bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential bias in peer review of grant applications at the Swiss National Science Foundation
Authors: Severin Anna , Martins João , Delavy François , Jorstad Anne , Egger Matthias
Published: March 2019

Background: The Swiss National Science Foundation (SNSF) supports fundamental and use-inspired research in all academic disciplines. As part of the evaluation procedure, grant applications to the SNSF are reviewed by external reviewers. The legitimacy of funding decisions depends on its ability to base funding decisions solely on the scientific merit of grant applications.

Aim: We examined whether the following factors influenced the scores given to grant applications submitted to the SNSF: (1) source of nomination of the reviewer, (2) the gender of the applicant and the reviewer, and (3) the country of affiliation of the reviewer.

Methods and Data: We gathered data on 38,250 external reviews of 12,294 unique grant applications across all disciplines between 2006 and 2016. Proposals were rated on a scale from 1 (=poor) to 6 (=outstanding) by 26,836 reviewers. We used linear mixed effects regression models adjusted for research topic, applicant’s age, nationality and affiliation.

Results: We found that in univariable analysis applicant-nominated reviewers awarded higher evaluation scores than reviewers nominated by the SNSF. Further, reviewers affiliated with research institutions outside of Switzerland gave more favourable evaluation scores than reviewers affiliated with Swiss institutions. Finally, male reviewers awarded higher evaluation scores than female reviewers and male applicants received more favourable evaluation scores than female applicants. When we controlled for confounding factors, adjusted differences changed little for source of nomination and country of affiliation. In contrast, the gender differences nearly disappeared, which indicates that most of the gender effects observed in univariable analysis is explained by differences in scores between research topics and applicant affiliations.

Conclusions: Our study showed that peer review of grant applications at SNSF may be prone to biases stemming from different applicant and reviewer characteristics. Based on this study the SNSF abandoned nomination of reviewers by applicants, and made members of panels aware of the other systematic differences in scores. We encourage other public funding bodies to conduct similar studies.
Dissociation rate compensation mechanism for budding yeast pioneer transcription factors
Authors: Donovan Benjamin T , Chen Hengye , Jipa Caroline , Bai Lu , Poirier Michael G
Published: March 2019

Nucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To understand this process mechanistically, we investigated two Saccharomyces cerevisiae TFs, Reb1 and Cbf1. We show that these factors bind to their sites within nucleosomes with similar binding affinities as to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to those for naked DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes in order to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to those of human pioneer factors (PFs), suggesting that the mechanism of nucleosome targeting is conserved from yeast to humans.
Guy1, a Y-linked embryonic signal, regulates dosage compensation in Anopheles stephensi by increasing X gene expression
Authors: Qi Yumin , Wu Yang , Saunders Randy , Chen Xiao-Guang , Mao Chunhong , Biedler James Kite , Tu Zhijian Jake
Published: March 2019

We previously showed that Guy1, a primary signal expressed from the Y chromosome, is a strong candidate for a male-determining factor that confers female-specific lethality in Anopheles stephensi (Criscione et al., 2016). Here, we present evidence that Guy1 increases X gene expression in Guy1-transgenic females from two independent lines, providing a mechanism underlying the Guy1-conferred female lethality. The median level gene expression (MGE) of X-linked genes is significantly higher than autosomal genes in Guy1-transgenic females while there is no significant difference in MGE between X and autosomal genes in wild-type females. Furthermore, Guy1 significantly upregulates at least 40% of the 996 genes across the X chromosome in transgenic females. Guy1-conferred female-specific lethality is remarkably stable and completely penetrant. These findings indicate that Guy1 regulates dosage compensation in An. stephensi and components of dosage compensation may be explored to develop novel strategies to control mosquito-borne diseases.
On prominence scale interactions in Hayu: a Harmonic Grammar account
Authors: Georgi Doreen
Published: March 2019

This paper investigates prominence scale interactions in verbal agreement in Hayu (Kiranti). The agreement system is very complex in several ways. First, the person and the number scale interact in interesting ways, i.e. they need to be ranked in order to produce the correct output in cases of conflicting preferences; second, the general ranking seems to be reversed in one particular context. This pattern poses a challenge to existing analysis of scale-driven agreement. I propose a Harmonic Grammar-based analysis where an argument’s prominence is quantified. In this way, all interactions are correctly derived. The apparent exceptions fall out automatically as cumulative effects.
Increased risk of thyroid disease in patients with Sjogren's syndrome: a systematic review and meta-analysis
Authors: Sun Xin , Lu Li , Li Yanbin , Yang Rong , Shan Ling , Wang Yang
Published: March 2019

Background

Sjogren’s syndrome (SS) is a chronic autoimmune epithelitis characterized by disruption of epithelial cells, ensuing lymphoplasmocytic infiltration of exocrine glands, and subsequent dryness of the mouth and eyes. Individuals with SS are more likely to have the thyroid disease. However, this association remains controversial. This meta-analysis aimed to evaluate the risk of thyroid disease in patients with SS.

Methods

We performed this systematic review by searching both English and Chinese literature databases. Random- or fixed-effects models were used to summarize the association between thyroid disease and SS. The results were subjected to meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

Results

The eight articles in this meta-analysis included 988 SS cases and 2,884 controls. Overall, the risk of thyroid disease in patients with SS was significantly increased compared with controls (OR, 3.29; 95% CI [2.08–5.21]). The risk of autoimmune thyroid disease (AITD) and non-AITD were also higher in patients with SS than in controls (OR, 3.48; 95% CI [1.59–7.63]; and OR, 2.90; 95% CI [1.51–5.57], respectively).

Conclusions

To the best of our knowledge, this systematic review is the first to demonstrate that the risk of thyroid disease was increased in SS compared to controls, suggesting that SS patients should be screened for thyroid disease.
Efficiency of Maize Production among Smallholder Farmers in Southwest, Nigeria
Authors: Abdulaleem M. A. , Oluwatusin F. M. , Ojo O. S.
Published: March 2019

Maize is cereal crops commonly grown in Nigeria and it is a source of livelihood for many farming households. This study analyzed the resource use efficiency in maize production among smallholder farmers in southwest, Nigeria. A multistage sampling method was used to select two hundred and seventy (270) farmers for this study. Primary data were collected using well-structured questionnaires. Descriptive statistics, gross margin analysis and stochastic frontier production function were used as analytical tools. The results showed that the mean age of the farmers was 47.7 years. Most (76.3%) are males which were married (82.2%) with household size of 5.8. There is high (82.9%) level of literacy among the farmers. The average output of production was 5,038.25kg which were gotten from planting of improved maize seeds (88.5%). Maize cultivation is profitable enterprise because for every ₦1 invested, ₦1.74will be realized as gain. The Maximum Likelihood Estimate (MLE) results revealed that the technical efficiency of maize farmers varied due to the presence of technical inefficiency effects on maize production. Farm size (5%), quantity of fertilizer (10%) and capital input (1%) are the factors significantly affecting technical efficiency. Also, household size (5%), marital status (1%) and gender (10%) are the factors that significantly influence technical inefficiency. The explanatory variables can account for 66% of the total variations in the efficiencies of production, while 34% of the variations are given to error. Policies and programmes that focus on encouraging more young people and women to agriculture should be enacted and implemented.
The Relationship between Trunk Leg Ratio and Peak Expiratory Flow Rate in 200 Level MBBS/BDS Students of Bayero University Kano
Authors: Adama Jibril I. , Ibrahim Salisu A. , Abdulmumin Y. , Zahra Mukhtar F.
Published: March 2019

Background: Being an important physiological and clinical tool in assessing respiratory conditions, it is common knowledge that Peak expiratory flow rate (PEFR) may be affected by some factors affecting the normal function of the respiratory system. Such factors include the body constitution such as height, built, sex, age etc.; The trunk-leg ratio (TLR) was used in apparently normal young adults. A better understanding of the association between Trunk-leg ratio and PEFR may identify those with elevated risk of respiratory diseases.

Methods: The study was an analytical cross-sectional design, involving 83 Level 200 MBBS/BDS students of Bayero University, Kano. There were a total of 39 males and 44 females.  A peak flow meter and a measuring tape to scale were used to measure the PEFR, trunk length and leg length respectively. A questionnaire was used to determine any history of cardio-respiratory disease A consent of the participants and ethical approval was obtained before the commencement of the study.

Results: The males had higher PEFR value (491.79±67.19L/min) while the females had a lower PEFR of 366.82±43.28L/min and the difference was statistically significant. The males had higher values of trunk length, leg length and TLR and there was no significant different between that male and female trunk length ratio. There was A significant correlation between PEFR and leg length indicating that the longer the leg length, the higher the PEFR.

Conclusion and Recommendation: Significant correlation was found between the TLR, which is an anthropometric parameter and the PEFR which is an important diagnostic tool in determination of some types of respiratory diseases. This relationship signifies that the taller the person, irrespective of the trunk length, the higher the PEFR. It is recommended that further studies should be explored involving other anthropometric parameters like trunk-leg volume in future studies.
Effectiveness of Training on Food Processing among Women in Haryana, India
Authors: . Nisha , Rani Seema
Published: March 2019

The study was conducted in seven villages purposively selected namely Dhanakurd, Ramayan and Beer Hansi from Hansi-I block, Ludas and Patan from Hisar-II block, Sulakhni and Balawas from Hisar-I block. A training program regarding food processing was very useful among trainees, with maximum training effectiveness score of picking of seasonal vegetables (WMS 2.43), preservation of fruits and vegetables (WMS 2.26), milk and milk products (WMS 2.40) and baking (WMS 2.22). Regarding the coverage of training, it was found that content of the training was considered very well covered by most of the respondents (61.54%) followed by (31.73%) respondents who considered training content as of medium level. The methodology used in training programmed was considered very well by nearly half of the respondents irrespective of the type of training. The working environment was also rated as excellent and very good by (40.00%) of the respondents. Rest of the respondents (15.38%) considered the working environment as good. Majority of the respondents found training material as very much useful and practical sessions satisfactory. Nearly half of the respondents (52.88%) were ready to start training on food processing as an income generating activity.
Cardiovascular Risk Assessment among Patients with Hypertension Presenting at a Family Medicine Clinic in Southwest Nigeria
Authors: Ilori H. T. , Adebusoye L. A. , Daramola O. O. , Ajetunmobi O. A.
Published: March 2019

Aims: To determine the 10-year cardiovascular risk (CV) and its association with socio-demographic characteristics of hypertensive patients. 

Study Design: This was a cross-sectional study.

Place and Duration of Study: Family Medicine Clinic of the University College Hospital, Ibadan, Nigeria, between June 2013 and September 2013.

Methodology: We included 345 hypertensive patients (84 men, 261 women) aged 30 years and above with no clinical history suggestive of cardiovascular disease. Data collection was with an interviewer-administered semi-structured questionnaire, physical examination and blood investigation. CV risk was determined by using General Framingham cardiovascular risk profile for use in primary care.

Results: The mean+ SD age of the 345 respondents was 57.4+9.7 years and 75.7% were female. High proportion of the respondents (42.3%) were in the high CV risk category of 10-year risk for cardiovascular disease while 27.0% and 30.7% had intermediate and low CV risk respectively.  CV risk was significantly associated with age (p < .001), sex (p < .001), family type (p= .047), level of education (p=.02), employment status (p<.001) and occupational class (p=.007). Logistic regression showed advanced age (OR=0.014, 95% CI =0.002-0.094) and male gender (OR=26.765, 95% CI = 8.802-81.383) as the predictors of high CV risk.

Conclusion: The findings show that CV risk assessment should be part of patients’ evaluation by physicians and necessary intervention should be instituted on time in order to reduce the burden of cardiovascular disease in Nigeria.
Integrating Security in Process Control Loop: A Case for Proportional-Integral-Derivative Algorithm
Authors: Weyinmi Omagbemi Oghogho , Samuel Mbonu Ekene
Published: March 2019

This work presented mathematical models and flow charts for implementing secure Proportional-Integral-Derivative (PID) algorithm in a process control loop. A number of security solutions have been recommended and some deployed in a process control system. Majority of these solutions are network based while others leverage on good security policy. A security solution based on network can be effective for securing control system from external threat agents who have to first of all, gain access to the control network. But for an internal threat agent or a disgruntled insider who does not only have the right privilege but also has a good understanding of the control system's operation, a network security is definitely not going to be effective. This work used system analysis to identify the possible things an internal threat agent can do to manipulate a control system using PID control algorithm as a case study. A secured PID mathematical model is proposed as a proactive mitigation technique to embedding security in a process control loop. As ongoing research, future work will concentrate on simulation and prototyping of the secured algorithm presented in this work. The proposed secured algorithm will not only serve as an additional security layer in industrial control system (ICS) but will also be relevant in the control domain of Internet of Things.
Sensitivity of dose‐volume indices to computation settings in high‐dose‐rate prostate brachytherapy treatment plan evaluation
Authors: van der Meer Marjolein C. , Bosman Peter A. N. , Pieters Bradley R. , Niatsetski Yury , van Wieringen Niek , Alderliesten Tanja , Bel Arjan
Published: March 2019

Purpose

To investigate the variation in computed dose‐volume (DV) indices for high‐dose‐rate (HDR) prostate brachytherapy that can result from typical differences in computation settings in treatment planning systems (TPSs).

Methods

Five factors were taken into account: number of dose‐calculation points, radioactive source description, interpolation between delineated contours, intersections between delineated organ contours, and organ shape at the top and bottom contour using either full or partial slice thickness. Using in‐house developed software, the DV indices of the treatment plans of 26 patients were calculated with different settings, and compared to a baseline setting that closely followed the default settings of the TPS used in our medical center. Studied organs were prostate and seminal vesicles, denoted as targets, and bladder, rectum, and urethra, denoted as organs at risk (OARs), which were delineated on MRI scans with a 3.3 mm slice thickness.

Results

When sampling a fixed number of points in each organ, in order to achieve a width of the 95% confidence interval over all patients of the DV indices of 1% or less, only 32,000 points had to be sampled per target, but 256,000 points had to be sampled per OAR. For the remaining factors, DV indices changed up to 0.4% for rectum, 1.3% for urethra, and 2.6% for prostate. DV indices of the bladder changed especially if the high‐dose‐region was (partly) located at the most caudal contour, up to 8.5%, and DV indices of the vesicles changed especially if there were few delineated contours, up to 9.8%, both due to the use of full slice thickness for the top and bottom contour.

Conclusions

The values of DV indices used in prostate HDR brachytherapy treatment planning are influenced by the computation settings in a TPS, especially at the most caudal part of the bladder, as well as in the seminal vesicles.
Immunotherapy with ponezumab for probable cerebral amyloid angiopathy
Authors: Leurent Claire , Goodman James A. , Zhang Yao , He Ping , Polimeni Jonathan R. , Gurol Mahmut Edip , Lindsay Monica , Frattura Linda , Sohur Usharbudh Shivraj , Viswanathan Anand , Bednar Martin M. , Smith Eric E. ,   the Ponezumab Trial Study Group, Greenberg Steven M.
Published: March 2019

Objective

Cerebral amyloid angiopathy (CAA) is caused by cerebrovascular deposition of β‐amyloid fragments leading to cerebrovascular dysfunction and other brain injuries. This phase 2, randomized, double–blind trial in patients with probable CAA assessed the efficacy and safety of ponezumab, a novel monoclonal antibody against Aβ1–40.

Methods

Thirty‐six participants aged 55–80 years with probable CAA received intravenous placebo (n = 12) or ponezumab (n = 24). The change from baseline to Days 2 and 90 in cerebrovascular reactivity (CVR) was measured in the visual cortex as the natural log of the rising slope of the BOLD fMRI response to a visual stimulus. Safety and tolerability were also assessed.

Results

The mean change from baseline to Day 90 was 0.817 (ponezumab) and 0.958 (placebo): a mean ratio of 0.852 (90% CI 0.735–0.989) representing a trend towards reduced CVR in the ponezumab group. This trend was not present at Day 2. There was one asymptomatic occurrence of amyloid–related imaging abnormality–edema in the ponezumab group. The total number of new cerebral microbleeds from baseline to day 90 did not differ between groups. The ponezumab group had a participant with nonfatal new cerebral hemorrhage with aphasia and a participant with subdural hemorrhage that site investigators deemed to be nondrug related. In the placebo group one participant had a fatal intracerebral hemorrhage and one participant had migraine with aura.

Interpretation

Ponezumab was safe and well‐tolerated. The ponezumab group showed a trend towards treatment effect at Day 90 that was opposite to the hypothesized direction. The prespecified efficacy criteria were thus not met.
Visualization analysis of heart diseases using two‐dimensional electrocardiogram sequences
Authors: Fang Ying , Ying Hang , Lai Xiaobo , Xu Xiaomei , Ruan Xinming
Published: March 2019

During the last years, there have been large advances in the understanding of cardiac mechanics, and in particular shape, motion and deformation. However, it is important to comprehend how these features interrelate and how they can be interpreted to refine the clinical diagnosis. The goal of our study is to illustrate the use of two‐dimensional ultrasound cardiac motion sequences on some typical cardiac pathologies. The method is applied to preprocessed data from two‐dimensional ultrasound sequences of four different subjects, namely, two healthy volunteers, one patient with left ventricular mechanical dyssynchrony from the left bundle branch block, and one patient with hypertrophic cardiomyopathy. The interpretation based on these features is corroborated with other analyzing techniques such as electrocardiogram and visual interpretation by experienced clinical observers. The proposed method realizes a computer program, which allows the user to easily obtain and visualize information about myocardial shape, motion (displacement and velocity), and deformation (strain) along the left ventricle myocardium wall during the cardiac cycle.
Lightweight C/SiC Ceramic Matrix Composite Structures with High Loading Capacity
Authors: Zhang Lu , Yin Dezheng , He Rujie , Yu Zejun , Zhang Keqiang , Chen Yanfei , Bai Xuejian , Yang Yazheng , Fang Daining
Published: March 2019

Lightweight is one of the key issues for ceramic matrix composites during application. A lightweight concept of lattice core sandwich panel structure is applied for C/SiC composite. In this paper, C/SiC composite lattice core sandwich panel structures with different core angles are proposed and manufactured by using precursor infiltration and pyrolysis (PIP) method. The density, microstructure, and lightweight efficiency, as well as bending behavior, out‐of‐plane compression behavior and in‐plane compression behavior of the lightweight C/SiC structures with different core angles are studied. It is found that the lightweight C/SiC composite lattice core sandwich panel structures can maintain an excellent combination of lightweight characteristic and high loading capacity. And it is believed that this work can give some understanding of C/SiC composite and their structures.
Recent Challenges in Perovskite Solar Cells Toward Enhanced Stability, Less Toxicity, and Large‐Area Mass Production
Authors: Liu Wen‐Wu , Wu Te‐Hui , Liu Mao‐Cheng , Niu Wen‐Jun , Chueh Yu‐Lun
Published: March 2019

In recent years, organic–inorganic halide perovskites have emerged as prospective materials for high‐efficiency, inexpensive, and environmentally friendly perovskite solar cells (PSCs). Despite their superiority in synthesizing route, the poor stability of PSCs with regard to humidity, heat, UV radiation, and oxygen limits their applications. Moreover, the toxicity of perovskite films and suitable ways to achieve large‐area production need to be taken into account before commercialization. Herein, reports of recent technological improvement on cell stability, interfacial modification, the substitution of electron and hole transport layers, strategies on lowering the toxicity of lead‐based perovskites, and large‐area production are summarized. The purpose of this review is to pave the way for the promising structure as well as the stability of the PSCs, and thereby promoting their commercial application.
Geometry‐Dependent Nonequilibrium Steady‐State Diffusion and Adsorption of Lipid Vesicles in Micropillar Arrays
Authors: Liu Fangjie , Abel Steven M. , Collins Liam , Srijanto Bernadeta R. , Standaert Robert , Katsaras John , Collier Charles Patrick
Published: March 2019

Micro‐ and nanofabricated sample environments are useful tools for characterizing diffusion in confined aqueous environments. The steady‐state diffusion and adsorption of unilamellar lipid vesicles in arrays of hydrophilic micropillars is investigated. Gradients in the coverage of fluorescently labeled, pillar‐supported lipid films, formed from vesicle fusion, are determined from 3D z‐stack images using confocal microscopy. The gradients are the result of preferential adsorption of vesicles near the tops of the pillars, which progressively deplete them from solution as they diffuse toward the base of the array. However, the increased propensity for vesicle adsorption near the pillar tops compared to the confined spaces between pillars results in the formation of confluent supported lipid bilayers at the pillar tops that resist the adsorption of additional vesicles while leaving the pillar surfaces below available for binding. This results in a reduction in the numbers of depleted vesicles compared to what one would anticipate based on diffusive fluxes. The resulting inhomogeneous spatial profiles of lipid structures on the pillars are the result of the system being maintained in a dissipative, nonequilibrium steady state during incubation of the pillar arrays in the vesicle solution, which is ultimately quenched by rinsing away the unbound, freely diffusing vesicles.
Optical Control of Ferroelectric Domains: Nanoscale Insight into Macroscopic Observations
Authors: Vats Gaurav , Bai Yang , Zhang Dawei , Juuti Jari , Seidel Jan
Published: March 2019

Domain wall nanoelectronics constitutes a potential paradigm shift for next‐generation energy conversion and von‐Neumann devices. In this context, attempts have been made to achieve energy‐efficient control over ferromagnetic, ferroelectric, and ferroelastic domain walls through electric and magnetic fields or applied stress. However, optical control of ferroic domains offers an additional degree of freedom and significant advantages of reduced hysteresis and Joule heating losses, creating novel opportunities in the regime of nanoelectronics and photonics. Herein, the reversible optical control of ferroelectric domains and domain walls in a novel band‐gap‐engineered lead‐free ferroelectric ceramic ((K0.5Na0.5)NbO3–2 mol% Ba(Ni0.5Nb0.5)O3−δ
) is demonstrated. The optical poling behaves similar to electrical poling and is governed by the bulk ferroelectric photovoltaic effect. The light‐generated charge carriers are transported toward domain walls or electrodes due to a nonzero field in the samples. This causes a change in internal electric field influencing the nanoscale state of polarization, which could also be interesting for other ferroelectrics if the voltage generated by light is in the range of the switching voltages. This work establishes a relationship between light‐induced macroscopic observations and nanoscale changes in the ferroelectric response, providing fundamental insight and facilitating research into ferroelectric photovoltaics and optoelectronics.
Micro‐CT assessment of dental mineralization defects indicative of vitamin D deficiency in two 17th–19th century Dutch communities
Authors: Veselka Barbara , Brickley Megan B. , D'Ortenzio Lori , Kahlon Bonnie , Hoogland Menno L. P. , Waters‐Rist Andrea L.
Published: March 2019

Objectives

This study investigates vitamin D deficiency patterns in individuals from birth to the beginning of adolescence. Microscopic computed tomography (micro‐CT) evaluation of interglobular dentine (IGD) in teeth provides information on the age of disease onset and the number of deficient periods per individual, which will increase our understanding of factors influencing vitamin D deficiency prevalence, including sociocultural practices and latitude.

Materials and methods

Beemster and Hattem, two Dutch 17th–19th century communities, yielded relatively high prevalences of rickets (15–24%) and residual rickets (15–24%). From the affected individuals, a subsample of 20 teeth were selected for micro‐CT scanning. Thin sections were made of 17 teeth, consisting of 6 teeth with and 11 teeth without observable IGD on micro‐CT that were included for method comparison.

Results

About 19 out of 29 (65.5%) individuals (one tooth was deemed unobservable) presented with IGD on micro‐CT. Eight of the 11 (72.7%) individuals without IGD on micro‐CT demonstrated histologically visible IGD. In 40.7% (11/27) of the affected individuals (combined micro‐CT and histology results), vitamin D deficiency was recurrent, and in four individuals, some episodes occurred at approximately annual intervals suggesting vitamin D deficiency was seasonal. In three individuals, IGD occurred in the dentine formed around birth, suggesting maternal vitamin D deficiency.

Discussion

Micro‐CT analysis of IGD is found to be a valuable non‐destructive method that can improve our understanding of the influence of sociocultural practices and latitude on disease development within age and sex groups in past communities.
Freisetzung der Spannung kondensierter Fünfringe des Fullerenkäfigs durch chemische Funktionalisierung
Authors: Guan Runnan , Chen Muqing , Jin Fei , Yang Shangfeng
Published: March 2019

Ein Übersichtsartikel, der sich speziell mit der Stabilisierung kondensierter Fünfringe bei vor 2009 isolierten Fullerenen befasst, wurde von Xie et al. 2009 veröffentlicht. In diesem Aufsatz geben wir nun einen allgemeinen Überblick über Fullerene, die kondensierte Fünfringe enthalten, wobei wir uns auf die hochinteressanten neuen Fortschritte auf diesem Themengebiet seit 2009 konzentrieren. Anhand einer vollständigen Auflistung aller bisher beschrieben Arten von Fullerenen mit kondensierten Fünfringen werden wir verdeutlichen, wie die Spannung kondensierter Fünfringe auf unterschiedliche Weise freigesetzt werden kann. Wir werden außerdem die Auswirkungen der kondensierten Fünfringe auf die Stabilität, die elektronischen Eigenschaften und die chemische Reaktivität des Fullerenkäfigs diskutieren und damit ein tiefgehendes Verständnis der Rolle kondensierter Fünfringe ermöglichen. Am Schluss werden wir die Perspektiven von Fullerenen mit kondensierten Fünfringen erörtern, insbesondere ungeklärte Fragen wie die Stabilität reiner, leerer Nicht‐IPR‐Fullerene und deren Bildungsmechanismen.
In Situ Engineering of Intracellular Hemoglobin for Implantable High‐Performance Biofuel Cells
Authors: Chen Huifeng , Bai Zhengyu , Dai Xianqi , Zeng Xiaoqiao , Cano Zachary P. , Xie Xiaoxiao , Zhao Mingyu , Li Matthew , Wang He , Chen Zhongwei , Yang Lin , Lu Jun
Published: March 2019

The key challenge for the broad application of implantable biofuel cells (BFCs) is to achieve inorganic–organic composite biocompatibility while improving the activity and selectivity of the catalysts. We have fabricated nanoengineered red blood cells (NERBCs) by an environmentally friendly method by using red blood cells as the raw material and hemoglobin (Hb) embedded with ultrasmall hydroxyapatite (HAP, Ca10(PO4)6(OH)2) as the functional BFC cathode material. The NERBCs showed greatly enhanced cell performance with high electrocatalytic activity, stability, and selectivity. The NERBCs maintained the original biological properties of the natural cell, while enhancing the catalytic oxygen reduction reaction (ORR) through the interaction between −OH groups in HAP and the Hb in RBCs. They also enabled direct electron transportation, eliminating the need for an electron‐transfer mediator, and showed catalytic inactivity for glucose oxidation, thus potentially enabling the development of separator‐free BFCs.
(3‐Oxo‐[1,2,4]triazolidin‐1‐yl)bis (butane‐1‐sulfonic acid) functionalized magnetic γ‐Fe2O3 nanoparticles: A novel and heterogeneous nanocatalyst for one‐pot and efficient four‐component synthesis of novel spiro[indeno[1,2‐b]quinoxaline derivatives
Authors: Mohammadi Hadi , Shaterian Hamid Reza
Published: March 2019

The efficient synthesis of novel spiro[indeno[1,2‐b]quinoxaline derivatives via the four‐component condensation of amines, ninhydrin, isatoic anhydride, and о‐phenylenediamine derivatives catalyzed by (3‐oxo‐[1,2,4]triazolidin‐1‐yl)bis (butane‐1‐sulfonic acid) supported on γ‐Fe2O3 as novel heterogenous magnetic nanocatalyst was described. The novel nanocatalyst was characterized by X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FT‐IR), vibrating sample magnetometry (VSM), Field Emission Scanning Electron Microscopy (FE‐SEM), and thermal analysis (TGA‐DTG). The nanoparticles covered by (3‐oxo‐[1,2,4]triazolidin‐1‐yl)bis (butane‐1‐sulfonic acid) showed enhanced catalytic performance in the preparation of spiro[indeno[1,2‐b]quinoxaline derivatives in excellent yields. Moreover, this method showed several advantages such as mild conditions, high yields, easy work‐up, and being environmentally friendly. The catalyst can be easily separated from the reaction mixture by an external magnet, recycled, and reused several times without a noticeable decrease in catalytic activity.
Potential impacts of agricultural development on freshwater biodiversity in the Lake Victoria basin
Authors: van Soesbergen Arnout , Sassen Marieke , Kimsey Samuel , Hill Samantha
Published: March 2019

The Lake Victoria basin (LVB) and its tributary rivers are a major biodiversity hot spot, containing at least 234 native fish species, 135 native aquatic plant species, and 50 native freshwater mollusc species. Lake Victoria itself is home to around 500 fish species, most of which are haplochromine cichlids.

The LVB is increasingly under threat from unsustainable land conversion and the intensification of agriculture. High population growth is driving the expansion of agriculture, urbanization, and freshwater abstractions, which have a profound impact on freshwater biodiversity. In addition, increased demand for agricultural crops from domestic and international markets are likely to lead to larger agricultural operations, further threatening freshwater biodiversity.

This study explores these potential future impacts on the biodiversity found in freshwater rivers in the LVB as a result of projected future changes in land use.

A newly developed database of land‐use impacts on freshwater biodiversity is introduced, with a focus on ecological community composition data from freshwater habitats under human pressures. Impacts on freshwater biodiversity are then projected under four different scenarios of land‐use change.

Results show that land use has a significant impact on freshwater biodiversity. Freshwater biodiversity is projected to be at most risk in sub‐basins in the Tanzanian, Rwandan, and Burundian part of the LVB, such as the Kagera and Magoga/Isonga sub‐basins. Local species richness levels are particularly affected in the Magoga/Isonga sub‐basin in Tanzania, with an average loss of 10.8% across all scenarios.

Model results show the potential to identify broad spatial patterns of likely threats and pressures on freshwater ecosystems under different socio‐economic futures. The analysis of these patterns, where they are consistent and where they differ, can support the production of policy that strives to find the optimal balance between development and conservation in an uncertain future.
An Investigation of the Impact of Data Breach Severity on the Readability of Mandatory Data Breach Notification Letters: Evidence From U.S. Firms
Authors: Jackson Stephen , Vanteeva Nadia , Fearon Colm
Published: March 2019

The aim of this article is to investigate the impact of data breach severity on the readability of mandatory data breach notification letters. Using a content analysis approach to determine data breach severity attributes (measured by the total number of breached records, type of data accessed, the source of the data breach, and how the data were used), in conjunction with readability measures (reading complexity, numerical intensity, length of letter, word size, and unique words), 512 data breach incidents from 281 U.S. firms across the 2012–2015 period were examined. The results indicate that data breach severity has a positive impact on reading complexity, length of letter, word size, and unique words, and a negative impact on numerical terms. Interpreting the results collectively through the lens of impression management, it can be inferred that business managers may be attempting to obfuscate bad news associated with high data breach severity incidents by manipulating syntactical features of the data breach notification letters in a way that makes the message difficult for individuals to comprehend. The study contributes to the information studies and impression management behavior literatures by analyzing linguistic cues in notifications following a data breach incident.
Reversible Shape‐Morphing and Fluorescence‐Switching in Supramolecular Nanomaterials Consisting of Amphiphilic Cyanostilbene and Cucurbit[7]uril
Authors: Lee Eung‐Chang , Kim Hyeong‐Ju , Park Soo Young
Published: March 2019

We demonstrate a reversible shape‐morphing with concurrent fluorescence switching in the nanomaterials which are complexed with cucurbit[7]uril (CB[7]) in water. The cyanostilbene derivative alone forms ribbon‐like two‐dimensional (2D) nanocrystals with bright yellow excimeric emission in water (λem=540 nm, ΦF=42 %). Upon CB[7] addition, however, the ribbon‐like 2D nanocrystals immediately transform to spherical nanoparticles with significant fluorescence quenching and blue‐shifting (λem=490 nm, ΦF=1 %) through the supramolecular complexation of the cyanostilbene and CB[7]. Based on this reversible fluorescence switching and shape morphing, we could demonstrate a novel strategy of turn‐on fluorescence sensing of spermine and also monitoring of lysine decarboxylase activity.
An epitope‐directed antibody affinity maturation system utilizing mammalian cell survival as readout
Authors: Eguchi Akihiro , Nakakido Makoto , Nagatoishi Satoru , Kuroda Daisuke , Tsumoto Kouhei , Nagamune Teruyuki , Kawahara Masahiro
Published: March 2019

Upon developing therapeutically potent antibodies, there are significant requirements, such as increasing their affinity, regulating their epitope, and using native target antigens. Many antibody selection systems, such as a phage display method, have been developed, but it is still difficult to fulfill these requirements at the same time. Here, we propose a novel epitope‐directed antibody affinity maturation system utilizing mammalian cell survival as readout. This system is based on the competition of antibody binding, and can target membrane proteins expressed in a native form on a mammalian cell surface. Using this system, we successfully selected an affinity‐matured anti‐ErbB2 single‐chain variable fragment variant, which had the same epitope as the original one. In addition, the affinity was increased mainly due to the decrease in the dissociation rate. This novel cell‐based antibody affinity maturation system could contribute to directly obtaining therapeutically potent antibodies that are functional on the cell surface.
Efficient production of poly γ‐d‐glutamic acid from the bloom‐forming green macroalgae, Ulva sp., by Bacillus sp. SJ‐10
Authors: Kim Jang‐Ho , Lee Jong Min , Jang Won Je , Park Hae Dae , Kim Young‐Ok , Kim Chang‐Hoon , Kong In‐Soo
Published: March 2019

Numerous studies on poly γ‐d‐glutamicacid (γ‐PGA) production have investigated terrestrial renewable sources for reducing production costs, but there are no studies using waste marine resources so far. We aimed to develop a cost‐effective production method of γ‐d‐PGA by Bacillus sp. SJ‐10 using green macroalgae (Ulva sp.) as a major substrate without hydrolysis pretreatment. The SJ‐10 was shown to not only cause immediate tissue degradation of the Ulva membrane but also grew well as a sole substrate. The γ‐d‐PGA yield was 6.29 ± 0.34 g/L under optimized conditions via the response surface method, and the produced γ‐d‐PGA had a thermal decomposition temperature of 310°C and molecular weight of 250–1780 kDa. The calculated cost efficiency for the final yield was 32% when compared with complex media. Therefore, the present study provided a strategy for promoting an ecofriendly and cost‐effective means to produce γ‐d‐PGA via a marine renewable resource.
Immunoglobulin G transport increases in an in vitro blood–brain barrier model with amyloid‐β and with neuroinflammatory cytokines
Authors: Mantle Jennifer L. , Lee Kelvin H.
Published: March 2019

Immunotherapies are a promising strategy for the treatment of neurological diseases such as Alzheimer's disease (AD), however, transport of antibodies to the brain is severely restricted by the blood–brain barrier (BBB). Furthermore, molecular transport at the BBB is altered in disease, which may affect the mechanism and quantity of therapeutic antibody transport. To better understand the transport of immunotherapies at the BBB in disease, an in vitro BBB model derived from human induced pluripotent stem cells (iPSCs) was used to investigate the endocytic uptake route of immunoglobulin G (IgG). In this model, uptake of fluorescently labeled IgGs is a saturable process. Inhibition of clathrin‐mediated endocytosis, caveolar endocytosis, and macropinocytosis demonstrated that macropinocytosis is a major transport route for IgGs at the BBB. IgG uptake and transport were increased after the addition of stimuli to mimic AD (Aβ1–40 and Aβ1–42) and neuroinflammation (tumor necrosis factor‐α and interleukin‐6). Lastly, caveolar endocytosis increased in the AD model, which may be responsible for the increase in IgG uptake in disease. This study presents an iPSC‐derived BBB model that responds to disease stimuli with physiologically relevant changes to molecular transport and can be used to understand fundamental questions about transport mechanisms of immunotherapies in health and neurodegenerative disease.
Optimized protocol for the hepatic differentiation of induced pluripotent stem cells in a fluidic microenvironment
Authors: Danoy Mathieu , Bernier Myriam Lereau , Kimura Keiichi , Poulain Stephane , Kato Sachi , Mori Daiki , Kido Taketomo , Plessy Charles , Kusuhara Hiroyuki , Miyajima Atsushi , Sakai Yasuyuki , Leclerc Eric
Published: March 2019

In the present study, we evaluated the performance of different protocols for the hepatic differentiation of human‐induced pluripotent stem cells (hiPSCs) in microfluidic biochips. Strategies for complete and partial on‐chip differentiation were tested. Unlike full on‐chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared with control cultures in Petri dishes. The tissue in biochips was constituted of cells expressing either stabilin‐1 or albumin, while no stabilin‐1 was detected in controls. Functional analysis also revealed double the production rate for albumin in biochips (about 2,000 ng per day per 106 cells). Besides this, tissues obtained in biochips and controls exhibited the metabolism of a specific bile acid. Whole transcriptome analysis with nanoCAGE exhibited a differential expression of 302 genes between control and biochip cultures and a higher degree of hepatic differentiation in biochips, together with increased promoter motif activity for typical liver transcription factors such as estrogen related receptor alpha (
ESRRA), hepatic nuclear factor 1 (
HNF1A), hepatic nuclear factor 4 (
HNF4A), transcription factor 4 (
TCF4), and CCAAT enhancer binding protein alpha (
CEBPA). Gene set enrichment analysis identified several pathways related to the extracellular matrix, tissue reorganization, hypoxia‐inducible transcription factor, and glycolysis that were differentially modulated in biochip cultures. However, the presence of CK19/ALB‐positive cells and the
ɑ‐fetoprotein levels measured in the cultures still reflect primitive differentiation patterns. Overall, we identified key parameters for improved hepatic differentiation on‐chip, including the maturation stage of hepatic progenitors, inoculation density, adhesion time, and perfusion flow rate. Optimization of these parameters further led to establish a protocol for reproducible differentiation of hiPSCs into hepatocyte‐like cells in microfluidic biochips with significant improvements over Petri dish cultures.
Coping with inadvertent lysis of Escherichia coli cultures: Strains resistant to lysogeny and infection by the stealthy lysogenic phage Φ80
Authors: Srinivas Swaminath , Cronan John E
Published: March 2019

Phage Φ80 can infect Escherichia coli in a stealthy manner and persist by forming lysogens. Such Φ80 lysogens are fairly common and often go undetected unless the host is grown at temperatures below 37°C. Since low growth temperatures are required for growing temperature‐sensitive mutants and often preferred for large‐scale applications such as protein production, Φ80‐resistant strains would be useful. We report the construction of E. coli strains that cannot be efficiently lysogenized or infected by bacteriophage Φ80. These strains contain combinations of deletions or mutations in the bacterial attachment site for Φ80 integration and/or deletions in the genes required for phage absorption to the host outer membrane. These strains should help contain and prevent Φ80 infection of E. coli cultures in a laboratory or industrial setting.
Adenovirus 5 recovery using nanofiber ion‐exchange adsorbents
Authors: Turnbull Jordan , Wright Bernice , Green Nicola K. , Tarrant Richard , Roberts Iwan , Hardick Oliver , Bracewell Daniel G.
Published: March 2019

Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high‐quality virus remains a challenge. It is desirable to use the adsorption‐based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry. In this study, the behaviour of a cellulose nanofiber ion‐exchange sorbent derivatised with quaternary amine ligands at defined densities is characterised to address this. This material was selected as it has a large accessible surface area for viral particles and rapid process times. Initially, the impact of surface chemistry on infective product recovery using low (440 µmol/g), medium (750 µmol/g), and high (1029 µmol/g) ligand densities is studied. At higher densities product stability is reduced, this effect increased with prolonged adsorption durations of 24 min with just ~10% loss at low ligand density versus ~50% at high. This could be mitigated by using a high flow rate to reduce the cycle time to ~1 min. Next, the impact of ligand density on the separation's resolution was evaluated. Key to understanding virus quality is the virus particle: infectious virus particle ratio. It was found this parameter could be manipulated using ligand density and elution strategy. Together this provides a basis for viral vector separations that allows for their typically low titres and labile nature by using high liquid velocity to minimise both load and on‐column times while separating key product and process‐related impurities.