigens within the nervous system and is usually associated with an underlying malignancy. Neurologic symptoms frequently precede the cancer diagnosis, which is most often seen in women with breast or gynecologic tumors. Anti-Yo-related PCD is the most common PCD syndrome, and one of the best understood. Although cerebellar signs are characteristic of anti-Yo PCD, myelopathy is an unusual presentation of anti-Yo PCD based on published case series and reports. Unfortunately, the prognosis for anti-Yo PCD is often poor, and most patients become bedridden. We report a case highlighting a severe presentation of cerebellar degeneration along with an unusual finding of myelopathy in a patient with a newly diagnosed gynecologic cancer.
Green Vehicle Routing and Scheduling Optimization of Ship Steel Distribution Center Based on Improved Intelligent Water Drop Algorithms
Authors: Chen Gang , Wu Xiaoyuan , Li Jinghua , Guo Hui
Published: January 2020

The timeliness of the steel distribution center process contributes to the smooth progress of ship construction. However, carbon emissions from vehicles in the distribution process are a major source of pollution. Reasonable vehicle routing and scheduling can effectively reduce the carbon emissions of vehicles and ensure the timeliness of distribution. To solve this problem, a green vehicle routing and scheduling problem model with soft time windows was proposed in this study. An intelligent water drop algorithm was designed and improved and then compared with the genetic algorithm and the traditional intelligent water drop algorithm. The applicability of the improved intelligent water drop algorithm was demonstrated. Finally, this algorithm was applied to a specific example to demonstrate that the improved intelligent water drop algorithm effectively reduced the cost of such green vehicle problems, thus reducing the carbon emissions of vehicles during the distribution process and achieving reductions in environmental pollution. Ultimately, this algorithm facilitates the achievement of green shipbuilding.
The Rational Spectral Method Combined with the Laplace Transform for Solving the Robin Time-Fractional Equation
Authors: Yang Lufeng
Published: January 2020

In this paper, the rational spectral method combined with the Laplace transform is proposed for solving Robin time-fractional partial differential equations. First, a time-fractional partial differential equation is transformed into an ordinary differential equation with frequency domain components by the Laplace transform. Then, the spatial derivatives are discretized by the rational spectral method, the linear equation with the parameter s is solved, and the approximation Ux,s is obtained. The approximate solution at any given time, which is the numerical inverse Laplace transform, is obtained by the modified Talbot algorithm. Numerical experiments are carried out to demonstrate the high accuracy and efficiency of our method.
Transient Sox9 Expression Facilitates Resistance to Androgen-Targeted Therapy in Prostate Cancer
Authors: Nouri Mannan , Massah Shabnam , Caradec Josselin , Lubik Amy A. , Li Na , Truong Sarah , Lee Ahn R. , Fazli Ladan , Ramnarine Varune R. , Lovnicki Jessica M. , Moore Jackson , Wang Mike , Foo Jane , Gleave Martin E. , Hollier Brett G. , Nelson Colleen , Collins Colin , Dong Xuesen , Buttyan Ralph
Published: January 2020

Purpose:

Patients with metastatic prostate cancer are increasingly presenting with treatment-resistant, androgen receptor–negative/low (AR−/Low) tumors, with or without neuroendocrine characteristics, in processes attributed to tumor cell plasticity. This plasticity has been modeled by Rb1/p53 knockdown/knockout and is accompanied by overexpression of the pluripotency factor, Sox2. Here, we explore the role of the developmental transcription factor Sox9 in the process of prostate cancer therapy response and tumor progression.

Experimental Design:

Unique prostate cancer cell models that capture AR−/Low stem cell–like intermediates were analyzed for features of plasticity and the functional role of Sox9. Human prostate cancer xenografts and tissue microarrays were evaluated for temporal alterations in Sox9 expression. The role of NF-κB pathway activity in Sox9 overexpression was explored.

Results:

Prostate cancer stem cell–like intermediates have reduced Rb1 and p53 protein expression and overexpress Sox2 as well as Sox9. Sox9 was required for spheroid growth, and overexpression increased invasiveness and neural features of prostate cancer cells. Sox9 was transiently upregulated in castration-induced progression of prostate cancer xenografts and was specifically overexpressed in neoadjuvant hormone therapy (NHT)–treated patient tumors. High Sox9 expression in NHT-treated patients predicts biochemical recurrence. Finally, we link Sox9 induction to NF-κB dimer activation in prostate cancer cells.

Conclusions:

Developmentally reprogrammed prostate cancer cell models recapitulate features of clinically advanced prostate tumors, including downregulated Rb1/p53 and overexpression of Sox2 with Sox9. Sox9 is a marker of a transitional state that identifies prostate cancer cells under the stress of therapeutic assault and facilitates progression to therapy resistance. Its expression may index the relative activity of the NF-κB pathway.
Analysis of Pre- and Posttreatment Tissues from the SWOG S0800 Trial Reveals an Effect of Neoadjuvant Chemotherapy on the Breast Cancer Genome
Authors: Powles Ryan L. , Wali Vikram B. , Li Xiaotong , Barlow William E. , Nahleh Zeina , Thompson Alastair M. , Godwin Andrew K. , Hatzis Christos , Pusztai Lajos
Published: January 2020

Purpose:

We performed whole-exome sequencing (WES) of pre- and posttreatment cancer tissues to assess the somatic mutation landscape of tumors before and after neoadjuvant taxane and anthracycline chemotherapy with or without bevacizumab.

Experimental Design:

Twenty-nine pretreatment biopsies from the SWOG S0800 trial were subjected to WES to identify mutational patterns associated with response to neoadjuvant chemotherapy. Nine matching samples with residual cancer after therapy were also analyzed to assess changes in mutational patterns in response to therapy.

Results:

In pretreatment samples, a higher proportion of mutation signature 3, a BRCA-mediated DNA repair deficiency mutational signature, was associated with higher rate of pathologic complete response (pCR; median signature weight 24%, range 0%–38% in pCR vs. median weight 0%, range 0%–19% in residual disease, Wilcoxon rank sum, Bonferroni P = 0.007). We found no biological pathway level mutations associated with pCR or enriched in posttreatment samples. We observed statistically significant enrichment of high functional impact mutations in the “E2F targets” and “G2–M checkpoint” pathways in residual cancer samples implicating these pathways in resistance to therapy and a significant depletion of mutations in the “myogenesis pathway” suggesting the cells harboring these variants were effectively eradicated by therapy.

Conclusions:

These results suggest that genomic disturbances in BRCA-related DNA repair mechanisms, reflected by a dominant mutational signature 3, confer increased chemotherapy sensitivity. Cancers that survive neoadjuvant chemotherapy frequently have alterations in cell-cycle–regulating genes but different genes of the same pathways are affected in different patients.
Elite Intratumoral T-cell Clonotypes (The 1%) Effect “Trickle-Down Cytotoxicity”
Authors: Henick Brian S.
Published: January 2020

Careful study of T-cell clonal dynamics in patients with non–small cell lung cancer treated with neoadjuvant nivolumab suggests that successful trafficking of clones from a proliferative burst in the periphery to the tumor associates with major pathologic response. Integration of these findings with functional analysis may augment current therapeutic strategies.

See related article by Zhang et al., p. 1327
Turner Syndrome Systematic Review: Spontaneous Thelarche and Menarche Stratified by Karyotype
Authors: Dabrowski Elizabeth , Jensen Rachel , Johnson Emilie K. , Habiby Reema L. , Brickman Wendy J. , Finlayson Courtney
Published: January 2020

Background: Girls with Turner syndrome (TS) have a high incidence of primary ovarian insufficiency. Recent data show rates of spontaneous thelarche (ST) of 38% and spontaneous menarche (SM) of 15–16%, with higher rates in those with mosaicism. Summary: We systematically reviewed the literature for evidence regarding rates of ST and SM in TS and evaluated rates based on the type of chromosomal mosaicism. We searched MEDLINE via PubMed, Embase, and the Cochrane Database of Controlled Trials. Reference lists were screened. Studies reporting outcomes of ST and SM in girls with TS, diagnosed by genetic analysis, were included. Data was collected regarding study design, cohort type, cohort age, the number of participants with ST and SM, the individual age at diagnosis of ST and SM, the mean age of patients with ST and SM, sample size, the number of participants with secondary amenorrhea, and karyotype. Key Messages: In total 2,699 patients were assessed for ST and 2,890 for SM from 43 articles. Overall the rates of ST were 32% (95% CI 26.4–38.9) and SM 20.8% (95% CI 19.3–22.4). Girls with X monosomy had the lowest rates of ST (i.e., 13%; 95% CI 8.7–19.7) and SM (i.e., 9.1%; 95% CI 7.3–11.3). Girls with 45,X/47,XXX had the highest rates of ST (i.e., 88.1%; 95% CI 62–97.1) and SM (i.e., 66.2%; 95% CI 49.3–79.6). Conclusions: Rates of ST and SM differ by karyotype in TS. When counseling patients, the karyotype should strongly influence discussions regarding pubertal development and the future reproductive potential.
Endophthalmitis Caused by Agrobacterium radiobacter following Intravitreal Aflibercept for Diabetic Retinopathy
Authors: Rohowetz Landon J. , Yannuzzi Nicolas A. , Gupta Sunil , Patel Nimesh A. , Miller Darlene , Flynn Jr. Harry W.
Published: January 2020

Agrobacterium (Rhizobium) radiobacter is a gram-negative bacillus rarely implicated in ocular disease. A 79-year-old male who performed extensive yardwork following intravitreal injection with aflibercept for diabetic macular edema developed endophthalmitis caused by Agrobacterium radiobacter on post-injection day 7. The patient was treated with vitreous tap and intravitreal injection of vancomycin and ceftazidime with clearance of the infection and restoration of his baseline visual acuity at 20/80.
Sensibilidade performativa e comunicação das coisas
Authors: Lemos André Luiz Martins , Bitencourt Elias Cunha
Published: January 2020

O objetivo deste artigo é afirmar o caráter social dos objetos e apresentar o que diferencia as redes sociotécnicas de objetos cotidianos daquelas de objetos aumentados digitalmente – as quais caracterizam a Internet das Coisas. Denominamos essa diferença de sensibilidade performativa. Mostraremos que a sensibilidade performativa não é uma característica técnica de sensores e atuadores, mas uma propriedade que amplia o objeto de modo infocomunicacional em uma rede de comunicação também mais ampla, a partir de performances e procedimentos algorítmicos. Destacamos como essa sensibilidade performativa pode ser vista como um elemento fundamental para pensar um modelo de comunicação das coisas, explorando as narrativas procedimentais da Fitbit Charge HR2.