bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcineurin inhibition enhances Caenorhabditis elegans lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling
Authors: Das Priyanka , Aballay Alejandro , Singh Jogender
Published: November 2024

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension.
Synaptic interactions between stellate cells and parvalbumin interneurons in layer 2 of the medial entorhinal cortex are organized at the scale of grid cell clusters
Authors: Huang Li-Wen , Garden Derek LF , McClure Christina , Nolan Matthew F
Published: November 2024

Interactions between excitatory and inhibitory neurons are critical to computations in cortical circuits but their organization is difficult to assess with standard electrophysiological approaches. Within the medial entorhinal cortex, representation of location by grid and other spatial cells involves circuits in layer 2 in which excitatory stellate cells interact with each other via inhibitory parvalbumin expressing interneurons. Whether this connectivity is structured to support local circuit computations is unclear. Here, we introduce strategies to address the functional organization of excitatory-inhibitory interactions using crossed Cre- and Flp-driver mouse lines to direct targeted presynaptic optogenetic activation and postsynaptic cell identification. We then use simultaneous patch-clamp recordings from postsynaptic neurons to assess their shared input from optically activated presynaptic populations. We find that extensive axonal projections support spatially organized connectivity between stellate cells and parvalbumin interneurons, such that direct connections are often, but not always, shared by nearby neurons, whereas multisynaptic interactions coordinate inputs to neurons with greater spatial separation. We suggest that direct excitatory-inhibitory synaptic interactions may operate at the scale of grid cell clusters, with local modules defined by excitatory-inhibitory connectivity, while indirect interactions may coordinate activity at the scale of grid cell modules.
A scenario for an evolutionary selection of ageing
Authors: Roget Tristan , Macmurray Claire , Jolivet Pierre , Meleard Sylvie , Rera Michael
Published: November 2024

Signs of ageing become apparent only late in life, after organismal development is finalized. Ageing, most notably, decreases an individual’s fitness. As such, it is most commonly perceived as a non-adaptive force of evolution and considered a by-product of natural selection. Building upon the evolutionarily conserved age-related Smurf phenotype, we propose a simple mathematical life-history trait model in which an organism is characterized by two core abilities: reproduction and homeostasis. Through the simulation of this model, we observe (1) the convergence of fertility’s end with the onset of senescence, (2) the relative success of ageing populations, as compared to non-ageing populations, and (3) the enhanced evolvability (i.e. the generation of genetic variability) of ageing populations. In addition, we formally demonstrate the mathematical convergence observed in (1). We thus theorize that mechanisms that link the timing of fertility and ageing have been selected and fixed over evolutionary history, which, in turn, explains why ageing populations are more evolvable and therefore more successful. Broadly speaking, our work suggests that ageing is an adaptive force of evolution.
Cyber Security Risk Assessment and Optimal Risk Management of a National Vulnerability Database
Authors: Sahinoglu Mehmet
Published: November 2024

This research article focuses principally on a certain quantitative rather than qualitatively subjective and non-numerical cyber security risk assessment method, the Security Meter (SM) algorithm, to compute vital security indices in a national vulnerability database case study. The primary purpose will be followed up by a secondary, although critical, goal of managing an unfavorable risk percentage by optimally mitigating it to one selected acceptable level. This objective will be realized by an optimization method using the well-known Linear Programming (LP) technique via both SM and an alternate LP-feasible solution method, EXCEL (XL) Solver. Information and cyber security risks become essential to an organization’s or user’s daily operations in today’s IT-centric world. Vulnerabilities and threats can pose many challenges to the core security of any system, second only to the electric power grid that supplies the Internet. Without the vulnerability and associated threat-exposure management process, organizations remain blind and indifferent to those risks directly related to their IT infrastructure security. This advantage allows any organization or user (given they understand the security risks they face) to take well-advised decisions concerning remediating actions for managing the risks seriously with a cost-effective roadmap. Along with the rampant rise of the potential risks from unexpected cyber-attacks, damage due to uncountable breaches of cyber security is growing at an unprecedented rate and becoming a serious economic concern and peril to users, organizations, and nations. This research article proposes application-based quantitative analyses of commonly encountered security risks in a national vulnerability database, as initial steps toward the optimal security-centric technological investment-savvy evaluations and cost-effective decision-making processes to best manage and prioritize risk mitigation. The SM optimization results favorably compare with XL Solver solutions although SM’s cumulative percentage of countermeasure changes to achieve the mitigation target is demonstrated to be less than that of the XL Solver’s, and therefore, the more cost-optimal. As a major takeaway, the proposed quantitative algorithms are more competitive, practical, goal-oriented, functional, and cost-conscious than conventionally limited descriptive and categorical cyber security risk assessment and management options.
Highly Conductive Thin Uniform Gold‐Coated DNA Nanowires
Authors: Stern Avigail , Eidelshtein Gennady , Zhuravel Roman , Livshits Gideon I. , Rotem Dvir , Kotlyar Alexander , Porath Danny
Published: May 2018

Over the past decades, DNA, the carrier of genetic information, has been used by researchers as a structural template material. Watson‐Crick base pairing enables the formation of complex 2D and 3D structures from DNA through self‐assembly. Various methods have been developed to functionalize these structures for numerous utilities. Metallization of DNA has attracted much attention as a means of forming conductive nanostructures. Nevertheless, most of the metallized DNA wires reported so far suffer from irregularity and lack of end‐to‐end electrical connectivity. An effective technique for formation of thin gold‐coated DNA wires that overcomes these drawbacks is developed and presented here. A conductive atomic force microscopy setup, which is suitable for measuring tens to thousands of nanometer long molecules and wires, is used to characterize these DNA‐based nanowires. The wires reported here are the narrowest gold‐coated DNA wires that display long‐range conductivity. The measurements presented show that the conductivity is limited by defects, and that thicker gold coating reduces the number of defects and increases the conductive length. This preparation method enables the formation of molecular wires with dimensions and uniformity that are much more suitable for DNA‐based molecular electronics.
Low‐Cost Fabrication of Large‐Area Broccoli‐Like Multiscale Micro‐ and Nanostructures for Metallic Super‐Hydrophobic Surfaces with Ultralow Water Adhesion and Superior Anti‐Frost Ability
Authors: Long Jiangyou , He Zhijian , Zhou Peiyang , Xie Xiaozhu , Zhou Caixia , Hong Wenjie , Hu Wei
Published: May 2018

Metallic super‐hydrophobic surfaces with ultralow water adhesion are essential for a wide variety of applications, such as enhanced condensation heat transfer and anti‐icing applications. Broccoli‐like multiscale micro‐ and nanostructures composed of four different microscale and nanoscale features are fabricated on different metal surfaces by an inexpensive nanosecond laser system in this study. The surface shows high stability during evaporation, and the surface water adhesion of this structure is only 1.4 ± 0.4 µN, much lower than that of typical reported surfaces. Slight changes to the surface morphology results in an increase in the surface water adhesion, and this unique broccoli‐like surface structure shows an much better anti‐frost ability compared with similar structures with slightly higher water adhesion. The results provide a cost‐effective method to achieve large‐area metallic super‐hydrophobic surfaces with extremely low water adhesion and superior anti‐frost ability.
Iron‐Catalyzed exo‐Selective Synthesis of Cyanoalkyl Indolines via Cyanoisopropylarylation of Unactivated Alkenes
Authors: Li Yanni , Chang Yu , Li Yufen , Cao Cheng , Yang Jinshuang , Wang Baoling , Liang Deqiang
Published: May 2018

An iron‐catalyzed cyanoalkylation using azobisisobutyronitrile (AIBN) is reported. With unactivated double bond as the radical acceptor, N‐allyl anilines underwent cyanoisopropylation/cyclization cascade to afford 3‐cyanoalkyl indolines bearing a tertiary nitrile moiety, which were otherwise unavailable. Excellent exo‐selectivity was always observed, and such a selectivity and the unusual performance of the iron catalyst might be related to the metal bridging between the radical and the substrate.

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µ‐Graphene Crosslinked CsPbI3 Quantum Dots for High Efficiency Solar Cells with Much Improved Stability
Authors: Wang Qian , Jin Zhiwen , Chen Da , Bai Dongliang , Bian Hui , Sun Jie , Zhu Ge , Wang Gang , Liu Shengzhong (Frank)
Published: May 2018

All‐inorganic perovskite CsPbI3 quantum dots (QDs) offer much better stability for photovoltaic applications. Unfortunately, their cell efficiencies are hindered by the low carrier transport efficiency of QD‐assembled films. In addition, agglomeration‐induced phase change of QDs poses another problem for material and device degradation. Herein, the use of µ‐graphene (µGR) to crosslink QDs to form µGR/CsPbI3 film is demonstrated. It is found that the resultant QDs film provides not only an effective channel for carrier transport, as witnessed by much improved conductivity but also significantly better stability against moisture, humidity, and high temperature stresses. The µGR/CsPbI3 based solar cell shows increased device performance. More specifically, compared to the solar cell without the µGR treatment, VOC is improved to 1.18 from 1.16 V, JSC to 13.59 from 13.17 mA cm−2, and FF to 72.6 from 68.1%, and overall power conversion efficiency to as high as 11.40 from 10.41%, a 12% increase. In addition, the instability originating from the thermal/moisture‐induced QD agglomeration is also greatly suppressed by the µGR crosslinking. The optimized device retains >98% of its initial efficiency after being stored in N2 atmosphere for one month. Importantly, under 60% humidity and 100 °C thermal stresses, the µGR/CsPbI3 devices show much better stability.
Low‐Cost N,N′‐Bicarbazole‐Based Dopant‐Free Hole‐Transporting Materials for Large‐Area Perovskite Solar Cells
Authors: Yin Chengrong , Lu Jianfeng , Xu Yachao , Yun Yikai , Wang Kai , Li Jiewei , Jiang Liangcong , Sun Jingsong , Scully Andrew D. , Huang Fuzhi , Zhong Jie , Wang Jianpu , Cheng Yi‐Bing , Qin Tianshi , Huang Wei
Published: May 2018

Despite the recent unprecedented development of efficient dopant‐free hole transporting materials (HTMs) for high‐performance perovskite solar cells (PSCs) on small‐area devices (≤0.1 cm2), low‐cost dopant‐free HTMs for large‐area PSCs (≥1 cm2) with high power conversion efficiencies (PCEs) have rarely been reported. Herein, two novel HTMs, 3,3′,6,6′ (or 2,2′,7,7′)‐tetrakis(N,N′‐di‐p‐methoxyphenylamine)‐N,N′‐bicarbazole (3,6 BCz‐OMeTAD or 2,7 BCz‐OMeTAD), are synthesized via an extremely simple route from very cheap raw materials. Owing to their excellent film‐forming abilities and matching energy levels, 3,6 BCz‐OMeTAD and 2,7 BCz‐OMeTAD can be successfully employed as a perfect ultrathin (≈30 nm) hole transporting layer in large‐area PSCs up to 1 cm2. The 3,6 BCz‐OMeTAD and 2,7 BCz‐OMeTAD based large‐area PSCs show highest PCEs up to 17.0% and 17.6%, respectively. More importantly, high performance large‐area PSCs based on 2,7 BCz‐OMeTAD retain 90% of the initial efficiency after 2000 h storage in an ambient environment without encapsulation.
Networks of High Performance Triboelectric Nanogenerators Based on Liquid–Solid Interface Contact Electrification for Harvesting Low‐Frequency Blue Energy
Authors: Li Xiaoyi , Tao Juan , Wang Xiandi , Zhu Jing , Pan Caofeng , Wang Zhong Lin
Published: May 2018

Blue energy harvested from the ocean is an important and promising renewable energy for the sustainable development of society. Triboelectric nanogenerators (TENGs) are considered one of the most promising approaches for harvesting blue energy. In this work, a liquid–solid‐contact triboelectric nanogenerator (LS TENG) is fabricated to enhance the friction and magnify energy output by 48.7 times, when compared with the solid–solid‐contact TENG with the same area. The buoy‐like LS TENG can harvest energy from different types of low‐frequency vibration (including up–down, shaking, and rotation movements). Moreover, the outputs of the LS TENGs network can reach 290 µA, 16 725 nC, and 300 V, and the LS TENGs network can directly power hundreds of LEDs and drive a radio frequency emitter to form a self‐powered wireless save our souls (SOS) system for ocean emergencies. This work renders an innovative and effective approach toward large‐scale blue energy harvesting and applications.
Influence of Fatty Acid Moieties of Sorbitan Esters on Polymorphic Occurrence of the Palm Mid‐Fraction
Authors: Ishibashi Chinami , Hondoh Hironori , Ueno Satoru
Published: May 2018

The influence of chain length and subcell packing of fatty‐acid moieties in sorbitan esters (SE) on the polymorphism of the palm midfraction (PMF) was examined. SE with different fatty‐acid moieties (sorbitan tripalmitate; sorbitan tristearate [STS]; and sorbitan tribehenate [STB]) were blended with PMF and PMF polymorph formation was examined using synchrotron radiation X‐ray diffraction and differential interference contrast microscopy. PMF without additives was crystallized in the β′ form under the isothermal condition at 22 °C; however, the addition of STS, which forms an α subcell structure, promoted the crystallization of PMF in the α form. In contrast, crystallization of PMF in the β′ form was accelerated by the addition of STB. These results showed that when the chain length of the fatty‐acid moiety between fat and emulsifiers was similar, the crystallization of PMF in the α form was promoted by the α subcell packing in STS crystals that were nucleated prior to PMF crystallization. In contrast, STB crystals, which have an α subcell packing, accelerated the crystallization of PMF in the β′ form because of the large difference between the chain lengths of STB and PMF. Therefore, structural similarities in both the chain length and the subcell packing are essential features that regulate the template effect, and the promotion of the crystallization of PMF in the β′ form by the addition of STB was caused by heterogeneous nucleation.
Emerging bioeconomy sectors in energy systems modeling – Integrated systems analysis of electricity, heat, road transport, aviation, and chemicals: a case study for the Netherlands
Authors: Tsiropoulos Ioannis , Hoefnagels Ric , de Jong Sierk , van den Broek Machteld , Patel Martin , Faaij André
Published: May 2018

Several studies that have assessed the role of bioenergy in the energy system have primarily focused on electricity, heat, and road transport. However, sectors that have few alternatives to biomass, namely aviation and the chemical industry, are expected to become increasingly important. We have extended a bottom‐up energy systems model with fossil‐based and bio‐based chemicals and with renewable jet fuels to assess the deployment of biomass conversion technologies in the Netherlands until 2030. The model comprises detailed cost‐structures and mid‐term developments for the energy system with detailed cost‐supply curves for biomass, renewable energy technologies, and carbon capture and storage. The framework incorporates multi‐output processes, such as biorefineries, to address cross‐sectoral synergies. To capture the uncertainty in technical progress, technology development scenarios are used to assess cost‐optimal biomass utilization pathways over time. Slow technical progress (LowTech) leads to biomass applications for heating, first‐generation biofuels from hydrotreated oils, and bio‐based chemicals based on first‐generation fermentation systems. Enhanced technology development (HighTech) allows the production of second‐generation biofuels, large volumes of diverse bio‐based chemicals and renewable jet fuels. The required biomass may range from 230 PJ (LowTech) to 300 PJ (HighTech) in 2030, supplied primarily from imported resources. Both scenarios show that, under existing policies, CO2 emissions will only gradually be reduced to reach 1990 levels (140–145 Mt CO2). Further scenario analysis is recommended to assess model sensitivity and the necessary preconditions for future biomass conversion pathways and robust directions towards the required greenhouse‐gas mitigation pathways. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd.
TfOH/Fe(OTf)3 Cocatalyzed Reaction of Arylallenes with Alcohols for Structurally Diverse Indene Derivatives
Authors: Liu Congrong , Zhang Haiyun , Ding Lianghui , Liu Juan
Published: May 2018

The indene moiety is an important unit because of its presence in many chemical catalysts, functional materials and biologically relevant molecules. Herein, we report a facile reaction of arylallenes with benzylic or allylic alcohols through TfOH/Fe(OTf)3 cocatalyzed cleavage of sp3 carbon‐oxygen. In the presence of 5 mol% TfOH and 5 mol% Fe(OTf)3, a range of arylallenes undergo carbocation initiated cyclization reaction with alkyl alcohols to give structurally diverse polysubstituted indenes in good to excellent yields. H2O is the sole byproduct that makes this transformation highly atom‐economic and environmentally benign.
Methods for Generating Vascularized Islet‐Like Organoids Via Self‐Condensation
Authors: Takahashi Yoshinobu , Takebe Takanori , Taniguchi Hideki
Published: May 2018

Despite the promise of emerging organoid‐based approaches, building additional complexity, such as the vascular network, remains a major challenge toward regenerative therapy. Recently, we developed a complex organoid engineering method by "self‐condensation," wherein mesenchymal cell–dependent contraction enables large‐scale condensation from heterotypic multiple progenitors. Here, we describe the adaptation of this protocol for generating three‐dimensional (3D) pancreatic condensates from dissociated β cell lines (MIN6) together with blood vessel–forming progenitors. This protocol achieves 3D pancreatic islet‐like organoid self‐organization with endothelialized networks through mesenchymal stem cell–dependent contraction. Transplantation of pancreatic islet‐like organoids treats diabetes in mice effectively. Given the donor shortage associated with clinical islet transplantation, our approach offers a promising alternative toward therapeutic organoid transplantation. © 2018 by John Wiley & Sons, Inc.
Derivation of Epithelial‐Only Airway Organoids from Human Pluripotent Stem Cells
Authors: McCauley Katherine B. , Hawkins Finn , Kotton Darrell N.
Published: May 2018

New protocols to efficiently generate functional airway epithelial organoids from human pluripotent stem cells (PSCs) would represent a major advance towards effective disease modeling, drug screening and cell based therapies for lung disorders. This unit describes an approach using stage‐specific signaling pathway manipulation to differentiate cells to proximal airway epithelium via key developmental intermediates. Cells are directed via definitive endoderm (DE) to anterior foregut, and then specified to NKX2‐1+ lung epithelial progenitors. These lung progenitors are purified using cell surface marker sorting and replated in defined culture conditions to form three‐dimensional, epithelial‐only airway organoids. This directed differentiation approach using serum‐free, defined media also includes protocols for evaluation of DE induction, intracellular FACS analysis of NKX2‐1 specification efficiency and enrichment, and approaches for characterization and expansion of airway organoids. Taken together, this represents an efficient and reproducible approach to generate expandable airway organoids from human PSCs for use in numerous downstream applications. © 2018 by John Wiley & Sons, Inc.
An FPGA‐based smart camera for accurate chlorophyll estimations
Authors: Pérez‐Patricio Madaín , Aguilar‐González Abiel , Camas‐Anzueto Jorge L , Morales Navarro Nestor Antonio , Grajales‐Coutiño Rubén
Published: May 2018

In this work, a new chlorophyll estimation approach based on the reflectance/transmittance from the leaf being analyzed is proposed. First, top/underside images from the leaf under analysis are captured, then, the base parameters (reflectance/transmittance) are extracted. Finally, a double‐variable linear regression model estimates the chlorophyll content. To estimate the base parameters, a novel optical arrangement is presented. On the other hand, in order to provide a portable device suitable for chlorophyll estimation under large scale food crops, we have implemented our optical arrangement and our algorithmic formulation inside an field‐programmable gate array (FPGA)‐based smart camera fabric. Experimental results demonstrated that the proposed approach outperforms (in terms of accuracy and processing speed) most previous vision‐based approaches, reaching more than 97% accuracy and delivering fast chlorophyll estimations (near 5 ms per estimation).
International telecytology: Current applications and future potential
Authors: Caron Justin E. , Ying Yong , Ye Qin , Cheng Lirong , Rao Jian Yu
Published: May 2018

International telecytology can improve patient care by increasing access to regional and international expertise in cytopathology. The majority of international telecytology studies published to date have been based on static telepathology platforms. Overall concordance rates for these studies ranged from 71% to 93%. This is comparable to the concordance rates published for other studies comparing diagnoses made by digital still images to reference glass slides, which vary from 80% to 95%. Static telepathology systems are relatively cheap and easy to use, and have the potential to increase access to international experts in developing countries with limited resources. In contrast, resource‐rich academic and private medical centers can use whole slide digital imaging (WSI) for telecytology consultation, though few studies have been published addressing this topic. International telepathology consultation services with digital whole slide image capabilities have been established at several academic medical centers including the University of Pittsburgh Medical Center (UPMC) and the University of California at Los Angeles (UCLA), through the UCLA Center for Telepathology and Digital Pathology. In a small series of 20 telecytology cases submitted to UCLA from 2014 to 2017 (10 gynecologic and 10 fine needle aspiration cases), a meaningful diagnosis was rendered for 100% of cases, with 100% concordance between the submitting institution, versus consultation diagnosis provided by UCLA. These limited results are promising, and in the future both WSI and static telecytology consultation may have a place serving clinical needs in different practice settings.
Microvascular complications in diabetes patients with heart failure and reduced ejection fraction—insights from the Beta‐blocker Evaluation of Survival Trial
Authors: Kristensen Søren L. , Rørth Rasmus , Jhund Pardeep S. , Shen Li , Lee Matthew M. Y. , Petrie Mark C. , Køber Lars , McMurray John J.V. ,   on behalf of the BEST Investigators
Published: May 2018

Aims

The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown.

Methods and results

We studied 2707 HFrEF patients in the Beta‐blocker Evaluation of Survival Trial (BEST), stratified into three groups: no diabetes and diabetes without or with microvascular complications (neuropathy, nephropathy, or retinopathy). The risks of the composite of cardiovascular death or heart failure hospitalization, and all‐cause death, were studied using Cox regression analyses adjusted for other prognostic variables. Overall, 964 (36%) patients had diabetes, of which 313 (32%) had microvascular complications. Patients with microvascular complications had more severe symptoms (New York Heart Association class IV 12% vs. 9% diabetes with no complications and 7% no diabetes), and worse quality of life (Minnesota Living with Heart Failure median score 60 vs. 54 and 51 points). In patients with diabetes and complications, the rate of the composite outcome was 50 per 100 person‐years of follow‐up (compared with 34 and 29 in those with diabetes and no microvascular complications and participants without diabetes, respectively). Compared to patients without diabetes, the adjusted hazard ratio (HR) for the composite outcome was 1.44 [95% confidence interval (CI) 1.22–1.70] and 1.18 (95% CI 1.03–1.35) for patients with diabetes with and without complications, respectively. The risk of all‐cause mortality was similarly elevated: adjusted HR 1.42 (95% CI 1.16–1.74) and 1.20 (95% CI 1.01–1.42), respectively.

Conclusion

In HFrEF, diabetes with microvascular complications is associated with worse symptoms and outcomes than diabetes without microvascular complications. Prevention of microvascular complications has the potential to improve HFrEF outcomes.
Numerical simulation of a two‐stage pulse tube refrigerator based on adiabatic model
Authors: Thejaswini M.N. , Chandan V. , Kasthurirengan S. , Vasudevan K.
Published: May 2018

Cryocoolers are devices that are capable of achieving and maintaining cryogenic temperatures for a number of applications such as high‐energy physics, cooling of superconducting magnets, sensors, high‐vacuum production, cryotronics, cryonics, and so on. All the above applications need coolers with high reliability, efficiency, low maintenance, and low cost. The absence of moving parts at the cryogenic temperatures makes the pulse tube (PT) coolers quite suitable for the above applications. In spite of considerable developments in the area of PT cryocoolers, many of the fundamental processes responsible for the cold production are not fully understood. In this work, we present the results of numerical simulations of two‐stage pulse tube refrigerators (PTR) using adiabatic flow of gas through the pulse tube system. A two‐stage PTR is the improved version of single‐stage system to achieve temperature close to 4 K. Assuming adiabatic gas flow through PTs, the algebraic equations for pressure, mass flow, and volumes at different locations have been derived and solved by a MATLAB based program. Using the above, the performance of PTR has been optimized for different operational parameters. The cooling powers predicted by the model have been compared with the experimental data, and they are in good agreement with each other.
mRNA expression of IFN‐λs in the gingival tissue of patients with chronic or aggressive periodontitis: A polymerase chain reaction study
Authors: Bilichodmath Shivaprasad , Nair Sruthi K. , Bilichodmath Rekha , Mangalekar Sachin B.
Published: May 2018

Background

Several studies have proven the existence of herpesviruses in periodontal pockets of patients with chronic or aggressive periodontitis. Recently discovered interferon lambda (IFN‐λ) has antiviral properties and is induced by herpesviruses. The present study was a quantitative analysis of messenger RNA (mRNA) expression of IFN‐λs (IFN‐λ1, IFN‐λ2, IFN‐λ3) in the gingival tissues of patients with chronic or aggressive periodontitis.

Methods

A total of 90 participants (50 men and 40 women; age range 19–50 years, mean age 31.50 ± 7.8) were categorized into three groups: healthy participants, patients with chronic periodontitis, and patients with aggressive periodontitis. mRNA expression of IFN‐λs in gingival tissues was estimated using reverse transcriptase polymerase chain reaction and was correlated with clinical parameters such as gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL).

Results

mRNA of IFN‐λ1, IFN‐λ2, and IFN‐λ3 was expressed in gingival tissues of healthy participants and in patients with chronic or aggressive periodontitis. The highest level of IFN‐λ1 was observed in patients with aggressive periodontitis (3.049 ± 9.793), whereas IFN‐λ2 (4.322 ± 11.310) and IFN‐λ3 (11.932 ± 27.479) were highest in patients with chronic periodontitis. The difference in mRNA expression of IFN‐λ1 (P = 0.008) and IFN‐λ3 (P = 0.043) among three groups was statistically significant

Conclusion

Increased quantity of IFN‐λs in patients with chronic and patients with aggressive periodontitis suggests a role in periodontitis. Variation in the expression of IFN‐λ1 and IFN‐λ3 in patients with periodontitis needs to be further evaluated. The mRNA expression of antiviral IFN‐λs in gingival tissues might enhance our understanding related to viral pathogenesis of periodontal diseases.
Dimensional evaluation of blood clot gap distances within intrabony defects following grafting and EDTA root surface treatment—experimental study in dogs
Authors: Gamal Ahmed Y. , Abdel‐Ghaffar Khaled A. , Zouair Mohamed G. , Salama Mohamed H. , El Destawy Mahmoud T.
Published: May 2018

Background

Because it is important to establish and maintain a firm blood clot to the surrounding tissues within the intrabony lesion; we have to investigate the potentials of different materials in resisting clot retraction that disrupt clot adhesion to the root surface. This study was designed to measure the gap distance created by clot retraction within the defect following intrabony defects grafting with and without root surface EDTA etching.

Methods

Eight mongrel dogs with surgically created acute‐chronic bilateral mandibular interproximal intrabony defects in the premolar‐molar areas were enrolled in this study (total 8 defects per dog). Intrabony defects were divided into four groups, the first group (OFD): control open flap debridement, the second group, (EDTA treated defects) in which debridement of the defects was followed by two minute root surface etching with a neutral 24% EDTA gel followed by two minute copious saline irrigation, the third group (only grafted defects): defects received closely packed β‐TCP of a particle size ranged from 150 to 500 mm, and the fourth group, (Graft + EDTA treated defects): defects were etched for 2 minutes with a neutral 24% EDTA gel and saline irrigation followed by intrabony defect fill of β‐TCP. Twenty four hours post treatment, animal euthanasia was carried out for histomorphometric analysis of the tooth and root side gap distances.

Results

EDTA treated group and EDTA + graft group showed statistically significant lower degree of clot shrinkage compared to both the control and only grafted group. Clot shrinkage in EDTA treated group showed no significant difference from that of the EDTA + graft group (p = 0.197). OFD and only grafted groups were found to show statistically higher clot retraction percnetage compared to both EDTA and EDTA+graft groups.

Conclusion

following intrabony defect debridement, blood clot undergoes clot retraction creating a micro gap with the root surface. EDTA root surface etching before graft application into the defect area significantly reduced the amount of gap distance.
Primary care physicians and nurses: Targets for basic periodontal education
Authors: Varela‐Centelles Pablo , Diz‐Iglesias Pedro , Estany‐Gestal Ana , Ulloa‐Morales Yaima , Bugarín‐González Rosendo , Seoane‐Romero Juan M.
Published: May 2018

Background

Early diagnosis may improve patients’ quality of life and reduce the lifelong social and financial burden inherent to treatment. Growing evidence supports the importance of a healthy periodontium in systemic health. Diagnosis depends on the patient and the healthcare professional. As many patients seek physicians’ advice first, this study aims at assessing periodontal knowledge in a general population and their primary care physicians and nurses.

Methods

This is a cross‐sectional study using an anonymous questionnaire applied to randomly selected laypersons (March to June 2016), and to physicians and nurses at their workplaces (October to December 2016) in Ourense, Spain. Sample size for the general population was determined by quota sampling.

Results

A total of 1,469 people entered the study. All healthcare workers and 624 (47.1%) laypersons were familiar with periodontitis. Bacterial etiology of periodontitis was recognized by 25 (4%) laypersons, 23 (34.3%) physicians, and 11 (16.6%) nurses. The following periodontal problems were experienced: 1) gingival redness: laypersons 14.4%, physicians 16.4%, and nurses 21.2%; 2) gingival bleeding: laypersons 22.2%, physicians 50.7%, and nurses 50%; 3) tooth mobility: laypersons 34.9%, physicians 7.4%, and nurses 6%; and 4) bleeding while toothbrushing: laypersons 44.3%, physicians 8.9%, and nurses 15.1%. More than a third of laypersons (37%) think periodontitis is related to other health problems, together with 53% of physicians and 47% of nurses.

Conclusions

Our results show a low degree of periodontal knowledge both amongst the public and their primary care physicians and nurses and unveil unreliable targets (primary healthcare workers) for educational interventions to improve early diagnosis and treatment of periodontal disorders.
Evaluation of the association between the number of natural teeth and anemia among Korean adults using nationally representative data
Authors: Han Kyungdo , Park Jun‐Beom
Published: May 2018

Background

Anemia as a chronic disease is defined as anemia occurring in chronic infections with inflammatory conditions. The purpose of this study is to assess the association between the number of natural teeth and anemia using nationally representative data.

Methods

This study involved a cross‐sectional analysis using data from the Korean National Health and Nutrition Examination Survey from 2010 to 2012. A total of 16,875 respondents aged > 19 years without missing values were included in this study. The association between the number of natural teeth and anemia was evaluated by multivariable logistic regression analyses after adjusting for age, sex, body mass index, smoking habits, drinking habits, exercise levels, income levels, education levels, vitamin D levels, diabetes, toothbrushing frequency, energy intake, and percentage of fat in total energy intake among Korean adults.

Results

There was a significant decrease in prevalence of anemia and a significant increase in hemoglobin levels in participants with more natural teeth (P < 0.05). Adjusted odds ratios and their 95% confidence intervals for anemia in participants with numbers of natural teeth of < 15, 15 to 19, 20 to 24, or 24 to 28 were 1 (reference), 0.856(0.591 to 1.24), 0.659(0.5 to 0.868), and 0.607(0.463 to 0.797), respectively, with adjustment for confounding factors (P < 0.05).

Conclusion

The number of natural teeth is negatively associated with anemia in Korean adults, and the number of natural teeth may be considered an independent risk indicator of anemia.
Active matrix metalloproteinase‐8 and periodontal bacteria—interlink between periodontitis and inflammatory bowel disease?
Authors: Schmidt J. , Weigert M. , Leuschner C. , Hartmann H. , Raddatz D. , Haak R. , Mausberg R.F. , Kottmann T. , Schmalz G. , Ziebolz D.
Published: May 2018

Background

The aim of this study was the investigation of concentration and prevalence of selected periodontal pathogenic bacteria and concentration of active matrix metalloproteinase‐8 (aMMP‐8) within a group of patients with inflammatory bowel diseases (IBD) and to compare the results with a group of healthy control subjects (HC).

Methods

Fifty‐nine IBD patients with Crohn`s disease (CD, n = 30) or ulcerative colitis (UC, n = 29) and 59 HC were included in this cross‐sectional study. Based on periodontal probing depth (PD) and clinical attachment level (CAL), periodontitis was classified as healthy/mild, moderate, or severe. aMMP‐8 was analyzed from gingival crevicular fluid using enzyme linked immunosorbent assay. Eleven selected periodontal pathogenic bacteria were analyzed in subgingival plaque samples using polymerase chain reaction.

Results

IBD patients showed higher CAL (P < 0.01), more severe periodontitis (P = 0.04), gingival bleeding (P < 0.01) and aMMP‐8 concentration (P < 0.01) than HC. Only in CD, increasing severity of periodontitis was associated with an increase in aMMP‐8 concentration (P = 0.02). The prevalences of Eubacterium nodatum and Eikenella corrodens were significantly lower in IBD compared to HC (P = 0.01). Additionally, the prevalence of Eikenella corrodens was significantly higher in CD compared to the UC group (P = 0.04). Further statistically significant differences in selected bacteria between IBD and HC or CD and UC groups could not be found (P > 0.05).

Conclusions

The results reveal changes in host immune response of IBD patients in terms of aMMP‐8. Only in CD increasing aMMP‐8 was associated with severity of periodontal disease. The role of periodontal pathogenic bacteria in the interrelationship between IBD and periodontitis remains unclear.
Gene expression analysis of neuropeptides in oral mucosa during periodontal disease in non‐human primates
Authors: Ferrin John , Kirakodu Sreenatha , Jensen David , Al‐Attar Ahmad , Peyyala Rebecca , Novak M. John , Dawson Dolph , Al‐Sabbagh Mohanad , Stromberg Arnold J. , Orraca Luis , Gonzalez‐Martinez Janis , Burgos Armando , Ebersole Jeffrey L. , Gonzalez Octavio A.
Published: May 2018

Background

Neuropeptides (NPs) are innate pivotal regulators of the immunoinflammatory response. Nevertheless, their role in the pathogenesis of periodontal disease remains unknown. Changes in gene expression of 10 NPs and 16 NP receptors (NPRs) coincident with the initiation, progression, and resolution of periodontitis were determined.

Methods

The ligature‐induced periodontitis model was used in rhesus monkeys (n = 18). Gingival tissue samples were taken at baseline (preligatures), at 2 weeks and at 1 month (initiation), and at 3 months (progression) postligation. Ligatures were removed and samples taken 2 months later (resolution). Total RNA was isolated from tissues and NP/NPR gene expression microarray analysis was performed. Gene expression changes were validated by quantitative polymerase chain reaction and immunohistochemistry.

Results

Unexpectedly, the expression of pro‐inflammatory NPs/NPRs did not change during periodontitis or with resolution. However, increased expression of the anti‐inflammatory NPs adrenomedullin (ADM) and galanin (GAL), and the NPRs calcitonin receptor‐like (CALCRL) and receptor activity‐modifying protein‐2 and ‐3 (RAMP2 and RAMP3) were observed during initiation and progression of disease. The expression of the same NPs/NPRs exhibited a significant positive correlation with both molecular (interleukin‐1ß, matrix mettaloproteinase‐9, and receptor activator of nuclear factor‐kappa B ligand) and clinical measures of gingival inflammation and tissue destruction.

Conclusion

Initiation and progression of periodontitis involve significant overexpression of ADM, GAL, CALCRL, RAMP2, and RAMP3. These anti‐inflammatory NPs/NPRs could play a role in the unresolved infection and inflammation that normally drives tissue destruction in periodontitis. Both ADM and GAL potentially are new candidates to consider as biomolecules associated with periodontal disease activity.
Validity of self‐reported periodontal measures, demographic characteristics, and systemic medical conditions
Authors: Chatzopoulos Georgios S. , Cisneros Alejandro , Sanchez Miguel , Lunos Scott , Wolff Larry F.
Published: May 2018

Background

The objective of the present study was to assess self‐reported periodontal screening questions, demographic characteristics, systemic medical conditions, and tobacco use for predicting periodontal disease among individuals seeking dental therapy in a university dental clinic.

Methods

In this retrospective study, a total of 4,890 randomly selected dental charts were evaluated from among patients who had attended the University of Minnesota School of Dentistry clinics for treatment. Radiographic bone loss measurements were used to assess the severity of periodontal disease. Demographic characteristics as well as medical history of the patients were also recorded. Five self‐reported periodontal screening questions were included, with answers limited to Yes/No. Generalized logit models were used to assess the association between bone loss and the predictors.

Results

The sample's mean age was 54.1 years and included 52.6% males and 14.9% smokers, with a mean of 3.5 missing teeth. Self‐reported tooth mobility, history of “gum treatment,” and the importance of retaining teeth as well as age, tobacco use, and cancer were statistically significant predictors (P < 0.05) of a radiographic diagnosis of moderate and severe periodontal disease. With respect to severe periodontal disease, significant associations (P < 0.05) were also found with “bleeding while brushing,” gender, diabetes, anxiety, and arthritis.

Conclusions

Self‐reported periodontal screening questions as well as demographic characteristics, smoking, and systemic medical conditions were significant predictors of periodontal disease, and they could be used as valid, economic, and practical measures.
Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group
Authors: van der Sluis Inge M. , de Groot‐Kruseman Hester , te Loo Maroeska , Tissing Wim J.E. , van den Bos Cor , Kaspers Gertjan J.L. , Bierings Marc , Kollen Wouter J.W. , König Thorsten , Pichlmeier Uwe , Kühnel Hans‐Jürgen , Pieters Rob
Published: May 2018

Background

The efficacy and safety of recombinant Escherichia coli–asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac).

Methods

One hundred and ninety‐nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high‐risk patients; standard‐ and medium‐risk patients received pegaspargase).

Results

Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti‐asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5‐year event‐free survival, and 5‐year cumulative incidence of relapse did not differ between both groups.

Conclusion

The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006‐003180‐31.
Multifactorial analysis of opsoclonus‐myoclonus syndrome etiology (“Tumor” vs. “No tumor”) in a cohort of 356 US children
Authors: Pranzatelli Michael R. , Tate Elizabeth D. , McGee Nathan R.
Published: May 2018

Background

Pediatric opsoclonus‐myoclonus syndrome (OMS) presents a paradox of etiopathogenesis: A neuroblastic tumor (NB) is found in only one half of the cases, the others are ascribed to infections or designated as idiopathic.

Method

From an IRB‐approved observational study of 356 US children with OMS, secondary analysis of “etiology” and related factors was performed on a well‐characterized cohort. The “Tumor” (n = 173) and “No Tumor” groups (n = 183), as defined radiologically, were compared according to multiple factors considered potentially differentiating. Data were analyzed retrospectively using parametric and nonparametric tests as indicated.

Results

Patients with NB were not distinguishable by prodromal symptoms, OMS onset age, gender, race/ethnicity, OMS severity, rank order of neurological sign appearance, or geographic distribution. Various CSF immunologic biomarker abnormalities of OMS did not vary in the presence or absence of a detectable tumor: frequency of six lymphocyte subsets, or concentrations of 18 cytokines/chemokines, cytokine antagonists, chemokine receptors, cell adhesion molecules, or neuronal/glial markers. Prior responsiveness to conventional immunotherapy was not contingent on tumor/no tumor designation.

Conclusions

Multiple convergent factors provide compelling empirical evidence and rationalize the concept that OMS is one neurological disorder, regardless of apparent etiology. Limitations to the current clinical etiologic classifications as paraneoplastic, parainfectious/post‐infectious, and idiopathic etiology require antigen‐based biological solutions to tease out the molecular pathophysiology of viral/tumoral mechanisms. Systematic studies, regardless of presumed etiology, will be necessary to find the highest‐yield combination of imaging approaches, screening for infectious agents, and new biomarkers. Two testable hypotheses for future research are presented.