bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell phenotypes as macrostates of the GRN dynamics
Authors: Borriello Enrico , Walker Sara I. , Laubichler Manfred D. 
Published: March 2020

AbstractThe two most fundamental processes describing change in biology, development, and evolution, occur over drastically different timescales. Development involves temporal sequences of cell states controlled by hierarchies of regulatory structures. It occurs over the lifetime of a single individual and is associated with gene expression level change of a given genotype. Evolution, by contrast, entails genotypic change through mutation, the acquisition/loss of genes and changes in the network topology of interactions among genes. It involves the emergence of new, environmentally selected phenotypes over the lifetimes of many individuals. We start by reviewing the most limiting aspects of the theoretical modeling of gene regulatory networks (GRNs) which prevent the study of both timescales in a common, mathematical language. We then consider the simple framework of Boolean network models of GRNs and point out its inadequacy to include evolutionary processes. As opposed to one‐to‐one maps to specific attractors, we adopt a many‐to‐one map which makes each phenotype correspond to multiple attractors. This definition no longer requires a fixed size for the genotype and opens the possibility for modeling the phenotypic change of a genotype, which is itself changing over evolutionary timescales. At the same time, we show that this generalized framework does not interfere with established numerical techniques for the identification of the kernel of controlling nodes responsible for cell differentiation through external signals.
Preparative scale mass spectrometry: A brief history of the calutron
Authors: Yergey Alfred L. , Yergey A. Karl 
Published: March 2020

AbstractCalutrons were developed in the laboratory of E. O. Lawrence at the University of California at Berkeley. They were a modification of the cyclotrons he had invented and used in his Nobel Prize‐winning investigations of the atomic nucleus. At the time their construction was undertaken, calutrons represented the only certain means of preparing enriched uranium isotopes for the construction of a fission bomb. The effort was successful enough that every atom of the 42 kg of 235U used in the first uranium bomb had passed through at least one stage of calutron separation. At peak production, the first stage separators, α tanks, yielded an aggregate 258‐g/day 235U enriched to about 10 at. % from its natural abundance level of 0.72 at. %. The second stage separators, β tanks, used the 10 at. % material as feedstock and produced a total 204‐g/day 235U enriched to at least 80 at. %. The latter, weapons grade, material was used in fission bombs. Under typical operating conditions, each α tank operated at a uranium beam intensity at the collectors of approximately 20 mA and each β tank at a beam intensity of approximately 215 mA at the collectors. Bulk separation of isotopes for bomb production ceased in 1945. Since that time calutrons have been used to separate stable isotopes, but on a more limited scale than wartime weapons production. Stable isotope separations since 1960 have taken place using one modified β tank.
Neuroendocrine function and associated mental health outcomes following mild traumatic brain injury in OEF‐deployed service members
Authors: Ciarlone Stephanie L. , Statz Jonathan K. , Goodrich Jessica A. , Norris Jacob N. , Goforth Carl W. , Ahlers Stephen T. , Tschiffely Anna E. 
Published: March 2020

AbstractMild traumatic brain injury (mTBI) has been linked to mental health disorders (MHDs) and pituitary function alterations. Due to the complex relationship of mTBI, the neuroendocrine system, and MHDs, we propose that neuroendocrine dysfunction (NED) may play a role in negative long‐term health outcomes. The goal of this study was to determine if blast‐concussed service members (SMs) have a stronger likelihood of developing NED. We hypothesized that NED either pre‐ or post‐injury is associated with poor mental and physical health outcomes. Serum samples from the Armed Forces Health Surveillance Branch were obtained from concussed (n = 59) and non‐concussed (n = 72) SMs treated at the Concussion Restoration Care Center (CRCC) in Afghanistan. Serum was collected within 2 years prior to deployment and one or two times within 3 years following their CRCC visit. Samples were analyzed for luteinizing hormone (LH), testosterone, human growth hormone, cortisol, and prolactin to assess post‐injury neuroendocrine function. Results indicate that SMs who incurred an mTBI exhibited long‐term LH and testosterone deficiencies 3 years following injury compared to controls. Specifically, 47.6% of head‐injured SMs displayed hypofunction in at least one of five hormones at 3 years post‐injury. Anxiety disorders were the most common MHD observed in concussed SMs with hypopituitarism, while there was also a trend for SMs with chronic pituitary dysfunction to have MHD diagnoses. Findings indicate blast‐related mTBI may be associated with long‐term health outcomes following a period of incubation. Neuroendocrine screenings may increase treatment opportunities, inform rehabilitation strategies, and improve overall quality of life for patients.
Dispersive liquid–liquid extraction based on magnetic Pickering emulsion followed by gas chromatography–tandem mass spectrometry for the simultaneous determination of aldehydes in environmental water samples
Authors: Cao Xiaoji , Fang Mei , Dong Danqi , Ye Beibei , Xu Jiahui , Ye Xuemin , Mo Weimin 
Published: March 2020

AbstractA dispersive liquid–liquid extraction based on Pickering emulsion stabilized with ferroferric oxide grafted nitrogen‐doped graphitized carbon black has been developed to simultaneously determine seven aldehydes in environmental water samples, in combination with pentafluorobenzyl hydroxylamine precolumn derivatization gas chromatography–tandem mass spectrometry. The nitrogen‐doped graphitized carbon was prepared from dicyandiamide waste residue with a simple acid wash process. The effects of magnetic emulsifier amount, extraction time, solution pH, and oil/water volume ratio on the formation of magnetically responsive Pickering emulsion and the extraction efficiency of the proposed dispersive liquid–liquid extraction were also investigated. Under the optimized conditions, satisfactory linearities were obtained for all aldehydes with correlation coefficients larger than 0.9984. The limits of detection and quantitation of seven aldehydes were in the range of 17.3–30.1 ng/L and 54.3–103.4 ng/L, respectively, with intra‐ and interday relative standard deviations less than 8.6%. The mean recoveries at three spiked levels ranged from 70.0 to 101.4%. With the Pickering emulsion as a “minimized extractor”, the extraction was accomplished within 5 min. After extraction, the magnetic disperser could be recovered for reuse at least five times by an external magnetic field. The proposed method was demonstrated to be feasible, simple, and economic for the trace analysis of the aldehydes in environmental water samples.
Riparian Conservation Facilitated Expansion of Gray Hawks
Authors: La Porte Ariana M. , Mannan R. William , Brewer Samantha 
Published: March 2020

ABSTRACTDesert riparian ecosystems are among the most threatened biodiversity hotspots in the United States, and efforts to conserve them have been increasing. In 2010–2011 and 2014–2016, we examined shifts in the distribution, habitat characteristics, diet, nest success, and productivity of the gray hawk (Buteo plagiatus), 25 years after a Riparian National Conservation Area was established along the San Pedro River in Arizona, USA, to determine how the removal of grazing and agriculture may have affected the ecosystem. The gray hawk population increased and expanded from mesquite (Prosopis spp.)‐dominated areas that they historically occupied into areas that were dominated by grassland. In contrast with the 1990s, percent of mesquite cover in pairs' territories did not correlate with their productivity. Gray hawk diets also included more mammals in our study period, particularly in territories with more grassland. We propose that conservation measures created habitat for gray hawks in areas that were previously unsuitable by allowing grasslands to regenerate and become habitat for their prey, and that management strategies in the San Pedro Riparian National Conservation Area could serve as a model for conservation of other desert riparian ecosystems. © 2020 The Wildlife Society.
HPV‐Related Multiphenotypic Sinonasal Carcinoma: A Case Report and Literature Review
Authors: Ward Matthew L. , Kernig Mikelle , Willson Thomas J. 
Published: March 2020

ObjectivesHuman papilloma virus‐related multi phenotypic sinonasal carcinoma (HMSC), a recently characterized sinonasal malignancy, is discussed including histology, clinical presentation, and treatment outcomes.Study DesignCase report with literature review.MethodsA case of HMSC is reported, as well as a retrospective review of all cases of HMSC reported in the English literature from January 2000 through May 2018 in the MEDLINE, EMBASE, and Scopus databases. Case data from selected articles was pooled along with the presented case and analyzed.ResultsIncluding the present case report, a total of 57 cases of HMSC were identified through literature review. Of the 42 cases with staging information, 25 (60%) presented as early‐stage disease (T1/T2). No nodal metastasis or disease‐specific mortalities were reported. Among the 44 cases with posttreatment follow‐up data, 16 cases (36.4%) developed local recurrence. The majority of recurrences occurred 24 to 60 months posttreatment, although reports of recurrence 10 and 29 years posttreatment exist. Local recurrence occurred in 40% and 60% of patients with perineural invasion and bone invasion, respectively. Patients who developed local recurrence had a longer disease‐free interval when treated with adjuvant radiotherapy, which approached statistical significance.ConclusionsHMSC is a distinct entity with paradoxically aggressive morphology paired with an indolent clinical course characterized by high rates of local recurrence but no reported disease‐specific mortalities to date. Surgery with or without adjuvant radiotherapy is the most common treatment modality, and adjuvant radiotherapy may be associated with an increased disease‐free interval among patients with local recurrence.Level of Evidence4 Laryngoscope, 131:106–110, 2021
Association of cough with asthma in chronic rhinosinusitis patients
Authors: Marino Michael J. , Lal Devyani 
Published: March 2020

AbstractObjectiveTo determine whether the complaint of cough in chronic rhinosinusitis (CRS) patients is associated with asthma and if there is a potential predictive value for asthma diagnosis.MethodConsecutive patients presenting for initial evaluation at a tertiary rhinology clinic who were diagnosed with CRS were considered for inclusion in a cross‐sectional study. The presence and severity of cough was determined using the 22‐item Sinonasal Outcome Test (SNOT‐22). Subgroup analysis included asthma diagnosis confirmed by pulmonary function testing (PFT) in our institution, and for chronic rhinosinusitis patients with (CRSwNP) and without nasal polyps (CRSsNP).ResultsThe total study population included 297 patients with a diagnosis of CRS, with 63.9% of patients reporting cough. Physician‐confirmed diagnosis of asthma was made in 38.7% of patients, and confirmed in 69.6% by PFT. Cough was more frequently reported by CRS patients diagnosed with asthma (relative risk [RR] = 1.60, 95% confidence interval [CI], 1.13‐2.25), with sensitivity of 73.9% (95% CI, 65.0%‐81.1%). This remained significant in the CRSsNP subgroup (RR = 2.65, 95% CI, 1.32‐5.30), with sensitivity of 83.3% (95% CI, 70.4%‐91.3%) and specificity of 41.2% (95% CI, 33.2%‐49.8%). Cough was not associated with asthma in CRSwNP patients (RR = 1.26, 95% CI, 0.89‐1.79). Cough severity had poor predication for asthma diagnosis (AUC = 0.60, 95% CI, 0.54‐0.65).ConclusionsComplaint of cough is associated with diagnosis of asthma in CRS patients. In CRSsNP, complaint of cough was sensitive for asthma diagnosis, although specificity was low. Cough in CRS patients can be multifactorial and asthma may be an important diagnostic consideration.Level of evidence4.
An Effective Strategy to Achieve Ultralow Electrical Percolation Threshold with CNTs Anchoring at the Interface of PVDF/PS Bi‐Continuous Structures to Form an Interfacial Conductive Layer
Authors: Yang Yi , Li Ling‐yan , Yin Bo , Yang Ming‐bo 
Published: March 2020

AbstractConductive composites based on polymers and conductive nanofillers are widely studied as a promising material. The rational design of 3D conductive networks in composites is crucial to improve their electrical conductivity and reduce the dosage of nanofillers. Herein, poly(vinylidene fluoride) (PVDF) and polystyrene (PS) bi‐continuous structures with modified carbon nanotubes (CNTs) tailored to anchor at the interface are designed to achieve an ultralow electrical percolation threshold because of the formation of a thin interfacial conductive layer. In this work, the modification of CNTs with poly(methyl methacrylate) (PMMA), which contributes to the improvement of the compatibility between PVDF and CNTs, is effective to control the distribution of CNTs in composites. It promotes the migration of CNTs from the PS phase to the interface of PVDF and PS. Consequently, the interfacial conductive layer is formed at a low CNT content, and the electrical percolation threshold of PVDF/PS/CNTs‐PMMA nanocomposites is only 0.07 vol%, having a great decrease of about 50% compared with that of PVDF/PS/CNTs nanocomposites. Thus, it is demonstrated that the distribution of CNTs can be tailored to anchor at the interface by proper chemical modification to form an interfacial conductive layer and a decrease of percolation threshold can also be achieved.
Problems in variation interpretation guidelines and in their implementation in computational tools
Authors: Vihinen Mauno 
Published: March 2020

AbstractBackgroundACMG/AMP and AMP/ASCO/CAP have released guidelines for variation interpretation, and ESHG for diagnostic sequencing. These guidelines contain recommendations including the use of computational prediction methods. The guidelines per se and the way they are implemented cause some problems.MethodsLogical reasoning based on domain knowledge.ResultsAccording to the guidelines, several methods have to be used and they have to agree. This means that the methods with the poorest performance overrule the better ones. The choice of the prediction method(s) should be made by experts based on systematic benchmarking studies reporting all the relevant performance measures. Currently variation interpretation methods have been applied mainly to amino acid substitutions and splice site variants; however, predictors for some other types of variations are available and there will be tools for new application areas in the near future. Common problems in prediction method usage are discussed. The number of features used for method training or the number of variation types predicted by a tool are not indicators of method performance. Many published gene, protein or disease‐specific benchmark studies suffer from too small dataset rendering the results useless. In the case of binary predictors, equal number of positive and negative cases is beneficial for training, the imbalance has to be corrected for performance assessment. Predictors cannot be better than the data they are based on and used for training and testing. Minor allele frequency (MAF) can help to detect likely benign cases, but the recommended MAF threshold is apparently too high. The fact that many rare variants are disease‐causing or ‐related does not mean that rare variants in general would be harmful. How large a portion of the tested variants a tool can predict (coverage) is not a quality measure. ConclusionMethods used for variation interpretation have to be carefully selected. It should be possible to use only one predictor, with proven good performance or a limited number of complementary predictors with state‐of‐the‐art performance. Bear in mind that diseases and pathogenicity have a continuum and variants are not dichotomic i.e. either pathogenic or benign, either.
Novel compound heterozygous pathogenic variants in ASCC1 in a Chinese patient with spinal muscular atrophy with congenital bone fractures 2 : Evidence supporting a "Definitive" gene‐disease relationship
Authors: Lu Weiliang , Liang Mingxing , Su Jiasun , Wang Jin , Li Lingxiao , Zhang Shujie , Qin Zailong , Huang Limei , Lu Yingchi , Yi Shang , Yi Sheng , Xie BoBo , Zheng Haiyang , Luo Jingsi , Gao Xiaoyan , Shen Yiping 
Published: March 2020

AbstractBackgroundA very limited spectrum of ASCC1 pathogenic variants had been reported in six (mostly consanguineous) families with spinal muscular atrophy with congenital bone fractures 2 [OMIM #616867] since 2016.MethodsA proband from a non‐consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness, and atrophy, as well as congenital bone fractures was performed by exome sequencing.ResultsA compound heterozygosity of a nonsense (c.932C>G,p.Ser311Ter) and an exon 5 deletion in ASCC1 segregating with phenotypes was detected, both variants are novel and pathogenic. Since ASCC1 is a relatively new disease gene, we performed the gene curation by ClinGen SOP. The existing evidence is sufficient to support a "Definitive" level of disease‐gene relationship.ConclusionThis case report expended the mutation spectrum of ASCC1 and support the notion that this novel disease also occurs in outbreed populations and this is a rare disease but may still be underdiagnosed due to its perinatal lethal outcomes.
Creation of an anthropomorphic CT head phantom for verification of image segmentation
Authors: Holmes Robin B. , Negus Ian S. , Wiltshire Sophie J. , Thorne Gareth C. , Young Peter ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: March 2020

PurposeMany methods are available to segment structural magnetic resonance (MR) images of the brain into different tissue types. These have generally been developed for research purposes but there is some clinical use in the diagnosis of neurodegenerative diseases such as dementia. The potential exists for computed tomography (CT) segmentation to be used in place of MRI segmentation, but this will require a method to verify the accuracy of CT processing, particularly if algorithms developed for MR are used, as MR has notably greater tissue contrast.MethodsTo investigate these issues we have created a three‐dimensional (3D) printed brain with realistic Hounsfield unit (HU) values based on tissue maps segmented directly from an individual T1 MRI scan of a normal subject. Several T1 MRI scans of normal subjects from the ADNI database were segmented using SPM12 and used to create stereolithography files of different tissues for 3D printing. The attenuation properties of several material blends were investigated, and three suitable formulations were used to print an object expected to have realistic geometry and attenuation properties. A skull was simulated by coating the object with plaster of Paris impregnated bandages. Using two CT scanners, the realism of the phantom was assessed by the measurement of HU values, SPM12 segmentation and comparison with the source data used to create the phantom.ResultsRealistic relative HU values were measured although a subtraction of 60 was required to obtain equivalence with the expected values (gray matter 32.9–35.8 phantom, 29.9–34.2 literature). Segmentation of images acquired at different kVps/mAs showed excellent agreement with the source data (Dice Similarity Coefficient 0.79 for gray matter). The performance of two scanners with two segmentation methods was compared, with the scanners found to have similar performance and with one segmentation method clearly superior to the other.ConclusionThe ability to use 3D printing to create a realistic (in terms of geometry and attenuation properties) head phantom has been demonstrated and used in an initial assessment of CT segmentation accuracy using freely available software developed for MRI.
Stable generalized finite element methods for elasticity crack problems
Authors: Cui Cu , Zhang Qinghui 
Published: March 2020

SummaryGeneralized or eXtended finite element methods (GFEM/XFEM) for crack problems have been studied extensively. The GFEM/XFEM are called extrinsic if additional functions are enriched at every node in certain domains, while they are called degree of freedom (DOF)‐gathering if the singular enriched functions are gathered using cutoff functions. The DOF‐gathering GFEM/XFEM save the additional DOFs compared with the extrinsic approach. Both extrinsic and DOF‐gathering GFEM/XFEM suffer from difficulties of stabilities in a sense that their scaled condition numbers (SCN) of stiffness matrices could be much larger than those of the standard FEM. A GFEM/XFEM is referred to as stable GFEM (SGFEM) if it reaches optimal convergence orders, and its SCN is of same order as that of FEM. An extrinsic SGFEM was established in Zhang et al for the Poisson crack problems. Objective of this article is to propose the SGFEM for elasticity crack problems; both extrinsic and DOF‐gathering schemes are addressed. The main idea is to modify the enriched functions by subtracting their FE interpolants, which was developed by Babuška and Banerjee. To remove local almost linear dependence introduced by multifold enrichments at one node, we propose a local principal component analysis technique to identify and analyze “contributions” of multifold enrichments at one node. Numerical studies demonstrate that the proposed SGFEM and DOF‐gathering SGFEM are of optimal convergence and have the SCNs of same order as in the
FEM.
Poly(2‐(dimethylamino)ethyl methacrylate)‐b‐poly(hydroxypropyl methacrylate) copolymers/bovine serum albumin complexes in aqueous solutions
Authors: Sentoukas Theodore , Pispas Stergios 
Published: March 2020

AbstractComplexation ability of poly(2‐(dimethylamino)ethyl methacrylate)‐b‐poly(hydroxy propyl methacrylate) (PDMAEMA‐b‐PHPMA) amphiphilic doubly thermo‐responsive block copolymers, and their quaternized counterparts QPDMAEMA‐b‐PHPMA, toward bovine serum albumin (BSA) is studied in aqueous solutions. The PDMAEMA‐b‐PHPMA amphiphilic block copolymers self‐assemble in nanostructured aggregates with PDMAEMA coronas having different inner structure and micro‐polarity depending on the solubilization protocol utilized when inserted in aqueous media. By incorporating different BSA concentrations, we investigate the copolymer–protein interactions by light scattering measurements in aqueous solutions in a broad temperature range, utilizing different solubilization protocols for the copolymers. Fluorescence spectroscopy and ζ‐potential measurements were also utilized to investigate the structure and properties of the copolymer/protein complexes formed in each case. Such knowledge may lead to a better understanding of the inner structure and micro polarity of the nanostructured aggregates formed by the novel (Q)PDMAEMA‐b‐PHPMA copolymers, along with their potential abilities in nanocarrier formation, protein complexation, stabilization, and delivery.