bluuebunny/crossref_metadata_2025 huggingface dataset:
16p13.11 microduplication in 45 new patients: refined clinical significance and genotype–phenotype correlations
Authors: Allach El Khattabi Laïla , Heide Solveig , Caberg Jean-Hubert , Andrieux Joris , Doco Fenzy Martine , Vincent-Delorme Caroline , Callier Patrick , Chantot-Bastaraud Sandra , Afenjar Alexandra , Boute-Benejean Odile , Cordier Marie Pierre , Faivre Laurence , Francannet Christine , Gerard Marion , Goldenberg Alice , Masurel-Paulet Alice , Mosca-Boidron Anne-Laure , Marle Nathalie , Moncla Anne , Le Meur Nathalie , Mathieu-Dramard Michèle , Plessis Ghislaine , Lesca Gaetan , Rossi Massimiliano , Edery Patrick , Delahaye-Duriez Andrée , De Pontual Loïc , Tabet Anne Claude , Lebbar Aziza , Suiro Lesley , Ioos Christine , Natiq Abdelhafid , Chafai Elalaoui Siham , Missirian Chantal , Receveur Aline , François-Fiquet Caroline , Garnier Pascal , Yardin Catherine , Laroche Cécile , Vago Philippe , Sanlaville Damien , Dupont Jean Michel , Benzacken Brigitte , Pipiras Eva
Published: October 2018

Background

The clinical significance of 16p13.11 duplications remains controversial while frequently detected in patients with developmental delay (DD), intellectual deficiency (ID) or autism spectrum disorder (ASD). Previously reported patients were not or poorly characterised. The absence of consensual recommendations leads to interpretation discrepancy and makes genetic counselling challenging. This study aims to decipher the genotype–phenotype correlations to improve genetic counselling and patients’ medical care.

Methods

We retrospectively analysed data from 16 013 patients referred to 12 genetic centers for DD, ID or ASD, and who had a chromosomal microarray analysis. The referring geneticists of patients for whom a 16p13.11 duplication was detected were asked to complete a questionnaire for detailed clinical and genetic data for the patients and their parents.

Results

Clinical features are mainly speech delay and learning disabilities followed by ASD. A significant risk of cardiovascular disease was noted. About 90% of the patients inherited the duplication from a parent. At least one out of four parents carrying the duplication displayed a similar phenotype to the propositus. Genotype–phenotype correlations show no impact of the size of the duplicated segment on the severity of the phenotype. However, NDE1 and miR-484 seem to have an essential role in the neurocognitive phenotype.

Conclusion

Our study shows that 16p13.11 microduplications are likely pathogenic when detected in the context of DD/ID/ASD and supports an essential role of NDE1 and miR-484 in the neurocognitive phenotype. Moreover, it suggests the need for cardiac evaluation and follow-up and a large study to evaluate the aortic disease risk.
Changes in exercise capacity and serum BDNF following long-term sprint interval training in well-trained cyclists
Authors: Hebisz Paulina , Hebisz Rafał , Murawska-Ciałowicz Eugenia , Zatoń Marek
Published: October 2018

The study determined the effects of sprint interval training on the acute and chronic changes of serum brain-derived neurotrophic factor (BDNF) and aerobic capacity. Twenty-six cyclists were divided into experimental (E) and control groups. Both groups executed a 6-month exercise intervention involving high-intensity interval training (HIIT) and continuous endurance training (CET) with group E replacing HIIT and CET sessions with sprint interval training (SIT) that was executed twice a week. Two exercise tests were administered prior to the intervention and at 2 and 6 months after study outset. Incremental exercise test assessed aerobic capacity by measuring maximal oxygen uptake and work output; the sprint interval exercise test (SIXT) comprises 3 sets of four 30-s all-out repetitions interspersed with 90 s of rest with sets separated by 25–40 min of active recovery. Oxygen uptake, work output, BDNF, and vascular endothelial growth factor A (VEGF-A) concentrations (baseline, 10 min after first set, and 10 and 60 min after third SIXT set) were taken during the SIXT. Significant decreases in BDNF relative to baseline values were observed 10 min after the first set and 60 min after the third set in group E at the 2- and 6-month assessments. Increases in baseline VEGF-A after 2 and 6 months of training and increases in maximal oxygen uptake after 2 months of training were also observed only in group E. The inclusion of SIT with HIIT and CET shows positive long-term effects, including increased maximal oxygen uptake and baseline VEGF-A and a reduction in BDNF below baseline levels during and after SIXT.
Tree resin flow dynamics during an experimentally induced attack by Ips avulsus, I. calligraphus, and I. grandicollis
Authors: Denham Sander O. , Coyle David R. , Oishi A. Christopher , Bullock Bronson P. , Heliövaara Kari , Novick Kimberly A.
Published: October 2018

The success of tree colonization by bark beetles depends on their ability to overcome host tree defenses, including resin exudation and toxic chemicals, which deter bark beetle colonization. Resin defenses during insect outbreaks are challenging to study in situ, as outbreaks are stochastic events that progress quickly and thus preclude the establishment of baseline observations of non-infested controls. We use synthetic aggregation pheromones to demonstrate that confined Ips bark beetle herbivory can be successfully initiated to provide opportunities for studying interactions between bark beetles and their hosts, including the dynamics of constitutive and induced resin exudation. In Pinus taeda L. plantations between 12 and 19 years old in North and South Carolina, U.S., trees were affixed with pheromone lures, monitored for evidence of bark beetle attacks, and resin samples were collected throughout the growing season. Baiting increased beetle herbivory to an extent sufficient to produce an induced resin response. Attacked trees exuded about three times more resin at some time than control trees. This supports previous work that demonstrated that information on constitutive resin dynamics alone provides an incomplete view of a host tree’s resistance to bark beetle attack.
Activity Dependent Mammalian Target of Rapamycin Pathway and Brain Derived Neurotrophic Factor Release is Required for the Rapid Antidepressant Effects of Puerarin
Authors: Huang Chih-Chia , Tsai Mang-Hung , Wu Ya-Chieh , Chen Kuang-Ti , Chuang Han-Wen , Chen Yun , Tseng Guan-Woei , Fu Pin-I , Wei I-Hua
Published: October 2018

Puerarin is a traditional Chinese medicine with beneficial effects of reduced depression-like behaviors in mice with stress. Previous studies also show that puerarin can produce neuroprotective effect via activating the Akt or increased brain-derived neurotrophic factor (BDNF) expression. Interestingly, BDNF and Akt downstream target, mammalian target of rapamycin (mTOR) mediate the fast-acting antidepressant properties of ketamine. Until now, the involvement of the mTOR signaling pathway or BDNF on puerarin-induced antidepressant effect remains unknown. We aimed to investigate whether the antidepressant-like effect induced by puerarin would associate mTOR signaling pathway and BDNF release. The antidepressant-like effects of puerarin were evaluated using the forced swim test. The activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptor (AMPAR)-mTOR signaling pathway and release of BDNF in the prefrontal cortex were determined. We also investigated the effect of puerarin on AMPAR trafficking through measuring the PKA phosphorylation of AMPAR subunit GluR1. Our present results show that puerarin exerted antidepressant-like responses that was mediated by AMPAR-induced mTOR signaling pathway and associated with increased BDNF release. Moreover, a significant increase in the GluR1 phosphorylation at its PKA site was noted following puerarin treatment. Our findings are the first to demonstrate that the antidepressant-like actions of puerarin require AMPAR–mTOR signaling pathway activation, are associated with an increased BDNF level and facilitate AMPAR membrane insertion. These findings provide preclinical evidence that puerarin may possess antidepressant property which is mediated by the glutamatergic system.
Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells
Authors: Zhang Zengjie , Wang Chenggui , Lin Jialiang , Jin Haiming , Wang Ke , Yan Yingzhao , Wang Jianle , Wu Congcong , Nisar Majid , Tian Naifeng , Wang Xiangyang , Zhang Xiaolei
Published: October 2018

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.
Sophora flavescensContaining-QYJD Formula Activates Nrf2 Anti-Oxidant Response, Blocks Cellular Transformation and Protects Against DSS-Induced Colitis in Mouse Model
Authors: Fang Ruoming , Wu Renyi , Zuo Qian , Yin Ran , Zhang Chengyue , Wang Chao , Guo Yue , Yang Anne Yuqing , Li Wenji , Lin Lizhu , Kong Ah-Ng
Published: October 2018

Qu-Yu-Jie-Du decoction (QYJD) is a commercially available traditional Chinese medicine (TCM). It is an aqueous extract of a Chinese herbal formula primarily consisting of eight TCM herbs: Taraxacum campylodes G.E. Haglund, Coix lacryma-jobi L., Smilax glabra Roxb., Sanguisorba officinalis L, Styphnolobium japonicum (L.) Schott, Prunus persica (L.) Batsch, Sophora flavescens Aiton, and Eupolyphaga sinensis Walker. Matrine and oxymatrine are two of the major phytochemical constituents of QYJD. Inflammation and oxidative stress are strongly associated with colon carcinogenesis. Colorectal cancer (CRC) is the third most common type of cancer. Therefore, cancer chemopreventive agents targeting CRC are urgently needed. This study was conducted to investigate the potential anticancer effects and the underlying mechanisms of QYJD and its active constituents, matrine and oxymatrine, in human colon cancer HT29 cells and in a dextran sulfate sodium (DSS)-induced colitis mouse model. QYJD and matrine effectively inhibited the proliferation and anchorage-independent growth of HT29 cells in a dose-dependent manner. QYJD and matrine also induced an Nrf2-mediated anti-oxidant response element-luciferase activity and upregulated the Nrf2-mediated anti-oxidative stress genes HO-1 and NQO1 at both the mRNA and protein levels. In the DSS-induced colitis mouse model, QYJD reduced the disease activity index (DAI) and alleviated colonic shortening. Elevated Nrf2 and HO-1 mRNA levels were also observed in QYJD-treated mice. These findings showed that QYJD could elicit anti-inflammatory and anti-oxidative stress response in vitro in a cell line and in vivo in a DSS-induced colitis mouse model. These responses may contribute to the overall anticolon cancer effect of QYJD.
Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells
Authors: Chen Hung-En , Lin Ji-Fan , Tsai Te-Fu , Lin Yi-Chia , Chou Kuang-Yu , Hwang Thomas I-Sheng
Published: October 2018

Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals, inhibits the survival of human prostate cancer cells while minimally affecting normal prostate epithelial cells. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging from the increased level of LC3-II protein in a dose- and time-dependent manner, but not in the normal prostate epithelial cell (PrEC). Inhibition of autophagy in AITC-treated cells decreased cell viability and enhanced apoptosis, suggesting that the autophagy played a protective role. There are several pathways activated in ATIC-treated cells. We detected the phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK activation were also detected. However, inhibition of AITC-activated ERK, AMPK and JNK by pre-treatment of specific inhibitors did not alter autophagy induction. Finally, increased beclin-1 expression was detected in AITC-treated cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction, indicating that AITC-induced autophagy occurs through upregulating beclin-1. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through upregulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in prostate cancer patients.
The effect of a finite two-photon detuning on the quantum tricriticality and phase transitions in a spin-orbit coupled Bose gas
Authors: Chen Lei , Xu Xingran , Kang Shuai
Published: October 2018

In the current experiments, realizing the synthetic spin-orbital coupling (SOC) with ultracold atoms, a finite two-photon detuning (TPD) is present. However, in most relevant theoretical studies so far, the TPD has been assumed as zero. Here, we investigate how a finite detuning affects the ground phase diagram in a Bose gas with equal-weight Rashba and Dresselhuas SOC. We show that the single-particle dispersion relation in the presence of a finite TPD can be significantly modified compared to the case with zero detuning, which gives rise to experimentally observable effects on quantum tricriticality and phase transitions. In particular, the zero-momentum phase that can arise for a zero TPD becomes unstable against a finite TPD and disappears. Our results are relevant to the current cold atom experiments using the Raman laser-induced gauge field.
INVESTIGATING THE INNOVATION IMPACTS OF USER-CENTRED AND PARTICIPATORY STRATEGIES ADOPTED BY EUROPEAN LIVING LABS
Authors: DELL’ERA CLAUDIO , LANDONI PAOLO , GONZALEZ SARA JANE
Published: October 2018

The advantages of innovation strategies that are based on collaboration with users have been demonstrated by several studies, which have highlighted emerging shifts from a user-centred approach (in which the user is a subject) to a participatory one (in which the user is a partner). The Living Lab methodology, which is a design research methodology aimed at co-creating innovation through the involvement of aware users in a real-life setting, can provide new perspectives in the passage from user-centred to participatory design. In this paper, answers received by 92 Living Labs belonging to the European Network of Living Labs are used to (i) investigate the strategies adopted by Living Labs to involve users in their innovation processes and (ii) analyse the relationships between strategies and achieved innovation performance outcomes. The user-centred strategy positively impacts all innovation performance outcomes (e.g., time, cost, quality and go to market), but only time performance shows a significant difference between non-adopters and adopters. Observing user behaviors, capturing user insights and receiving user feedback positively impact the efficiency of innovation projects and allow them to be concluded in a timely manner. The participatory strategy shows that adopters are characterised by a significantly higher percentage of projects that are able to reach the market by moving from the research stage to the innovation stage. Practices such as co-design, collaboration through digital platforms and development of experience prototypes allow for the achievement of better results in terms of quality and, consequently, marketability of the project outcome, but reduce the efficiency of the innovation project in terms of time and cost.
Analysis of Lassa hemorrhagic fever model with non-local and non-singular fractional derivatives
Authors: Jain Sonal , Atangana Abdon
Published: October 2018

In this paper, we investigate a possible applicability of the newly established fractional differentiation in the field of epidemiology. To do this, we extend the model describing the Lassa hemorrhagic fever by changing the derivative with the time fractional derivative for the inclusion of memory. Detailed analysis of existence and uniqueness of exact solution is presented using the Banach fixed point theorem. Finally, some numerical simulations are shown to underpin the effectiveness of the used derivative.
A finite result for the set of associated prime ideals of formal local cohomology modules
Authors: Khanh Pham Huu
Published: October 2018

Let [Formula: see text] be a Noetherian local ring, [Formula: see text] two ideals of [Formula: see text], and [Formula: see text] two finitely generated [Formula: see text]-modules. It is first shown that [Formula: see text] is a finite set. We also prove that except the maximal ideal [Formula: see text], the set [Formula: see text] is stable for large [Formula: see text], where we use [Formula: see text] to denote [Formula: see text]-module [Formula: see text] or [Formula: see text] and [Formula: see text] is the eventual value of [Formula: see text].
The generalized solutions of a certain nth order Cauchy–Euler equation
Authors: Sangsuwan Amornrat , Nonlaopon Kamsing , Orankitjaroen Somsak
Published: October 2018

In this paper, we propose the generalized solutions of a certain [Formula: see text]th order Cauchy–Euler equation of the form [Formula: see text], where [Formula: see text] and [Formula: see text] are any integers with [Formula: see text], and [Formula: see text] using Laplace transform technique. We find that the types of solutions either distributional solutions or weak solutions, depend on the values of [Formula: see text]. At the end of the paper, we give some examples showing the types of solutions.
On coefficient bounds of some new subfamilies of close-to-convex functions of complex order related to generalized differential operator
Authors: Bulut Serap , Hussain Manzoor , Ghafoor Abdul
Published: October 2018

We aim to estimate coefficient inequalities for some new subfamilies of close-to-convex functions, which are here, defined by generalized differential operator and Cauchy–Euler type non-homogeneous differential equation. The results presented here would extend, unify and improve some recent results in literature.
Establishing an Efficient Care Paradigm for Trigger Finger
Authors: Usmani Rashad H. , Abrams Samuel S. , Merrell Gregory A.
Published: October 2018

Background: To identify the time course for efficacy of corticosteroid injections in the treatment of trigger finger.

Methods: A prospective single-center observational study was conducted, consisting of 38 patients with 41 trigger digits that were injected. Enrolled patients completed an initial Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire to determine the severity of their symptoms. Following the injection, patients were contacted at scheduled time points for up to 12 weeks to determine if, and when, objective resolution of symptoms occurred. Patients who received additional treatment, such as a second injection or surgery, and those who did not have objective relief of symptoms by 12 weeks were classified as failed. Upon symptom resolution or injection failure, patients were given a DASH exit questionnaire.

Results: 30 of 41 injected trigger digits resolved and 11 failed treatment with a single corticosteroid injection. The latest that any study participant experienced resolution of symptoms was 69 days. At 38 days, the rate of resolution of the study population slowed significantly.

Conclusions: Although symptomatic resolution of trigger finger from a single corticosteroid injection can occur early on, a follow-up of 4 weeks (28 days) does not allow enough time for symptom resolution. The earliest a surgeon and patient should consider a secondary treatment is at 38 days. After 69 days without resolution, both surgeon and patient can be confident that further treatment is needed.
Continuous Peripheral Nerve Blocks for Early Active Mobilization after Hand Surgery: Four Case Reports
Authors: Otsuka Takanobu , Okamoto Hideki , Mizutani Jun , Goto Hideyuki , Sekiya Isato
Published: October 2018

Early active mobilization after hand surgery is extremely important for preventing scar tissue and adhesion. We examined four patients for whom continuous peripheral nerve blocks (CPNB) were used during and after hand surgery. This method was used for three median nerves and one ulnar nerve. A 2-cm incision was made at distal one-third of the forearm with local analgesia. The catheter tip was placed in the distal one-fourth of the forearm, and the hand surgery was begun. Early active mobilization and the self-rehabilitation exercise started immediately after the operation. The VAS scores during exercise were 0–2 (mean: 1.3); pain was controlled sufficiently. Regarding ROM, excellent results were obtained for tenolysis, with good results for arthrolysis. No infection or postoperative nerve compression was found. This method, using CPNB with a portable infusion pump, is effective and safe for use at home for postoperative pain control.
Hepatitis E Virus: Animal Models and Zoonosis
Authors: Kenney Scott P. , Meng Xiang-Jin
Published: October 2018

Hepatitis E virus (HEV) is an important human pathogen that historically has been difficult to study. Limited levels of replication in vitro hindered our understanding of the viral life cycle. Sporadic and low-level virus shedding, lack of standardized detection methods, and subclinical infections made the development of animal models difficult. Better diagnostic techniques and understanding of the virus increased our ability to identify and characterize animal strains and animals that are amenable to model human-relevant infection. These advances are translating into the development of useful HEV animal models so that some of the greatest concerns associated with HEV infection, including host immunology, chronic infection, severe pregnancy mortality, and extrahepatic manifestations, can now be studied. Continued development of these animal models will be instrumental in understanding the many complex questions associated with HEV infection and for assessing therapeutics and prevention strategies to minimize HEV becoming a greater risk to the human population.
The Engineering of Climate Engineering
Authors: MacMartin Douglas G. , Kravitz Ben
Published: October 2018

While reducing anthropogenic greenhouse gas emissions remains the most essential element of any strategy to manage climate change risk, it is also in principle possible to directly cool the climate by reflecting some sunlight back to space. Such climate engineering approaches include adding aerosols to the stratosphere and marine cloud brightening. Assessing whether these ideas could reduce risk requires a broad, multidisciplinary research effort spanning climate science, social sciences, and governance. However, if such strategies were ever used, the effort would also constitute one of the most critical engineering design and control challenges ever considered: making real-time decisions for a highly uncertain and nonlinear dynamic system with many input variables, many measurements, and a vast number of internal degrees of freedom, the dynamics of which span a wide range of timescales. Here, we review the engineering design aspects of climate engineering, discussing both progress to date and remaining challenges that will need to be addressed.
Girls’ and Women’s Violence: The Question of General Versus Uniquely Gendered Causes
Authors: Giordano Peggy C. , Copp Jennifer E.
Published: October 2018

In this review, we consider theory and research focused on girls’ and women's violence, with an emphasis on studies that inform long-running debates about whether uniquely gendered explanations are required to understand such behaviors. The review emphasizes potentially malleable social processes and influences as well as studies that have explored neighborhood, family, and peer-based sources of risk. We also examine contemporary research on precursors of a specific type of aggression—intimate partner violence—where self-reports of perpetration have been found to be similar across gender, but research has consistently shown that the consequences are generally more serious for female victims. Our review draws on findings from analyses of large-scale survey data as well as qualitative approaches that explore meanings and motivations. The results point to significant areas of overlap, as well as some distinctive patterns in gender, support learning, and intersectionality theories, and identify potentially fruitful areas for additional research.
Biology and Control of the Khapra Beetle, Trogoderma granarium, a Major Quarantine Threat to Global Food Security
Authors: Athanassiou Christos G. , Phillips Thomas W. , Wakil Waqas
Published: October 2018

The khapra beetle, Trogoderma granarium, is a voracious feeder of stored products and is considered one of the most important quarantine pests globally. Its ability to survive for long periods under extreme conditions facilitates its spread through international commerce, which has led to invasions of new geographic regions. The khapra beetle is an important quarantine pest for many countries, including the major wheat-producing countries the United States, Canada, Russia, and Australia, and has been classified as one of the 100 worst invasive species worldwide. This species cannot always be controlled by insecticides and other nonchemical methods that are usually effective against other pests of stored products, particularly owing to its diapausing late larval stage. It can rapidly develop at elevated temperatures and under dry conditions, which are not favorable for many major stored-product insects. We synthesize key published work to draw attention to advances in biology, detection and control of the khapra beetle, and directions to consider for future research.
Manipulating fenestrations in young and old liver sinusoidal endothelial cells
Authors: Hunt Nicholas J. , Lockwood Glen P. , Warren Alessandra , Mao Hong , McCourt Peter A. G. , Le Couteur David G. , Cogger Victoria C.
Published: October 2018

Fenestrations are pores within liver sinusoidal endothelial cells (LSECs) that enable the transfer of substrates (particularly insulin and lipoproteins) between blood and hepatocytes. With increasing age, there are marked reductions in fenestrations, referred to as pseudocapillarization. Currently, fenestrations are thought to be regulated by vascular endothelial growth factor and nitric oxide (NO) pathways promoting remodeling of the actin cytoskeleton and cell membrane lipid rafts. We investigated the effects of drugs that act on these pathways on fenestrations in old (18–24 mo) and young mice (3–4 mo). Isolated LSECs were incubated with either cytochalasin 7-ketocholesterol, sildenafil, amlodipine, simvastatin, 2, 5-dimethoxy-4-iodoamphetamine (DOI), bosentan, TNF-related apoptosis-inducing ligand (TRAIL) or nicotinamide mononucleotide (NMN). LSECs were visualized under scanning electron microscopy to quantify fenestration porosity, diameter, and frequency, as well as direct stochastic optical reconstruction microscopy to examine actin and NO synthase. In young and old LSECs, fenestration porosity, diameter and frequency were increased by 7-ketocholesterol, while porosity and/or frequency were increased with NMN, sildenafil, amlodipine, TRAIL, and cytochalasin D. In old mice only, bosentan and DOI increased fenestration porosity and/or frequency. Modification of the actin cytoskeleton was observed with all agents that increased fenestrations, while NO synthase was only increased by sildenafil, amlodipine, and TRAIL. In conclusion, agents that target NO, actin, or lipid rafts promote changes in fenestrations in mice LSECs. Regulation of fenestrations occurs via both NO-dependent and independent pathways. This work indicates that age-related defenestration can be reversed pharmacologically, which has potential translational relevance for dyslipidemia and insulin resistance.

NEW & NOTEWORTHY We demonstrate the effects of multiple nitric oxide-dependent and -independent pharmaceutical agents on fenestrations of the liver sinusoidal endothelium. Fenestrations are reorganized in response to nicotinamide mononucleotide, sildenafil, amlodipine, and TNF-related apoptosis-inducing ligand. This work indicates that age-related defenestration can be reversed pharmacologically, which has potential translational relevance for dyslipidemia and insulin resistance in old age.
A nutrient cocktail prevents lipid metabolism alterations induced by 20 days of daily steps reduction and fructose overfeeding: result from a randomized study
Authors: Damiot Anthony , Demangel Rémi , Noone John , Chery Isabelle , Zahariev Alexandre , Normand Sylvie , Brioche Thomas , Crampes François , de Glisezinski Isabelle , Lefai Etienne , Bareille Marie Pierre , Chopard Angèle , Drai Jocelyne , Collin-Chavagnac Delphine , Heer Martina , Gauquelin-Koch Guillemette , Prost Michel , Simon Patrick , Py Guillaume , Blanc Stéphane , Simon Chantal , Bergouignan Audrey , O’Gorman Donal J.
Published: October 2018

Physical inactivity and sedentary behaviors are independent risk factors for numerous diseases. We examined the ability of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E, and selenium to prevent the expected metabolic alterations induced by physical inactivity and sedentary behaviors. Healthy trained men ( n = 20) (averaging ∼14,000 steps/day and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps (averaging ∼3,000 steps/day). During the last 10 days, metabolic changes were further triggered by fructose overfeeding. On days 0, 10, and 20, body composition (dual energy X-ray), blood chemistry, glucose tolerance [oral glucose tolerance test (OGTT)], and substrate oxidation (indirect calorimetry) were measured. OGTT included 1% fructose labeled with (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and related cellular markers were assessed from muscle biopsies collected on days 0 and 20. While the cocktail did not prevent the decrease in insulin sensitivity and its muscular correlates induced by the intervention, it fully prevented the hypertriglyceridemia, the drop in fasting HDL and total fat oxidation, and the increase in de novo lipogenesis. The cocktail further prevented the decrease in the type-IIa muscle fiber cross-sectional area and was associated with lower protein ubiquitination content. The circulating antioxidant capacity was improved by the cocktail following the OGTT. In conclusion, a cocktail of nutrient compounds from dietary origin protects against the alterations in lipid metabolism induced by physical inactivity and fructose overfeeding.

NEW & NOTEWORTHY This is the first study to test the efficacy of a novel dietary nutrient cocktail on the metabolic and physiological changes occurring during 20 days of physical inactivity along with fructose overfeeding. The main findings of this study are that 1) reduction in daily steps leads to decreased insulin sensitivity and total fat oxidation, resulting in hyperlipemia and increased de novo lipogenesis and 2) a cocktail supplement prevents the alterations on lipid metabolism.
Dynamics Analysis of Deployable Structures considering a Two-Dimensional Coupled Thermo-Structural Effect
Authors: Peng Qi’an , Wang Sanmin , Li Bo , Zhi Changjian , Li Jianfeng
Published: October 2018

The deployment accuracy of deployable structures is affected by temperature and flexibility. To obtain the higher accuracy, various measures such as the optimization design and the control process are employed, and they are all based on deployment dynamics characteristics of deployable structures. So a precise coupled thermo-structural deployment dynamics analysis is important and necessary. However, until now, only a one-dimensional thermal effect is considered in the literatures because of simplicity, which reduces the accuracy of the model. Therefore, in this paper, a new model coupling mechanical field with a temperature field is presented to analyze the deployment dynamics of a deployable structure with scissor-like elements (SLEs). The model is based on the absolute nodal coordinate formulation (ANCF) and is established via a new locking-free beam element whose formulation is extended to account for the two-dimensional thermally induced stresses due to the heat expansion for the first time. Namely, in the formulation, the thermal influences are along two-dimensional directions, the axial direction and the transverse direction, rather than along a one-dimensional direction. The validity and precision of the proposed model are verified using a flexible pendulum example. Finally, the dynamics of a linear deployable structure with three SLEs modeled by the element is simulated under a temperature effect.
Modelling Rail-Based Park and Ride with Environmental Constraints in a Multimodal Transport Network
Authors: Chen Xinyuan , Kim Inhi
Published: October 2018

Environmental sustainability is a significant aspect in the sustainable development of modern urban cities, especially in the road transport system. As traffic demands increase, public transport requires more promotion to accommodate the increasing travel demands while maintaining the environmental quality. Public transport, however, is less attractive in vast suburb areas mainly due to its longer travel distance and waiting time. Therefore, this paper proposes a rail-based Park-and-Ride (RPR) scheme to promote public transport in the multimodal transport network. To remedy the heterogeneous distribution of vehicle pollutants in the network, regulations in environmental sensitive districts are required and studied in this paper. To quantitatively evaluate and analyse this joint RPR and environmental regulation strategy in multimodal transport systems, this paper develops an environmental constrained combined modal split and traffic assignment (EC-CMSTA) model. The proposed formulation adopts the concept of fix-point to reformulate the nonlinear complementarity conditions associated with the combined modal split and user equilibrium conditions, which is subsequently incorporated into a VI formulated nonlinear complementarity conditions associated with environmental constraints. The proposed VI formulation can handle a general constraint structure, which enhances the modelling adaptability and flexibility. The strictly monotone and Lipschitz continuity properties of this model are rigorously proved, giving rise to efficient algorithms for the model. A customized projection based self-adaptive gradient projection (SAGP) algorithm is then developed. Numerical studies demonstrate that the EC-MSTA model could enhance the behavioural modelling of network users’ travel decisions and assist in quantitatively evaluating the effectiveness of RPR schemes and environmental regulations.
Effects of Bright Light with Reduced Blue Light on Sleepiness on Rising: A Small Exploratory Study
Authors: Miura Jun , Yuasa Tomonori , Sugai Yasunori , Yamagami Kana , Aizu Yoshihisa
Published: October 2018

Bright light therapy is a treatment modality for seasonal affective disorder and circadian rhythm disorders in which artificial light of 2,500 lux or higher at the eye is effective. Although short-wavelength visible light is more effective than long-wavelength visible light, it may be hazardous to the retina. Recently, light-emitting diodes (LEDs) have been used as the light source in bright light therapy apparatuses. We developed goggles for bright light therapy equipped with LEDs as the light source. The aim of this study was to examine the efficacy and safety of our goggles when emitting 10,000-lux light with its short-wavelength light content reduced by 30% or 50% (denoted as 30%-cut and 50%-cut light, respectively, henceforth). Six healthy young males participated in this study. They were administered no light, 50%-cut light, and 30%-cut light for 30 min early in the morning for 4 days each. Subjective sleepiness and sleep quality were evaluated by the Stanford Sleepiness Scale (SSS) and the Oguri–Shirakawa–Azumi sleep inventory MA version (OSA-MA), respectively. Subjective sleepiness evaluated by the SSS and the subscale of the OSA-MA significantly decreased with 30%-cut light compared with no light. Psychomotor performance evaluated by a calculation task improved with the 30%-cut light, although not significant after multiple comparisons were considered. No abnormality was found by ophthalmoscopy and the vision test. In conclusion, our goggles with 30%-cut light may be safe and have an awakening effect.
(−)- and (+)-Securidanes A and B, Natural Triarylmethane Enantiomers: Structure and Bioinspired Total Synthesis
Authors: Zhou B. , Liu D. X. , Yuan X. J. , Li J. Y. , Xu Y. C. , Li J. , Li Y. , Yue J. M.
Published: October 2018

Two pairs of enantiomers, (−) and (+)-securidanes A (
1
and
2
) and B (
3
and
4
) featuring unprecedented triarylmethane (TAM) skeletons, were isolated from
Securidaca inappendiculata
. Their structures were established by spectroscopic data, X-ray crystallography, and CD analysis. A plausible biosynthetic pathway for
1
−
4
based on the co-isolated precursors was proposed. Bioinspired total synthesis of
1
−
4
was completed in high yield, which in turn corroborated the biosynthetic hypothesis. Compounds
1
−
4
showed good inhibition against protein tyrosine phosphatase 1B (PTP1B). The molecular docking demonstrated that the strongest inhibitor
3
(IC
50
= 7.52

μ

M) reaches deeper into the binding pocket and has an additional H-bond.
An Efficient 2-D DOA Estimation for a Cylindrical Conformal Array with Unknown Mutual Coupling
Authors: Liu Chao , Yin Shunian
Published: October 2018

The limited space of a conformal array may lead to a serious mutual coupling effect, which will significantly affect the performance of direction of arrival (DOA) estimation algorithms. In this paper, an efficient 2-D direction finding method is developed in the presence of unknown mutual coupling for the uniform cylindrical conformal array (CCA). To avoid the time-consuming two-dimensional spectral peak searching, the 2-D DOA estimation is decoupled and divided into two 1-D DOA estimations. Elevation is first estimated based on a subarray estimation of signal parameters via rotation invariant technique (ESPRIT), and then azimuth is estimated based on the rank reduction (RARE) method by using the elevation estimation result. Consequently, the mutual coupling coefficients can be estimated after getting the DOA estimates. The proposed method can well calibrate the mutual coupling effect of a cylindrical array with a low computational complexity. The final simulation results corroborate our analysis.
Transfection of Peripheral Blood Monocytes withSOX2Enhances Multipotency, Proliferation, and Redifferentiation into Neohepatocytes and Insulin-Producing Cells
Authors: Hyder Ayman , Ehnert Sabrina , Fändrich Fred , Ungefroren Hendrik
Published: October 2018

Following a several-day incubation in medium containing IL-3 and M-CSF to generate a more plastic intermediate “reprogrammed multipotent cells of monocytic origin (RMCMO),” peripheral blood mononuclear cells (PBMCs) can be efficiently converted to hepatocyte-like cells (neohepatocytes) and insulin-producing cells. However, continuous efforts are devoted to enhancing the proliferative capacity of these multipotent cells while maintaining or further increasing their redifferentiation potential. In the present work, PBMCs were transfected with one pluripotency gene (SOX2) and the resulting RMCMO compared to standard RMCMO with respect to cell viability, proliferative activity, and redifferentiation potential. EctopicSOX2expression increased the number of viable RMCMO, activated cell cycle genes, and enhanced proliferation as shown by quantitative RT-PCR and Ki67 immunofluorescent staining, respectively. Redifferentiation of RMCMO derived fromSOX2-transfected PBMCs to neohepatocytes was more complete in comparison to control cells as revealed by higher urea and glucose secretion, increased activity of cytochrome P450 isoforms, and a phase II enzyme, while the same was true for insulin-producing cells as assessed by the expression ofINS,PDX1, andGLUT2and glucose-stimulated insulin secretion. Our results indicate thatSOX2transfection increases both multipotency and proliferation of RMCMO, eventually allowing production of neohepatocytes and insulin-producing cells of higher quality and quantity for transplantation purposes.
Dynamical Criticality in Gene Regulatory Networks
Authors: Villani Marco , La Rocca Luca , Kauffman Stuart Alan , Serra Roberto
Published: October 2018

A well‐known hypothesis, with far‐reaching implications, is that biological evolution should preferentially lead to states that are dynamically critical. In previous papers, we showed that a well‐known model of genetic regulatory networks, namely, that of random Boolean networks, allows one to study in depth the relationship between the dynamical regime of a living being’s gene network and its response to permanent perturbations. In this paper, we analyze a huge set of new experimental data on single gene knockouts in S. cerevisiae, laying down a statistical framework to determine its dynamical regime. We find that the S. cerevisiae network appears to be slightly ordered, but close to the critical region. Since our analysis relies on dichotomizing continuous data, we carefully consider the issue of an optimal threshold choice.
A Perception-Driven Transcale Display Scheme for Space Image Sequences
Authors: Zi Lingling , Cong Xin , Peng Yanfei , Yang Pei
Published: October 2018

With the rapid development of multimedia technology, the way of obtaining high-quality motion reproduction for space targets has attracted much attention in recent years. This paper proposes a Perception-driven Transcale Display Scheme, which significantly improves the awareness of multimedia processing. This new scheme contains two important modules, transcale description based on visual saliency and perception-driven display of space image sequences. The former concentrates on describing the transcle feature of space targets, including three algorithms, attention region computing, frame rate conversion, and image resolution resizing. On this basis, the latter focuses on high-quality display of space movements under different scales, including three algorithms, namely, target trajectory computing, space transcale display, and space movement display. Extensive quantitative and qualitative experimental evaluations demonstrate the effectiveness of the proposed scheme.
A Coding Sequence-Embedded Principle Governs Translational Reading Frame Fidelity
Authors: Wan Ji , Gao Xiangwei , Mao Yuanhui , Zhang Xingqian , Qian Shu-Bing
Published: October 2018

Upon initiation at a start codon, the ribosome must maintain the correct reading frame for hundreds of codons in order to produce functional proteins. While some sequence elements are able to trigger programmed ribosomal frameshifting (PRF), very little is known about how the ribosome normally prevents spontaneous frameshift errors that can have dire consequences if uncorrected. Using high resolution ribosome profiling data sets, we discovered that the translating ribosome uses the 3′ end of 18S rRNA to scan the AUG-like codons after the decoding process. The postdecoding mRNA:rRNA interaction not only contributes to predominant translational pausing, but also provides a retrospective mechanism to safeguard the ribosome in the correct reading frame. Partially eliminating the AUG-like “sticky” codons in the reporter message leads to increased +1 frameshift errors. Remarkably, mutating the highly conserved CAU triplet of 18S rRNA globally changes the codon “stickiness”. Further supporting the role of “sticky” sequences in reading frame maintenance, the codon composition of open reading frames is highly optimized across eukaryotic genomes. These results suggest an important layer of information embedded within the protein-coding sequences that instructs the ribosome to ensure reading frame fidelity during translation.
Distributed Control of a Manufacturing System with One‐Dimensional Cellular Automata
Authors: Barragan-Vite Irving , Seck-Tuoh-Mora Juan C. , Hernandez-Romero Norberto , Medina-Marin Joselito , Hernandez-Gress Eva S.
Published: October 2018

We present a distributed control modeling approach for an automated manufacturing system based on the dynamics of one‐dimensional cellular automata. This is inspired by the fact that both cellular automata and manufacturing systems are discrete dynamical systems where local interactions given among their elements (resources) can lead to complex dynamics, despite the simple rules governing such interactions. The cellular automaton model developed in this study focuses on two states of the resources of a manufacturing system, namely, busy or idle. However, the interaction among the resources such as whether they are shared at different stages of the manufacturing process determines the global dynamics of the system. A procedure is shown to obtain the local evolution rule of the automaton based on the relationships among the resources and the material flow through the manufacturing process. The resulting distributed control of the manufacturing system appears to be heterarchical, and the evolution of the cellular automaton exhibits a Class II behavior for some given disordered initial conditions.
Anisotropically Shaped Magnetic/Plasmonic Nanocomposites for Information Encryption and Magnetic-Field-Direction Sensing
Authors: Wang Xiaojing , Feng Ji , Yu Huakang , Jin Yue , Davidson Andrew , Li Zhiyuan , Yin Yadong
Published: October 2018

Instantaneous control over the orientation of anisotropically shaped plasmonic nanostructures allows for selective excitation of plasmon modes and enables dynamic tuning of the plasmonic properties. Herein we report the synthesis of rod-shaped magnetic/plasmonic core-shell nanocomposite particles and demonstrate the active tuning of their optical property by manipulating their orientation using an external magnetic field. We further design and construct an IR-photoelectric coupling system, which generates an output voltage depending on the extinction property of the measured nanocomposite sample. We employ the device to demonstrate that the nanocomposite particles can serve as units for information encryption when immobilized in a polymer film and additionally when dispersed in solution can be employed as a new type of magnetic-field-direction sensor.