bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of multifunctional fusion proteins with a laminin‐derived short peptide to promote neural differentiation of mouse induced pluripotent stem cells
Authors: Sharmin Afroza , Adnan Nihad , Haque Amranul , Mashimo Yasumasa , Mie Masayasu , Kobatake Eiry
Published: March 2020

There is growing interest in the functional roles of the extracellular matrix (ECM) in regulating the fate of pluripotent stem cells (PSCs). An artificially bioengineered ECM provides an excellent model for studying the molecular mechanisms underlying self‐renewal and differentiation of PSCs, without multiple unknown and variable factors associated with natural substrates. Here, we have engineered multifunctional fusion proteins that are based on peptides from laminin, including p20, RGD, and elastin‐like polypeptide (ELP), where laminin peptides work as cell adhesion molecules (CAMs) and ELP to promote anchorage. The functionality of these chimeric proteins, referred to as ERE‐p20 and E‐p20, was assessed by determining their ability to immobilize cells on a hydrophobic polystyrene surface, improve mouse induced pluripotent stem cells (miPSCs) attachment, and promote miPSC differentiation to neural progenitors. ERE‐p20 and E‐p20 proteins showed hydrophobic binding saturation to the polystyrene plates around 500 nM (2.39 μg/cm2) and 750 nM (2.27 μg/cm2) protein concentrations, respectively. The apparent maximum cell binding to ERE‐p20 and E‐p20 was approximately 81% and 73%, respectively, relative to gelatin. For neural precursors, neurite outgrowth was enhanced by the presence of RGD and p20 peptides. The expression levels of neuronal marker protein MAP2 were upregulated approximately 2.5‐fold and threefold by ERE‐p20 and E‐p20, respectively, relative to laminin. Overall, we have shown that elastin‐mimetic fusion proteins consisting of p20 with and without RGD peptides are able to induce neuronal differentiation. In conclusion, our newly designed bioengineered fusion proteins allow preparation of specific bioactive matrices or coating/scaffold for miPSCs differentiation.
Modeling-Based Bone Formation in the Human Femoral Neck in Subjects Treated With Denosumab
Authors: Dempster David W , Chines Arkadi , Bostrom Mathias P , Nieves Jeri W , Zhou Hua , Chen Li , Pannacciulli Nico , Wagman Rachel B , Cosman Felicia
Published: March 2020

Denosumab is associated with continued gains in hip and spine BMD with up to 10 years of treatment in postmenopausal women with osteoporosis. Despite potent inhibition of bone remodeling, findings in nonhuman primates suggest modeling-based bone formation (MBBF) may persist during denosumab treatment. This study assessed whether MBBF in the femoral neck (FN) is preserved in the context of inhibited remodeling in subjects receiving denosumab. This open-label study enrolled postmenopausal women with osteoporosis who had received two or more doses of denosumab (60 mg subcutaneously every 6 months [Q6M]) per standard of care and were planning elective total hip replacement (THR) owing to osteoarthritis of the hip. Transverse sections of the FN were obtained after THR and analyzed histomorphometrically. MBBF, based on fluorochrome labeling and presence of smooth cement lines, was evaluated in cancellous, endocortical, and periosteal envelopes of the FN. Histomorphometric parameters were used to assess MBBF and remodeling-based bone formation (RBBF) in denosumab-treated subjects (n = 4; mean age = 73.5 years; range, 70 to 78 years) and historical female controls (n = 11; mean age = 67.8 years; range, 62 to 80 years) obtained from the placebo group of a prior study and not treated with denosumab. All analyses were descriptive. All subjects in both groups exhibited MBBF in the periosteal envelope; in cancellous and endocortical envelopes, all denosumab-treated subjects and 81.8% of controls showed evidence of MBBF. Compared with controls, denosumab-treated subjects showed 9.4-fold and 2.0-fold higher mean values of MBBF in cancellous and endocortical envelopes, respectively, whereas RBBF mean values were 5.0-fold and 5.3-fold lower. In the periosteal envelope, MBBF and RBBF rates were similar between subjects and controls. These results demonstrate the occurrence of MBBF in the human FN and suggest that denosumab preserves MBBF while inhibiting remodeling, which may contribute to the observed continued gains in BMD over time after remodeling is maximally inhibited. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Abstract

Femoral neck histomorphometry was assessed in adult subjects (n = 4) with osteoporosis who received at least two doses of denosumab and were scheduled for total hip replacement. Compared with historical controls (n = 11), denosumab-treated subjects showed 9.4-fold and 2.0-fold higher values of MBBF in cancellous and endocortical envelopes, respectively. RBBF values were 5.0-fold and 5.3-fold lower. Thus, denosumab may preserve MBBF while inhibiting RBBF, resulting in the continued increases in BMD observed with long-term treatment. MBBF = modeling-based bone formation; RBBF = remodeling-based bone formation.
Homozygous familial hypercholesterolemia with severe involvement of the aortic valve—A sibling‐controlled case study on the efficacy of lipoprotein apheresis
Authors: Galiano Matthias , Hammersen Johanna , Sauerstein Katja , Blessing Holger , Rümmele Petra , Purbojo Ariawan , Schöber Martin , Moosmann Julia , Raffelsbauer Gunter , Heibges Andreas , Klingel Reinhard
Published: March 2020

Background

Homozygous familial hypercholesterolemia (hoFH) can cause severe atherosclerotic cardiovascular disease (ASCVD) in early infancy. Diagnosis and initiation of effective lipid‐lowering therapy (LLT) are recommended as early as possible to prevent ASCVD‐related morbidity and mortality.

Methods

The clinical courses of a pair of siblings with an identical hoFH genotype, who exhibited major similarities of their clinical phenotype were analyzed in a case‐control fashion including the family.

Results

The older sibling was diagnosed with hoFH at the age of 4. Untreated LDL‐cholesterol (LDL‐C) was 17 mmol/L (660 mg/dL). LLT including lipoprotein apheresis (LA) was initiated and has been successful for 8 years now. A reduction of estimated cholesterol burden by 74% was achieved by LA and combined drug therapy including statins and ezetimibe. The efficacy of escalation of drug therapy was limited because the underlying LDL receptor (LDLR) mutation in the family resulted in substantially reduced receptor function. Treatment with proprotein convertase subtilisin‐kexin type 9 (PCSK9)‐antibodies failed. His younger brother died at the age of 2 years shortly after the hoFH diagnosis of the elder sibling. Postmortem examination revealed advanced aortic root atheroma and aortic valve stenosis. In the older sibling, aortic valve stenosis and insufficiency were treated at the age of 9 years with mechanical aortic valve replacement.

Conclusions

LLT including LA should be initiated as early as possible following the diagnosis of hoFH with very high LDL‐C levels. With the same genotype, the phenotype of hoFH can exhibit similar patterns but outcome is substantially related to treatment.
Novel composite oxygen‐containing resins with effective adsorption towards anilines: physical & chemical adsorption
Authors: Xu Chao , Yu Wenhao , Zheng Kexin , Ling Chen , Yu Shitao , Jiang Long
Published: March 2020

BACKGROUND

The adsorption resins have been successfully used for the treatment of various types of industrial wastewater due to their excellent advantages of high degree of harmlessness, wonderful resource utilization effect, and adjustable material structure. However, the adsorption capacity of traditional resin to the high polarity aniline has been limited since the adsorption mainly relies on hydrophobic adsorption.

RESULTS

In this study, novel oxygen‐containing resins were prepared by modifying a benzene skeleton through chemical functional groups screening and physical structure regulation. The influences of functional groups to the precursor resins were thoroughly studied and the adsorption capacity of the dihydrofuran‐2,5‐dione modified resins was 7.9% higher than the precursor resins, exhibiting the unparalleled adsorption activity to p‐aminobenzoic acid (PABA). Subsequently, a series of dihydrofuran‐2,5‐dione modified crosslinking resins named FSG1‐5 were prepared with various physical structures. The resin FSG‐2 exhibited the best adsorption property, as the adsorption capacity to p‐aminobenzoic acid was 28.3% higher than H‐103 (a commercial hyper‐cross‐linked resin).

CONCLUSION

On the basis of the comparison of kinetics, thermodynamics, and resin's physicochemical structure, FSG‐2 could achieve efficient adsorption to aniline compounds by physical adsorption, such as π‐π conjugation, molecular size effect, and chemical adsorption, including hydrogen bonding and acid–base effect enhanced the adsorption interaction, which laid a theoretical foundation for the design and preparation of new materials. © 2020 Society of Chemical Industry
Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia
Authors: Sun Weiwei , Zhang Tian , Zhang Xiaoguang , Wang Jieyu , Chen Yuqing , Long Yun , Zhang Gong , Wang Yajian , Chen Ye , Fang Tao , Chen Mingwu
Published: March 2020

Background

Sitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention.

Methods

We evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio‐whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved.

Results

We identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965‐1G>A, c.323‐1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes.

Conclusions

Our findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.
Long term effects of stress on hippocampal function: Emphasis on early life stress paradigms and potential involvement of neuropeptide Y
Authors: Alviña Karina , Jodeiri Farshbaf Mohammad , Mondal Amit Kumar
Published: March 2020

The brain is both central in orchestrating the response to stress, and, a very sensitive target when such response is not controlled. In fact, stress has long been associated with the onset and/or exacerbation of several neuropsychiatric disorders such as anxiety, depression, and drug addiction. The hippocampus is a key brain region involved in the response to stress, not only due to its anatomical connections with the hypothalamic‐pituitary‐adrenal axis but also as a major target of stress mediators. The hippocampal dentate gyrus (DG)‐CA3 circuit, composed of DG granule cells axons (mossy fibers) synapsing onto CA3 pyramidal cells, plays an essential role in memory encoding and retrieval, functions that are vulnerable to stress. Although naturally excitatory, this circuit is under the inhibitory control of GABAergic interneurons that maintain the excitation/inhibition balance. One subgroup of such interneurons produces neuropeptide Y (NPY), which has emerged as a promising endogenous stress “resilience molecule” due to its anxiolytic and anti‐epileptic properties. Here we examine existing evidence that reveals a potential role for hilar NPY+ interneurons in mediating stress‐induced changes in hippocampal function. We will focus specifically on rodent models of early life stress (ELS), defined as adverse conditions during the early postnatal period that can have profound consequences for neurodevelopment. Collectively, these findings suggest that the long‐lasting effects of ELS might stem from the loss of GABAergic NPY+ cells, which then can lead to reduced inhibition in the DG‐CA3 pathway. Such change might then lead to hyperexcitability and concomitant hippocampal‐dependent behavioral deficits.
Similitude of cement‐bone micromechanics in cemented rat and human knee replacement
Authors: Mann Kenneth A. , Miller Mark A. , Tatusko Megan E. , Oest Megan E.
Published: March 2020

A preclinical rat knee replacement model was recently developed to explore the biological and mechanobiological changes of trabecular resorption for cement‐bone interdigitated regions. The goal here was to evaluate the relevance of this model compared with human knee replacement with regards to functional micromechanics. Eight nonsurvival, cemented knee replacement surgeries were performed, the interdigitated gap morphology was quantified, and interface micromotion between cement and bone was measured for 1 to 5 bodyweight loading. Computational fluid dynamics modeling of unit cell geometries with small gaps between trabeculae and cement was used to estimate fluid flow. Gap width (3.6 μm) was substantially smaller compared with cement‐bone gaps reported in human knee replacement (11.8 μm). Micromotion at the cement‐bone border was also decreased for the rat knee replacement (0.48 μm), compared with human (1.97 μm), for 1 bodyweight loading. However, the micromotion‐to‐gap width ratio (0.19 and 0.22 for, rat and human), and estimated fluid shear stress (6.47 and 7.13 Pa, for rat and human) were similar. Replicating the fluid dynamic characteristics of cement‐bone interdigitated regions in human knee replacements using preclinical models may be important to recapitulate trabecular resorption mechanisms due to proposed supraphysiologic fluid shear stress. Statement of clinical significance: local cement‐bone micromotion due to joint loading may contribute to the process of clinical loosening in total joint replacements. This work shows that while micromotion and gap morphology are diminished for the rat knee model compared to human, the motion‐to‐gap ratio, and corresponding fluid shear stress are of similar magnitudes
Outcomes of palliative‐intent surgery in retroperitoneal sarcoma—Results from the US Sarcoma Collaborative
Authors: Thalji Sam Z. , Tsai Susan , Gamblin T. Clark , Clarke Callisia , Christians Kathleen , Charlson John , Ethun Cecilia G. , Poultsides George , Grignol Valerie P. , Roggin Kevin K. , Votanopoulos Konstantinos , Fields Ryan C. , Abbott Daniel E. , Cardona Kenneth , Mogal Harveshp ,   other members of the US Sarcoma Collaborative
Published: March 2020

Background and Objectives

Outcomes of palliative‐intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative‐intent RPS resection.

Methods

Using a retrospective 8‐institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox‐proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS).

Results

Of 3088 patients, 70 underwent 87 palliative‐intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n = 17, 24%), leiomyosarcoma (n = 13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91‐23.23). R2 resection (OR, 8.60; CI, 1.42‐52.15; P = .019), larger tumors (OR, 10.87; CI, 1.44‐82.11; P = .021) and low preoperative albumin (OR, 0.14; CI, 0.04‐0.57; P = .006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02‐3.71; P = .043) and high‐grade histology (HR, 6.56; CI, 1.72‐25.05; P = .006) rather than resection status were associated with reduced OS. However, in R2‐resected patients, development of postoperative complications significantly reduced survival (P = .042).

Conclusions

Postoperative complications and high‐grade histology rather than resection status impacts survival in palliative‐intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative‐intent R2 resection should be offered only after cautious consideration.
Sarcopenia is associated with increased mortality but not complications following resection and reconstruction of sarcoma of the extremities
Authors: Hendrickson Nathan R. , Mayo Zachary , Shamrock Alan , Kesler Kyle , Glass Natalie , Nau Peter , Miller Benjamin J.
Published: March 2020

Background and Objectives

Evidence regarding the impact of sarcopenia on operative outcomes in patients with sarcoma is lacking. We evaluated the relationship between sarcopenia and postoperative complications or mortality among patients undergoing tumor excision and reconstruction. ​

Methods

We retrospectively reviewed 145 patients treated with tumor excision and limb reconstruction for sarcoma of the extremities. Sarcopenia was defined as psoas index (PI) < 5.45 cm2/m2 for men and <3.85 cm2/m2 for women from preoperative axial CT. Regression analyses were used to assess the association between postoperative complications or mortality with PI, age, gender, race, body mass index, tumor histology, grade, depth, location, size, and neoadjuvant/adjuvant therapy.

Results

There were 101 soft tissue tumors and 44 primary bone tumors. Sarcopenia was present in 38 patients (26%). Sarcopenic patients were older (median age: 72 vs 59 years, P = .0010) and had larger tumors (86.5%, >5 cm vs 77.7%, P = .023). Seventy‐three patients experienced complications (51%) and 18 patients died within 1 year. Sarcopenia and metastatic disease were associated with increased 12‐month mortality (hazard ratio [HR] = 6.68, P < .001; HR: 8.51, P < .001, respectively) but not complications (HR 1.45, P = .155, odds ratio, 1.32, P = .426, respectively).

Conclusions

Sarcopenia and metastatic disease were independently associated with postoperative mortality but no complications following surgery.
Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma
Authors: Stein Matthew K. , Williard Forrest W. , Xiu Joanne , Tsao Miriam W. , Martin Michael G. , Deschner Benjamin W. , Dickson Paxton V. , Glazer Evan S. , Yakoub Danny , Shibata David , Grothey Axel F. , Philip Philip A. , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Korn W. Michael , Lenz Heinz‐Josef , Deneve Jeremiah L.
Published: March 2020

Background and Objectives

Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined.

Methods

We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next‐generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test‐defined as pathogenic (PATH).

Results

Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right‐sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left‐sided PM. Nine percent of pCRC and 6% of PM were MSI‐high (P = NS). There was no difference in TMB‐high, TMB‐intermediate, or TMB‐low between PM and pCRC.

Conclusions

PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.
Gradient Photonic Materials Based on One‐Dimensional Polymer Photonic Crystals
Authors: Schedl Andreas E. , Howell Irene , Watkins James J. , Schmidt Hans‐Werner
Published: March 2020

In nature, animals such as chameleons are well‐known for the complex color patterns of their skin and the ability to adapt and change the color by manipulating sophisticated photonic crystal systems. Artificial gradient photonic materials are inspired by these color patterns. A concept for the preparation of such materials and their function as tunable mechanochromic materials is presented in this work. The system consists of a 1D polymer photonic crystal on a centimeter scale on top of an elastic poly(dimethylsiloxane) substrate with a gradient in stiffness. In the unstrained state, this system reveals a uniform red reflectance over the entire sample. Upon deformation, a gradient in local strain of the substrate is formed and transferred to the photonic crystal. Depending on the magnitude of this local strain, the thickness of the photonic crystal decreases continuously, resulting in a position‐dependent blue shift of the reflectance peak and hence the color in a rainbow‐like fashion. Using more sophisticated hard‐soft‐hard‐soft‐hard gradient elastomers enables the realization of stripe‐like reflectance patterns. Thus, this approach allows for the tunable formation of reflectance gradients and complex reflectance patterns. Envisioned applications are in the field of mechanochromic sensors, telemedicine, smart materials, and metamaterials.
Design and manufacture of a high precision personalized electron bolus device for radiation therapy
Authors: Aldawood Faisal Khaled , Chang Sha X. , Desai Salil
Published: March 2020

This paper investigates a novel design and manufacturing methodology for an unmet need in radiation therapy—dose optimization of electron beam bolus. A thin‐walled bolus design was proposed which when filled with water, optimized the dose distribution for the electron beam radiation therapy. The fabrication of this design was accomplished by the fused deposition modelling (FDM) additive manufacturing (3D Printing) technique. Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) materials were employed for fabricating the electron boluses. Our data show that both the materials displayed expected radiation modulation. The designed boluses were subjected to higher radiation doses (50 Gy) and revealed permissible deformations based on the dimensional deviation analysis. Mechanical deformation tests were performed to evaluate the bolus design and materials under different loading conditions. The results showed that the ABS material had superior mechanical strength and deformation behaviour as compared to PC. Finite element analysis of the bolus designs revealed regions of stress concentration and potential failure modes which were validated by experimental results. The design of experiments analysis showed that bolus thickness and material type had a profound influence on the mechanical deformation of the bolus. The proposed radiation device technology is cost‐effective, eco‐friendly and amenable to changes in the tumour size and shape, compared to current methods. This paper provides a framework for the design and manufacture of radiation modulation devices that can be implemented for proton, electron and photon cancer therapies.
Whole exome sequencing identifies multiple novel candidate genes in familial gastroschisis
Authors: Salinas‐Torres Víctor M. , Gallardo‐Blanco Hugo L. , Salinas‐Torres Rafael A. , Cerda‐Flores Ricardo M. , Lugo‐Trampe José J. , Villarreal‐Martínez Daniel Z. , Ibarra‐Ramírez Marisol , Martínez de Villarreal Laura E.
Published: March 2020

Background

Genetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis.

Methods

We employed WES in two affected half‐sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS–PhoRank and Ensembl–Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS–PhoRank) and functional properties (Ensembl–Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes.

Results

No single gene‐disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63‐linked ubiquitination, protein‐containing complex assembly, and regulation of transcription DNA‐templated.

Conclusion

Considering the likely gene‐disrupting prediction results and similar biological pattern of mechanisms, we propose a joint “multifactorial model” in gastroschisis pathogenesis.
On the method of preliminary group classification applied to the nonlinear heat equation ut=f(x,ux)uxx+g(x,ux)
Authors: Edelstein Rochelle M. , Govinder Keshlan S.
Published: March 2020

We apply the method of preliminary group classification to a specific class of the nonlinear heat equation, ie,
. This results in an optimal system of one‐dimensional subalgebras, which will be used to find specific forms of the equation, which admit more symmetries and so allow us to find additional group invariant solutions. We extend this work by determining the potential symmetries of a closely related system, which gives rise to many new, additional solutions of the original equation.
A novel random discrete element analysis of rock fragmentation
Authors: Zhao Tao , Liu Yong
Published: March 2020

This paper presents a novel probabilistic approach of random discrete element analysis (RDEA) to investigate the mechanism of rock fragmentation under uniaxial compression. This model combines the advantages of both random field theory and discrete element method in characterizing the spatial variation and uncertainty of microscopic material properties. The numerical results reveal that the stress‐strain curves of a group of tests can match well the general trend of the experimental data, with the mean uniaxial compressive strength (UCS) of 10.18 MPa and the mean Young modulus of 1.73 GPa. The coefficient of variation (COV) for the rock samples is much lower than that of the initial random fields of particles because of the averaging effect of microscopic material property in obtaining the bulk values. The rock fragmentation is initiated by the breakage of weak particles within the rock mass, and it develops rapidly as the vertical loading stress approaches the UCS. The final damage zone resides dominantly in the weak region of the rock sample, and the distribution of material property coefficients follows a similar beta distribution as the corresponding initial random field. Rock samples with persistent “pillar‐like” structures of strong particles can effectively resist the normal compression, resulting in high rock strengths. The traditional DEM simulation with a set of constant material properties can only represent one extreme realization of random field, which could significantly overestimate the rock strength. The proposed RDEA approach can effectively capture the uncertainty and complex interactions of rock fragmentation in a more realistic and reliable way.
Effectiveness and robustness revisited for a preconditioning technique based on structured incomplete factorization
Authors: Xin Zixing , Xia Jianlin , Cauley Stephen , Balakrishnan Venkataramanan
Published: March 2020

In this work, we provide new analysis for a preconditioning technique called structured incomplete factorization (SIF) for symmetric positive definite matrices. In this technique, a scaling and compression strategy is applied to construct SIF preconditioners, where off‐diagonal blocks of the original matrix are first scaled and then approximated by low‐rank forms. Some spectral behaviors after applying the preconditioner are shown. The effectiveness is confirmed with the aid of a type of two‐dimensional and three‐dimensional discretized model problems. We further show that previous studies on the robustness are too conservative. In fact, the practical multilevel version of the preconditioner has a robustness enhancement effect, and is unconditionally robust (or breakdown free) for the model problems regardless of the compression accuracy for the scaled off‐diagonal blocks. The studies give new insights into the SIF preconditioning technique and confirm that it is an effective and reliable way for designing structured preconditioners. The studies also provide useful tools for analyzing other structured preconditioners. Various spectral analysis results can be used to characterize other structured algorithms and study more general problems.
Function and mutual interaction of BiP‐, PERK‐, and IRE1α‐dependent signalling pathways in vascular tumours
Authors: Anspach Laura , Tsaryk Roman , Seidmann Larissa , Unger Ronald E , Jayasinghe Caren , Simiantonaki Nektaria , Kirkpatrick C James , Pröls Felicitas
Published: March 2020

Spontaneously regressing infantile haemangiomas and aggressive angiosarcomas are vascular tumours with excessive angiogenesis. When analysing haemangiomas and angiosarcomas immunohistochemically with respect to their chaperone profiles we found that angiosarcomas have significantly elevated protein levels of binding immunoglobulin protein (BIP) and PERK with concomitant attenuated IRE1α levels, whereas haemangioma tissue exhibits the same pattern as embryonal skin tissue. We show that BiP is essential for the maintenance of VEGFR2 protein, which is expressed in the endothelium of both tumour types. When studying the effects of BiP, the IRE1α/Xbp1 ‐, and PERK/ATF4‐signalling pathways on the migration and tube‐forming potential of endothelial cells, we show that downregulation of BiP, as well as inhibition of the kinase activity of IRE1α, inhibit in vitro angiogenesis. Downregulation of PERK (PKR‐like kinase; PKR = protein kinase R) levels promotes Xbp1 splicing in endoplasmic reticulum (ER)‐stressed cells, indicating that in angiosarcoma the elevated PERK levels might result in high levels of unspliced Xbp1, which have been reported to promote cell proliferation and increase tumour malignancy. The data presented in this study revealed that in addition to BiP or PERK, the kinase domains of IRE1α and Xbp1 could be potential targets for the development of novel therapeutic approaches for treating angiosarcomas and to control tumour angiogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
PVDF/ZnO composite films for photocatalysis: A comparative study of solution mixing and melt blending methods
Authors: Dossin Zanrosso Crissiê , Piazza Diego , Lansarin Marla Azário
Published: March 2020

Heterogeneous photocatalysis represents a solution for several environmental problems. However, achieving photocatalyst separation from reaction media on a large scale remains a challenge, one that might be overcome by the immobilization of photocatalysts into supports. To this end, composites of polyvinylidene fluoride and zinc oxide (ZnO) were prepared by three different techniques: solution mixing (SM) followed by Nonsolvent Induced Phase Separation; and melt blending at both low‐ and high‐shear rates (LS and HS) in a rheometer and mixing chamber, respectively, to compare the resultant morphology in photocatalysis. Photocatalytic efficiency was assessed by methylene blue (MB) discoloration in a batch reactor liquid phase and by resazurin (RZ) reduction. The changes promoted by nanoparticle inclusion, processing conditions and UV effect were demonstrated by FTIR‐ATR, XRD, DSC, and SEM. Results showed that ZnO incorporation was successful under all processing conditions, providing effective photocatalytic composites. However, samples prepared by SM had a twofold increase in discoloration efficiency and fourfold increase in surface photoactivity, when compared with LS or HS‐produced samples, explained by its higher porosity of 88% ± 1.3%. The covering of the photocatalyst surface was also evident on SEM analysis for melt blended samples, further contributing to reduction in their photocatalytic activity.
Exercise Programs to Reduce the Risk of Musculoskeletal Injuries in Military Personnel: A Systematic Review and Meta‐Analysis
Authors: Dijksma Iris , Arslan Ilgin G. , van Etten‐Jamaludin Faridi S. , Elbers Roy G. , Lucas Cees , Stuiver Martijn M.
Published: March 2020

Objective

To evaluate the effect of exercise programs on reduction of musculoskeletal injury (MSI) risk in military populations.

Design

Systematic review and meta‐analysis.

Literature Survey

A database search was conducted in PubMed/MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTdiscus, WHO International Clinical Trials Registry Platform Search Portal, Open Gray, National Technical Reports Library, and reference lists of included articles up to July 2019. Randomized and cluster‐randomized controlled trials evaluating exercise programs as preventive interventions for MSIs in armed forces compared to other exercise programs or to usual practice were eligible for inclusion.

Methodology

Two authors independently assessed risk of bias and extracted data. Data were adjusted for clustering if necessary and pooled using the random‐effects model when appropriate.

Synthesis

We included 15 trials in this review, with a total number of 14 370 participants. None of the included trials appeared to be free of any risk of bias. Meta‐analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment could be performed for static stretching compared to no stretching (3532 participants), showing low quality of evidence indicating no favorable effect of stretching. Gait retraining, an anterior knee‐pain targeted program, and resistance exercises showed cautious favorable effects on reducing injury risk in military personnel.

Conclusion

The current evidence base for exercise‐based MSI prevention strategies in the military is of low quality. Areas worthy of further exploration include the effects of gait retraining, anterior knee‐pain targeted programs, agility training, and resistance training programs, on medial tibial stress syndrome incidence, anterior knee pain incidence, attrition due to injuries and any type of MSI, respectively.
A CD24‐p53 axis contributes to African American prostate cancer disparities
Authors: Liu Wei , Zhang Yue , Wei Shi , Bae Sejong , Yang Wei‐Hsiung , Smith Gary J. , Mohler James L. , Fontham Elizabeth T. H. , Bensen Jeannette T. , Sonpavde Guru P. , Chen Guo‐Yun , Liu Runhua , Wang Lizhong
Published: March 2020

Background

Using a functional analysis of prostate cancer cells, we found a CD24‐dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24‐p53 axis in racial disparities of prostate cancer.

Methods

Samples of formalin‐fixed, paraffin‐embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53R175H and TP53R273H.

Results

CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late‐stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r = .308, P < .001) and MDM2 (r = .227, P = .004). There was a negative correlation for CD24 with ARF (r = −.280, P < .001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P = .004) but not for mutant p53 (AA/EA: 28% vs 21%; P = .152). In 32 CD24+/mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found.

Conclusion

The CD24‐p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities.
Process safety management in China: Progress and performance over the last 10 years and future development
Authors: Tong Ruipeng , Yang Xuesong , Zhao Hui , Parker Trent , Wang Qingsheng
Published: March 2020

In this work, 790 documents involving Process Safety Management (PSM) published from 1998 to 2018 are collected. These papers are classified and VOSviewer is employed to conduct keyword co‐occurrence analysis. Furthermore, this work discusses the current situation of Chinese PSM in terms of incidents, regulations, and rules involving PSM, and compares the development of PSM in China with that of other countries. Through a Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis, this work proposes tasks that are necessary to improve the effectiveness of Chinese PSM. The results show that the numbers of documents involving PSM in China have experienced enormous growth after 2010, and safety management has been the most prominent topic. In addition, severe chemical incidents triggered by similar causes tend to reoccur in China because of failures of PSM. Therefore, to improve the effectiveness of Chinese PSM, much work remains to be done, with the primary task being to ensure that comprehensive PSM programs are implemented effectively. To improve the effects of implementation, strengthened regulations and legal systems related to PSM are the most important measures to be taken. Additionally, China should learn from the experiences of other countries and should share its experiences with other emerging economies.
Epigenetic regulation of kidney progenitor cells
Authors: Huang Biao , Liu Zhenqing , Vonk Ariel , Zeng Zipeng , Li Zhongwei
Published: March 2020

The reciprocal interactions among the different embryonic kidney progenitor populations lay the basis for proper kidney organogenesis. During kidney development, three types of progenitor cells, including nephron progenitor cells, ureteric bud progenitor cells, and interstitial progenitor cells, generate the three major kidney structures—the nephrons, the collecting duct network, and the stroma, respectively. Epigenetic mechanisms are well recognized for playing important roles in organism development, in fine-tuned control of physiological activities, and in responses to environment stimuli. Recently, evidence supporting the importance of epigenetic mechanisms underlying kidney organogenesis has emerged. In this perspective, we summarize the research progress and discuss the potential contribution of novel stem cell, organoid, and next-generation sequencing tools in advancing this field in the future.

Significance statement Kidney dysplasia is usually attributed to the failure of kidney progenitor cells during kidney development. Recently, great progress has been made in understanding the epigenetic mechanisms controlling the activities of kidney progenitor cells in mammalian kidney development. This perspective summarizes this progress and offers new insights into the potential application of novel technical tools in advancing this field.
In Situ Investigation on the Protein Corona Formation of Quantum Dots by Using Fluorescence Resonance Energy Transfer
Authors: Qu Shaohua , Sun Fangying , Qiao Zihan , Li Juanmin , Shang Li
Published: March 2020

A fundamental understanding of nanoparticle–protein corona and its interactions with biological systems is essential for future application of engineered nanomaterials. In this work, fluorescence resonance energy transfer (FRET) is employed for studying the protein adsorption behavior of nanoparticles. The adsorption of human serum albumin (HSA) onto the surface of InP@ZnS quantum dots (QDs) with different chirality (d‐ and l‐penicillamine) shows strong discernible differences in the binding behaviors including affinity and adsorption orientation that are obtained upon quantitative analysis of FRET data. Circular dichroism spectroscopy further confirms the differences in the conformational changes of HSA upon interaction with d‐ and l‐chiral QD surfaces. Consequently, the formed protein corona on chiral surfaces may affect their following biological interactions, such as possible protein exchange with serum proteins plasma as well as cellular interactions. These results vividly illustrate the potential of the FRET method as a simple yet versatile platform for quantitatively investigating biological interactions of nanoparticles.
All Roads Lead to the Liver: Metal Nanoparticles and Their Implications for Liver Health
Authors: Boey Adrian , Ho Han Kiat
Published: March 2020

Metal nanoparticles (NPs) are frequently encountered in daily life, and concerns have been raised about their toxicity and safety. Among which, they naturally accumulate in the liver after introduction into the body, independent of the route of administration. Some NPs exhibit intrinsic pharmaceutical effects that are related to their physical parameters, and their inadvertent accumulation in the liver can exert strong effects on liver function and structure. Even as such physiological consequences are often categorically dismissed as toxic and deleterious, there are cell type‐specific and NP‐specific biological responses that elicit distinctive pharmacological consequences that can be harnessed for good. By limiting the scope of discussion to metallic NPs, this work attempts to provide a balanced perspective on their safety in the liver, and discusses both possible therapeutic benefits and potential accidental liver damage arising from their interaction with specific parenchymal and nonparenchymal cell types in the liver.
Seismic performance assessment of new dry‐assembled prefabricated composite shear wall system with beam‐only connection
Authors: Wang Dayang , Zhang Yongshan , Chen Haishen
Published: March 2020

Two types of prefabricated composite shear wall systems were proposed using modular and separated dry‐assembled ways, respectively. The seismic performance of four composite shear wall systems, two for the modular assembly way and two for the separated assembly way, was numerically evaluated including failure mode, loading and deformation capacities, hysteresis behavior, ductility, stiffness degradation, and energy dissipation. The nonlinear numerical simulations were conducted based on plastic‐damage constitutive laws for both concrete and steel materials using ABAQUS platform, which were further verified by the experimental investigations. The results showed that the mechanical performance of the modular assembly system is superior than that of the separated assembly system. The former exhibited good bearing and deformation capacities: The peak force is enhanced by 50% on average, the ultimate drift ratio reaches an average value of 3.7%, and the ductility coefficient has an average value of 10.5. As for the same assembly way, the prefabricated system with inner steel plate appeared better seismic properties compared to that with outer steel plate. Furthermore, the modular assembly system behaved prominent energy dissipation capacity with plentiful hysteresis loops. The equivalent damping ratio of this system reaches 15.93% at the drift ratio of 2%, which is the limit drift ratio for normal buildings in rare earthquakes.
Typification of names in the Dianthus plumarius group in the Carpatho‐Pannonian region
Authors: Barina Zoltán , Somogyi Gabriella , Pifkó Dániel
Published: March 2020

Lectotypes are designated for D. plumarius, D. lumnitzeri, D. lumnitzeri subsp. pseudopraecox, D. praecox, D. serotinus (superseding a previous lectotypification) and D. serotinus subsp. kitaibelianus. Epitypes are designated for D. plumarius, D. hungaricus and D. praecox, and a neotype is designated for D. serotinus var. regis‐stephani. The application of the name D. lumnitzeri in the sense of D. plumarius subsp. plumarius and the application of the name D. hungaricus as a collective species are adopted here. It is also concluded, that D. serotinus subsp. kitaibelianus and D. serotinus var. regis‐stephani were described from the same population. According to the results of the present typifications, 4(–5) taxa of the D. plumarius group can be distinguished in the Carpathian Basin and the Western Carpathians.
Combination Effect of Organically Modified Montmorillonite and Nano‐Silica on Reducing the Fire Hazards of Intumescent Flame‐Retarded Epoxy Resins
Authors: Yan Long , Xu Zhisheng , Jia Hongyu , Chu Zhiyong
Published: March 2020

The combination effect of organically modified montmorillonite (OMMT) and nano‐SiO2 on the fire behavior of intumescent flame‐retarded epoxy resins (EPs) was evaluated. The results from fire tests show that the combination of intumescent flame retardant (IFR), OMMT, and nano‐SiO2 exerts an outstanding synergistic effect on improving the flame retardancy and smoke suppression properties of EPs. For example, the IFR‐3 sample, filled with 27 wt% IFR, 1.5 wt% OMMT, and 1.5 wt% nano‐SiO2, achieves the limiting oxygen index value of 28.2% and passes the UL 94 V‐0 rating, and exhibits a 33.2% reduction in total heat release and 49.3% reduction in total smoke release compared to those of IFR‐0 filled with 30 wt% IFR. Thermo‐gravimetric analysis shows that the combination of IFR, OMMT, and nano‐SiO2 shows a notable improvement in the char‐forming ability of EPs. More importantly, the combination of OMMT and nano‐SiO2 exerts a better synergistic effect on the char‐forming and fire safety of the intumescent flame‐retarded EPs compared to the case of OMMT or nano‐SiO2 alone. This phenomenon is ascribed to the fact that the uniform dispersions of OMMT and nano‐SiO2 particles can facilitate the formation of a more compact and continuous intumescent char against the transmission of heat and combustible gases, thus effectively reducing the fire hazards of the EP composites.