bluuebunny/crossref_metadata_2025 huggingface dataset:
Violation Prompts Treatment Changes
Authors: Chapin John C. , Adams Terry
Published: June 2018

This article discusses a project by the Cuesta La Honda Guild (CLHG), La Honda, California, to explore the use of chloramination as an alternative to free chlorine. Seasonal variations in surface water quality made the process challenging and required laboratory testing for more than a year to determine the best approach. The article discusses a pilot study by CLHG to assess the benefits of using posttreatment aeration (PTA).
Porto‐Puller Helps Prevent Injuries
Authors: Porto Nate
Published: June 2018

The valve‐can lid Porto‐puller can be used as an alternative to the hand‐held lifting tool previously used to lift 12‐in. valve‐can covers. Using the Porto‐Puller is helping to prevent injuries, reduce ergonomic stress to the upper body, and decrease the amount of labor required to open stuck lids.
Sludgeulator Cleans Up
Authors: Pickard Brian
Published: June 2018

The Sludgeulator efficiently removes sludge build‐up from sedimentation basins and squeegees the sludge toward the drains. It minimizes scraping damage to basin floors; conserves water; saves about 480 labor hours annually; decreases injury risks; and, allows plant staff more time for other duties. In addition, taste‐and‐odor problems have been reduced, and faster maintenance turnaround has increased treatment capacity. The process returns sedimentation basins and redundant systems to service sooner.
Cultivating Young Volunteers
Authors: Knox Kimberley M.
Published: June 2018

This article discusses how volunteer opportunities offered by the Washington Suburban Sanitary Commission (WSSC) created an interest in careers in watershed management by high school students. WSSC recruited high school students who needed service‐learning hours to work on its watershed, removing invasive weeds at five of its nine recreation areas. When the students began asking about careers in water and wastewater, WSSC reformatted the program to include career education. WSSC has used its volunteer program to market itself as a utility interested in working with the community's future leaders.
Eliminate Dead‐End Water
Authors: Galvin Robert
Published: June 2018

Uncirculated potable water in distribution deadends can pose a serious health problem for consumers. As this water ages, disinfectant residuals decline and disinfectant byproducts (DBPs) increase, creating health risks for consumers and regulatory issues for distribution and water quality managers. This article discusses several tools and methods that can help determine whether a dead‐end is potentially hazardous.
In‐Tank Aeration Predicts and Reduces THMs
Authors: Fiske Peter S. , Oppenheimer Jason , Moore Randall , Everett Randy
Published: June 2018

This article discusses an investigation by the city of Ballinger, Texas, to achieve a 60 percent reduction of trihalomethanes (THMs). The city and its contractor analyzed three technologies ‐ bubbler aerators, surface aerators, and spray aerators ‐ to be used in a single 250,000‐gal elevated storage tank. Because the tank was small and had rapid turnover, an aeration system would need to quickly and efficiently remove a large amount of brominated THM species. The analysis considered equipment and installation costs, as well as energy consumption and maintenance life‐cycle costs.
Water Auditing: Top‐Down vs. Bottom‐Up Approach
Authors: Leauber Chris
Published: June 2018

Intake offers Opflow readers guidelines and best practices collected from AWWA Manuals of Water Supply Practices.
Vitamin D Supplementation in Elderly Black Women Does Not Prevent Bone Loss: A Randomized Controlled Trial
Authors: Aloia John , Fazzari Melissa , Islam Shahidul , Mikhail Mageda , Shieh Albert , Katumuluwa Subhashini , Dhaliwal Ruban , Stolberg Alexandra , Usera Gianina , Ragolia Louis
Published: June 2018

Black Americans have lower levels of serum 25(OH)D but superior bone health compared to white Americans. There is controversy over whether they should be screened for vitamin D deficiency and have higher vitamin D requirements than recommended by the Institute of Medicine (IOM). The purpose of this trial was to determine whether Vitamin D supplementation in elderly black women prevents bone loss. A total of 260 healthy black American women, 60 years of age and older were recruited to take part in a two-arm, double-dummy 3-year randomized controlled trial (RCT) of vitamin D3 versus placebo. The study was conducted in an ambulatory clinical research center. Vitamin D3 dose was adjusted to maintain serum 25(OH)D above 75 nmol/L. Bone mineral density (BMD) and serum were measured for parathyroid hormone (PTH), C-terminal crosslink telopeptide (CTX), and bone-specific alkaline phosphatase (BSAP) every 6 months. Baseline serum 25(OH)D3 was 54.8 ± 16.8 nmol/L. There was no group × time interaction effect for any BMD measurement. For all BMD measurements, except for total body and spine, there was a statistically significant negative effect of time (p < 0.001). An equivalency analysis showed that the treatment group was equivalent to the control group. Serum PTH and BSAP declined, with a greater decline of PTH in the treatment group. The rate of bone loss with serum 25(OH)D above 75 nmol/L is comparable to the rate of loss with serum 25(OH)D at the Recommended Dietary Allowance (RDA) of 50 nmol/L. Black Americans should have the same exposure to vitamin D as white Americans. © 2018 American Society for Bone and Mineral Research.
Combination with miR‐124a improves the protective action of BMSCs in rescuing injured rat podocytes from abnormal apoptosis and autophagy
Authors: Sun Jiping , Lv Jing , Zhang Wenjing , Li Lili , Lv Jia , Geng Yingzhou , Yin Aiping
Published: June 2018

This in vitro study was performed to identify the role of miR‐124a in bone marrow stromal stem cells (BMSCs) therapy for H2O2‐induced rat podocyte injury, and determine whether combination treatment with miR‐124a could improve the protective effect of BMSCs. Cell viability of podocytes was detected by CCK‐8 assay. Detection of ROS level, apoptotic rate, and autophagy rate was carried out using flow cytometry assays. Oxidative stress parameters were analyzed using the ELISA assays. MiR‐124a and mRNA levels were determined using real‐time PCR. Protein expression was detected using Western blotting. Our study revealed a pivotal role of miR‐124a in the protective action of BMSCs on podocyte injury driven by oxidative stress. BMSCs could rescue injured podocytes from aberrant apoptosis and autophagy by regulating cleaved caspase‐3, Bax, Bcl‐2, LC3‐II/I, and p62. Suppression of the PI3 K/Akt/mTOR signaling pathway is likely one of the main mechanisms underlying the protective action of BMSCs transfected with miR‐124a. Our study revealed that miR‐124a further improves the protective effect of BMSCs in injured podocytes. Thus, the combination of BMSCs and microRNAs could be a beneficial treatment for renal diseases in the near future.
Actin binding LIM 1 (abLIM1) negatively controls osteoclastogenesis by regulating cell migration and fusion
Authors: Narahara Haruna , Sakai Eiko , Yamaguchi Yu , Narahara Shun , Iwatake Mayumi , Okamoto Kuniaki , Yoshida Noriaki , Tsukuba Takayuki
Published: June 2018

Actin binding LIM 1 (abLIM1) is a cytoskeletal actin‐binding protein that has been implicated in interactions between actin filaments and cytoplasmic targets. Previous biochemical and cytochemical studies have shown that abLIM1 interacts and co‐localizes with F‐actin in the retina and muscle. However, whether abLIM1 regulates osteoclast differentiation has not yet been elucidated. In this study, we examined the role of abLIM1 in osteoclast differentiation and function. We found that abLIM1 expression was upregulated during receptor activator of nuclear factor kappa‐B ligand (RANKL)‐induced osteoclast differentiation, and that a novel transcript of abLIM1 was exclusively expressed in osteoclasts. Overexpression of abLIM1 in the murine monocytic cell line, RAW‐D suppressed osteoclast differentiation and decreased expression of several osteoclast‐marker genes. By contrast, small interfering RNA‐induced knockdown of abLIM1 enhanced the formation of multinucleated osteoclasts and markedly increased the expression of the osteoclast‐marker genes. Mechanistically, abLIM1 regulated the localization of tubulin, migration, and fusion in osteoclasts. Thus, these results indicate that abLIM1 negatively controls osteoclast differentiation by regulating cell migration and fusion mediated via actin formation.
Lumichrome inhibits osteoclastogenesis and bone resorption through suppressing RANKL‐induced NFAT activation and calcium signaling
Authors: Liu Chuan , Cao Zhen , Zhang Wen , Tickner Jennifer , Qiu Heng , Wang Chao , Chen Kai , Wang Ziyi , Tan Renxiang , Dong Shiwu , Xu Jiake
Published: June 2018

The dynamic balance between bone resorption and bone formation is crucial to maintain bone mass. Osteoclasts are key cells that perform bone resorption while osteoblasts and osteocytes function in bone formation. Osteoporosis, a bone metabolism disease characterized by bone loss and degradation of bone microstructure, occurs when osteoclastic bone resorption outstrips osteoblastic bone synthesis. The interaction between receptor activator of nuclear factor κB ligand (RANKL) and RANK on the surface of bone marrow macrophages promotes osteoclast differentiation and activation. In this study, we found that lumichrome, a photodegradation product of riboflavin, inhibits RANKL‐induced osteoclastogenesis and bone resorption as determined by tartrate‐resistant acid phosphatase staining, immunofluorescence, reverse transcription‐polymerase chain reaction, and western blot. Our results showed that lumichrome represses the expression of osteoclast marker genes, including cathepsin K (Ctsk) andNfatc1. In addition, lumichrome suppressed RANKL‐induced calcium oscillations, NFATc1, NF‐κB, and MAPK signaling activation. Moreover, lumichrome promoted osteoblast differentiation at an early stage, as demonstrated by upregulated expression of osteoblast marker genesAlp,Runx2, andCol1a1. We also found that lumichrome reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis. In summary, our data suggest the potential of lumichrome as a therapeutic drug for osteolytic diseases.
Longitudinal analysis of tibiofemoral cartilage contact area and position in ACL reconstructed patients
Authors: Chen Ellison , Amano Keiko , Pedoia Valentina , Souza Richard B. , Ma C. Benjamin , Li Xiaojuan
Published: June 2018

Patients who have suffered ACL injury are more likely to develop early onset post‐traumatic osteoarthritis despite reconstruction. The purpose of our study was to evaluate the longitudinal changes in the tibiofemoral cartilage contact area size and location after ACL injury and reconstruction. Thirty‐one patients with isolated unilateral ACL injury were followed with T2 weighted Fast Spin Echo, T1ρ and T2 MRI at baseline prior to reconstruction, and 6 months, 1 year, and 2 years after surgery. Areas were delineated in FSE images with an in‐house Matlab program using a spline‐based semi‐automated segmentation algorithm. Tibiofemoral contact area and centroid position along the anterior‐posterior axis were calculated along with T1ρ and T2 relaxation times on both the injured and non‐injured knees. At baseline, the injured knees had significantly smaller and more posteriorly positioned contact areas on the medial tibial surface compared to corresponding healthy knees. These differences persisted 6 months after reconstruction. Moreover, subjects with more anterior medial centroid positions at 6 months had elevated T1ρ and T2 measures in the posterior medial tibial plateau at 1 year. Changes in contact area and centroid position after ACL injury and reconstruction may characterize some of the mechanical factors contributing to post‐traumatic osteoarthritis. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2718–2727, 2018.
Corrosion behaviour of oxide dispersion strengthened iron‐chromium steels in liquid lead at 973 K
Authors: Ricci Enrica , Giuranno Donatella , Canu Giovanna , Amore Stefano , Novakovic Rada
Published: June 2018

The corrosion behaviour of oxide dispersion strengthened (ODS) steels with different chromium contents (9, 12 and 14 wt% Cr) is investigated in stagnant liquid lead at a temperature of 973 K for 2000 h. Under an oxygen concentration close to the passivation domain (i.e. Co ∼10−5–10−4 wt% O), neither an internal oxidation zone in the steel matrix, nor dissolution attack caused by liquid lead or its penetration is observed. Indeed, thin layers of chromium rich oxides with different compositions are detected.
Pneumococcal vaccination coverage among children with sickle cell anemia, sickle cell trait, and normal hemoglobin
Authors: Reeves Sarah L. , Jary Hannah K. , Gondhi Jennifer P. , Kleyn Mary , Wagner Abram L. , Dombkowski Kevin J.
Published: June 2018

Background

Children with sickle cell anemia and sickle cell trait are at an increased risk of invasive pneumococcal disease compared to children with normal hemoglobin. We assessed and compared pneumococcal vaccination status among these three groups.

Procedure

Children with sickle cell anemia and sickle cell trait were identified using Michigan newborn screening records (1997–2014); each child was matched to four children with normal hemoglobin based on age, Medicaid enrollment (at least 1 year from 2012–2014), race, and census tract. Vaccination records were obtained from the state's immunization system. Pneumococcal vaccine coverage (PCV7 or PCV13 depending on date of administration) was assessed at milestone ages of 3, 5, 7, and 16 months. The proportion of children with vaccine coverage at each milestone was calculated overall and compared among children with sickle cell anemia, sickle cell trait, and normal hemoglobin using chi‐square tests.

Results

The study population consisted of 355 children with sickle cell anemia, 17,319 with sickle cell trait, and 70,757 with normal hemoglobin. The proportion of children with age‐appropriate pneumococcal vaccination coverage was low at each milestone and generally decreased over time. Children with sickle cell anemia were more likely to be covered compared to children with sickle cell trait or normal hemoglobin.

Conclusions

Despite higher pneumococcal vaccination coverage among children with sickle cell anemia, opportunities for improvement exist among all children. Targeted interventions will benefit from mechanisms to identify children with increased risks such as sickle cell anemia or trait to improve pneumococcal vaccination coverage among these groups.
Growth‐ and stress‐related defects associated with wall hypoacetylation are strigolactone‐dependent
Authors: Ramírez Vicente , Xiong Guangyan , Mashiguchi Kiyoshi , Yamaguchi Shinjiro , Pauly Markus
Published: June 2018

Mutants affected in the Arabidopsis TBL29/ESK1 xylan O‐acetyltransferase display a strong reduction in total wall O‐acetylation accompanied by a dwarfed plant stature, collapsed xylem morphology, and enhanced freezing tolerance. A newly identified tbl29/esk1 suppressor mutation reduces the expression of the MAX4 gene, affecting the biosynthesis of methyl carlactonoate (MeCLA), an active strigolactone (SL). Genetic and biochemical evidence suggests that blocking the biosynthesis of this SL is sufficient to recover all developmental and stress‐related defects associated with the TBL29/ESK1 loss of function without affecting its direct effect—reduced wall O‐acetylation. Altered levels of the MAX4 SL biosynthetic gene, reduced branch number, and higher levels of MeCLA, were also found in tbl29/esk1 plants consistent with a constitutive activation of the SL pathway. These results suggest that the reduction in O‐acetyl substituents in xylan is not directly responsible for the observed tbl29/esk1 phenotypes. Alternatively, plants may perceive defects in the structure of wall polymers and/or wall architecture activating the SL hormonal pathway as a compensatory mechanism.
How Does Social Capital Associate With Being a Victim of Online Hate? Survey Evidence From the United States, the United Kingdom, Germany, and Finland
Authors: Kaakinen Markus , Keipi Teo , Oksanen Atte , Räsänen Pekka
Published: June 2018

Although online hate has become a phenomenon in online interaction, we do not know how the quality of online social relations is linked to the risk of being a target of hostile behavior online. In this article, we examine how cognitive social capital online (i.e., trust and sense of belonging) is associated with the risk of being a victim of online hate by utilizing cross‐national data collected in 2013–14 among American (n = 1,033), British (n = 999), German (n = 978), and Finnish (n = 555) adolescents and young adults (aged 15–30). We find online cognitive social capital to be associated with online hate victimization in all samples, even after controlling for social capital offline, size of offline and online social networks, social networking site activity, offline victimization experiences, age, and gender. The form of this relationship varied between our samples; in the American and German samples we found a linear relationship between online cognitive social capital and online hate victimization, whereas in the British and Finnish samples, we found a more complex association. However, in general, high cognitive social capital was related to a heightened risk of becoming a victim of online hate.
Inspiromatic‐safety and efficacy study of a new generation dry powder inhaler in asthmatic children
Authors: Steuer Guy , Prais Dario , Mussaffi Huda , Mei‐Zahav Meir , Bar‐On Ophir , Levine Hagit , Gendler Yulia , Blau Hannah , Stafler Patrick
Published: June 2018

Background

Dry powder inhalers (DPI) are effective but forceful inhalation required to fluidize the powder may be difficult for children and patients with airway disease. Inspiromatic is a new generation active DPI that actively suspends drugs in synchrony with inhalation. We evaluated safety and efficacy of Formoterol delivery via Inspiromatic, compared to Aerolizer, a conventional DPI, in pediatric asthmatic subjects.

Methods

A phase I/II, randomized, single‐center, double‐blind, double‐dummy, placebo‐controlled, cross‐over study. Subjects aged 8‐18 years with FEV1 40‐80% predicted were included. Patients were randomized to inhale Formoterol via the Inspiromatic, immediately followed by the placebo via the Aerolizer or vice versa, in a double‐blind fashion. Spirometry, blood pressure, and heart rate were measured at baseline and 15, 30, and 60 min after drug administration. Capsule emptying, comfort of use, confidence in efficacy, and patient satisfaction were assessed. At a subsequent visit, three months later, patients inhaled the active drug via the other DPI.

Results

Twenty‐nine patients, aged 12.6 (±2.3) years, mean (SD), completed the study. Baseline FEV1 was 69.1 (±6.7) % at visit one and 65.3 (±9) % at visit two. Maximal FEV1 increase was 16.6 (±7.1) % with Inspiromatic and 15.5 (±7.5) % with Aerolizer (P = 0.47). No differences in heart rate or blood pressure were observed; 24/28 capsules were emptied using the Inspiromatic and 19/28 with the Aerolizer (P = 0.5); 21/28 preferred the Inspiromatic and 7/28 the Aerolizer (P < 0.001). There were no adverse events.

Conclusions

Formoterol inhalation via the Inspiromatic is safe and as efficacious as with the Aerolizer. The device is well accepted by asthmatic subjects.
PyPNS: Multiscale Simulation of a Peripheral Nerve in Python
Authors: Lubba Carl H. , Le Guen Yann , Jarvis Sarah , Jones Nick S. , Cork Simon C. , Eftekhar Amir , Schultz Simon R.
Published: June 2018

Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms. To reduce experimentation load and allow for a faster, more detailed analysis of peripheral nerve stimulation and recording, computational models incorporating experimental insights will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealised extracellular space models in one environment. We modelled the extracellular space as a three-dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed in finite element models for different media (homogeneous, nerve in saline, nerve in cuff) and imported into our simulator. Axons, on the other hand, were modelled more abstractly as one-dimensional chains of compartments. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibres, we adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibres along the nerve with a variable tortuosity fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity alters recorded signal shapes and increases stimulation thresholds. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.
Ensemble of convolutional neural networks for bioimage classification
Authors: Nanni Loris , Ghidoni Stefano , Brahnam Sheryl
Published: June 2018

This work presents a system based on an ensemble of Convolutional Neural Networks (CNNs) and descriptors for bioimage classification that has been validated on different datasets of color images. The proposed system represents a very simple yet effective way of boosting the performance of trained CNNs by composing multiple CNNs into an ensemble and combining scores by sum rule. Several types of ensembles are considered, with different CNN topologies along with different learning parameter sets. The proposed system not only exhibits strong discriminative power but also generalizes well over multiple datasets thanks to the combination of multiple descriptors based on different feature types, both learned and handcrafted. Separate classifiers are trained for each descriptor, and the entire set of classifiers is combined by sum rule. Results show that the proposed system obtains state-of-the-art performance across four different bioimage and medical datasets. The MATLAB code of the descriptors will be available at https://github.com/LorisNanni.
Influence of structural factors on the strength properties of aluminum alloys under shock wave loading
Authors: Razorenov S.V.
Published: June 2018

The results of measurements of the strength characteristics - Hugoniot elastic limit and spall strength of aluminum and aluminum alloys in different structural states under shock wave loading are presented. Single-crystals and polycrystalline technical grade aluminum А1013 and aluminum alloys А2024, АА6063Т6, А1421, A7, А7075, А3003, A5083, АА1070 in the initial coarse-grained state and ultrafine-grained or nanocrystalline structural state were investigated. The refinement of the grain structure was carried out by different methods of severe plastic deformation such as Equal Chanel Angular Pressing, Dynamic Channel Angular Pressing, High-Pressure Torsion and Accumulative Roll-Bonding. The strength characteristics of shock-loaded samples in different structural states were obtained from the analysis of the evolution of the free surface velocity histories recorded by means of laser Doppler velocimeter VISAR. The strain rates before spall fracture of the samples were in the range of 104-105 s−1, the maximum pressure of shock compression did not exceed 7 GPa. The results of these studies clearly demonstrate the influence of structural factors on the resistance to high-rate deformation and dynamic fracture, and it is much less than under the static and quasi-static loading.
Rotation of a low-Reynolds-number watermill: theory and simulations
Authors: Zhu Lailai , Stone Howard A.
Published: June 2018

Recent experiments have demonstrated that small-scale rotary devices installed in a microfluidic channel can be driven passively by the underlying flow alone without resorting to conventionally applied magnetic or electric fields. In this work, we conduct a theoretical and numerical study on such a flow-driven ‘watermill’ at low Reynolds number, focusing on its hydrodynamic features. We model the watermill by a collection of equally spaced rigid rods. Based on the classical resistive force (RF) theory and direct numerical simulations, we compute the watermill’s instantaneous rotational velocity as a function of its rod number $N$, position and orientation. When $N\geqslant 4$, the RF theory predicts that the watermill’s rotational velocity is independent of $N$ and its orientation, implying the full rotational symmetry (of infinite order), even though the geometrical configuration exhibits a lower-fold rotational symmetry; the numerical solutions including hydrodynamic interactions show a weak dependence on $N$ and the orientation. In addition, we adopt a dynamical system approach to identify the equilibrium positions of the watermill and analyse their stability. We further compare the theoretically and numerically derived rotational velocities, which agree with each other in general, while considerable discrepancy arises in certain configurations owing to the hydrodynamic interactions neglected by the RF theory. We confirm this conclusion by employing the RF-based asymptotic framework incorporating hydrodynamic interactions for a simpler watermill consisting of two or three rods and we show that accounting for hydrodynamic interactions can significantly enhance the accuracy of the theoretical predictions.
Comment on “The Campi Flegrei Deep Drilling Project (CFDDP): New Insight on Caldera Structure, Evolution and Hazard Implications for the Naples Area (Southern Italy)” by G. De Natale et al.
Authors: Torrente Maurizio M. , Milia Alfonsa
Published: June 2018

The paper by De Natale et al. (2016, https://doi.org/10.1002/2015GC006183) reported new stratigraphic and geochronological data for a borehole located at Campi Flegrei volcanic area. The authors failed to mention several significant articles on the geological evolution of the region and proposed an interpretation of their data according to the caldera model. Herein, we provide tectonic and stratigraphic data to support a fault model of ignimbrite emission. This comment will also show the inconsistency of the proposed Campi Flegrei caldera.
2.5-Dimensional Parylene C micropore array with a large area and a high porosity for high-throughput particle and cell separation
Authors: Liu Yaoping , Xu Han , Dai Wangzhi , Li Haichao , Wang Wei
Published: June 2018

Large-area micropore arrays with a high porosity are in high demand because of their promising potential in liquid biopsy with a large volume of clinical sample. However, a micropore array with a large area and a high porosity faces a serious mechanical strength challenge. The filtration membrane may undergo large deformation at a high filtration throughput, which will decrease its size separation accuracy. In this work, a keyhole-free Parylene molding process has been developed to prepare a large (>20 mm × 20 mm) filtration membrane containing a 2.5-dimensional (2.5D) micropore array with an ultra-high porosity (up to 91.37% with designed pore diameter/space of 100 μm/4 μm). The notation 2.5D indicates that the large area and the relatively small thickness (approximately 10 μm) of the fabricated membranes represent 2D properties, while the large thickness-to-width ratio (10 μm/ < 4 μm) of the spaces between the adjacent pores corresponds to a local 3D feature. The large area and high porosity of the micropore array achieved filtration with a throughput up to 180 mL/min (PBS solution) simply driven by gravity. Meanwhile, the high mechanical strength, benefiting from the 2.5D structure of the micropore array, ensured a negligible pore size variation during the high-throughput filtration, thereby enabling high size resolution separation, which was proven by single-layer and multi-layer filtrations for particle separation. Furthermore, as a preliminary demonstration, the prepared 2.5-dimensional Parylene C micropore array was implemented as an efficient filter for rare cancer cell separation from a large volume, approximately 10 cells in 10 mL PBS and undiluted urine, with high recovery rates of 87 ± 13% and 56 ± 13%, respectively.
Co-regulatory activity of hnRNP K and NS1-BP in influenza and human mRNA splicing
Authors: Thompson Matthew G. , Muñoz-Moreno Raquel , Bhat Prasanna , Roytenberg Renat , Lindberg John , Gazzara Matthew R. , Mallory Michael J. , Zhang Ke , García-Sastre Adolfo , Fontoura Beatriz M. A. , Lynch Kristen W.
Published: June 2018

Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5′ splice site (5′ss). NS1-BP binds most proximal to the 5′ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins.
A convenient protocol for generating giant unilamellar vesicles containing SNARE proteins using electroformation
Authors: Witkowska Agata , Jablonski Lukasz , Jahn Reinhard
Published: June 2018

Reconstitution of membrane proteins in artificial membranes is an essential prerequisite for functional studies that depend on the context of an intact membrane. While straight-forward protocols for reconstituting proteins in small unilamellar vesicles were developed many years ago, it is much more difficult to prepare large membranes containing membrane proteins at biologically relevant concentrations. Giant unilamellar vesicles (GUVs) represent a model system that is characterised by low curvature, controllable tension, and large surface that can be easily visualised with microscopy, but protein insertion is notoriously difficult. Here we describe a convenient method for efficient generation of GUVs containing functionally active SNARE proteins that govern exocytosis of synaptic vesicles. Preparation of proteo-GUVs requires a simple, in-house-built device, standard and inexpensive electronic equipment, and employs a straight-forward protocol that largely avoids damage of the proteins. The procedure allows upscaling and multiplexing, thus providing a platform for establishing and optimizing preparation of GUVs containing membrane proteins for a diverse array of applications.
Lysyl oxidase-like 2 inhibition ameliorates glomerulosclerosis and albuminuria in diabetic nephropathy
Authors: Stangenberg Stefanie , Saad Sonia , Schilter Heidi C. , Zaky Amgad , Gill Anthony , Pollock Carol A. , Wong Muh Geot
Published: June 2018

Diabetic nephropathy is characterised by the excessive amount of extracellular matrix in glomeruli and tubulointerstitial space. Lysyl oxidase-like 2 (LOXL2) is elevated in renal fibrosis and known to play key roles in ECM stabilisation by facilitating collagen cross-links, epithelial to mesenchymal transition and myofibroblast activation. Thus, targeting LOXL2 may prove to be a useful strategy to prevent diabetic nephropathy. We explored the renoprotective effect of a selective small molecule LOXL2 inhibitor (PXS-S2B) in a streptozotocin-induced diabetes model. Diabetic mice were treated with PXS-S2B for 24 weeks and outcomes compared with untreated diabetic mice and with telmisartan treated animals as comparator of current standard of care. Diabetic mice had albuminuria, higher glomerulosclerosis scores, upregulation of fibrosis markers and increased renal cortical LOXL2 expression. Treatment with PXS-S2B reduced albuminuria and ameliorated glomerulosclerosis. This was associated with reduced expression of glomerular fibronectin and tubulointerstitial collagen I. The renoprotective effects of both PXS-S2B and telmisartan were more marked in the glomerular compartment than in the tubulointerstitial space. The study reveals that LOXL2 inhibition was beneficial in preserving glomerular structure and function. Thus, LOXL2 may be a potential therapeutic target in diabetic nephropathy.
Validation of biofilm formation on human skin wound models and demonstration of clinically translatable bacteria-specific volatile signatures
Authors: Ashrafi Mohammed , Novak-Frazer Lilyann , Bates Matthew , Baguneid Mohamed , Alonso-Rasgado Teresa , Xia Guoqing , Rautemaa-Richardson Riina , Bayat Ardeshir
Published: June 2018

Biofilms are major contributors to delayed wound healing and there is a need for clinically relevant experimental models to assess theranostics. Microorganisms release volatile organic compounds (VOCs) and the ability to identify these in infected cutaneous wounds could lead to efficient non-invasive diagnosis. The aims here were to develop and assess bacterial biofilm formation and identify their VOC profiles in an in vitro model and validate in human ex vivo incisional and excisional cutaneous wound models. Biofilm development was assessed using multiple microscopy techniques with biofilm-forming deficient controls and quantified using metabolic and biomass assays; and VOC production measured by gas chromatography-mass spectrometry. The production of most VOCs was affected by biofilm development and model used. Some VOCs were specific either for planktonic or biofilm growth. The relative abundance of some VOCs was significantly increased or decreased by biofilm growth phase (P < 0.05). Some Staphylococcus aureus and Pseudomonas aeruginosa VOCs correlated with biofilm metabolic activity and biomass (R ≤ −0.5; ≥0.5). We present for the first time bacterial biofilm formation in human ex vivo cutaneous wound models and their specific VOC profiles. These models provide a vehicle for human skin-relevant biofilm studies and VOC detection has potential clinical translatability in efficient non-invasive diagnosis of wound infection.
Origins of Moiré Patterns in CVD-grown MoS2 Bilayer Structures at the Atomic Scales
Authors: Wang Jin , Namburu Raju , Dubey Madan , Dongare Avinash M.
Published: June 2018

The chemical vapor deposition (CVD)-grown two-dimensional molybdenum disulfide (MoS2) structures comprise of flakes of few layers with different dimensions. The top layers are relatively smaller in size than the bottom layers, resulting in the formation of edges/steps across adjacent layers. The strain response of such few-layer terraced structures is therefore likely to be different from exfoliated few-layered structures with similar dimensions without any terraces. In this study, the strain response of CVD-grown few-layered MoS2 terraced structures is investigated at the atomic scales using classic molecular dynamics (MD) simulations. MD simulations suggest that the strain relaxation of CVD-grown triangular terraced structures is observed in the vertical displacement of the atoms across the layers that results in the formation of Moiré patterns. The Moiré islands are observed to nucleate at the corners or edges of the few-layered structure and propagate inwards under both tensile and compressive strains. The nucleation of these islands is observed to happen at tensile strains of ~ 2% and at compressive strains of ~2.5%. The vertical displacements of the atoms and the dimensions of the Moiré islands predicted using the MD simulation are in excellent agreement with that observed experimentally.
Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer
Authors: Desir Snider , O’Hare Patrick , Vogel Rachel Isaksson , Sperduto William , Sarkari Akshat , Dickson Elizabeth L. , Wong Phillip , Nelson Andrew C. , Fong Yuman , Steer Clifford J. , Subramanian Subbaya , Lou Emil
Published: June 2018

Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.
Lifestyle Factors, Colorectal Tumor Methylation, and Survival Among African Americans and European Americans
Authors: Busch Evan L. , Galanko Joseph A. , Sandler Robert S. , Goel Ajay , Keku Temitope O.
Published: June 2018

Differences in tumor characteristics might partially account for mortality disparities between African American (AA) and European American (EA) colorectal cancer patients. We evaluated effect modification by race for exposure and patient-outcomes associations with colorectal tumor methylation among 218 AA and 267 EA colorectal cancer cases from the population-based North Carolina Colon Cancer Study. Tumor methylation was assessed in CACNA1G, MLH1, NEUROG1, RUNX3, and SOCS1. We used logistic regression to assess whether associations between several lifestyle factors—intake of fruits, vegetables, folate, and non-steroidal anti-inflammatory drugs—and tumor methylation were modified by race. Proportional hazards models were used to evaluate whether race modified associations between tumor methylation and time to all-cause mortality. Greater fruit consumption was associated with greater odds of high NEUROG1 methylation among EA at methylation cut points of 15–35% (maximum OR 3.44, 95% CI 1.66, 7.13) but not among AA. Higher folate intake was associated with lower odds of high CACNA1G methylation among EAs but not AAs. Tumor methylation was not associated with all-cause mortality for either group. Race might modify associations between lifestyle factors and colorectal tumor methylation, but in this sample did not appear to modify associations between tumor methylation and all-cause mortality.
Resistive switching in optoelectronic III-V materials based on deep traps
Authors: Schnedler M. , Portz V. , Semmler U. , Moors M. , Waser R. , Dunin-Borkowski R. E. , Ebert Ph.
Published: June 2018

Resistive switching random access memories (ReRAM) are promising candidates for energy efficient, fast, and non-volatile universal memories that unite the advantages of RAM and hard drives. Unfortunately, the current ReRAM materials are incompatible with optical interconnects and wires. Optical signal transmission is, however, inevitable for next generation memories in order to overcome the capacity-bandwidth trade-off. Thus, we present here a proof-of-concept of a new type of resistive switching realized in III-V semiconductors, which meet all requirements for the implementation of optoelectronic circuits. This resistive switching effect is based on controlling the spatial positions of vacancy-induced deep traps by stimulated migration, opening and closing a conduction channel through a semi-insulating compensated surface layer. The mechanism is widely applicable to opto-electronically usable III-V compound semiconductors.
Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure
Authors: Polina Evelise Regina , Araújo Raquel Rosa Candebat Vallejo , Sbruzzi Renan Cesar , Biolo Andréia , Rohde Luís Eduardo , Clausell Nadine , dos Santos Kátia Gonçalves
Published: June 2018

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the −418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the −418 G > C polymorphism was very rare in our population (frequency < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the −418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians.
RETRACTED ARTICLE: Peri-implantitis-associated methanogens: a preliminary report
Authors: Belkacemi Souad , Mazel Anthony , Tardivo Delphine , Tavitian Patrick , Stephan Grégory , Bianca Giancarlo , Terrer Elodie , Drancourt Michel , Aboudharam Gérard
Published: June 2018

Methanogens have already been described in periodontitis but not in peri-implantitis. Thirty peri-implantitis samples and 28 control samples were collected in 28 consenting peri-implantitis patients. PCR-sequencing of the 16S rRNA gene was used as a broad-spectrum screening method and results were further confirmed by real-time quantitative PCR targeting the mcrA genes. Results showed a methanogen community dominated by Methanobrevibacter oralis in 31/58 (51%) samples including 16/28 (57%) control samples and 15/30 (50%) peri-implantitis samples. Methanobrevibacter massiliense was detected in 5/58 (8.6%) samples including 3/28 (1%) control samples and 2/30 (6.7%) peri-implantitis samples. The prevalence of M. oralis or M. massiliense did not significantly differ in peri-implantitis and control samples (exact Fisher test, P = 0.61 and P = 0.67, respectively). Further ponderation of the methanogen load by the real-time quantitative PCR for actin human gene again indicated non-significant difference (Wilcoxon-Mann-Whitney test, P = 0.48 and P = 0.40, respectively). These data show that the prevalence of methanogens does not differ in peri-implantitis lesions and healthy sites, when individuals are their own control. These data do not allow assigning a specific pathogenic role to methanogens in peri-implantitis; methanogens rather are part of the commensal and normal flora of the oral cavity.
Carriage of multi-drug resistant bacteria among foreigners seeking medical care
Authors: Benenson Shmuel , Nir-Paz Ran , Golomb Mordechai , Schwartz Carmela , Amit Sharon , Moses Allon E. , Cohen Matan J.
Published: June 2018

Medical tourism has a potential of spreading multi-drug resistant bacteria (MDR). The Hadassah Medical Center serves as a referral center for global medical tourists and for Palestinian Authority residents. In order to assess whether patients of these groups are more likely to harbor MDR bacteria than local residents, we reviewed data from all patients admitted to our institution between 2009 and 2014. We compared MDR rates between countries of residency, controlling for gender, age, previous hospitalization and time from admission to MDR detection. Overall, among 111,577 patients with at least one microbiological specimen taken during hospitalization, there were 3,985 (3.5%) patients with at least one MDR-positive culture. Compared to Israeli patients, tourists and patients from the Palestinian Authority had increased rates of MDR positivity (OR, 95%CI): 2.3 (1.6 to 2.3) and 8.0 (6.3 to 10.1), respectively. Our data show that foreign patients seeking advanced medical care are more likely to carry MDR bacteria than the resident population. Strategies to minimize MDR spread, such as pre-admission screening or pre-emptive isolation should be considered in this population.
An innovative and efficient route to the synthesis of metal-based glycoconjugates: proof-of-concept and potential applications
Authors: Pettenuzzo Andrea , Montagner Diego , McArdle Patrick , Ronconi Luca
Published: June 2018

An innovative, facile and efficient synthetic route to the functionalization of metallodrugs with carbohydrates in high yields and purity is reported.
A multi-shelled CoP nanosphere modified separator for highly efficient Li–S batteries
Authors: Chen Xiaoxia , Ding Xuyang , Wang Chunsheng , Feng Zhenyu , Xu Liqiang , Gao Xue , Zhai Yanjun , Wang Debao
Published: June 2018

Multi-shelled CoP nanospheres are designed as a new kind of coated separator material for highly efficient Li–S batteries, which exhibits outstanding cycling stability with a capacity degradation of 0.078% per cycle over 500 cycles at 1 C and also excellent rate performances.
Biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D
Authors: Dethe Dattatraya H. , B. Vijay Kumar , Maiti Rakesh
Published: June 2018

The first biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D have been completed.
A facile route to bespoke macro- and mesoporous block copolymer microparticles
Authors: He Guping , Bennett Thomas M. , Alauhdin Mohammad , Fay Michael W. , Liu Xin , Schwab Simon T. , Sun Cheng-gong , Howdle Steven M.
Published: June 2018

A facile and versatile strategy to fabricate macro- and mesoporous block copolymer microparticles with bespoke characteristics using supercritical CO2.
Guiding protein delivery into live cells using DNA-programmed membrane fusion
Authors: Sun Lele , Gao Yanjing , Wang Yaoguang , Wei Qin , Shi Jiye , Chen Nan , Li Di , Fan Chunhai
Published: June 2018

A DNA-programmed membrane fusion strategy for directing intracellular delivery of proteins into live cells.