bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new NOTCH3 damaging variant in a thrombocytopenia family of Miao ethnic group
Authors: Zhao Yingling , Li Juheng 
Published: November 2019

AbstractBackgroundPediatric inherited thrombocytopenia, also known as a deficiency of platelets in children, is caused by genetic factors and it is hard to obtain an effective treatment. Thus, it is necessary to identify the possible genetic variants that are responsible for thrombocytopenia.MethodsWhole exome sequencing was used to detect genetic variants in two members of a thrombocytopenia family of Miao ethnic group. Multiple in silico analyses were performed to evaluate the effects of the novel missense variants.ResultsFinally, a novel variant (chr19: g.15170364G>A) in the NOTCH3 gene was found, as confirmed with Sanger sequencing, which could result in a R1694Q substitution in the protein. This variant was consistently suggested to be damaging by sift (Sorting Tolerant From Intolerant; http://sift.jcvi.org), polyphen (Polymorphism Phenotyping, version 2.0; http://genetics.bwh.harvard.edu/pph2) and mutationtaster (http://www.mutationtaster.org) software. By building the 3D model of the key region of NOTCH3 protein and performing the structure simulation, we found that (i) this variant affected the 3D structure model with a root‐mean‐square deviation = 0.46 between wild‐type and mutant type; (ii) this variant caused the protein to reduce the solvent accessible surface area by 421 Å2; and (iii) compared to the wild‐type protein, the mutant protein had two less amino acids to maintain protein stability.ConclusionsA novel damaging variant in the NOTCH3 gene was identified in a thrombocytopenia family with respect to decreasing the stability of NOTCH3, which may help with the prognosis and therapy of inherited thrombocytopenia.
Bortezomib induces HSV-1 lethality in mice with neutrophil deficiency
Authors: Yao Hui-Wen , Wang Li-Chiu , Tsai Hsien-Yang , Fang Yi-Hsuan , Zheng Chunfu , Chen Shun-Hua , Hsu Sheng-Min 
Published: November 2019

Abstract
Bortezomib suppressing NF-κB activity is an effective therapy for patients with myeloma or lymphoma. However, this drug can cause adverse effects, neutropenia, and recurrent infections of herpes viruses. Among herpes viruses, HSV-1 can reactivate to induce mortality. The important issues regarding how bortezomib diminishes neutrophils, whether bortezomib can induce HSV-1 reactivation, and how bortezomib exacerbates HSV-1 infection, need investigation. Using the murine model, we found that bortezomib induced HSV-1 reactivation. Bortezomib diminished neutrophil numbers in organs of uninfected and HSV-1-infected mice and turned a nonlethal infection to lethal with elevated tissue viral loads. In vitro results showed that bortezomib and HSV-1 collaborated to enhance the death and apoptosis of mouse neutrophils. The leukocyte deficiency induced by chemotherapies is generally believed to be the cause for aggravating virus infections. Here we show the potential of pathogen to exacerbate chemotherapy-induced leukocyte deficiency.
Olefinic reagents tested for peptide derivatization with switchable properties: Stable upon collision induced dissociation and cleavable by in‐source Paternò‐Büchi reactions
Authors: Esch Patrick , Fischer Moritz , Heiles Sven , Schäfer Mathias 
Published: November 2019

AbstractThis contribution is part of our ongoing efforts to develop innovative cross‐linking (XL) reagents and protocols for facilitated peptide mixture analysis and efficient assignment of cross‐linked peptide products. In this report, we combine in‐source Paternò‐Büchi (PB) photo‐chemistry with a tandem mass spectrometry approach to selectively address the fragmentation of a tailor‐made cross‐linking reagent. The PB photochemistry, so far exclusively used for the identification of unsaturation sites in lipids and in lipidomics, is now introduced to the field of chemical cross‐linking. Based on trans‐3‐hexenedioic acid, an olefinic homo bifunctional amine reactive XL reagent was designed and synthesized for this proof‐of‐principle study. Condensation products of the olefinic reagent with a set of exemplary peptides are used to test the feasibility of the concept. Benzophenone is photochemically reacted in the nano‐electrospray ion source and forms oxetane PB reaction products. Subsequent CID‐MS triggered retro‐PB reaction of the respective isobaric oxetane molecular ions and delivers reliably and predictably two sets of characteristic fragment ions of the cross‐linker. Based on these signature ion sets, a straightforward identification of covalently interconnected peptides in complex digests is proposed. Furthermore, CID‐MSn experiments of the retro‐PB reaction products deliver peptide backbone characteristic fragment ions. Additionally, the olefinic XL reagents exhibit a pronounced robustness upon CID‐activation, without previous UV‐excitation. These experiments document that a complete backbone fragmentation is possible, while the linker‐moiety remains intact. This feature renders the new olefinic linkers switchable between a stable, noncleavable cross‐linking mode and an in‐source PB cleavable mode.
Treating Adults With Complex Posttraumatic Stress Disorder Using a Modular Approach to Treatment: Rationale, Evidence, and Directions for Future Research
Authors: Karatzias Thanos , Cloitre Marylene 
Published: November 2019

AbstractICD‐11 complex PTSD (CPTSD) is a new condition, and, therefore, there are as yet no clinical trials evaluating interventions for its treatment. In this paper, we provide the rationale for a flexible multimodular approach to the treatment of CPTSD, its feasibility, and some evidence suggesting its potential benefits. The approach highlights flexibility in the selection of empirically supported interventions (or a set of interventions) and the order of delivery based on symptoms that are impairing, severe, and of relevance to the patient. The approach has many potential benefits. It can incorporate the use of interventions for which there is already evidence of efficacy allowing the leveraging of past scientific efforts. It is also consistent with patient‐centered care, which highlights the importance of patient choice in identification of the problems to target, interventions to select, and outcomes to monitor. Researchers on modular treatments of other disorders have found that, compared to disorder‐specific manualized protocols, flexible multimodular treatment programs are superior in resolving identified problems and are associated with greater therapist satisfaction and reduced patient burden. We briefly identify types of interventions that have been successful in treating trauma‐exposed populations as well as emerging interventions that are relevant to the particular problems associated with exposure to complex trauma. We conclude with examples of how such treatments can be organized and tested. Research is now urgently needed on the effectiveness of existing and new intervention approaches to ICD‐11 CPTSD treatment.
Construction and evaluation of an efficient C‐Jun siRNA to downregulate matrix metalloproteinase in human keratinocytes and fibroblasts under UV exposure
Authors: Xiao Hong , Yang Ruinian , Yang Fang , Zhao Yanan , Liu Yin 
Published: November 2019

AbstractBackgroundC‐Jun and EGFR have not been explored as targets via the mechanism of RNA silencing. Hence, this study designed an efficient C‐Jun‐h‐825 small interfering RNA (siRNA) and investigated its effect on matrix metalloproteinase (MMP) and collagen expression in human keratinocytes exposed to UV radiation.MethodsFive C‐Jun siRNAs were designed and screened for their ability to downregulate C‐Jun expression in human fibroblasts. These constructs were used to study changes in skin cancer‐related protein expression. HaCaT cells were grouped into 5‐carboxyfluorescien (FAM‐labeled) C‐Jun‐h‐825 siRNA + 2 hr prior irradiation; mock transfected + 2 hr prior irradiation; normal control; irradiation only for 2 hr; and Blank. Twenty‐four hours posttransfection, mRNA and protein levels of MMP‐I, MMP‐III, collagen‐I and collagen‐III were determined using standard RT‐PCR and ELISA kits.ResultsFAM‐labeled C‐Jun siRNA showed 80%–90% transfection efficiency. There was a significant increase in MMP‐I and MMP‐III and decrease in Col‐I and III mRNA levels when the cells were exposed to UV irradiation without siRNA transfection compared to blank (p < .05). This effect was reversed upon transfection with C‐Jun‐h‐825 (p < .01).ConclusionThus, C‐Jun‐h‐825 siRNA might help restore skin collagen by decreasing MMP expression in cells exposed to UVA. Constructs and vectors designed herein have the potential to be translated into a treatment for photoaging induced skin cancer.
Description of stability for linear time‐invariant systems based on the first curvature
Authors: Wang Yuxin , Sun Huafei , Huang Shoudong , Song Yang 
Published: November 2019

This paper focuses on using the first curvature κ(t) of trajectory to describe the stability of linear time‐invariant system. We extend the results for two and three‐dimensional systems (Wang, Sun, Song et al, arXiv:1808.00290) to n‐dimensional systems. We prove that for a system
, (a) if there exists a measurable set whose Lebesgue measure is greater than zero, such that
or
does not exist for any initial value in this set, then the zero solution of the system is stable; (b) if the matrix A is invertible, and there exists a measurable set whose Lebesgue measure is greater than zero, such that
for any initial value in this set, then the zero solution of the system is asymptotically stable.
Accuracy, uncertainty, and adaptability of automatic myocardial ASL segmentation using deep CNN
Authors: Do Hung P. , Guo Yi , Yoon Andrew J. , Nayak Krishna S. 
Published: November 2019

PurposeTo apply deep convolution neural network to the segmentation task in myocardial arterial spin labeled perfusion imaging and to develop methods that measure uncertainty and that adapt the convolution neural network model to a specific false‐positive versus false‐negative tradeoff.MethodsThe Monte Carlo dropout U‐Net was trained on data from 22 subjects and tested on data from 6 heart transplant recipients. Manual segmentation and regional myocardial blood flow were available for comparison. We consider 2 global uncertainty measures, named “Dice uncertainty” and “Monte Carlo dropout uncertainty,” which were calculated with and without the use of manual segmentation, respectively. Tversky loss function with a hyperparameter β was used to adapt the model to a specific false‐positive versus false‐negative tradeoff.ResultsThe Monte Carlo dropout U‐Net achieved a Dice coefficient of 0.91 ± 0.04 on the test set. Myocardial blood flow measured using automatic segmentations was highly correlated to that measured using the manual segmentation (R2 = 0.96). Dice uncertainty and Monte Carlo dropout uncertainty were in good agreement (R2 = 0.64). As β increased, the false‐positive rate systematically decreased and false‐negative rate systematically increased.ConclusionWe demonstrate the feasibility of deep convolution neural network for automatic segmentation of myocardial arterial spin labeling, with good accuracy. We also introduce 2 simple methods for assessing model uncertainty. Finally, we demonstrate the ability to adapt the convolution neural network model to a specific false‐positive versus false‐negative tradeoff. These findings are directly relevant to automatic segmentation in quantitative cardiac MRI and are broadly applicable to automatic segmentation problems in diagnostic imaging.
Changes in Fish Assemblages at the Mirror Lake Complex in the Lower Columbia River Before and After a Culvert Modification
Authors: Sol Sean Y. , Hanson Amanda C. , Marcoe Keith , Johnson Lyndal L. 
Published: November 2019

Abstract
Changes in fish assemblages were examined before and after a culvert was modified to improve the fish passage at the Mirror Lake Complex (MLC), located along the Columbia River Gorge, Oregon. Conditions at the culvert limited water flow between the Columbia River and the MLC during certain portions of the year; thus, the outlet and interior of the culvert were modified to improve fish passage. Prior to the culvert modification, three sites were sampled monthly between April and August 2008, 5.0 km and 0.5 km upstream of the culvert and immediately downstream of the culvert. Following the culvert modification in the late summer of 2008, the same sites were sampled from 2009 to 2012, with two additional sites added in 2010. Prior to the culvert modification, the lower sites (i.e., the sites closest to the Columbia River) supported native and nonnative fish species, while the upper sites were dominated by native species. During the 4 years of monitoring after culvert modification, these distinctions between the upper and lower sites remained. A significant increase in water temperature and species richness was observed at the site just upstream of the culvert, but other changes in fish composition (density, diversity, percent of nonnative species) were not observed. However, at the upper sites, while nonnative species were absent before culvert modification, they were present after modification. Modifications made at the culvert, in combination with seasonal variation in water level and water temperature, may have influenced fish communities in the MLC. Given predicted regional and global climatic changes, our study indicates the importance of long-term monitoring of restoration sites for the presence of nonnative species and the effects of environmental variables, such as water temperature.
Oligopolistic contracting: Channel coordination under competition
Authors: Gallego Guillermo , Talebian Masoud 
Published: November 2019

AbstractWe study contracts between a single retailer and multiple suppliers of two substitutable products, where suppliers have fixed capacities and present the retailer cost contracts for their supplies. After observing the contracts, the retailer decides how much capacity to purchase from each supplier, to maximize profits from the purchased capacity from the suppliers plus his possessed inventory (endowment). This is modeled as a noncooperative, nonzero‐sum game, where suppliers, or principals, move simultaneously as leaders and the retailer, the common agent, is the sole follower. We are interested in the form of the contracts in equilibrium, their effect on the total supply chain profit, and how the profit is split between the suppliers and the retailer. Under mild assumptions, we characterize the set of all equilibrium contracts and discuss all‐unit and marginal‐unit quantity discounts as special cases. We also show that the supply chain is coordinated in equilibrium with a unique profit split between the retailer and the suppliers. Each supplier's profit is equal to the marginal contribution of her capacity to supply chain profits in equilibrium. The retailer's profit is equal to the total revenue collected from the market minus the payments to the suppliers and the associated sales costs.
Metamaterial topology optimization of nonpneumatic tires with stress and buckling constraints
Authors: Maharaj Yeshern , James Kai A. 
Published: November 2019

SummaryThis article presents the design of a metamaterial for the shear layer of a nonpneumatic tire using topology optimization, under stress and buckling constraints. These constraints are implemented for a smooth maximum function using global aggregation. A linear elastic finite element model is used, implementing solid isotropic material with penalization. Design sensitivities are determined by the adjoint method. The method of moving asymptotes is used to solve the numerical optimization problem. Two different optimization statements are used. Each requires a compliance limit and some aspect of continuation. The buckling analysis is linear, considering the generalized eigenvalue problem of the conventional and stress stiffness matrices. Various symmetries, base materials, and starting geometries are considered. This leads to novel topologies that all achieve the target effective shear modulus of 10 MPa, while staying within the stress constraint. The stress‐only designs generally were susceptible to buckling failure. A family of designs (columnar, noninterconnected representative unit cells) that emerge in this study appears to exhibit favorable properties for this application.
Hyperandrogenemia is Common in Asymptomatic Women and is Associated with Increased Metabolic Risk
Authors: Torchen Laura C. , Tsai Joy N. , Jasti Prathima , Macaya Rodrigo , Sisk Ryan , Dapas Matthew L. , Hayes M. Geoffrey , Urbanek Margrit , Dunaif Andrea 
Published: November 2019

ObjectiveWomen with metabolic syndrome (MetS) have higher endogenous testosterone (T) levels than unaffected women. This study investigated whether hyperandrogenemia (HA) was a marker for increased cardiometabolic risk in reproductively normal premenopausal women.MethodsReproductive hormones and metabolic parameters were assessed in 198 women with regular menses and no clinical hyperandrogenism (eumenorrheic [EM]). Hyperandrogenic EM women were compared with 110 women with NIH criteria polycystic ovary syndrome.ResultsTwenty‐two percent of EM women had HA. Levels of non–sex hormone–binding globulin (SHBG)‐bound T were elevated in 68% of women, total T levels were elevated in 43% of women, and dehydroepiandrosterone sulfate levels were elevated in 30% of women. The prevalence of HA increased with BMI category (P = 0.01): 12% for BMI < 25 kg/m2, 22% for BMI of 25 to 30 kg/m2, and 31% for BMI ≥ 30 kg/m2. MetS (adjusted odds ratio 2.9; 95% CI: 1.2‐6.9) and dysglycemia risks (adjusted odds ratio 2.7; 95% CI: 1.2‐5.8) were increased in hyperandrogenic EM women compared with normoandrogenic EM women, with adjustment for BMI. SHBG levels were independently associated with these metabolic end points (P < 0.001), whereas androgen levels were not. A cluster analysis confirmed that there was a discrete subset of EM women with HA and metabolic abnormalities.ConclusionsHA is common in EM women and is associated with increased risks for MetS and dysglycemia. However, low SHBG levels rather than elevated androgen levels may be the primary predictor of this relationship with metabolic dysfunction.
Synthesis, characterization, and dynamic‐mechanical properties of styrene‐acrylate/nanoclay interpenetrating polymer network
Authors: Fatemi Khadar Parisa , Maghsoud Zahra , Dashti Ali 
Published: November 2019

AbstractWaterborne styrene/acrylate latex interpenetrating polymer network (LIPN) with core‐shell structure was synthesized via a three‐stage emulsion polymerization method. A natural montmorillonite (MMt) and an organically modified montmorillonite (OMMt) were used to see their effect on the morphology and damping properties of polymer‐clay nanocomposite LIPN. The samples were characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic mechanical thermal analysis (DMTA), and X‐ray diffraction (XRD). The appearance of a single peak in the particle size distribution curve and nearly monodisperse latex particles observed in the SEM images indicated that all LIPN particles were of nanoscale size, without evidence for new nucleation occurrence. TEM images demonstrated that latex particles had clearly core‐shell structures. It also showed that most of the OMMt clay platelets were encapsulated in the polymer latex particles. According to the tan δ‐temperature curve, addition of 0.5 wt% OMMt to the core layer improved the damping properties of the LIPN, while MMt could not affect the damping curve significantly. The results indicated that the diffusion of polymer chains into the OMMt clay galleries has increased the internal friction and so improved the damping properties.
Epidemiology of multimorbidity in Iran: An investigation of a large pharmacy claims database
Authors: Ebrahimoghli Reza , Janati Ali , Sadeghi‐Bazargani Homayoun , Hamishehkar Hadi , Ghaffari Samad , Sanaat Zohreh , Farahbakhsh Mostafa , Farhoudi Mehdi , Khalili‐Azimi Atefeh 
Published: November 2019

AbstractPurposeMultimorbidity (MM) (presence of more than one chronic condition within a same patient) imposes a heavy burden on patients and health care systems. In contrast to high‐income countries, the epidemiology of this phenomenon is unclear in low‐ and middle‐income countries, particularly among Iranian population.MethodsThis was a retrospective cohort study using Iranian Health Insurance Organization claims database. A framework was developed for identifying a set of 18 chronic conditions from the pharmacy claims data in Iran. All 2013 outpatient utilizers (aged 18 years or older) were included. Data were analyzed according to number of chronic conditions, gender, and age. The association between MM and utilizations of health services was examined for 2013 to 2016.ResultsIn total, 481 733 people were included. Cardiovascular diseases (including hypertension) (19.1%), depression/anxiety/sleep disorders (13.7%), and acid‐related disorders (10.3%) were the three most prevalent conditions. MM was present in 21.1%. Although prevalence of MM is higher in older age groups and was present in 40% of individuals aged 65 and older, the absolute number of multimorbid patients was higher in those younger than 65 years (66 271 vs 35 386). MM was more prevalent among women (22.1%) compared with men (19.5). After multivariate adjustment for age group and sex, each additional chronic condition was associated with an increase of 2.23 physician visits, 2.86 drugs dispensed, 2.32 laboratory tests, and 1.6 medical imaging.ConclusionsOur findings challenge the current single‐disease–based assumption implicit in Iranian health care system. To take account of MM, complementary strategies should be designed and implement in health care system.
The role of photovoltaics in a sustainable European energy system under variable CO2emissions targets, transmission capacities, and costs assumptions
Authors: Victoria Marta , Zhu Kun , Brown Tom , Andresen Gorm B. , Greiner Martin 
Published: November 2019

AbstractPyPSA‐Eur‐Sec‐30 is an open‐source, hourly resolved, networked model of the European energy system that includes one node per country as well as electricity, heating, and transport sectors. The capacity and dispatch of generation and storage technologies in every country can be cost optimized under different CO2emissions constraints. This paper presents an overview of the most relevant results previously obtained with the model, highlighting the influence of solar photovoltaic (PV) generation on them. For 95% CO2emissions reduction, relative to 1990 level, PV generation supplies in average 33% of the electricity demand. Southern European countries install large PV capacities together with electric batteries, while northern countries install onshore and offshore wind capacities and use hydrogen storage and reinforced interconnections to deal with wind fluctuations. The strong daily generation profile of solar PV heavily impacts the dispatch time series of backup generation and storage technologies. The optimal PV and wind capacities are investigated for variable CO2emissions, transmission interconnection among neighbouring countries, and cost assumptions.