bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentimento: A 21st Century View on the Canvas of Motor Development
Authors: Clark Jane E.
Published: July 2017

How we understand the emergence and development of motor behavior and skillfulness has itself developed over the last 50 years. In reflecting on the history of motor development, it is important to recognize that these ‘reflections’ are much like the painter’s “pentimento.” That is, the ‘canvas’ we paint today of what our science was decades ago is actually a painting with many layers—each representing where our views have changed along the journey. I do not “repent” with these reflections, as suggested by the term, pentimento, but rather I seek to bring a developmental perspective to our scientific inquiries into motor development with an element of a revisionist’s approach. What were the key discoveries and the seminal papers that influenced our canvas of motor development that we view today? Almost three decades ago, we (Clark & Whitall, 1989) outlined an historical framework for the field of motor development. Today, we can look back at that framework and the ensuing science and consider where we have been and what we have learned and ask: What does the pentimento of our motor development canvas reveal?
High–bit rate ultra-compact light routing with mode-selective on-chip nanoantennas
Authors: Guo Rui , Decker Manuel , Setzpfandt Frank , Gai Xin , Choi Duk-Yong , Kiselev Roman , Chipouline Arkadi , Staude Isabelle , Pertsch Thomas , Neshev Dragomir N. , Kivshar Yuri S.
Published: July 2017

We show directional light routing and high–bit rate data transmission using a nanoantenna integrated on a low-loss waveguide.
Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs
Authors: vonHoldt Bridgett M. , Shuldiner Emily , Koch Ilana Janowitz , Kartzinel Rebecca Y. , Hogan Andrew , Brubaker Lauren , Wanser Shelby , Stahler Daniel , Wynne Clive D. L. , Ostrander Elaine A. , Sinsheimer Janet S. , Udell Monique A. R.
Published: July 2017

We hypothesize that selection during dog domestication targeted CNVs associated with hypersociability.
Prediction and synthesis of a family of atomic laminate phases with Kagomé-like and in-plane chemical ordering
Authors: Dahlqvist Martin , Lu Jun , Meshkian Rahele , Tao Quanzheng , Hultman Lars , Rosen Johanna
Published: July 2017

Atomically laminated materials: A family of quaternary phases with chemical order is designed from theory and experiments.
Unlocking a key to maize's amazing success
Authors: Pennisi Elizabeth
Published: July 2017

Malleable flowering time may help crop in cooler climates
Acknowledging Africa
What Do Science, Technology, and Innovation Mean From Africa?
Clapperton Chakanetsa Mavhunga, Ed.
MIT Press, 2017. 255 pp.
Authors: Emeagwali Gloria
Published: July 2017

The continent's innovation often occurs outside the formal sector, but it should still count as science
The Human Virome: Implications for Clinical Practice in Transplantation Medicine
Authors: Tan Susanna K. , Relman David A. , Pinsky Benjamin A.
Published: July 2017

Advances in DNA sequencing technology have provided an unprecedented opportunity to study the human virome. Transplant recipients and other immunocompromised hosts are at particular risk for developing virus-related pathology; thus, the impact of the virome on health and disease may be even more relevant in this population. Here, we discuss technical considerations in studying the human virome, the current literature on the virome in transplant recipients, and near-future applications of sequence-based findings that can further our understanding of viruses in transplantation medicine.
Prevalence of Human Papillomavirus in Self-Taken Samples from Screening Nonattenders
Authors: Lam J. U. H. , Rebolj M. , Ejegod D. M. , Pedersen H. , Rygaard C. , Lynge E. , Harder E. , Thomsen L. T. , Kjaer S. K. , Bonde J.
Published: July 2017

The Copenhagen Self-Sampling Initiative (CSi) has shown how human papillomavirus (HPV)-based self-sampling can be used to increase screening participation among 23,632 nonattenders in the Capital Region of Denmark. In this study, we describe HPV prevalence and genotype frequency in 4,824 self-samples as determined by three HPV assays (the CLART, Onclarity, and Hybrid Capture 2 [HC2] assays) and compare the results with those for physician-taken follow-up samples. The HPV self-sample findings were also compared to the findings for a reference population of 3,347 routinely screened women from the Horizon study, which had been undertaken in the same screening laboratory. Nonattenders had an HPV prevalence of 11.3% as determined by the CLART assay, which was lower than that for women from the Horizon study (18.5%). One-third of the CSi women who tested HPV positive by self-sampling tested HPV negative on the physician-taken follow-up sample. The CLART and Onclarity assays agreed on 64% (95% confidence interval [CI], 60 to 68%) of the HPV-positive self-taken samples. When the HC2 assay results were added into a three-way comparison, the level of agreement decreased to 27% (95% CI, 24 to 29%). Our findings suggest that further validation of HPV assays on self-taken samples is needed for optimal HPV detection and correct clinical management of HPV-positive women.
ISG15 Modulates Type I Interferon Signaling and the Antiviral Response during Hepatitis E Virus Replication
Authors: Sooryanarain Harini , Rogers Adam J. , Cao Dianjun , Haac Mary Etna R. , Karpe Yogesh A. , Meng Xiang-Jin
Published: July 2017

Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals, especially in solid-organ transplant recipients. Innate immunity, via the type I interferon (IFN) response, plays an important role during the initial stages of a viral infection. IFN-stimulated gene 15 (ISG15), an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role and can have a direct antiviral effect on a wide spectrum of virus families. In the present study, we investigated the antiviral effect as well as the potential immunomodulatory role of ISG15 during HEV replication. The results revealed that HEV induced high levels of ISG15 production both
in vitro
(Huh7-S10-3 liver cells) and
in vivo
(liver tissues from HEV-infected pigs); however, ISG15 is not required for virus replication. We also demonstrated that ISG15 silencing potentiates enhanced type I IFN-mediated signaling, resulting in an increase in the type I IFN-mediated antiviral effect during HEV replication. This observed enhanced type I IFN signaling correlated with an increase in IFN-stimulated gene expression levels during HEV replication. Furthermore, we showed that PKR and OAS1 played important roles in the ISG15-mediated type I IFN sensitivity of HEV. Taken together, the results from this study suggest that ISG15 plays an important immunomodulatory role and regulates HEV sensitivity to exogenous type I IFN.

IMPORTANCE
Hepatitis E virus (HEV) infection typically causes self-limiting acute viral hepatitis. However, chronic HEV infection has recently become a significant clinical problem in immunocompromised patients. Pegylated interferon (IFN) has been used to treat chronic HEV infection in solid-organ transplant patients with some success. However, the mechanism behind the type I IFN-mediated antiviral effect against HEV remains unclear. This report demonstrates that ISG15 induced by HEV replication in Huh7-S10-3 human liver cells plays an immunomodulatory role by negatively regulating type I IFN signaling and, thus, HEV sensitivity to type I IFN. Our results also show that PKR and OAS1 play important roles in the ISG15-mediated type I IFN sensitivity of HEV.
Binding of Herpes Simplex Virus 1 UL20 to GODZ (DHHC3) Affects Its Palmitoylation and Is Essential for Infectivity and Proper Targeting and Localization of UL20 and Glycoprotein K
Authors: Wang Shaohui , Mott Kevin R. , Wawrowsky Kolja , Kousoulas Konstantin G. , Luscher Bernhard , Ghiasi Homayon
Published: July 2017

Herpes simplex virus 1 (HSV-1) UL20 plays a crucial role in the envelopment of the cytoplasmic virion and its egress. It is a nonglycosylated envelope protein that is regulated as a γ1 gene. Two-hybrid and pulldown assays demonstrated that UL20, but no other HSV-1 gene-encoded proteins, binds specifically to GODZ (also known as DHHC3), a cellular Golgi apparatus-specific Asp-His-His-Cys (DHHC) zinc finger protein. A catalytically inactive dominant-negative GODZ construct significantly reduced HSV-1 replication
in vitro
and affected the localization of UL20 and glycoprotein K (gK) and their interactions but not glycoprotein C (gC). GODZ is involved in palmitoylation, and we found that UL20 is palmitoylated by GODZ using a GODZ dominant-negative plasmid. Blocking of palmitoylation using 2-bromopalmitate (2-BP) affected the virus titer and the interaction of UL20 and gK but did not affect the levels of these proteins. In conclusion, we have shown that binding of UL20 to GODZ in the Golgi apparatus regulates trafficking of UL20 and its subsequent effects on gK localization and virus replication. We also have demonstrated that GODZ-mediated UL20 palmitoylation is critical for UL20 membrane targeting and thus gK cell surface expression, providing new mechanistic insights into how UL20 palmitoylation regulates HSV-1 infectivity.

IMPORTANCE
HSV-1 UL20 is a nonglycosylated essential envelope protein that is highly conserved among herpesviruses. In this study, we show that (i) HSV-1 UL20 binds to GODZ (also known as DHHC3), a Golgi apparatus-specific Asp-His-His-Cys (DHHC) zinc finger protein; (ii) a GODZ dominant-negative mutant and an inhibitor of palmitoylation reduced HSV-1 titers and altered the localization of UL20 and glycoprotein K; and (iii) UL20 is palmitoylated by GODZ, and this UL20 palmitoylation is required for HSV-1 infectivity. Thus, blocking of the interaction of UL20 with GODZ, using a GODZ dominant-negative mutant or possibly GODZ shRNA, should be considered a potential alternative therapy in not only HSV-1 but also other conditions in which GODZ processing is an integral component of pathogenesis.
Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission
Authors: Sherman Michael B. , Kakani Kishore , Rochon D'Ann , Jiang Wen , Voss Neil R. , Smith Thomas J.
Published: July 2017

Cucumber necrosis virus
(CNV) is a member of the genus
Tombusvirus
and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus
Olpidium bornovanus
. As with other members of the
Tombusvirus
genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507–517, 2004,
https://doi.org/10.1016/j.jmb.2004.03.008
). P73 lies immediately adjacent to a putative zinc binding site (M. Li et al., J Virol 87:12166–12175, 2013,
https://doi.org/10.1128/JVI.01965-13
) that is formed by three icosahedrally related His residues in the N termini of the C subunit at the quasi-6-fold axes. To better understand how this buried residue might affect vector transmission, we determined the cryo-electron microscopy structure of wild-type CNV in the native and swollen state and of the transmission-defective mutant, P73G, under native conditions. With the wild-type CNV, the swollen structure demonstrated the expected expansion of the capsid. However, the zinc binding region at the quasi-6-fold at the β-annulus axes remained intact. By comparison, the zinc binding region of the P73G mutant, even under native conditions, was markedly disordered, suggesting that the β-annulus had been disrupted and that this could destabilize the capsid. This was confirmed with pH and urea denaturation experiments in conjunction with electron microscopy analysis. We suggest that the P73G mutation affects the zinc binding and/or the β-annulus, making it more fragile under neutral/basic pH conditions. This, in turn, may affect zoospore transmission.

IMPORTANCE
Cucumber necrosis virus
(CNV), a member of the genus
Tombusvirus
, is transmitted in nature via zoospores of the fungus
Olpidium bornovanus
. While a number of plant viruses are transmitted via insect vectors, little is known at the molecular level as to how the viruses are recognized and transmitted. As with many spherical plant viruses, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation that lies inside the capsid immediately adjacent to a putative zinc binding site (Li et al., J Virol 87:12166–12175, 2013,
https://doi.org/10.1128/JVI.01965-13
) blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507–517, 2004,
https://doi.org/10.1016/j.jmb.2004.03.008
). Here, we show that the P73G mutant is less stable than the wild type, and this appears to be correlated with destabilization of the β-annulus at the icosahedral 3-fold axes. Therefore, the β-annulus appears not to be essential for particle assembly but is necessary for interactions with the transmission vector.
NKp46 Recognizes the Sigma1 Protein of Reovirus: Implications for Reovirus-Based Cancer Therapy
Authors: Bar-On Yotam , Charpak-Amikam Yoav , Glasner Ariella , Isaacson Batya , Duev-Cohen Alexandra , Tsukerman Pinchas , Varvak Alexander , Mandelboim Michal , Mandelboim Ofer
Published: July 2017

The recent approval of oncolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK cell-activating receptor NKp46 and the orthologous mouse protein NCR1 recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify sites of NKp46/NCR1 binding to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation
in vitro
. Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy
in vivo
. Collectively, we have identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed both for clearance of reovirus infection and for reovirus-based tumor therapy.

IMPORTANCE
Reovirus infects much of the population during childhood, causing mild disease, and hence is considered to be efficiently controlled by the immune system. Reovirus also specifically infects tumor cells, leading to tumor death, and is currently being tested in human clinical trials for cancer therapy. The mechanisms by which our immune system controls reovirus infection and tumor killing are not well understood. We report here that natural killer (NK) cells recognize a viral protein named sigma1 through the NK cell-activating receptor NKp46. Using several mouse tumor models, we demonstrate the importance of NK cells in protection from reovirus infection and in reovirus killing of tumors
in vivo
. Collectively, we identify a new ligand for the NKp46 receptor and provide evidence for the importance of NKp46 in the control of reovirus infections and in reovirus-based cancer therapy.
Rab5 and Rab11 Are Required for Clathrin-Dependent Endocytosis of Japanese Encephalitis Virus in BHK-21 Cells
Authors: Liu Chun-Chun , Zhang Yun-Na , Li Zhao-Yao , Hou Jin-Xiu , Zhou Jing , Kan Lin , Zhou Bin , Chen Pu-Yan
Published: July 2017

During infection Japanese encephalitis virus (JEV) generally enters host cells via receptor-mediated clathrin-dependent endocytosis. The trafficking of JEV within endosomes is controlled by Rab GTPases, but which Rab proteins are involved in JEV entry into BHK-21 cells is unknown. In this study, entry and postinternalization of JEV were analyzed using biochemical inhibitors, RNA interference, and dominant negative (DN) mutants. Our data demonstrate that JEV entry into BHK-21 cells depends on clathrin, dynamin, and cholesterol but not on caveolae or macropinocytosis. The effect on JEV infection of dominant negative (DN) mutants of four Rab proteins that regulate endosomal trafficking was examined. Expression of DN Rab5 and DN Rab11, but not DN Rab7 and DN Rab9, significantly inhibited JEV replication. These results were further tested by silencing Rab5 or Rab11 expression before viral infection. Confocal microscopy showed that virus particles colocalized with Rab5 or Rab11 within 15 min after virus entry, suggesting that after internalization JEV moves to early and recycling endosomes before the release of the viral genome. Our findings demonstrate the roles of Rab5 and Rab11 on JEV infection of BHK-21 cells through the endocytic pathway, providing new insights into the life cycle of flaviviruses.

IMPORTANCE
Although Japanese encephalitis virus (JEV) utilizes different endocytic pathways depending on the cell type being infected, the detailed mechanism of its entry into BHK-21 cells is unknown. Understanding the process of JEV endocytosis and postinternalization will advance our knowledge of JEV infection and pathogenesis as well as provide potential novel drug targets for antiviral intervention. With this objective, we used systematic approaches to dissect this process. The results show that entry of JEV into BHK-21 cells requires a low-pH environment and that the process occurs through dynamin-, actin-, and cholesterol-dependent clathrin-mediated endocytosis that requires Rab5 and Rab11. Our work provides a detailed picture of the entry of JEV into BHK-21 cells and the cellular events that follow.
Induction of β-Lactamase Activity and Decreased β-Lactam Susceptibility by CO
2
in Clinical Bacterial Isolates
Authors: Mullen Nathan , Raposo Hugo , Gudis Polyxeni , Barker Linsey , Humphries Romney M. , Schmitt Bryan H. , Relich Ryan F. , May Meghan
Published: July 2017

β-Lactamase induction and concurrent β-lactam resistance in respiratory tract pathogens as a consequence of growth in a physiologically relevant level of CO
2
are of clinical significance, particularly given the ubiquity of TEM and SHV β-lactamase genes in diverse bacterial pathogens. This is the first report of β-lactamase induction by 5% CO
2
.
Long-term peritoneal port-catheter in a patient with cardiac ascites
Authors: Mecinaj Albulena , Reier-Nilsen Frode , Le Tri Minh , Steine Kjetil
Published: July 2017

A peritoneal port-catheter was inserted in a 70-year-old man because of repeated paracentesis due to cardiac ascites. Instead of frequent hospital admissions, the patient could drain his ascites at home, which dramatically improved his quality of life and enabled him to perform his daily activities.
An affinity-based probe for methyltransferase enzymes based on sinefungin
Authors: Lafreniere Matthew A. , Desrochers Geneviève F. , Mekbib Kedous , Pezacki John Paul
Published: July 2017

Epigenetics control numerous cellular processes such as gene transcription, signal transduction, and protein stabilization. An understanding of epigenetic mechanisms can lead to the development of therapeutic agents for various diseases. Herein, we report the design and synthesis of a sinefungin affinity-probe (BpyneSF) that targets methyltranferase enzymes and proteins involved in recognition of methylation. This probe contains a bioorthogonal alkyne residue for conjugation using the copper-catalyzed azide–alkyne cycloaddition and a photoactivatable crosslinker group for covalent attachment of the probe to its proteomic targets. We investigate the efficiency and selectivity of the probe to inhibit and label methyltransferase enzymes, and we demonstrate, through in-gel fluorescence, on-bead digestion, and tandem mass spectrometry, that BpyneSF can label methyltransferase SETD2 and reader proteins in vitro. These results establish the utility of BpyneSF as a tool for affinity-based protein profiling in complex biological environments.
The problems with pooling poop: confronting sampling method biases in wolf (Canislupus) diet studies
Authors: Gable T.D. , Windels S.K. , Bruggink J.G.
Published: July 2017

Wolf (Canis lupus L., 1758) diet is commonly estimated via scat analysis. Several researchers have concluded that scat collection method can bias diet estimates, but none of these studies properly accounted for interpack, age class, and temporal variability, all of which could bias diet estimates. We tested whether different scat collection methods yielded different wolf diet estimates after accounting for these other potential biases. We collected scats (n = 2406) monthly from four packs via three scat collection methods (at home sites, at clusters of GPS locations, and opportunistically) in and adjacent to Voyageurs National Park, Minnesota, USA, during April–October 2015. Diet estimates were not affected by scat collection method but did vary temporally, among packs, and by age class. To more accurately estimate wolf population diets, researchers should collect 10–20 adult scats/pack per month from home sites and (or) opportunistically from packs that are representative of the population of interest. Doing so will minimize the potential biases associated with temporal, interpack, and age-class variability.
Microsatellites mapping for non-model species with chromosomal rearrangement: a case study in the frog Quasipaa boulengeri (Anura: Dicroglossidae)
Authors: Yuan Xiuyun , Yuan Siqi , Liu Ya , Xia Yun , Zeng Xiaomao
Published: July 2017

Gene mapping is an important resource for understanding the evolution of genes and cytogenetics. Model species with a known genetic map or genome sequence allow for the selection of genetic markers on a desired chromosome, while it is hard to locate these markers on chromosomes of non-model species without such references. A frog species, Quasipaa boulengeri, shows chromosomal rearrangement polymorphisms, making itself a fascinating model for chromosomal speciation mediated by suppressed recombination. However, no markers have been located on its rearranged chromosomes. We present a complete protocol to map microsatellites based on mechanical microdissection and chromosome amplification techniques. Following this protocol, we mapped 71 microsatellites of Q. boulengeri at the chromosome level. In total, eight loci were assigned to rearranged chromosomes, and the other 63 loci might attach to other chromosomes. These microsatellites could be used to compare the gene flow and verify the chromosomal suppressed recombination hypothesis in Q. boulengeri. This integrated protocol could be effectively used to map genes to chromosomes for non-model species.
Dynamic Behavior of Transmission Tower-Line Systems Subjected to Insulator Breakage
Authors: Li Jia-Xiang , Li Hong-Nan , Fu Xing
Published: July 2017

Ice loads attached to a transmission tower-line system can not only increase the vertical loads on the insulators, but also cause flashover to occur more easily. Both effects can lead to an increased probability of insulator breakage. In this paper, a finite-element model of a transmission tower-line system with three towers and four span lines under the ice loads is established. Dynamic analyses of the tower-line system after insulator breakage are performed to study the dynamic responses of the system and its failure process. In addition, a parametric analysis is conducted to investigate the influence of span length and insulator length on the vibration of the system and the failure mode. The results show that a larger ice load can lead to more severe vibration of the tower-line system due to the insulator breakage. Moreover, as the span length increases, the insulator breakage can result in more serious consequences and even the cascading collapse of the transmission tower-line system. This study provides crucial reference for preventing the failure of transmission tower-line systems in heavy ice regions.
Development of partial extraction methods to estimate abundance of copper-iron sulphide minerals in the Escondida Norte porphyry copper deposit, Chile
Authors: Preece Richard K. , Williams Martin J. , Gilligan Jonathan M.
Published: July 2017

Studies were conducted by Minera Escondida, Ltda. (MEL) between 1995 and 2003 to support an investment decision to open Escondida Norte, an enriched porphyry copper deposit adjacent to the Escondida mine and processing facilities. Due to the importance of copper-iron sulphide minerals in predicting metallurgical performance in both process alternatives, a quantitative spatial model of copper-iron sulphide mineral abundances was determined to be a critical study component.

A suite of total and partial copper analyses already in common use was chosen to maximize relative selectivity among the major copper sulphide minerals in the mineral deposit. These analyses were merged with partial and total sulphur analysis and combined with a novel approach to interpret the analytical results as normative mineral estimates of chalcocite, covellite, chalcopyrite and pyrite content. Development and validation of the normative mineral estimates included verification on the analytical stability and reproducibility of the chemical analyses, determination of extraction rates on synthetic mineral standards, and comparison with modal mineral abundance on natural ore samples. Uncertainty of individual normative copper sulphide minerals is estimated at ±5% (95% confidence interval), while uncertainty on pyrite content is ±12%. The uncertainty of the normative mineral estimates are comparable to uncertainty of corresponding modal mineral estimates, and differences between modal and normative estimates are largely within the estimation uncertainty.

While the methods were originally developed for a simple association based on supergene chalcocite ± covellite replacing and overprinting hypogene chalcopyrite + pyrite, subsequent work developed normative mineral models for bornite + chalcopyrite hypogene and mixed copper oxide-sulphide supergene mineralization.
Thy-1+/−fibroblast subsets in the human peritoneum
Authors: Kawka Edyta , Witowski Janusz , Bartosova Maria , Catar Rusan , Rudolf András , Philippe Aurelie , Rutkowski Rafał , Schäfer Betti , Schmitt Claus Peter , Dragun Duska , Jörres Achim
Published: July 2017

Fibrotic thickening of the peritoneum develops in patients receiving peritoneal dialysis (PD) for renal failure. For unknown reasons, however, in some patients it progresses to extensive fibrosis that compromises dialysis capacity of the peritoneum. It is increasingly clear that fibroblasts display large heterogeneity not only between but also within tissues. Differential surface expression of thymocyte differentiation antigen 1 (Thy-1) has been shown to identify functionally distinct fibroblast subsets in several organs. Here, we isolated Thy-1+/−subsets of human peritoneal fibroblasts (HPFB) and analyzed them in terms of profibrotic myofibroblast features. In healthy individuals, Thy-1+cells constituted ~45% of the HPFB population found in the greater omentum but were not detected in the parietal peritoneum. When propagated in culture and compared with Thy-1−cells, omentum-derived Thy-1+HPFB consistently displayed an increased expression of α-smooth muscle actin, collagen I, and transforming growth factor-β1. They also showed greater proliferation capacity and enhanced contractile properties. The number of Thy-1+HPFB increased significantly in PD patients and made up more than 70 and 95% of all HPFB found in the omentum and parietal peritoneum, respectively. These data indicate that the expansion of Thy-1+fibroblasts may contribute to fibrotic thickening of the peritoneal membrane during PD.
Wideband Cylindrical Dielectric Resonator Antenna Operating in HEM11δ Mode with Improved Gain: A Study of Superstrate and Reflector Plane
Authors: Dash Sounik Kiran Kumar , Khan Taimoor , Kanaujia Binod Kumar , Nasimuddin N.
Published: July 2017

A wideband and high gain dielectric resonator antenna (DRA) operating in hybrid HEM11δ mode is proposed. The investigated geometry employs one cylindrical dielectric resonator partially covered with a transparent dielectric superstrate and backed up by a single side metal coated dielectric reflector plane. The reflector is dedicated for gain enhancement while the superstrate is employed for merging of two resonant bands resulting in a single wide band. The dielectric resonator is excited by simple microstrip feed slot coupling technique and operates over X-band, ranging from 7.12 GHz to 8.29 GHz, that is, of 15.18% impedance matching bandwidth with 11.34 dBi peak gain. The different development stages like standalone DRA, DRA with superstrate, DRA with reflector, and DRA with both superstrate and reflector plane with respect to bandwidth and gain performances are analyzed properly. To the best of authors’ knowledge, this is the first time this type of combination of both superstrate and reflector plane is demonstrated in DRA engineering. An antenna prototype was fabricated and characterized and a very good agreement is achieved between the simulated and measured results.
Functional, Cellular, and Molecular Remodeling of the Heart under Influence of Oxidative Cigarette Tobacco Smoke
Authors: Kaplan Abdullah , Abidi Emna , Ghali Rana , Booz George W. , Kobeissy Firas , Zouein Fouad A.
Published: July 2017

Passive and active chronic cigarette smoking (CS) remains an international epidemic and a key risk factor for cardiovascular disease (CVD) development. CS‐induced cardiac damage is divided into two major and interchangeable mechanisms: (1) direct adverse effects on the myocardium causing smoking cardiomyopathy and (2) indirect effects on the myocardium by fueling comorbidities such as atherosclerotic syndromes and hypertension that eventually damage and remodel the heart. To date, our understanding of cardiac remodeling following acute and chronic smoking exposure is not well elucidated. This manuscript presents for the first time the RIMD (oxidative stress (R), inflammation (I), metabolic impairment (M), and cell death (D)) detrimental cycle concept as a major player in CS‐induced CVD risks and direct cardiac injury. Breakthroughs and latest findings in the field with respect to structural, functional, cellular, and molecular cardiac remodeling following chronic smoking exposure are summarized. This review also touches the genetics/epigenetics of smoking as well as the smoker’s paradox and highlights the most currently prominent pharmacological venues to mitigate CS‐induced adverse cardiac remodeling.
Precompact Sets, Boundedness, and Compactness of Commutators for Singular Integrals in Variable Morrey Spaces
Authors: Wang Wei , Xu Jingshi
Published: July 2017

We give sufficient conditions for subsets to be precompact sets in variable Morrey spaces. Then we obtain the boundedness of the commutator generated by a singular integral operator and a BMO function on the variable Morrey spaces. Finally, we discuss the compactness of the commutator generated by a singular integral operator and a BMO function on the variable Morrey spaces.
Identification of the Impacts of Climate Changes and Human Activities on Runoff in the Jinsha River Basin, China
Authors: Liu Xiaowan , Peng Dingzhi , Xu Zongxue
Published: July 2017

Quantifying the impacts of climate changes and human activities on runoff has received extensive attention, especially for the regions with significant elevation difference. The contributions of climate changes and human activities to runoff were analyzed using rainfall-runoff relationship, double mass curve, slope variation, and water balance method during 1961–2010 at the Jinsha River basin, China. Results indicate that runoff at upstream and runoff at midstream are both dominated by climate changes, and the contributions of climate changes to runoff are 63%~72% and 53%~68%, respectively. At downstream, climate changes account for only 13%~18%, and runoff is mainly controlled by human activities, contributing 82%~87%. The availability and stability of results were compared and analyzed in the four methods. Results in slope variation, double mass curve, and water balance method except rainfall-runoff relationship method are of good agreement. And the rainfall-runoff relationship, double mass curve, and slope variation method are all of great stability. The four methods and availability evaluation of them could provide a reference to quantification in the contributions of climate changes and human activities to runoff at similar basins in the future.
Preoperative Factors Associated with Infiltrative Histologic Growth Patterns in Extremity Soft Tissue Sarcoma
Authors: Park Jong Woong , Kim Han-Soo , Lee Cheol , Yoo Hye Jin , Yun Ji Yeon , Han Ilkyu
Published: July 2017

Soft tissue sarcoma (STS) with an infiltrative histologic growth pattern, when compared to STS with an expansile pattern, may pose difficulties in local control. Preoperative assessment of the presence of infiltrative histologic growth pattern would be helpful in deciding treatment strategies. A review of 144 patients who underwent surgery for extremity STS was performed. Microscopically, the histologic growth pattern was defined as infiltrative if the penetration of the tumor cells into the surrounding tissue was observed. Possible clinicopathologic factors that might be associated with infiltrative histologic growth pattern were investigated with regard to patient demographics, tumor characteristics, and MRI findings. Of the 144 tumors, 71 (49%) showed infiltrative histologic growth pattern. On multivariate analysis, histological subtypes other than liposarcoma (OR = 4.57,p=0.02) and infiltrative border on MRI (OR = 2.48,p=0.01) were independent factors associated with infiltrative histologic growth pattern. Predictive index based on these two factors showed a significant improved accuracy (ROC-AUC = 0.647) for predicting infiltrative histologic growth pattern compared to either factor alone. Our data suggests that liposarcoma histology and tumor border on MRI can predict histologic growth pattern in extremity STS.
Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes
Authors: Bayer Andreas , Tohidnezhad Mersedeh , Lammel Justus , Lippross Sebastian , Behrendt Peter , Klüter Tim , Pufe Thomas , Jahr Holger , Cremer Jochen , Rademacher Franziska , Gläser Regine , Harder Jürgen
Published: July 2017

Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.
MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression
Authors: Jia Aijun , Wang Yueling , Sun Wenjin , Xiao Bing , Wei Yan , Qiu Lulu , Mu Lin , Xu Li , Li Jianmin , Zhang Xiufeng , Liu Da , Peng Cong , Zhang Dongshan , Xiang Xudong
Published: July 2017

Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4+ T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4+ T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. Under overexpression or silencing of the MBD2 and IRF4 gene, the differentiation of Th17 cells and IL-17 secretion showed positive changes. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was no significant difference in the expression of MBD2 under overexpression or silencing of the IRF4 gene. These data provide novel insights into epigenetic regulation of severe asthma.
Effects of Shrinkage Reducing Agent and Expansive Admixture on the Volume Deformation of Ultrahigh Performance Concrete
Authors: Anshuang Su , Ling Qin , Shoujie Zhang , Jiayang Zhang , Zhaoyu Li
Published: July 2017

This paper investigated the influences of shrinkage reducing agent and expansive admixture on autogenous and drying shrinkage of ultrahigh performance concrete (UHPC) containing antifoaming admixture. The shrinkage reducing agent was used at dosage of 0.5%, 1%, and 2% and the expansive admixture was used at dosage of 2% to 4% by mass of cementitious material. The results show that the air content of UHPC increases with the higher addition of shrinkage reducing agent and expansive admixtures. However, the fluidity, compressive strength, and shrinkage of UHPC exhibit a declining tendency. The usage of expansive agent at dosage of 4% significantly reduces the shrinkage of UHPC. The 7-day autogenous shrinkage was decreased by 16.0% and 28-day drying shrinkage was decreased by 29.5%, respectively. Shrinkage reducing agent at dosage of 2% reduced the 7-day autogenous shrinkage by 44.3% and 28-day drying shrinkage by 50.2%. Compared with expansive admixture, shrinkage reducing agent exhibits more efficient shrinkage reduction effect on UHPC.
Appropriate Weaning Practice and Associated Factors among Infants and Young Children in Northwest Ethiopia
Authors: Bewket Zeleke Liknaw , Welday Gebremichael Mengistu , Mehretie Adinew Yohannes , Abebe Gelaw Kelemeu
Published: July 2017

Background. The right nutrition from the start of a pregnancy to the child’s second birthday has a profound impact on the future health, wellbeing, and success of a child. This can be achieved through proper maternal nutrition during pregnancy, exclusive breastfeeding, and appropriate weaning practice. Objective. This study was aimed at assessing appropriate weaning practice and associated factors among infants and young children aged 6–23 months in Feres Bet Town, Northwest Ethiopia. Methods. A community based cross-sectional study was conducted among 351 children aged 6–23 months. Simple random sampling technique was used to select study participants. Interviewer administered questionnaires were used. Bivariate and multivariable logistic regression analyses were employed to identify factors associated with appropriate weaning practice. Results. Nearly quarter (23.9%) of mothers have practiced appropriate weaning. Proportion of children who started consumption of weaning food timely and met the recommended dietary diversity was 61.5% and 43.9%, respectively. Child age [AOR (Adjusted Odds Ratio): 7.04], husband’s occupation [AOR: 6.85], and maternal weaning advice [AOR: 4.38] were positively associated with appropriate weaning practice, while family size [AOR: 0.28] showed negative association. Conclusion. Appropriate weaning practice was found to be low. Health education at community level and one-on-one advice for mothers in health institutions are highly recommended to improve appropriate weaning.
Biochemical, Molecular, and Clinical Characterization of Succinate Dehydrogenase Subunit A Variants of Unknown Significance
Authors: Bannon Amber E. , Kent Jason , Forquer Isaac , Town Ajia , Klug Lillian R. , McCann Kelly , Beadling Carol , Harismendy Oliver , Sicklick Jason K. , Corless Christopher , Shinde Ujwal , Heinrich Michael C.
Published: July 2017

Purpose: Patients who inherit a pathogenic loss-of-function genetic variant involving one of the four succinate dehydrogenase (SDH) subunit genes have up to an 86% chance of developing one or more cancers by the age of 50. If tumors are identified and removed early in these high-risk patients, they have a higher potential for cure. Unfortunately, many alterations identified in these genes are variants of unknown significance (VUS), confounding the identification of high-risk patients. If we could identify misclassified SDH VUS as benign or pathogenic SDH mutations, we could better select patients for cancer screening procedures and remove tumors at earlier stages.

Experimental Design: In this study, we combine data from clinical observations, a functional yeast model, and a computational model to determine the pathogenicity of 22 SDHA VUS. We gathered SDHA VUS from two primary sources: The OHSU Knight Diagnostics Laboratory and the literature. We used a yeast model to identify the functional effect of a VUS on mitochondrial function with a variety of biochemical assays. The computational model was used to visualize variants' effect on protein structure.

Results: We were able to draw conclusions on functional effects of variants using our three-prong approach to understanding VUS. We determined that 16 (73%) of the alterations are actually pathogenic, causing loss of SDH function, and six (27%) have no effect upon SDH function.

Conclusions: We thus report the reclassification of the majority of the VUS tested as pathogenic, and highlight the need for more thorough functional assessment of inherited SDH variants. Clin Cancer Res; 23(21); 6733–43. ©2017 AACR.
3-D Volume Assessment of the Corpus Callosum and Cerebellar Vermis Using Various Volume Acquisition and Post-Processing Protocols
Authors: Frisova Veronika , Srutova Martina , Hyett Jon
Published: July 2017

Objectives: To determine which 3-D techniques are most effective for “real time” prenatal ultrasound assessment of the corpus callosum and cerebellar vermis. Methods: A prospective study involving 100 consecutive normal singleton pregnancies attending routine anomaly scan at 19-23 weeks' gestation. Midsagittal structures of the fetal brain were assessed using six different methods of 3-D image acquisition and three post-processing techniques. The quality of the resulting images were then assessed and scored by a second operator. The significance of the difference between various techniques was assessed using the Friedman test. Results: The best method for visualization of both corpus callosum and cerebellar vermis in one image involved 3-D acquisition in a sagittal plane through the sagittal suture with manipulated 3-D OVIX™ (Oblique View eXtended Imaging) reconstruction. Five other methods scored closely and were not significantly different; all were based on 3-D acquisition in the sagittal plane through either sagittal suture or anterior fontanel. Conclusions: We have applied described techniques for 3-D central nervous system volume acquisition and have shown that the best method of assessment, allowing assessment of both the corpus callosum and the cerebellar vermis, involves midsagittal acquisition through the sagittal suture with 3-D OVIX reconstruction. This technique can be applied successfully in 83% of cases.
Prevalence of Primary Headache Disorders in Kuwait
Authors: Al-Hashel Jasem Yousef , Ahmed Samar Farouk , Alroughani Raed
Published: July 2017

Background: Only an insignificant quantum of data exists on the prevalence of primary headaches among those living in Kuwait. We aimed to determine the prevalence of primary headaches among the Kuwaiti population. Methods: This community-based study included Kuwaiti population aged 18-65 years. Using systematic random sampling, data was collected by the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation questionnaire. Responses to the diagnostic questions were transformed into diagnoses algorithmically to confirm the diagnosis of primary headache. Results: A total of 15,523 patients were identified of whom 9,527 (61%) were diagnosed with primary headache disorder; a female predominance of 62.2% was observed. The mean age was 34.84 ± 10.19. Tension-type headache (TTH) was the most prevalent at 29% followed by episodic migraine (23.11%), chronic migraine (5.4%), and medication overuse headache (2.4%). Primary headache prevalence declined steadily from 71% in those aged 18-30 years to 23% in those over 50 (p < 0. 037). The female:male ratio was 1.7:1. Frequency and severity of primary headache were correlated significantly with lost work days (r = 0.611, p < 0.001 and r = 0.102, p = 0.001, respectively). Conclusions. In Kuwait, primary headache disorder is more frequent in young adults and females. TTH followed by episodic migraine were the more prevalent types of headache. Higher frequency and severe headaches were associated with increasing social and work-related burden.
Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice
Authors: Wu Mu-chao , Ye Wei-ran , Zheng Yi-jia , Zhang Shan-shan
Published: July 2017

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.