bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Highly Efficient and Stable Hole‐Transport Material‐Free Perovskite Solar Cells through Morphology and Interface Engineering: Full Ambient Process
Authors: Ke Kai , Kondamareddy Kiran Kumar , Gao Fan , Zhang Xiang , Yuan Xiao
Published: June 2019

Carbon‐based hole‐transport material (HTM)‐free perovskite solar cells (PVSCs) with low cost and high stability attract research interest. Herein, a facile way to improve the performance of HTM‐free PVSCs by employing two strategies is reported: first, adding a small amount of tetrahydrofuran (THF) in lead iodide (PbI2)/N,N‐dimethylformamide (DMF) solution to improve the quality of the perovskite film; second, introducing an ultra‐thin Al2O3 film at the interface of TiO2/perovskite to reduce charge recombination. THF is found to facilitate the formation of homogenous perovskite films with better coverage, while the ultra‐thin Al2O3 layer avoids the direct contact of TiO2 with CH3NH3PbI3. The Al2O3 layer can effectively block holes and prevent charge recombination, thus leading to a dramatic improvement of open‐circuit voltage and fill factor in PVSCs. Moreover, the PVSCs show excellent long‐term stability with no degradation for 1000 h under ambient conditions. A facile way for the future commercialization of efficient low‐cost HTM‐free PVSCs is provided.
Coverage and rate analysis in two‐tier heterogeneous networks under suburban and urban scenarios
Authors: Ghosh Arijeet , Saha Misra Iti , Kundu Anindita
Published: June 2019

Massive boost in data traffic demand and inconsistent user's behavior have necessitated modern cellular networks to evolve toward heterogeneous architectural framework consisting of macro and small cells to accommodate ever‐increasing user's density. Literature survey reveals that the deployment of additional small cells can encounter the booming coverage, capacity, and QoS constraints by maintaining the overall operational cost of the network. In this paper, at first, a suitable model based on nonhomogeneous Poisson point process (NHPPP) is designed for heterogeneous wireless network (HetNet) consisting of two‐tiers eNodeBs (Macro and Small Cell), where each of the tiers is differentiated in terms of transmitting power, eNodeB density, and supported data rate. Subsequently, analytical expressions are derived for coverage probability (CP) and average rate (AR) to assess the performance of the HetNet. The contribution of the paper further lies in integrating the K‐means clustering algorithm with NHPPP to find the optimal locations of the small cell eNodeBs for extended coverage and rate improvement. The proposed model is investigated under differently dense scenarios like urban and suburban areas in India. It establishes the requisite of an optimal number of small cells along with the traditional infrastructure to maximize the performance in terms of CP and AR. Finally, the proposed integrated model is compared with the traditional homogeneous Poisson point process (HPPP) and NHPPP for coverage and rate analysis. It is observed that the K‐means clustering algorithm in integration with NHPPP overshadows both HPPP and NHPPP in terms of coverage and rate under both urban and suburban deployment scenarios.
Transitions to greater legume inclusion in cropland: Defining opportunities and estimating benefits for the nitrogen economy
Authors: Squire Geoffrey R. , Quesada Nora , Begg Graham S. , Iannetta Pietro P. M.
Published: June 2019

Grain legumes have declined to a low base in many regions of intensified agriculture yet have the potential both to safeguard food security and satisfy rising ethical demands from food consumers. Here, the scope for legume expansion is examined in a long‐established agricultural region in eastern Scotland where grain legumes declined to <0.3% of cropped area in the 1930s and now vary around 1%. Data from the EU's Integrated Administrative and Control System (IACS) were combined with national agricultural survey to resolve uncertainties over possible restrictions to expansion following 20th‐century intensification. The grain legumes, peas and beans for animal and human consumption, were found to occupy six crop‐grass systems covering a wide range of agronomic input and geographical location. The phase of agricultural intensification between 1950 and 1990 had widened rather than restricted the systems in which they occur and could expand. Moreover, the diversity of the crop‐grass systems provides scope for complementary expansion of several products such as beans for aquaculture, pulses for human consumption, and peas for stockfeed without diminishing the areas of the most profitable crops. Among crop systems, N inputs following 20% legume inclusion would fall from the current 178 to 140 kg/ha (78.6%) at the high‐input end of the range and from 92 to 71 kg/ha (77.0%) at the low‐input end. Further reductions to 50%–60% of the existing N input to intensive crop sequences were estimated assuming a residual fixed nitrogen of 50–75 kg/ha and legume inclusion of 33%. Legume expansion would also bring a range of environmental benefits across all crop‐grass systems. While analysis using IACS brought many insights, major limitations to estimating national N‐balances were identified in lack of data on residual N following legumes, in imported animal feed and in the contribution of forage legumes to grassland.
Analysis of KRAS, NRAS, BRAF, PIK3CA and TP53 mutations in a large prospective series of locally advanced rectal cancer patients
Authors: Sclafani Francesco , Wilson Sanna Hulkki , Cunningham David , Gonzalez De Castro David , Kalaitzaki Eleftheria , Begum Ruwaida , Wotherspoon Andrew , Capdevila Jaume , Glimelius Bengt , Roselló Susana , Thomas Janet , Tait Daina , Brown Gina , Oates Jacqui , Chau Ian
Published: June 2019

Little information is available on the clinical significance of cancer‐related genes such as KRAS, NRAS, BRAF, PIK3CA and TP53 in nonmetastatic rectal cancer. We investigated mutations of these genes in a large prospective series of locally advanced rectal cancer (LARC) patients who were recruited into two phase II trials. Mutational analyses were performed with diagnostically validated methods including polymerase chain reaction, capillary electrophoresis single‐strand conformational analysis, Sanger sequencing and next‐generation sequencing. Associations between single or multiple gene mutations and clinicopathological characteristics and treatment outcomes were explored. Of these 269, 210 (78%) patients were assessable. Mutations of KRAS, NRAS, BRAF, PIK3CA and TP53 occurred in 43, 9, 4, 9 and 60% of patients, respectively. Concordance between paired biopsy and resection specimens was 82% for KRAS, 95% for NRAS, 99% for BRAF, 96% for PIK3CA and 63% for TP53. TP53 mutations were associated with extramural venous invasion on baseline MRI (78% vs. 65%, p = 0.04), poor pathological tumour regression (23% vs. 36%, p = 0.05) and a trend toward a worse 5‐year progression‐free survival (PFS; 60% vs. 74%, HR 1.59, p = 0.06). Patients with tumours harbouring mutation of TP53 and either KRAS or NRAS (32%) had a worse 5‐year PFS than those with TP53/KRAS/NRAS wild‐type tumours (54% vs. 72%, HR 1.75, p = 0.02). In univariate analysis, BRAF mutation predicted poor 5‐year overall survival only among patients treated without cetuximab (20% vs. 73%, HR 3.29, p = 0.03). This is one of the largest biomarker studies in a prospective, largely homogeneous, LARC population. Our findings are hypothesis generating and require validation in independent series.
Temporal and spatial effects and survival outcomes associated with concordance between tissue and blood KRAS alterations in the pan‐cancer setting
Authors: Mardinian Kristina , Okamura Ryosuke , Kato Shumei , Kurzrock Razelle
Published: June 2019

We investigated the impact of time interval, primary vs. metastatic biopsy site, variant allele fraction (VAF) and histology on concordance of KRAS alterations in tissue vs. circulating tumor DNA (ctDNA), and association of concordance with survival. Blood and tissue were evaluated by next‐generation sequencing in 433 patients with diverse cancers. Altogether, 101 patients (23.3%) had KRAS alterations: 56, ctDNA (12.9%); 81, tissue (18.7%); and 36, both (8.3%). The overall blood and tissue concordance rate for KRAS alterations was 85%, but was mainly driven by the large negative/negative subset. Therefore, specificity of one test for the other was high (88.1–94.3%), while sensitivity was not high (44.4–64.3%) and was lower still in patients with >6 vs. ≤2 months between blood and tissue sampling (31.0–40.9% vs. 51.2–84.0%; p = 0.14 time interval‐dependent sensitivity of blood for tissue; p = 0.003, tissue for blood). Positive concordance rate for KRAS alterations was 57.1% vs. 27.4% (colorectal vs. noncolorectal cancer; p = 0.01), but site of biopsy (primary vs. metastatic) and VAF (%ctDNA) was not impactful. The presence of KRAS alterations in both tests was independently associated with shorter survival from diagnosis (hazard ratio, 1.72; 95% confidence interval, 1.04–2.86) and from recurrent/metastatic disease (1.70; 1.03–2.81). Positive concordance of KRAS alterations between ctDNA and tissue was negatively affected by a longer time period between blood and tissue sampling and was higher in colorectal cancer than in other malignancies. The presence of KRAS alterations in both tests was an independent prognostic factor for poor survival.
Lifetime recreational moderate‐to‐vigorous physical activity and ovarian cancer risk: A case–control study
Authors: Grundy Anne , Ho Vikki , Abrahamowicz Michal , Parent Marie‐Élise , Siemiatycki Jack , Arseneau Jocelyne , Gilbert Lucy , Gotlieb Walter H. , Provencher Diane M. , Koushik Anita
Published: June 2019

Results of epidemiologic studies of physical activity and ovarian cancer risk are inconsistent. Few have attempted to measure physical activity over the lifetime or in specific age windows, which may better capture etiologically relevant exposures. We examined participation in moderate‐to‐vigorous recreational physical activity (MVPA) in relation to ovarian cancer risk. In a population‐based case–control study conducted in Montreal, Canada from 2011 to 2016 (485 cases and 887 controls), information was collected on lifetime participation in various recreational physical activities, which was used to estimate MVPA for each participant. MVPA was represented as average energy expenditure over the lifetime and in specific age‐periods in units of metabolic equivalents (METs)‐hours per week. Odds ratios (OR) and 95% confidence intervals (CI) for the relation between average MVPA and ovarian cancer risk were estimated using multivariable logistic regression models. Confounding was assessed using directed acyclic graphs combined with a change‐in‐estimate approach. The adjusted OR (95% CI) for each 28.5 MET‐hr/week increment of lifetime recreational MVPA was 1.11 (0.99–1.24) for ovarian cancer overall. ORs for individual age‐periods were weaker. When examined by menopausal status, the OR (95% CI) for lifetime MVPA was 1.21 (1.00–1.45) for those diagnosed before menopause and 1.04 (0.89–1.21) for those diagnosed postmenopausally. The suggestive positive associations were stronger for invasive ovarian cancers and more specifically for high‐grade serous carcinomas. These results do not support a reduced ovarian cancer risk associated with MVPA.
Design of graphene oxide by a one‐pot synthetic route for catalytic conversion of furfural alcohol to ethyl levulinate
Authors: Wu Jiaming , Shao Yuewen , Jing Guojian , Zhang Zhanming , Ye Zhengmao , Hu Xun
Published: June 2019

Background

Graphene oxide (GO) has abundant oxygen‐containing functionalities such as hydroxyl groups and carboxyl groups with distinct acidities. This feature makes GO a potential solid acid catalyst for the acid‐catalyzed reactions such as the production of ethyl levulinate (EL), a platform chemical, from the acid‐treatment of furfuryl alcohol (FA). The structure and functionalities of GO are closely related to its catalytic performance, and thus it is necessary to establish the relationship between the chemical structure and the catalytic properties of GO. To achieve this aim, in this work, the GO catalysts were designed by a facile one‐pot synthetic route with no subsequent modification. By controlling the parameters of oxidation process in preparation, multiple functional groups were immobilized onto graphitic substrate, significantly impacting the catalytic activity of GO in the conversion of FA to EL in an ethanol (EtOH) medium.

Results

The results showed that, the oxidation process significantly influenced the distribution of oxygen‐containing functionalities on the surface of GO. The amount of the oxygen‐containing functionalities can be adjusted by the oxidation parameters such as oxidizing agent equivalent, reaction time and temperature, while the organosulfate can only be remained at a moderate oxidation temperature. The existence of the synergistic effect between the oxygen‐containing functionalities and the organosulfate functionalities promoted the catalytic activity of GO for the acid‐catalyzed conversion of FA to EL.

Conclusions

This work provides a new strategy of design and development of functional graphene‐based catalysts for the acid‐catalyzed reactions, and lays foundation of the practicability of GO in biomass conversion. © 2019 Society of Chemical Industry
Evaluation of microleakage in class v cavities prepared by different caries removal methods
Authors: Ertürk Avunduk Ayşe T. , Bağlar Serdar
Published: June 2019

The purpose of this study was to comparatively evaluate the effects of different caries removal methods on microleakage success of class V adhesive restorations by means of light microscopy (stereomicroscope) and scanning electron microscopy (SEM) observations. Sixty‐four human teeth with class V caries that measured with DIAGNOdent were used. The samples were divided into four groups (n = 16) randomly according to caries removing methods of conventional method, Carisolv, Papacarie, and Er,Cr:YSGG laser system. The self‐etch Clearfıl SE Bond and Clearfıl Majesty Es‐II were used as restoration materials. After thermal cycles of 2,000 (5 and 55°C) samples were immersed in a 50% wt/wt AgNO3. Samples were finally imaged and scored under light microscopy and SEM, respectively. The data were statistically analyzed using Kruskal–Wallis H, pairwise comparison and Wilcoxon's T tests at 5% significance level (p < .05). Statistical analysis demonstrated that there was no significant difference between microleakage scores in dentin regions but there were significant difference between the Papacarie and Er,Cr:YSGGlaser in terms of leakage scores in enamel sites. No statistically significant difference in leakage scores emerged between light microscopy and SEM.
High‐quality sea surface temperature measurements along coast of the Bohai and Yellow Seas in China and their long‐term trends during 1960–2012
Authors: Li Yan , Mu Lin , Wang Qingyuan , Ren Guoyu , You Qinglong
Published: June 2019

As semi‐enclosed and shallow seas, the Bohai and Yellow Seas (hereafter, BYS) marine ecosystems are more easily affected by natural and anthropogenic climate changes than those in the open oceans. An accurate assessment of sea surface temperature (SST) change is crucial for the near‐shore water environment. In this work, new high‐quality monthly mean SST time series from 11 in situ coastal hydrological stations at BYS for the period of 1960–2012 have been generated. Monthly mean SST time series were initially subjected to penalized maximal t (PMT) test, using homogeneous monthly mean surface air temperature (SAT) series as references. Homogenized monthly mean SST series were obtained by adjusting all significant change points which have been supported by historic metadata. Our study shows that there are 29 significant change points in these 11 SST series. The majority of them are caused by instrument changes and station relocations—both account for about 51.7 and 31%, respectively. Then, homogeneous SST series are used to assess the long‐term trends. As the regional average, the annual mean homogeneous SST series shows a rapid warming trend, with the rate of 0.21°C/decade. Compared to the homogeneous SST series, the original SST series underestimate the long‐term trend (only 0.13°C/decade), indicating the artificial change points usually result in a warm‐bias in the early period measurements. Seasonally, the most significant warming occurs in boreal winter during the period analysed. The relationships of the significant warming in boreal winter and atmospheric circulation modes have also been investigated. Results reflect the remarkable and direct influence of the East Asian Trough (EAT) on SST along the coastal BYS.
Restructured organizational design: The secret sauce in a food manufacturer's recipe for growth
Authors: Afxentiou Georgios
Published: June 2019

The growth of new markets for a firm's products can create problems if business leaders fail to adapt their organization's structure accordingly. A consulting study of a small and medium‐size enterprise (SME) in Cyprus that produces sauces, appetizers, and salads for local and global markets underscores the influence that organizational design can have on a company's efficiency. Following an analysis of the food manufacturer's organization, the company's managers prepared a new strategic plan that clearly delineated responsibilities and called for improvements in recruitment and training, as well as investment in new technology. As a result, production processes, marketing, and product development were enhanced, boosting the organization's efficiency and market reach. The experiences of this firm suggest a number of practical lessons that could be applied to other businesses facing similar challenges.
Nitramine and nitrosamine formation is a minor pathway in the atmospheric oxidation of methylamine: A theoretical kinetic study of the CH3NH + O2 reaction
Authors: Alam Mohammad Ashraful , Ren Zhonghua , da Silva Gabriel
Published: June 2019

The atmospheric oxidation of amines proceeds via initial radical attack at C–H or N–H bonds to form carbon‐ and nitrogen‐centered radicals, respectively. It is conventionally assumed that nitrogen‐centered aminyl radicals react slowly with oxygen in the troposphere and
associate predominantly with the radicals •NO and NO2• to form toxic nitrosamines and nitramines. We have used theoretical kinetic modeling techniques to study the prototypical CH3N•H + O2 reaction and have shown that it proceeds to CH2NH + HO2• under tropospheric conditions with a rate coefficient of 3.6 × 10−17 cm3 molecule−1 s−1. Although this value is low compared to the competing NOx reactions (∼10−11 cm3 molecule−1 s−1), the much higher concentration of O2 versus NOx in air makes it the dominant process in the atmospheric oxidation of methylamine for NOx concentrations below 100 ppb. The mechanism identified here is available to amines with primary, secondary, and tertiary α carbons and suggests that they may be less likely to form nitramines and nitrosamines than is currently thought.
Corporate social responsibility: The implications of cost improvement and promotion effort
Authors: Li Chaofan , Zhou Pin
Published: June 2019

We investigate the interaction of these two strategic decisions when corporate social responsibility (CSR) is incorporated into supply chain partners' decisions. Our results show that, with a noncooperative CSR scenario, the upstream manufacturer is more aggressive in investing in innovation to reduce production costs, which strategically lowers the wholesale price to retailers, and the downstream retailer is also less reluctant to engage in more promotion efforts to induce demand in comparison with a cooperative CSR scenario. Furthermore, the customer's sensitivity to promotion effort may hurt the CSR level of each party.
KCNQ2 mutations in childhood nonlesional epilepsy: Variable phenotypes and a novel mutation in a case series
Authors: Lee Inn‐Chi , Chang Tung‐Ming , Liang Jao‐Shwann , Li Shuan‐Yow
Published: June 2019

Background

Epilepsy caused by a KCNQ2 gene mutation usually manifests as neonatal seizures during the first week of life. The genotypes and phenotypes of KCNQ2 mutations are noteworthy.

Methods

The KCNQ2 sequencings done were selected from 131 nonconsanguineous pediatric epileptic patients (age range: 2 days to 18 years) with nonlesional epilepsy.

Results

Seven (5%) index patients had verified KCNQ2 mutations: c.387+1 G>T (splicing), c.1741 C>T (p.Arg581*), c.740 C>T p.(Ser247Leu), c.853 C>A p.(Pro285Thr), c.860 C>T p.(Thr287Ile), c.1294 C>T p.(Arg432Cys), and c.1627 G>A p.(Val543Met). We found, after their paternity had been confirmed, that three patients had de novo p.(Ser247Leu), p.(Pro285Thr), and p.(Thr287Ile) mutations and neonatal‐onset epileptic encephalopathy; however, their frequent seizures remitted after they turned 6 months old. Those with the c.387+1G>T (splicing), (p.Arg581*), and p.(Val543Met) mutations presented with benign familial neonatal convulsions. In addition to their relatives, 14 patients had documented KCNQ2 mutations, and 12 (86%) had neonatal seizures. The seizures of all five patients treated with oxcarbazepine remitted.

Conclusion

KCNQ2‐related epilepsy led to varied outcomes (from benign to severe) in our patients. KCNQ2 mutations accounted for 13% of patients with seizure onset before 2 months old in our study. KCNQ2 mutations can cause different phenotypes in children. p.(Pro 285Thr) is a novel mutation, and the p.(Pro 285Thr), p.(Ser247Leu), and p.(Thr287Ile) variants can cause neonatal‐onset epileptic encephalopathy.
Mitochondria‐Mediated Pathogenesis and Therapeutics for Non‐Alcoholic Fatty Liver Disease
Authors: Li Zheng , Li Yan , Zhang Hui‐Xia , Guo Jian‐Ru , Lam Christopher Wai Kei , Wang Cai‐Yun , Zhang Wei
Published: June 2019

Non‐alcoholic fatty liver disease (NAFLD) has become a worldwide epidemic over the last decade. Remarkable progress has been made in understanding the pathogenesis of NAFLD and, subsequently, in developing medications to treat this disease. Although the mechanisms of NAFLD are complex and multifactorial, accumulating and emerging evidence indicates that mitochondria play a critical role in the pathogenesis and progression of NAFLD. Pharmacologic therapies acting on mitochondria may therefore pave the way to novel strategies for the prevention and protection against NAFLD. This review focuses on new insights into the role of hepatic mitochondrial dysfunction in NAFLD, and summarizes recent studies on mitochondria‐centric therapies for NAFLD utilizing new medications or repurposing of currently available drugs. Although some studies presented may feature controversial results or are still in lack of clinical verification, it is undoubted that medications that may spare the mitochondria from multiple levels of damage are highly promising, and have begun to be used with some degree of success.
Two‐dimensional EPID dosimetry for an MR‐linac: Proof of concept
Authors: Torres‐Xirau Iban , Olaciregui‐Ruiz Igor , van der Heide Uulke A. , Mans Anton
Published: June 2019

Purpose

At our institute, in vivo patient dose distributions are reconstructed for all treatments delivered using conventional linacs from electronic portal imaging device (EPID) transit images acquired during treatment using a simple back‐projection model. Currently, the clinical implementation of MRI‐guided radiotherapy systems, which aims for online and real‐time adaptation of the treatment plan, is progressing. In our department, the MR‐linac (Unity, Elekta AB, Stockholm, Sweden) is now in clinical use. The aim of this work is to demonstrate the feasibility of two‐dimensional (2D) EPID dosimetric verification for the magnetic resonance (MR)‐linac by comparing back‐projected EPID doses to ionization chamber (IC) array dose distributions.

Materials and methods

Our conventional back‐projection algorithm was adapted for the MR‐linac. The most important changes involve modeling of the attenuation by and scatter from the cryostat. The commissioning process involved the acquisition of square field EPID measurements using various phantom setups (varying SSD, phantom thickness, and field size). Commissioning models were created for gantry 0°, 90°, and 180° and verified by comparing EPID‐reconstructed 2D dose distributions to measurements made with the OCTAVIUS 1500 IC array (PTW, Freiburg, Germany) for two prostate and one rectum IMRT plans (25 beams total). The average of the γ parameters (y‐mean and y‐pass rate) and the dose difference at a reference point were reported. Due to their construction, the attenuation of couch, bridge, and cryostat shows a much stronger dependence on gantry angle in the MR‐linac compared to conventional linacs. We present a method to correct for these effects. This method is validated by dose reconstruction of the 25 intensity‐modulated radiation therapy beams recorded at a certain gantry angle using the model of another gantry angle, combined with the correction method.

Results

For dose verification performed at a gantry angle identical to the commissioned model, the average y‐mean and y‐pass rate values (3% global dose, 2 mm, 10% isodose) were 0.37 ± 0.07 and 98.1, 95% CI [98.1 ± 2.4], respectively. The average dose difference at the reference point was −0.5% ± 1.8%. Verification at gantry angles different from the commissioned model (i.e., using the gantry angle dependent correction) reported 0.39 ± 0.08 and 97.6, 95% CI [96.9, 98.3] average y‐mean and y‐pass rate values. The average dose difference at the reference point was −0.1% ± 1.8%.

Conclusion

The EPID dosimetry back‐projection model was successfully adapted for the MR‐linac at gantry 0°, 90°, and 180°, accounting for the presence of the MRI housing between phantom (or patient) and the EPID. A method to account for the gantry angle dependence was also tested reporting similar results.
Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database
Authors: Minassian Caroline , Williams Rachael , Meeraus Wilhelmine H. , Smeeth Liam , Campbell Oona M.R. , Thomas Sara L.
Published: June 2019

Purpose

Primary care databases are increasingly used for researching pregnancy, eg, the effects of maternal drug exposures. However, ascertaining pregnancies, their timing, and outcomes in these data is challenging. While individual studies have adopted different methods, no systematic approach to characterise all pregnancies in a primary care database has yet been published. Therefore, we developed a new algorithm to establish a Pregnancy Register in the UK Clinical Practice Research Datalink (CPRD) GOLD primary care database.

Methods

We compiled over 4000 read and entity codes to identify pregnancy‐related records among women aged 11 to 49 years in CPRD GOLD. Codes were categorised by the stage or outcome of pregnancy to facilitate delineation of pregnancy episodes. We constructed hierarchical rule systems to handle information from multiple sources. We assessed the validity of the Register to identify pregnancy outcomes by comparing our results to linked hospitalisation records and Office for National Statistics population rates.

Results

Our algorithm identified 5.8 million pregnancies among 2.4 million women (January 1987‐February 2018). We observed close agreement with hospitalisation data regarding completeness of pregnancy outcomes (91% sensitivity for deliveries and 77% for pregnancy losses) and their timing (median 0 days difference, interquartile range 0‐2 days). Miscarriage and prematurity rates were consistent with population figures, although termination and, to a lesser extent, live birth rates were underestimated in the Register.

Conclusions

The Pregnancy Register offers huge research potential because of its large size, high completeness, and availability. Further validation work is underway to enhance this data resource and identify optimal approaches for its use.
Parametrised Homotopy Theory and Gauge Enhancement
Authors: Braunack‐Mayer Vincent
Published: June 2019

We review a first‐principles derivation of Type IIA D‐brane charges from M‐theory degrees of freedom in the approximation of super rational homotopy theory.
On the presence of short‐range periodicities in protein structures that are not related to established secondary structure elements
Authors: Riziotis Ioannis G. , Glykos Nicholas M.
Published: June 2019

Standard secondary structure elements such as α‐helices or β‐sheets, are characterized by repeating backbone torsion angles (φ,ψ) at the single residue level. Two‐residue motifs of the type (φ,ψ)2 are also observed in nonlinear conformations, mainly turns. Taking these observations a step further, it can be argued that there is no a priori reason why the presence of higher order periodicities can not be envisioned in protein structures, such as, for example, periodic transitions between successive residues of the type (…‐α‐β‐α‐β‐α‐…), or (…‐β‐αL‐β‐αL‐β‐…), or (…‐α‐β‐αL‐α‐β‐αL‐…), and so forth, where the symbols (α,β,αL) refer to the established Ramachandran‐based residue conformations. From all such possible higher order periodicities, here we examine the deposited (with the PDB) protein structures for the presence of short‐range periodical conformations comprising five consecutive residues alternating between two (and only two) distinct Ramachandran regions, for example, conformations of the type (α‐β‐α‐β‐α) or (β‐αL‐β‐αL‐β), and so forth. Using a probabilistic approach, we have located several thousands of such peptapeptides, and these were clustered and analyzed in terms of their structural characteristics, their sequences, and their putative functional correlations using a gene ontology‐based approach. We show that such nonstandard short‐range periodicities are present in a large and functionally diverse sample of proteins, and can be grouped into two structurally conserved major types. Examination of the structural context in which these peptapeptides are observed gave no conclusive evidence for the presence of a persistent structural or functional role of these higher order periodic conformations.
Driven to near‐experimental accuracy by refinement via molecular dynamics simulations
Authors: Heo Lim , Arbour Collin F. , Feig Michael
Published: June 2019

Protein model refinement has been an essential part of successful protein structure prediction. Molecular dynamics simulation‐based refinement methods have shown consistent improvement of protein models. There had been progress in the extent of refinement for a few years since the idea of ensemble averaging of sampled conformations emerged. There was little progress in CASP12 because conformational sampling was not sufficiently diverse due to harmonic restraints. During CASP13, a new refinement method was tested that achieved significant improvements over CASP12. The new method intended to address previous bottlenecks in the refinement problem by introducing new features. Flat‐bottom harmonic restraints replaced harmonic restraints, sampling was performed iteratively, and a new scoring function and selection criteria were used. The new protocol expanded conformational sampling at reduced computational costs. In addition to overall improvements, some models were refined significantly to near‐experimental accuracy.
Fabrication of Medium Power Insulated Gate Bipolar Transistors Using 300 mm Magnetic Czochralski Silicon Wafers
Authors: Schulze Hans-Joachim , Öfner Helmut , Niedernostheide Franz-Josef , Lükermann Florian , Schulz Andreas
Published: June 2019

The use of silicon wafer substrates with a diameter of 300 mm for the manufacturing of electronic devices strongly increases the overall productivity of a device manufacturing line. However, float‐zone (FZ) silicon, which is traditionally used for insulated gate bipolar transistors (IGBTs), is not available for wafer diameters exceeding 200 mm. Therefore, a silicon material fabricated by the magnetic Czochralski (m:Cz) method has to be used for IGBT production on 300 mm wafers. Critical issues of this material are the so‐called crystal originated particles (COPs) and the strong axial variation of the doping level along the crystal. Furthermore, the m:Cz material contains a relatively high concentration of oxygen so that the influence of carbon/oxygen complexes has to be considered. CIOI complexes can be decorated with hydrogen atoms, resulting in donor‐like complexes. In particular, the application of proton irradiation for the doping of the field‐stop zone results in a relatively high concentration of interstitial carbon, which is continuatively associated with the generation of undesired donors. It is shown that the electrical behavior of IGBTs fabricated on FZ substrates can be well reproduced using the m:Cz material if the parameters of the hydrogen implantation are adjusted appropriately.
Fast quantum crystallography
Authors: Polkosnik Walter , Matta Chérif F. , Huang Lulu , Massa Lou
Published: June 2019

Typical contemporary X‐ray crystallography delivers the geometries and, at best, the electron densities of molecules or periodic systems in the crystalline phase. Energies, electron momentum densities, and information relating to the pair density such as electron delocalization measures—all crucial to chemistry—are simply missed. Quantum crystallography (QCr) is an emerging line of research aimed at filling this gap by solving the crystallographic problem under the constraints of quantum mechanics. In this way, not only geometries and electron densities become experimentally accessible but also the entire panoply of quantum mechanical properties that are in the output of any quantum chemical software package. However, QCr remains limited to smaller systems (small molecules or small unit cells) due to the exponential bottleneck that plagues quantum mechanical calculations. When combined with a fragmentation technique, termed the “kernel energy method (KEM)”, QCr's reach to larger molecules is extended considerably to almost “any size”, that is, systems of up to many hundreds of thousands of atoms. KEM has made this doable with any chemical model and is capable of providing the entire quantum mechanics of large molecular systems. The smallness of theR‐factor adjudicates the accuracy of the quantum mechanics extracted from the crystallography.
Nonadiabatic coupling and diabatic electronic population dynamics on 11A2 and 11B1 states of ozone molecule
Authors: Mirzaie‐Khalilabadi Elahe , Dehestani Maryam
Published: June 2019

In this work, we examine nonadiabatic population dynamics for 11B1 and 11A2 states of ozone molecule (O3). In O3, two lowest singlet excited states, 1A2 and 1B1, can be coupled. Thus, population transfer between them occurs through the seam involving these two states. At any point of the seam (conical intersection), the Born‐Oppenheimer approximation breaks down, and it is necessary to investigate nonadiabatic dynamics. We consider a linear vibronic coupling Hamiltonian model and evaluate vibronic coupling constant, diabatic frequencies for three modes of O3, bilinear and quadratic coupling constants for diabatic potentials, displacements, and Huang‐Rhys coupling constants using ab initio calculations. The electronic structure calculations have been performed at the multireference configuration interaction and complete active space with second‐order perturbation theory with a full‐valence complete active space self‐consistent field methods and augmented Dunning's standard correlation‐consistent‐polarized quadruple zeta basis set to determine ab initio potential energy surfaces for the ground state and first two excited states of O3, respectively. We have chosen active space comprising 18 electrons distributed over 12 active orbitals. Our calculations predict the linear vibronic coupling constant 0.123 eV. We have obtained the population on the 11B1 and 11A2 excited electronic states for the first 500 fs after photoexcitation.
A counterexample to the DeMarco‐Kahn upper tail conjecture
Authors: Šileikis Matas , Warnke Lutz
Published: June 2019

Given a fixed graph H, what is the (exponentially small) probability that the number XH of copies of H in the binomial random graph Gn,p is at least twice its mean? Studied intensively since the mid 1990s, this so‐called infamous upper tail problem remains a challenging testbed for concentration inequalities. In 2011 DeMarco and Kahn formulated an intriguing conjecture about the exponential rate of decay of  for fixed ε > 0. We show that this upper tail conjecture is false, by exhibiting an infinite family of graphs violating the conjectured bound.
Fabrication of Sulfur‐Incorporated Bismuth‐Based Perovskite Solar Cells via a Vapor‐Assisted Solution Process
Authors: Li Jihong , Liu Xiaolong , Xu Jia , Chen Jing , Zhao Chenxu , Salma Maneno Masawa , Zhang Bing , Yao Jianxi
Published: June 2019

Methylammonium (MA) bismuth iodide ((CH3NH3)3Bi2I9) is a promising perovskite material for solar cell application considering the air stability and the nontoxic lead‐free molecular constitution. However, the further improvement of the device performances is prohibited by the wide bandgap (≈2.1 eV) and unsatisfied crystallinity of the (CH3NH3)3Bi2I9 films. Herein, a developed low‐pressure vapor‐assisted solution process (LP‐VASP) method is applied to obtain the sulfur‐incorporated bismuth‐based perovskites films. Due to the presence of sulfur, both the crystal quality and the energy band property are improved effectively in the as‐fabricated lead‐free perovskite films. After a systematic study of the influence of the reaction time on the device performances, the optimized reaction time is found to be 30 min, under which, the sulfur‐incorporated MA3Bi2I9‐2xSx perovskite films exhibit a reduced bandgap of 1.67 eV and a compact morphology. The corresponding optimal PCE reaches 0.152%. This study provides a new way for the incorporation of sulfur in the lead‐free bismuth‐based perovskite solar cells.
PM2.5 upregulates rat mesenteric arteries 5‐HT2A receptor via inflammatory‐mediated mitogen‐activated protein kinases signaling pathway
Authors: Wang Rong , Cao Lei , Shen Zhen‐Xing , Cao Yong‐Xiao , Yu Jun
Published: June 2019

Fine particulate matter (PM2.5) is an important environmental risk factor for cardiovascular diseases. However, little is known about the effects of PM2.5 on arteries. The present study investigated whether PM2.5 alters 5‐hydroxytryptamine (5‐HT) receptor expression and inflammatory mediators on rat mesenteric arteries, and examined the underlying mechanisms. Isolated rat mesenteric arteries segments were cultured with PM2.5 in the presence or absence of ERK1/2, JNK, and p38 pathway inhibitors. Contractile reactivity was monitored by a sensitive myograph. The expression of 5‐HT2A/1B receptors and inflammatory mediators were studied by a real‐time polymerase chain reaction and/or by immunohistochemistry. The phosphorylation of mitogen‐activated protein kinases (MAPK) pathway was detected by Western blot. Compared with the fresh or culture alone groups, 1.0 μg/mL PM2.5 cultured for 16 hours significantly enhanced contractile response induced by 5‐HT and increased 5‐HT2A receptor mRNA and protein expressions, indicating PM2.5 upregulates 5‐HT2A receptor. SB203580 (p38 inhibitor) and U0126 (ERK1/2 inhibitor) significantly decreased PM2.5‐induced elevated contraction and mRNA and protein expression of 5‐HT2A receptor. Cultured with PM2.5 significantly increased the mRNA expression of inflammatory mediators (NOS2, IL‐1β, and TNF‐α), while SB203580 decreased mRNA expression level of NOS2, IL‐1β, and TNF‐α. SP600125 (JNK inhibitor) decreased mRNA expression level of TNF‐α and IL‐1β. After PM2.5 exposure, the phosphorylation of p38 and ERK1/2 protein were increased. SB203580 and U0126 inhibited the PM2.5 caused increased phosphorylation protein of p38 and ERK1/2. In conclusion, PM2.5 induces inflammatory‐mediated MAPK pathway in artery which subsequently results in enhanced vascular contraction responding to 5‐HT via the upregulated 5‐HT2A receptors.
Cover Image, Volume 10, Issue 4
Authors: Peck Sarah A. , Hughes Katlyn D. , Victorino Jose F. , Mosley Amber L.
Published: June 2019

The cover image is based on the Advanced Review Writing a Wrong: Coupled RNA Polymerase II Transcription and RNA Quality Control by Amber Mosley, Jose Victorino, Sarah Peck, and Katlyn Burriss. https://doi.org/10.1002/wrna.1529

image
Sequentially loop-generated quark and lepton mass hierarchies in an extended Inert Higgs Doublet model
Authors: Hernández A. E. Cárcamo , Kovalenko Sergey , Pasechnik Roman , Schmidt Ivan
Published: June 2019

Abstract

Extended scalar and fermion sectors offer new opportunities for generating the observed strong hierarchies in the fermion mass and mixing patterns of the Standard Model (SM). In this work, we elaborate on the prospects of a particular extension of the Inert Higgs doublet model where the SM hierarchies are generated sequentially by radiative virtual corrections in a fully renormalisable way, i.e. without adding any non-renormalisable Yukawa terms or soft-breaking operators to the scalar potential. Our model has a potential to explain the recently observed R

K
and R

K∗ anomalies, thanks to the non universal U1X
assignments of the fermionic fields that yield non universal Z′ couplings to fermions. We explicitly demonstrate the power of this model for generating the realistic quark, lepton and neutrino mass spectra. In particular, we show that due to the presence of both continuous and discrete family symmetries in the considered framework, the top quark acquires a tree-level mass, lighter quarks and leptons get their masses at one- and two-loop order, while neutrino masses are generated at three-loop level. The minimal field content, particle spectra and scalar potential of this model are discussed in detail.
From bean collection to seed bank: transformations in heirloom vegetable conservation, 1970–1985
Authors: CURRY HELEN ANNE
Published: June 2019

In 1975, the Missouri homesteaders Kent and Diane Ott Whealy launched True Seed Exchange (later Seed Savers Exchange), a network of ‘serious gardeners’ interested in growing and conserving heirloom and other hard-to-find plant varieties, especially vegetables. In its earliest years, the organization pursued its conservation mission through member-led exchange and cultivation, seeing members’ gardens and seed collections as the best means of ensuring that heirloom varieties remained both extant and available to growers. Beginning in 1981, however, Kent Whealy began to develop a central seed repository. As I discuss in this paper, the development of this central collection was motivated in part by concerns about the precariousness of very large individual collections, the maintenance of which was too demanding to entrust to most growers. Although state-run institutions were better positioned to take on large collections, they were nonetheless unsuitable stewards because they placed limits on access. For seed savers, loss of access to varieties via their accession into a state collection could be as much an ending for treasured collections as total physical loss, as it did not necessarily enable continued cultivation. As I show here, these imagined endings inspired the adoption of a new set of conservation practices that replicated those seen in the formal genetic conservation sector, including seed banking, cold storage and safety duplication.
Attributable mortality due to fluoroquinolone and extended-spectrum cephalosporin resistance in hospital-onset Escherichia coli and Klebsiella spp bacteremia: A matched cohort study in 129 Veterans Health Administration medical centers
Authors: Suzuki Hiroyuki , Perencevich Eli N. , Livorsi Daniel J. , Alexander Bruce , Beck Brice F. , Richardson Kelly K. , Goto Michihiko
Published: June 2019

In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.
Multi-Substrate Radiocarbon Data Constrain Detrital and Reservoir Effects in Holocene Sediments of the Great Salt Lake, Utah
Authors: Bowen Gabriel J , Nielson Kristine E , Eglinton Timothy I
Published: June 2019

The radiocarbon (14C) content of simultaneously deposited substrates in lacustrine archives may differ due to reservoir and detrital effects, complicating the development of age models and interpretation of proxy records. Multi-substrate14C studies quantifying these effects remain rare, however, particularly for large, terminal lake systems, which are excellent recorders of regional hydroclimate change. We report14C ages of carbonates, brine shrimp cysts, algal mat biomass, total organic carbon (TOC), terrestrial macrofossils, andn-alkane biomarkers from Holocene sediments of the Great Salt Lake (GSL), Utah.14C ages for co-deposited aquatic organic substrates are generally consistent, with small offsets that may reflect variable terrestrial organic matter inputs to the system. Carbonates and long-chainn-alkanes derived from vascular plants, however, are ∼1000–400014C years older than other substrates, reflecting deposition of pre-aged detrital materials. All lacustrine substrates are14C-depleted compared to terrestrial macrofossils, suggesting that the reservoir age of the GSL was > 1200 years throughout most of the Holocene, far greater than the modern reservoir age of the lake (∼300 years). These results suggest good potential for multi-substrate paleoenvironmental reconstruction from Holocene GSL sediments but point to limitations including reservoir-induced uncertainty in14C chronologies and attenuation and time-shifting of some proxy signals due to detrital effects.
Oligosaccharides in goats’ milk-based infant formula and their prebiotic and anti-infection properties
Authors: Leong Andrea , Liu Zhiqian , Almshawit Hala , Zisu Bogdan , Pillidge Christopher , Rochfort Simone , Gill Harsharn
Published: June 2019

Human milk contains an abundant supply and diverse array of oligosaccharides that are known to impart significant health benefits to the nursing infant including establishment and maintenance of a healthy gut microflora, immune development and protection against gastrointestinal infections. When breastfeeding is not possible or insufficient, infant formulas are commonly used as an alternative. However, limited information is available about the presence of naturally occurring oligosaccharides in these infant formulas and their likely health benefits. The present study examined the presence of naturally occurring oligosaccharides in commercial goats’ milk-based stage 1 and stage 2 infant formulas and their prebiotic and anti-infection properties. LC/MS was used to detect and quantify oligosaccharides and their prebiotic potential was assessed by their ability, at concentrations present in reconstituted ready-to-use infant formula, to promote the growth of Bifidobacterium animalis subsp. lactis BB12, B. longum BB536, Lactobacillus acidophilus 4461 and L. casei 2607 in vitro. For anti-infection properties, the ability of goat milk oligosaccharides to prevent the adhesion of Escherichia coli NCTC 10418 and a Salmonella typhimurium isolate to Caco-2 cells was investigated. The results showed the presence of fourteen quantifiable oligosaccharides in stage 1 and stage 2 goats’ milk-based infant formula. This was similar to the number of oligosaccharides detected in the fresh goats’ milk. Of these, five were structurally similar to those found in human milk. These oligosaccharides were shown to significantly enhance the growth of bifidobacteria and lactobacilli and reduce the adhesion of E. coli NCTC 10418 and S. typhimurium to Caco-2 cells. Together, these results suggest that oligosaccharides naturally present in goats’ milk-based infant formula exhibit strong prebiotic and anti-pathogen adhesion properties and may confer gut health benefits to infants.