bluuebunny/crossref_metadata_2025 huggingface dataset:
Schubversuche an hochwärmedämmendem Ziegelmauerwerk mit Dünnbettmörtel
Authors: Schermer Detleff , Meyer Udo Joachim , Lutman Marjana , Triller Petra
Published: June 2019

The paper presents the results of a series of 6 shear tests on full scale highly thermal insulating clay unit masonry walls. The walls consisted of units with large voids filled with mineral wool with a thermal conductivity of λ = 0,07 W/(m · K).

The aim of the investigations was the verification of the in‐plane‐shear resistance of this type of thermal insulating clay unit masonry in addition to the tests reported in [1].

The current design rules for clay unit masonry in DIN EN 1996‐1‐1/NA are rather conservative compared to the test results for thermal insulating units.
Climate and disturbance influence self‐sustaining stand dynamics of aspen (Populus tremuloides) near its range margin
Authors: Shinneman Douglas J. , McIlroy Susan K.
Published: June 2019

Species that are primarily seral may form stable (self‐sustaining) communities under certain disturbance regimes or environmental conditions, yet such populations may also be particularly vulnerable to ecological change. Aspen (Populusspp.) are generally considered seral throughout the Northern Hemisphere, includingP. tremuloides, the most widely distributed tree species in North America. Recent declines in aspen populations have occurred, especially along drought‐sensitive margins of its range and where fire exclusion and herbivory have promoted community transition. However, aspen also forms stable stands, and examination of the mechanisms that influence persistence can offer conservation insights, especially where populations are vulnerable to changing climate or altered disturbance dynamics. We sampled tree age and stand characteristics of isolated aspen forests in the arid Great Basin (USA) to determine if (1) aspen communities are more fire‐dependent and seral or fire‐independent and stable; (2) ungulate browsing inhibits aspen stability; and (3) temporal patterns of vegetative reproduction (i.e., ramet establishment or “suckering”) are correlated with climate. Aspen size and age class densities strongly fit negative exponential distributions, whether grouped geographically or by functional type, suggesting landscape‐scale persistence. Continuous age distributions and high proportions of recruitment‐sized to overstory trees suggest stability at stand scales, with exceptions including stands with higher browsing pressure. Few stands had evidence of fire, and relationships between dead tree size and variability in live tree size suggest a lack of fire dependency. Several 5‐yr averaged climate variables and one sea surface temperature index were correlated with aspen ramet establishment densities over time, with strongest relationships occurring ~5 yr prior to establishment year, often followed by inverse relationships ~1 yr after. Indeed, aspen establishment density for a recent 41‐yr period was reliably reconstructed using antecedent climate conditions derived from a single drought index. Temporally synchronized aspen ramet establishment across the study region may be due to climate‐driven storage of nonstructural carbohydrate reserves in clonal root systems later used for regeneration. Complex regeneration dynamics of these self‐sustaining aspen stands, especially sensitivity to climate variability, suggest they may serve as harbingers of ecological change in the arid Great Basin and in other aspen populations near their range margin.
Spatiotemporal variation in the sign and magnitude of ecosystem engineer effects on lake ecosystem production
Authors: Phillips Joseph S. , McCormick Amanda R. , Einarsson Árni , Grover Shannon N. , Ives Anthony R.
Published: June 2019

Ecosystem engineers can have diverse and conflicting effects on their ecosystems, and the balance between these effects can depend on the physical environment. This context dependence means that environmental variation can produce large differences in engineer effects through space and time. Here, we explore how local variability in environmental conditions can lead to large spatiotemporal variation in the effect of tube‐building midges on benthic ecosystem metabolism in a shallow subarctic lake. Using field experiments, we found that midge engineering increases both gross primary production (GPP) and respiration (RESP) in the sediment. Gross primary production and RESP have opposing influences on net ecosystem production, and the net effect of midges on the benthic ecosystem depends on the balance between their effects on GPP and RESP. Variation in light mediates this balance—under high light conditions, primary producers are able to exploit the structural benefits provided by midges, while in the dark, the elevation of respiration from midge engineering predominates. Benthic light levels vary spatially and temporally due to episodic cyanobacterial blooms that prevent almost all light from reaching the benthos. By quantifying the nonlinear relationship between midge engineering and light, we were able to project ecosystem‐wide consequences of natural variation in light conditions across the lake. Our results illustrate how the sign and magnitude of ecosystem‐wide effects of ecosystem engineers can vary through space and time.
Evaluating mechanisms of plant‐mediated effects on herbivore persistence and occupancy across an ecoregion
Authors: Wilkening Jennifer L. , Cole Evan J. , Beever Erik A.
Published: June 2019

Contemporary climate change is rapidly creating one of the greatest challenges for management and conservation during the 21st century. Mountain ecosystems, which have a high degree of spatial heterogeneity and contain numerous habitat specialists, have been identified as particularly vulnerable. We used data from multiple years across sites spanning a >40 million ha ecoregion to test hypotheses regarding how community‐level characteristics of vegetation may affect a mammalian generalist herbivore, the American pika (Ochotona princeps). We examined patterns of pika persistence across sites in the hydrographic Great Basin, and occupancy within a subset of these sites. We used mixed‐effects logistic regression models to compare evidence in support of competing explanations for each pattern within an information–theoretic framework (using Akaike's information criterion). Models reflected four hypothesized classes of mechanisms related to nutritional ecology, ecosystem function, indirect indication of climatic effects, and (synergistic) combinations of these three classes. At the site level, models reflecting synergistic effects received the most support. At the within‐site level, support appeared to be split equally among hypotheses containing predictors related to either nutritional ecology or indirect climate effects. Well‐supported predictors included cover of invasive plant species, cover of more‐xeric plant species, species evenness, and proportion of graminoid species. Our results both (1) identify important aspects of vegetation communities that may influence herbivore distribution in mountainous areas across a large, diverse geographic region, and (2) contribute to an improved understanding of how mountain ecosystems may be affected by ongoing climate change, more broadly.
Using Confocal Microscopy to Estimate the Distribution of Natural Antioxidants in Poultry Meal and Extruded Kibbles
Authors: Ye Liyun , Pham‐Mondala Alessandra , Li Jian , Joseph Poulson , Nahas Roger , Michel‐Salaun Francoise
Published: June 2019

With the increasing demand for natural ingredients from the pet food market, new sources of natural antioxidants have been identified. However, many of them have low solubility in the traditional oil‐based delivery systems. To improve their distribution in dry matrices, new carriers and processes have been developed. To evaluate the effect of new delivery systems, a confocal microscopy method is developed. Based on confocal images, an emulsion carrier improves the distribution of hydrophilic antioxidants in poultry meal. Shelf life study shows that it slows down the decomposition of some lipophilic antioxidants even though it does not improve the oxidative stability of poultry meal directly. In extruded kibbles, confocal images show that hydrophilic compounds distribute better when added into premix before extrusion, while lipophilic compounds distribute well no matter when they are added. Confocal microscopy is a great tool for evaluating the effect of new delivery systems on antioxidants’ distribution. The overall performance of the antioxidant needs to be further evaluated through a comprehensive oxidative stability study.

Practical Applications: Results presented in this paper may help renderers and pet food scientists to understand the distribution, migration, and performance of natural antioxidants in poultry meal and extruded kibbles. The confocal microscopy method developed in this study can be used to evaluate other delivery systems and in other protein‐rich dry matrices. Even though the water‐in‐oil emulsion improves the distribution of hydrophilic antioxidants and keeps the good distribution of lipophilic antioxidants, antioxidants in oil carrier still has the best performance in poultry meal. This reminds us of the importance of comprehensive oxidative stability studies in evaluating antioxidants performance.

Two proprietary carriers’ effect on antioxidants’ performance in poultry meal through confocal imaging and shelf life study are evaluated. The confocal imaging method has been also tentatively used to estimate the distribution of antioxidants when added before and after extrusion in kibbles.
Double‐hit lymphoma: So what?
Authors: Davies Andrew
Published: June 2019

The revised WHO classification moved all aggressive B‐cell lymphomas with a MYC translocation and a concurrent translocation of BCL2 and/or BCL6 into a single diagnostic category. These are the double‐ and triple‐hit lymphomas. These represent a group with typically a poor outcome to conventional therapy, and as a result, intensification of immunochemotherapy has been explored. The optimal approach is far from clear, and recent insight into the biology suggest that they may represent just a subgroup of molecular high‐grade B‐cell lymphomas that maybe identified by gene expression profiling. There are a number of novel therapeutic approaches under investigation.
Multiple myeloma: Every year a new standard?
Authors: Rajkumar S. Vincent
Published: June 2019

The treatment of myeloma is rapidly evolving. This article reviews the current diagnostic criteria, risk stratification, and approach to treatment of multiple myeloma. Treatment approach for both newly diagnosed and relapsed disease are discussed.
New treatment options in hairy cell leukemia with focus on BRAF inhibitors
Authors: Falini Brunangelo , Tiacci Enrico
Published: June 2019

Hairy cell leukemia (HCL) responds initially very well to chemotherapy with purine analogues. However, up to 50% of patients relapse, often multiple times, and become progressively less sensitive to these myelotoxic and immune‐suppressive drugs. At progression, viable therapeutic strategies include addition of rituximab to purine analogues, and treatment with the anti‐CD22 immunotoxin moxetumomab pasudotox, which has been recently approved by the FDA in HCL patients after at least two prior therapies. Identification of the BRAF‐V600E kinase mutation as the genetic cause of HCL has opened the way, in the relapsed/refractory experimental setting, to targeted and non‐myelotoxic effective strategies that are based on inhibition of BRAF with vemurafenib, co‐inhibition of BRAF and its target MEK with dabrafenib and trametinib, and BRAF inhibition with vemurafenib combined with anti‐CD20 immunotherapy. In particular, vemurafenib plus rituximab is emerging as a short, safe, chemotherapy‐free regimen able to induce deep complete remissions in most HCL patients refractory to, or relapsed multiple times, after chemo(immuno)therapy.
Managing the toxicities of CAR T‐cell therapy
Authors: Neelapu Sattva S.
Published: June 2019

Chimeric antigen receptor (CAR) T‐cell therapy has the potential to revolutionize the management of B‐cell lymphomas and possibly other cancers. Two anti‐CD19 CAR T‐cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for the management of relapsed/refractory large B‐cell lymphoma after two lines of systemic therapy. Additional trials are ongoing to evaluate these and other CAR T products at earlier stages of the disease course as well as in other lymphomas. While the potential to induce durable remissions with a single CAR T‐cell infusion even in patients who are chemorefractory has generated much enthusiasm in the field, practitioners need to familiarize themselves with the unique toxicities associated with these therapies. This review will discuss the grading and management of the two most common toxicities, cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS), observed acutely after this therapy. In addition, late toxicities including prolonged cytopenias and on‐target off‐tumor effects will be reviewed.
Adiposity and estrogen receptor‐positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol
Authors: Dashti S. Ghazaleh , Simpson Julie A. , Karahalios Amalia , Viallon Vivian , Moreno‐Betancur Margarita , Gurrin Lyle C. , MacInnis Robert J. , Lynch Brigid M. , Baglietto Laura , Morris Howard A. , Gunter Marc J. , Ferrari Pietro , Milne Roger L. , Giles Graham G. , English Dallas R.
Published: June 2019

Adiposity increases estrogen receptor (ER)‐positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex‐steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER‐positive postmenopausal breast cancer association. We used data from a case–cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER‐negative disease or breast cancer diagnosis within the first follow‐up year were excluded. We analyzed the study as a cumulative sampling case–control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression‐based multiple‐mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5–25 kg/m2, the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05–2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43–2.48). Percentage mediated effect through free estradiol was 72% (IIE‐RR 1.56; 95% CI 1.11–2.19). There was no evidence for an indirect effect through insulin (IIE‐RR 1.12; 95% CI 0.68–1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity–breast cancer relationship but does not explain all of the association.
ALDH1A1 in patient‐derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression
Authors: Namekawa Takeshi , Ikeda Kazuhiro , Horie‐Inoue Kuniko , Suzuki Takashi , Okamoto Koji , Ichikawa Tomohiko , Yano Akihiro , Kawakami Satoru , Inoue Satoshi
Published: June 2019

Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long‐term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor‐initiating potential, or cancer stem‐like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long‐term patient‐derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC‐dependent patient‐derived xenografts (PDXs) were basically similar to those of their corresponding patients’ specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all‐trans RA could rescue ALDH1A1 shRNA‐suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC‐derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.
Malignant melanoma of the male urethra with increased 5‐S‐cysteinyldopa: A case report
Authors: Aoki Yusuke , Soma Takahiko , Nakamura Yuki , Fukui Naotaka , Sakai Yasuyuki , Kageyama Yukio
Published: June 2019

Introduction

We herein present a case of malignant melanoma of the male urethra with an increased serum 5‐S‐cysteinyldopa concentration.

Case presentation

A 77‐year‐old man visited our hospital complaining dysuria and a dark brown mass protruding from the external urethral meatus. His serum 5‐S‐cysteinyldopa concentration was elevated beyond the upper limit of the reference range. Biopsy of the tumor was performed, and the histological diagnosis was malignant melanoma. He underwent total penectomy, and the serum 5‐S‐cysteinyldopa concentration was normalized. He remained alive without evidence of locoregional recurrence or distant metastases for 6 months after surgery.

Conclusion

Malignant melanoma of the male urethra is uncommon. The prognosis is favorable if it is detected in its early stages. This case report suggests that measurement of the serum concentration of 5‐S‐cysteinyldopa, a melanin metabolite, is useful for early diagnosis of male urethral melanoma.
Linear array arrangement using composite right‐/left‐handed transmission lines for magnetic resonance imaging
Authors: Hernandez Daniel , Seo Jeung‐Hoon , Kim Kyoung‐Nam
Published: June 2019

Array coils for magnetic resonance imaging have been used to improve field uniformity, improve signal‐to‐noise ratios, and increase imaging speed. Alternative radio frequency (RF) coils that use metamaterials, such as loop or microstrip coils, have recently been proposed and are expected to provide better performance than the traditional RF array coils. Transmission lines (TLs) based on metamaterials are known as composite right‐ and left‐handed (CRLH) TLs, which are artificially created by adding inductances and capacitances to a common TL. CRLH TLs have a zero‐order resonance mode, wherein wave propagation is independent of the TL's electrical length. Decoupling between array elements is important for obtaining the benefits of parallel imaging. In this study, we analyze the decoupling properties between two CRLH TLs. In addition, we design a linear array of four CRLH TLs to obtain a uniform magnetic (|B1|)‐field in the axial‐ and longitudinal‐direction at 7T for the corresponding frequency of 300 MHz.
Enhancement of Cr(VI) Ion Removal Using Nanochitosan Coated on Bituminous Activated Carbon
Authors: Chooaksorn Wanida , Nitisoravut Rachnarin , Polprasert Chongrak , Babel Sandhya , Laohhasurayotin Kritapas , Kangwansupamonkon Wiyong
Published: June 2019

Bituminous activated carbon (AC) has been widely used as a sorbent for adsorption of non‐polar species, but its performance for removal of ionic species such as heavy metals has not been as efficient. In this study, AC was modified with chitosan nanoparticles (CN) using facile methods of dip coating and wet impregnation. The CN‐coated AC demonstrated an increase in Cr(VI) removal efficiency in both kinetics and adsorption capacity. The adsorption capacity of the CN‐coated AC (mg/g) was more than twice that of the uncoated AC (36.36 mg/g), or pure chitosan (32.57 mg/g). The sizes of the synthesized CN (160‐2,000 nm) can be controlled by varying the concentration of the chitosan/reagents used. The adsorption isotherms are better described using the Freundlich rather than the Langmuir model and are in agreement with the heterogeneity of the surfaces. Adsorption kinetics followed that of the pseudo‐second‐order kinetics, suggesting chemisorption as a rate limiting step.
Updated Population Pharmacokinetic Model of Cabozantinib Integrating Various Cancer Types Including Hepatocellular Carcinoma
Authors: Nguyen Linh , Chapel Sunny , Tran Benjamin Duy , Lacy Steven
Published: June 2019

An integrated population pharmacokinetic (PPK) model was used to evaluate the effects of liver dysfunction on the pharmacokinetics (PK) of cabozantinib in patients with hepatocellular carcinoma and to determine whether clinical dosage adjustment may be necessary in this population. An integrated PPK model previously developed in healthy volunteers and patients with various cancer types was updated with cabozantinib concentration data from hepatocellular carcinoma patients in phase 2 and 3 studies (total 2023; hepatocellular carcinoma 489 patients). Covariate effects of cancer type including hepatocellular carcinoma population and liver dysfunction per the National Cancer Institute Organ Dysfunction Working Group criteria were evaluated (normal 1425; mild liver dysfunction 558; moderate/severe liver dysfunction 15/1 patients). With hepatocellular carcinoma patients, PK parameter estimates and covariate effects were similar to the previous PPK model (2 compartments with first‐ and zero‐order absorption and first‐order elimination). Only medullary thyroid cancer had appreciable PK differences from healthy volunteers. PK parameter estimates were similar with and without addition of liver dysfunction covariates. Patients with mild liver dysfunction were predicted to have minimal differences in apparent clearance of cabozantinib relative to patients with normal liver function. Therefore, no initial cabozantinib dosage adjustment is recommended for cancer patients with mild liver dysfunction. The small sample size for patients with moderate and severe liver dysfunction limited dosing recommendations in these subpopulations. The results from this PPK analysis were different from those of the single‐dose hepatic impairment study in healthy volunteers and more reflective of exposure in cancer patients following daily cabozantinib dosing.
Qualitative analysis of smear layer treated with different etidronate concentrations: A scanning electron microscopy study
Authors: Emre Erik C. , Onur Orhan E. , Maden Murat
Published: June 2019

The aim of this study was to examine the smear layer removal capacity of various etidronate treatments. Seventy‐eight roots were instrumented up to apical size X4 and randomly divided into five treatment groups and a positive control group (n = 13). Groups were as follows: irrigation with 5 ml of sterile saline (control) for 3 min, 5 ml of 17% ethylenediaminetetraacetic acid (EDTA) for 3 min, 5 ml of 9% A1‐hydroxyethylidene‐1,1‐bisphosphonate (HEBP) for 3 min, 5 ml of 18% HEBP for 3 min, irrigation with 5 ml of 1% sodium hypochlorite (NaOCl) + 9% HEBP for 3 min, and 5 ml of 2% NaOCl + 18% HEBP for 3 min. The roots were examined using a scanning electron microscope. The smear layer scores in the 2% NaOCl + 18% HEBP group were lower than those in the other treatment groups and the control group (p < .05). There were no significant differences among the treatment groups in the smear layer scores of the coronal and middle thirds. However, the smear layer scores in the 2% NaOCl + 18% HEBP treatment group were lower those in the 9% HEBP and 18% HEBP treatment groups in the apical third (p < .05). In the clinical setting, the recommended concentration of HEBP is 18%, and it should be used with an oxidizing agent to ensure optimum smear layer removal.
Embryonic and larval development of the northern pike: An emerging fish model system for evo‐devo research
Authors: Pospisilova Anna , Brejcha Jindřich , Miller Vojtech , Holcman Radek , Šanda Radek , Stundl Jan
Published: June 2019

The northern pike, Esox lucius, is one of the largest temperate freshwater apex predators with a characteristic morphology: an elongated body with pelvic, dorsal, and anal fins located at the rear as a functional feature to sprint predation. However, the typical pike character is its head, which is characterized by a long, flattened snout, a well‐armed mouth with numerous teeth, and large eyes characteristic of shallow water visual predators. Although the northern pike is becoming increasingly popular as a model system for ecology and evolutionary research, a detailed staging table has not yet been reported. In this study, we report the first comprehensive staging table for the northern pike, spanning from the one‐cell stage to the freely‐swimming juvenile stage. In addition to classical embryological descriptions, we use a DAPI staining to distinguish individual cells and embryonic structures during the early development. This dataset, in combination with the genomic and transcriptomic resources already available, serves as a foundation for in‐depth mechanistic studies dealing with development using this species.
A 5.5‐inch full HD foldable AMOLED display based on neutral‐plane splitting concept
Authors: Nishimura Masumi , Takebayashi Kisako , Hishinuma Masatomo , Yamaguchi Hajime , Murayama Akio
Published: June 2019

Splitting of the mechanical neutral plane is a promising concept for foldable displays because it reduces the folding stress in each layer of the display. We verified the splitting concept experimentally and revealed a linear relation between the relative position of the neutral plane and the logarithm of the adhesive's elastic modulus. As the modulus decreased, the position of the neutral plane approached that of perfect splitting. On the basis of the neutral‐plane splitting concept, we developed 5.5‐inch full high‐definition foldable active matrix organic light‐emitting diode (AMOLED) displays, which endured 150 k inward folding cycles and 150 k outward folding cycles with folding radii of 3 and 5 mm, respectively. This study is expected to improve the flexibility of designing foldable AMOLED displays, enabling better balance of the portability versus practicality trade‐off in mobile displays.
Sheoak woodlands: a newly identified habitat for western ringtail possums
Authors: Bader Jordan C. , Van Helden Bronte E. , Close Paul G. , Speldewinde Peter C. , Comer Sarah J.
Published: June 2019

Although critically endangered western ringtail possums (Pseudocheirus occidentalis) have been recorded from a variety of vegetation types in southwestern Australia, the extent to which many of these vegetation types are occupied by the species remains unknown. We conducted spotlight surveys for western ringtail possums between March and April 2018 in Albany, southwestern Australia, to determine the species’ occupancy in 2 vegetation types. Using occupancy models, we demonstrated that sheoak (Allocasuarina fraseriana) woodlands, previously unrecognized as providing western ringtail possum habitat, support the species, although the median probability of their occupancy was lower than in marri (Corymbia calophylla) and eucalypt (Eucalyptus marginata and E. staeri) woodlands. Use of trees and other habitat components by western ringtail possums varied within and between vegetation types. Sheoak woodlands are likely critical for western ringtail possums and given the apparent flexibility in vegetation types used by the species, investigation of the potential value of other vegetation types for this species has conservation merit. © 2019 The Wildlife Society.
TET2 missense variants in human neoplasia. A proposal of structural and functional classification
Authors: Bussaglia Elena , Antón Rosa , Nomdedéu Josep F. , Fuentes‐Prior Pablo
Published: June 2019

Background

The human TET2 gene plays a pivotal role in the epigenetic regulation of normal and malignant hematopoiesis. Somatic TET2 mutations have been repeatedly identified in age‐related clonal hematopoiesis and in myeloid neoplasms ranging from acute myeloid leukemia (AML) to myeloproliferative neoplasms. However, there have been no attempts to systematically explore the structural and functional consequences of the hundreds of TET2 missense variants reported to date.

Methods

We have sequenced the TET2 gene in 189 Spanish AML patients using Sanger sequencing and NGS protocols. Next, we performed a thorough bioinformatics analysis of TET2 protein and of the expected impact of all reported TET2 missense variants on protein structure and function, exploiting available structure‐and‐function information as well as 3D structure prediction tools.

Results

We have identified 38 TET2 allelic variants in the studied patients, including two frequent SNPs: p.G355D (10 cases) and p.I1762V (28 cases). Four of the detected mutations are reported here for the first time: c.122C>T (p.P41L), c.4535C>G (p.A1512G), c.4760A>G (p.D1587G), and c.5087A>T (p.Y1696F). We predict a complex multidomain architecture for the noncatalytic regions of TET2, and in particular the presence of well‐conserved α+β globular domains immediately preceding and following the actual catalytic unit. Further, we provide a rigorous interpretation of over 430 missense SNVs that affect the TET2 catalytic domain, and we hypothesize explanations for ~700 additional variants found within the regulatory regions of the protein. Finally, we propose a systematic classification of all missense mutants and SNPs reported to date into three major categories (severe, moderate, and mild), based on their predicted structural and functional impact.

Conclusions

The proposed classification of missense TET2 variants would help to assess their clinical impact on human neoplasia and may guide future structure‐and‐function investigations of TET family members.
Value of p‐Value
Authors: Golbraikh Alexander
Published: June 2019

The goal of this manuscript is to discuss important aspects of external validation of classification and category Quantitative Structure – Activity/Property/Toxicity Relationship QS/A/P/T/R models that to the best of author's knowledge are not addressed in publications. Statistical significance (in terms of p‐value) and accuracy of prediction (in terms of Correct Classification Rate (CCR)) of external validation set compounds are among most important characteristics of the models. We assert that in most cases the models built for classification or category response variable should be statistically significant and predictive for each class or category. We show that three thresholds of the number of compounds in each class or category of the external validation sets should be satisfied. 1) The p‐value criterion can never be satisfied, if the number of compounds is below the first threshold. 2) If the number of compounds is between the first and the second thresholds, p‐value criterion should be used. 3) If it is higher than the third threshold, classification or category accuracy criterion should be used. 4) If the number of compounds is between second and third thresholds, either one or the other criterion should be used depending on the value of p‐value. 5) When the number of compounds in the class approaches infinity, the maximum relative error of prediction approaches the relative expected error. The results are of interest in other areas of multidimensional data analysis.
Novel Electrotopological Atomic Descriptors for the Prediction of Xenobiotic Cytochrome P450 Reactions
Authors: Kaitoh Kazuma , Kotera Masaaki , Funatsu Kimito
Published: June 2019

Cytochrome P450 (CYP) is an enzyme family that plays a crucial role in metabolism, mainly metabolizing xenobiotics to produce non‐toxic structures, however, some metabolized products can cause hepatotoxicity. Hence, predicting the structures of CYP products is an important task in designing non‐hepatotoxic drugs. Here, we have developed novel atomic descriptors to predict the sites of metabolism (SoM) in CYP substrates. We proposed descriptors that describe topological and electrostatic characteristics of CYP substrates using Gasteiger charge. The proposed descriptors were applied to CYP3A4 data analysis as a case study. As a result of the descriptor selection, we obtained a gradient boosting decision tree‐based SoM classification model that used 139 existing descriptors and the proposed 45 descriptors, and the model performed well in terms of the Matthews correlation coefficient. We also developed a structure converter to predict CYP products. This converter correctly generated 51 structural formulas of experimentally observed CYP3A4 products according to a manual evaluation.
High‐Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review
Authors: Patel Jayshil J. , Venegas‐Borsellino Carla , Willoughby Rodney , Freed Julie K.
Published: June 2019

Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.
Effect of Magnesium Stearate Coating on Degradation of NH4ClO4/Mg by Moisture
Authors: Nishiwaki Yosuke , Matsunaga Takehiro , Kumasaki Mieko
Published: June 2019

Pyrotechnic compositions containing magnesium (Mg) powder face the problem of degradation by moisture. Although potassium dichromate is an effective stabilizer that avoids Mg degradation, it is detrimental for human health and environment. This study is aimed at developing a harmless stabilizer for Mg in pyrotechnics. We investigated the effect of magnesium stearate (MgSt) coating on stabilization and combustion properties of the coated Mg. The stabilization effect of MgSt coating was measured by aging test of ammonium perchlorate (AP) and Mg mixture (AP/Mg). The aging test revealed that MgSt coating reduced the generation of degradation product, Mg(OH)2. Results of burning test showed that MgSt has little effect on flame color, while it considerably decreased the burning rate. The influence of MgSt coating was lower than that of MgSt that was simply mixed with AP/Mg.
Design, Modeling, Fabrication, and Verification of New Multifunctional MEMS/NEMS Components
Authors: Freitag Markus , Sauppe Matthias , Auerswald Christian , Kriebel David , Schmidt Henry , Voigt Sebastian , Arnold Benjamin , Markert Erik , Hahn Susann , Hiller Karla , Heinkel Ulrich , Mehner Jan
Published: June 2019

The development of a new sensor generation with a significant performance gain is mainly aimed at increasing the sensitivity. In addition to that, a variety of properties such as integrability, power consumption, robustness, reliability, cross‐talk sensitivity, and others, can be equally important. Some properties scale directly with sensitivity, whereas others show trade‐off characteristics. An overview of different approaches for new sensor generations with enhanced performance is presented and discussed in this article. The main focus is on new microelectromechanical systems (MEMS) elements, fabricated within a standard high‐aspect‐ratio micromachining process and capacitive working principle. Herein, a novel MEMS‐based bandpass, a gap reduction technique, fluted electrodes for reduced damping, and a novel direct current/direct current (DC/DC) converter, is proposed. Acoustic emission sensing is chosen as example application to underline the challenging requirements for the design. Furthermore, the recent improvements in technology are presented. Based on bonding and deep reactive ion etching (BDRIE), it allows larger aspect ratios as well as through‐silicon vias and low‐pressure encapsulation. Consistent further miniaturization leads to the use of nanoscopic elements within MEMS as sensing component instead of the conventional electrostatic working principle. Unique properties of graphene rolls or carbon nanotubes (CNTs) enable promising sensitivity improvements if they are integrated at wafer‐level. Therefore, a design concept and formal verification‐tool is presented.
Preparation of Low‐Dimensional Bismuth Tungstate (Bi2WO6) Photocatalyst by Electrospinning
Authors: Zhao Gang , Hao Shuhua , Xing Yupeng , Wang Yanjun , Wang Yingjie , Xu Kang , Xu Xijin
Published: June 2019

Bismuth tungstate (Bi2WO6), with a narrow bandgap (2.7 eV), can degrade pollutants with a remarkable photocatalytic effect under visible light and has gained interest among researchers in recent years. Bi2WO6 photocatalysts have mainly a layered multistage structure with a strong adsorption capacity and weak photocatalytic activity. Usually, the Bi2WO6 photocatalysts are prepared by a hydrothermal method, which is not conducive to separation, treatment, and reuse. Therefore, it is necessary to design and synthesize Bi2WO6 with a spatial network structure to improve its catalytic activity and reusability, because the structure has the characteristics of high specific surface area, many active points, and strong flexibility. In this review, an electrospinning method for preparing different kinds of Bi2WO6 is introduced, in which the theoretical basis and experimental procedures are emphatically analyzed. In addition, their photocatalytic degradation activities under visible light are summarized.
Realization of Efficient Field Emitter Based on Reduced Graphene Oxide‐Bi2S3 Heterostructures
Authors: Gote Gorkshnath H. , Bhopale Somnath R. , More Mahendra A. , Late Dattatray J.
Published: June 2019

Herein, Bi2S3 nanorods and reduced graphene oxide (rGO)‐Bi2S3 heterostructures are synthesized using a simple hydrothermal method. The structural, morphological, chemical, and elemental analysis of as‐synthesized materials is performed using X‐ray diffraction (XRD), Raman spectroscopy, field‐emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and X‐ray photoelectron spectroscopy (XPS). Field emission (FE) studies are carried out on both pristine Bi2S3 nanorods and rGO‐Bi2S3 heterostructure samples at a base pressure of ≈1 × 10−8 mbar. The results show that the rGO‐Bi2S3 heterostructure emitter has superior FE performance compared to pristine Bi2S3 emitters in terms of the turn‐on field (2.6 V μm−1 at 10 μA cm−2) and threshold field (4.0 V μm−1 at 100 μA cm−2) along with a high emission current density of ≈1464 μA cm−2 at an applied electric field of 7.0 V μm−1. The rGO‐Bi2S3 heterostructure emitter exhibits very good emission current stability, tested for more than 3 h duration, characterized by standard deviation values ≈2.84 and 4.06, corresponding to preset values 12 and 100 μA. This study implies that one‐step hydrothermal route can be efficiently used to synthesize organic–inorganic heterostructures that possess unique morphology. Furthermore, the synthesized rGO‐Bi2S3 heterostructure emitter shows potential as an electron source for practical application in vacuum microelectronic devices.
Stretch/Compress‐Modulated Spin Splitting in One‐Dimensional Melem Chain with a Helical Structure
Authors: Han Dong , Chen Xue-Jiao , Xu Hai , Jiao Chen , Xu Ji-Lian , Li Ke-Xue , Liu Lei , Li Yao-Biao , Shen De-Zhen
Published: June 2019

It is demonstrated that spin splitting can be induced and further modulated in a one‐dimensional (1D) helical melem chain with a helical structure by first‐principles calculations. The spin splitting occurs at the charge‐localized states at valence band due to the breaking of inversion symmetry by the helical structure. The maximum spin‐split energy reaches 0.81 meV, without any heavy elements in the melem chain. The helical melem chain is facile to stretch or compress, as a molecule spring with a spring constant of 1.04 N m−1, leading to the spin‐split energy effectively varying from 0.81 (196 GHz) to 0.04 meV (10 GHz) along with the periodic lattice changing from 4.0 to 15.0 Å. These results exhibit a unique mechanism for driving the spin splitting in 1D materials, in particular for those helical big molecules, and that in fact offers an original way to not only design the regulatable 1D components in the fields of spintronics but also measure the helix of molecule chains by resonating with microwave frequency.
Proresolving Lipid Mediators and Receptors in Stem Cell Biology: Concise Review
Authors: Romano Mario , Patruno Sara , Pomilio Antonella , Recchiuti Antonio
Published: June 2019

Accumulating evidence indicates that stem cells (SCs) possess immunomodulatory, anti-inflammatory, and prohealing properties. The mechanisms underlying these functions are being investigated with the final goal to set a solid background for the clinical use of SCs and/or their derivatives. Specialized proresolving lipid mediators (SPMs) are small lipids formed by the enzymatic metabolism of polyunsaturated fatty acids. They represent a leading class of molecules that actively and timely regulate the resolution of inflammation and promote tissue/organ repair. SC formation of these mediators as well as expression of their receptors has been recently reported, suggesting that SPMs may be involved in the immunomodulatory, proresolving functions of SCs. In the present review, we summarize the current knowledge on SPMs in SCs, focusing on biosynthetic pathways, receptors, and bioactions, with the intent to provide an integrated view of SPM impact on SC biology. Stem Cells Translational Medicine  2019;8:992–998
Sustainable Amine Synthesis: Iron Catalyzed Reactions of Hydrosilanes with Imines, Amides, Nitroarenes and Nitriles
Authors: Shaikh Nadim S.
Published: June 2019

Iron catalyzed organic synthesis has emerged as a sustainable chemistry due to the highly competitive cost, high natural abundance and ecologically acceptable properties of iron. Moreover, its extensive range of oxidation states i. e. –II to +VI provides numerous opportunities to perform multiple organic reactions. Recently iron catalysis has started competing the established precious metals. Among organic scaffolds, amines are important building blocks that are useful in the various fields starting from drugs, crop protection chemicals to dyes and pigments. Typically, hydrogenation or reduction of functional groups such as imines, amides, nitroarenes and nitriles results into amines. In this context, homogeneous iron catalyzed hydrosilylation is a highly promising alternative to traditional hydrogenation and other reduction reactions. This review is focused on the synthesis of amine and its derivatives via hydrosilylation of imines, amides, nitroarenes and nitriles using iron as a catalyst. Some of the reduction methods of these functional groups that may not follow the typical hydrosilylation pathway are also included in this review due to their strong relevance to the theme. The phenomenal progress in this focused area is summarized to witness this transformation towards sustainable development in the field of amine synthesis.
An Overview of Surface‐Functionalized Magnetic Nanoparticles: Preparation and Application for Wastewater Treatment
Authors: Gao Fengfeng
Published: June 2019

The removal of contaminant and recovery of valuable matters from wastewater remain a challenge in the field of industrial production. Among the developed technologies, adsorption method is of interest for researchers due to its low‐cost and facile operation. However, the traditional adsorbents always meet the problem of difficult recycling. Nowadays, surface functionalized magnetic nanomaterials have become a new kind of adsorbents with the potential application in the wastewater treatment because of their large surface area, high stability, weak coagulation, and especially reusability due to its super‐paramagnetic properties in a magnetic field. The extraction capacity of pollutants is mainly related to the features of functional groups grafted on the surface of Fe3O4 nanoparticles. This review mainly focuses on recent progress on the functional modification methods of magnetic Fe3O4 nanoparticles by inorganic molecules, small organic molecules, and organic polymer materials. The advantages and disadvantages of magnetic Fe3O4 nanoparticles modified by various functional groups, application and interaction mechanism in the wastewater treatment are also reviewed. Finally, the development trend of surface modified magnetic adsorption materials in the future wastewater treatment field is prospected.
Synthesis of a Peptide Conjugated 5‐Fluorouracil Gelator Prodrug for Photo‐Controlled Release of the Antitumor Agent
Authors: Das Soumi , Horo Himali , Goswami Upashi , Kundu Lal Mohan
Published: June 2019

Widely used chemotherapeutic agent 5‐fluorouracil (5‐Fu) exhibits adverse effects by damaging the normal cells. Controlled delivery and release of such antitumor drugs is essential for better treatment. Herein, a low molecular weight peptide‐drug conjugate for the photo‐controlled delivery of 5‐Fu is demonstrated. 5‐Fu is covalently attached with a short peptide through a photo‐cleavable linker. With a careful choice of the peptide sequence, the peptide‐drug conjugate was able to form a hydrogel within a narrow pH window (pH 6.0 ‐ 8.0). MTT assay of the peptide‐drug conjugate in HeLa cells inferred almost no cytotoxicity up to a high concentration of 110 μg/mL. The gelator prodrug releases 5‐Fu in a controlled, does‐dependent manner under irradiation. The characterizations and controlled release of the drug were investigated using various analytical techniques including FTIR, HPLC and UV‐visible spectroscopy whereas, morphology of the gel was studied by FESEM. The gelation behaviour and rheology of the conjugate was also studied in details. Such covalently peptide‐conjugated 5‐Fu gel could be useful for effective delivery of antitumor agent.
Impact of 9‐(4‐methoxyphenyl) Carbazole and Benzodithiophene Cores on Performance and Stability for Perovskite Solar Cells Based on Dopant‐Free Hole‐Transporting Materials
Authors: Qiu Jianfeng , Liu Hongli , Li Xianggao , Wang Shirong , Zhang Fei
Published: June 2019

Perovskite solar cells (PSCs) possess both high‐power conversion efficiency (PCE) and good operation stability for future application. Although many different types of hole‐transporting materials (HTMs) are assessed, few dopant‐free small organic molecule HTMs‐based PSC cells exist, which exhibit excellent stability under both heat and illumination. Herein, two novel HTMs that are based on 9‐(4‐methoxyphenyl) carbazole and benzodithiophene cores are synthesized and named N1,N1′‐(9‐(4‐methoxyphenyl)‐9H‐carbazole‐3,6‐diyl)bis(N1‐(4‐(bis(4‐methoxyphenyl)amino)phenyl)‐N4,N4‐bis(4‐methoxyphenyl)benzene‐1,4‐diamine) (PhCz‐4MeOTPA) and N1,N1′‐(benzo[1,2‐b:4,5‐b′]dithiophene‐2,6‐diyl)bis(N1‐(4‐(bis(4‐methoxyphenyl)amino)phenyl)‐N4,N4‐bis(4‐methixyphenyl)benzene‐1,4‐diamine) (BDT‐4MeOTPA). Of the two HTMs, PhCz‐4MeOTPA possesses a lower level of planarity than that of BDT‐4MeOTPA, which inhibits molecular stacking to improve film quality and increases hole‐transport mobility and charge transport. A PCE of 16.04% is achieved with the application of dopant‐free PhCz‐4MeOTPA in PSCs, which is higher than that of dopant‐free BDT‐4MeOTPA. The unencapsulated PSC devices based on PhCz‐4MeOTPA maintain 82% of their initial values under continuous sun illumination in an ambient environment at 40–45 °C after 672 h and 92% of their initial values at 80 °C in an ambient environment after 1200 h in the dark.