bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wider neck circumference is related to severe asthma in children
Authors: Hacihamdioglu Bulent , Arslan Mutluay , Yeşilkaya Ediz , Gok Faysal , Yavuz Suleyman Tolga 
Published: May 2015

AbstractBackgroundObesity is an established risk factor for asthma in children. Measures of central obesity are reported to be more associated with the severity of asthma in adults. The aim of the study was to investigate the association between fat distribution, which is determined by anthropometric measures including neck circumference (NC) and asthma severity in children.MethodsChildren with asthma who were followed in our pediatric allergy unit were consecutively recruited. Asthma severity was graded according to GINA guidelines. Children whose asthma was controlled with Step 1 or 2 treatment options formed Group 1 (mild asthma), whereas children who needed Step 3, 4, or 5 treatment options formed Group 2 (moderate‐to‐severe asthma). Anthropometric measures including height, weight, NC, waist circumference, and hip circumference were obtained.ResultsA total of 127 children (82 male, 64.6%) with a median age of 8.3 (6.4–11.3) years were included. Atopy was present in 77 (60.6%) patients. 91 patients (71.6) were in the mild asthma group. NC of children with severe asthma was significantly wider than children with mild asthma (29.0 cm (27.0–32.0) vs. 28.0 (26.0–30.0), p = 0.019). The prevalence of children with NC higher than 90th percentile was also more frequent in children with severe asthma (15 [41.7%] vs. 21 [23.1%]). Result of multivariable logistic regression analysis revealed that presence of NC >90th percentile was associated with severe asthma in children (odds ratio; [95% confidence interval] (2.52 [1.05–6.01]; p = 0.038).ConclusionsNeck circumference, which is a simple anthropometric tool, is associated with asthma severity in children.
Considerations for Systemic Anticoagulation in ESRD
Authors: Dager William E. , Tsu Laura V. , Pon Tiffany K. 
Published: May 2015

AbstractIn the setting of end‐stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end‐stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low‐molecular‐weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.
Exploring Intuitions on Moral Twin Earth: A Reply to Sonderholm
Authors: Horgan Terry , Timmons Mark 
Published: May 2015

AbstractIn his 2013 Theoria article, “Unreliable Intuitions: A New Reply to the Moral Twin‐Earth Argument,” Jorn Sonderholm attempts to undermine our moral twin earth (MTE) argument against Richard Boyd's moral semantics by debunking the semantic intuitions that are prompted by reflection on the thought experiment featured in the MTE argument. We divide our reply into three main sections. In section 1, we briefly review Boyd's moral semantics and our MTE argument against this view. In section 2, we set forth what we take to be Sonderholm's master debunking argument, along with his proposed Boydian explanation of the semantic intuitions he seeks to debunk. Then in section 3, we mount our defence of the semantic intuitions under scrutiny, arguing on abductive grounds that, contrary to Sonderholm, the semantic intuitions generated by reflection on MTE scenarios are to be trusted in evaluating the plausibility of Boydian moral semantics. Section 4 is our summary and conclusion.
Genetic Identification of SEMA3F as an Antilymphangiogenic Metastasis Suppressor Gene in Head and Neck Squamous Carcinoma
Authors: Doçi Colleen L. , Mikelis Constantinos M. , Lionakis Michail S. , Molinolo Alfredo A. , Gutkind J. Silvio 
Published: May 2015

Abstract
Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCCs are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculature for malignant dissemination; however, the molecular mechanisms underlying lymphangiogenesis in HNSCC is still poorly understood. Of interest, we found that an axon guidance molecule, Semaphorin 3F (SEMA3F), is among the top 1% underexpressed genes in HNSCC, and that genomic loss of SEMA3F correlates with increased metastasis and decreased survival. SEMA3F acts on its coreceptors, plexins and neuropilins, among which neuropilin-2 (NRP2) is highly expressed in lymphatic endothelial cells (LEC) but not in oral epithelium and most HNSCCs. We show that recombinant SEMA3F promotes LEC collapse and potently inhibits lymphangiogenesis in vivo. By reconstituting all possible plexin and neuropilin combinations, we found that SEMA3F acts through multiple receptors, but predominantly requires NRP2 to signal in LECs. Using orthotopic HNSCC metastasis mouse models, we provide direct evidence that SEMA3F re-expression diminishes lymphangiogenesis and lymph node metastasis. Furthermore, analysis of a large tissue collection revealed that SEMA3F is progressively lost during HNSCC progression, concomitant with increased tumor lymphangiogenesis. SEMA3F is localized to 3p21, an early and frequently deleted locus in HNSCC and many other prevalent human malignancies. Thus, SEMA3F may represent an antilymphangiogenic metastasis suppressor gene widely lost during cancer progression, hence serving as a prognostic biomarker and an attractive target for therapeutic intervention to halt metastasis. Cancer Res; 75(14); 2937–48. ©2015 AACR.
A Potential Problem with the Application of Moist Static Energy in Tropical Cyclone Studies
Authors: Ma Zhanhong , Fei Jianfang , Huang Xiaogang , Cheng Xiaoping 
Published: May 2015

Abstract
The moist static energy (MSE) is derived from the first law of thermodynamics and has been widely used in tropical cyclone (TC) studies because of its energetic and conventionally recognized conservation properties. This study investigates the validation of the MSE application in TC systems based on cloud-resolving numerical simulations. By examining the approximations made in deriving the MSE, neglecting the horizontal advection of pressure (namely, the generation of kinetic energy) relative to the vertical advection of pressure is found to be in error in the boundary layer of TCs with the horizontal advection of pressure even being several times larger than the vertical advection of pressure near the surface. Such a problematic approximation has broken down the conservation property of MSE in adiabatic conditions. An investigation of the energetic characteristics based on an MSE budget equation demonstrates that the MSE has created significant bias in evaluating the energy transport in the inner region of the TC boundary layer. Neglecting the kinetic energy conversion term in the boundary layer leads to a more strengthened cool-pool feature of MSE relative to the equivalent potential temperature; therefore, the interchangeable relationship between these two terms may also be inaccurate in the boundary layer. It is concluded that, although the MSE is an instrumental term for TC studies, caution should be taken when it is used in the boundary layer of TCs.
Spatial Variability of Surface-Level State Variables over Arctic Sea Ice
Authors: Andreas Edgar L , Jordan Rachel E. 
Published: May 2015

AbstractNumerical models of the atmosphere, oceans, and sea ice are divided into horizontal grid cells that can range in size from a few kilometers to hundreds of kilometers. In these models, many surface-level variables are assumed to be uniform over a grid cell. Using a year of in situ data from the experiment to study the Surface Heat Budget of the Arctic Ocean (SHEBA), the authors investigate the accuracy of this assumption of gridcell uniformity for the surface-level variables pressure, air temperature, wind speed, humidity, and incoming longwave radiation. The paper bases its analysis on three statistics: the monthly average and, for each season, the spatial correlation function and the spatial bias. For five SHEBA sites, which had a maximum separation of 12 km, the analysis supports the assumption of gridcell uniformity in pressure, air temperature, wind speed, and humidity in all seasons. In winter, when the incidence of fractional cloudiness is largest, the incoming longwave radiation may not be uniform over a grid cell. In other seasons, the bimodal distribution in cloud cover—either clear skies or total cloud cover—tends to homogenize the incoming radiation at scales of 12 km and less.
Control Parameters for Track Continuity of Cyclones Passing over the South-Central Appalachian Mountains
Authors: Rostom Riem , Lin Yuh-Lang 
Published: May 2015

AbstractThe tracks of all 42 tropical cyclones (TCs) passing over the south-central Appalachians from the east or west during 1850–2011 are found to be continuous. By estimating the basic-flow and vortex Froude numbers, and the basic-flow and vortex Rossby numbers (U/Nh, Vmax/Nh, U/fLx, and Vmax/fR, respectively; where U is the basic-flow speed, Vmax is the maximum tangential wind speed, N is the buoyancy frequency, h is the mountain height, f is the Coriolis parameter, R is the radius of cyclone center to Vmax, and Lx is the mountain width), from the hurricane reanalysis data, the lack of track discontinuity is explained by weaker blocking associated with lower mountains. The track discontinuity is found to be mainly controlled by Vmax/Nh and Vmax/fR (greater than 1.5 and 4.0, respectively), and less sensitive to U/Nh and U/fLx, consistent with a previous study. It is hypothesized that stronger blocking associated with weaker near-surface tangential winds of extratropical cyclones tends to make their tracks across the Appalachians discontinuous. This hypothesis is verified by investigating 13 heavy snowstorms with discontinuous tracks during 1950–2003. The present results show that all Vmax/Nh fall below 1.5 and all Vmax/fR fall below 4.0. To help understand the dynamics associated with orographic blocking, the 2–5 February 1995 snowstorm is simulated by a numerical model. The simulated results indicate that the upstream Vmax/Nh and Vmax/fR are indeed less than 1.5 and 4.0, respectively. Therefore, it is concluded that track discontinuity of a cyclone passing over a mesoscale mountain is mainly controlled by strong orographic blocking as measured by lower vortex Froude number (i.e., Vmax/Nh) and/or lower vortex Rossby number (i.e., Vmax/fR).
SNOCRAFT: A Learning-Oriented Shorthand Notation for Creating, Representing, and Analyzing Fast Fourier Transform Algorithms
Authors: Meir Robert J. , Rao Sathyanarayan S. 
Published: May 2015

This paper presents a full and well-developed view of the Fast Fourier Transform (FFT). It is intended for the reader who wishes to learn and develop his own fast Fourier algorithm. The approach presented here utilizes the matrix description of fast Fourier transforms. This approach leads to a systematic method for greatly reducing the complexity and the space required by variety of signal flow graph descriptions. This reduced form is called SNOCRAFT. From this representation, it is then shown how one can derive all possible fast Fourier transform algorithms, including the Weinograd Fourier transform algorithm. It is also shown from the SNOCRAFT representation that one can easily compute the number of multiplications and additions required to perform a specified fast Fourier transform algorithm. After an elementary introduction to matrix representation of fast Fourier transform algorithm, the method of generating all possible fast Fourier transform algorithms is presented in detail and is given in three sections. The first section discusses the Generation of SNOCRAFT and the second section illustrates how Operations on SNOCRAFT are made. These operations include inversion and rotation. The last section deals with the FFT Analysis. In this section, examples are provided to illustrate how one counts the number of multiplications and additions involved in performing the transform that one has developed.
Inefficient Phosphorylation of 3′-fluoro-2′-dideoxythymidine in Liver Cells May Explain its Lack of Inhibition of Duck Hepatitis B virus Replication in vivo
Authors: Löfgren B. , Habteyesus A. , Nordenfelt E. , Eriksson S. , Öberg B. 
Published: May 2015

Duck hepatitis B virus (DHBV) was used as a model in the search for antiviral compounds against hepatitis B. The triphosphate of 3′-fluoro-2′,3′-dideoxythymidine (FLT) inhibits DHBV DNA polymerase in vitro. The aim of this investigation was to evaluate the in vivo inhibitory effect of FLT on DHBV in ducks. Four DHBV-positive ducklings were treated with FLT by intraperitoneal injections of 25 mg kg−1, two times daily for 17 days. No decrease of DHBV DNA in serum was observed. Therefore, it was investigated if FLT could be efficiently phosphorylated in duck liver. From DHBV-infected and non-infected duck livers protein extracts were prepared and partially purified by ion-exchange chromatography. Only one enzyme with thymidine (and deoxycytidine) kinase activity was found, corresponding to thymidine kinase 2 (i.e. the mitochondrial type of deoxynucleoside kinase). In contrast to extracts from duck spleen, the liver extracts showed a very low capacity to phosphorylate FLT, and this may explain the failure of FLT to prevent DHBV replication in vivo. These results suggest that new nucleoside analogues designed for treatment of hepatitis B should be evaluated with respect to phosphorylation by enzymes from non-dividing liver cells.
Human T-cell Lymphotropic Viruses: Review and Prospects for Antiviral Therapy
Authors: Palker T. J. 
Published: May 2015

The human T-cell lymphotropic viruses types I and II (HTLV-I, II) pose challenges to researchers and clinicians who seek to unveil mechanisms of viral transformation and pathogenesis. HTLV-I infection in humans is associated with a wide array of primary and secondary diseases ranging from mild immunosuppression to adult T-cell leukaemia/lymphoma and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurological degenerative syndrome. As retroviruses, HTLV-I and II share similar replicative cycles with human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome. However, in contrast to HIV-I which destroys CD4+ T cells, HTLV-I and II can preferentially transform a CD4+ T-cell subset to an unrestricted growth state. HTLV-I and II, along with simian T-lymphotropic virus (STLV) and bovine leukaemia virus (BLV), form a phylogenetic group which is distinct from ungulate, non-human primate and human lentiviruses such as visna, simian immunodeficiency virus (SIV), and human immunodeficiency viruses types 1 and 2. The proviral genome of HTLV-I is flanked at the 5′ and 3′ ends by long terminal repeats (LTR) and is further subdivided into structural gag and env genes, a pro gene encoding an aspartyl protease, a pol gene which encodes reverse transcriptase and endonuclease, and the regulatory gene elements tax and rex. Regions within the LTR contain recognition sites for cellular proteins and the tax gene product that collectively promote viral expression. Tax-mediated activation of cellular genes involved in growth and differentiation is suspected to play a dominant role in the leukaemogenic process associated with HTLV-I infection. Differential rex-regulated splicing of viral message gives rise to transcripts encoding the polyprotein precursor gag-pro-pol (unspliced), envelope (single spliced), or tax/rex (doubly spliced). The 100nm HTLV virion contains an electron-dense core surrounding a divalent-single stranded DNA genome. This core is in turn enclosed by concentric shells of matrix protein and an outer lipid bilayer, the latter acquired as the virus buds from the surface of the infected cell. Envelope glycoproteins associated with the outside of this lipid bilayer can interact with viral receptors on cells and mediate virus entry. Antiviral strategies have been directed at inhibiting viral entry into cells (sulphated and non-sulphated polysaccharides, vaccines), blocking of viral replication (AZT, suramin), intracellular immunization (transdominant repression of rex), and elimination of virus infected cells (IL-2 receptor-directed toxins). Serological screening of the blood supply and curtailing breast feeding of children by HTLV-I + mothers have likely had a major impact in preventing HTLV-I infection.
Synthesis and Evaluation of Anti-Rhinovirus 1B Activity of Oxazolinyl-Isoflavans and -3(2H)-Isoflavenes
Authors: Desideri N. , Conti C. , Sestili I. , Tomao P. , Stein M. L. , Orsi N. 
Published: May 2015

Oxazolinyl-isoflavans and −3(2H)-isoflavenes, substituted or not with a chlorine atom, were synthesized in order to compare their anti-rhinovirus activity with that of previously studied analogous compounds. The activity of the oxazolines and of the esters and acids, which are intermediates in the synthesis, was studied in vitro against rhinovirus serotype 1B infection in HeLa cells. The ability of various non cytotoxic concentrations to interfere with the development of the viral cytopathic effect and plaque formation was examined. All the tested compounds exerted a significant antiviral activity, and most of them were as active as some representative compounds of the oxazolinyl-phenoxyalkylisoxazole (WIN) series. 6-Oxazolinylisoflavan (VI) appeared to be the most interesting compound due to its high activity and therapeutic index. Among the substituted isoflavans and isoflavenes tested so far, the intermediate compound 6-chloro-3 (2H)-isoflavene-4′-carboxylic acid (XIX) was unexpectedly the most potent inhibitor of rhinovirus 1B plaque formation.
In vitro Selection of Human Immunodeficiency Virus Type 1 Resistant to Ro 31-8959 Proteinase Inhibitor
Authors: Dianzani F. , Antonelli G. , Turriziani O. , Riva E. , Dong G. , Bellarosa D. 
Published: May 2015

Human immunodeficiency virus type I (HIV-1) resistant to the proteinase inhibitor Ro 31–8959 has been obtained by growing HIV-IIIB in C8166 cell cultures in the presence of inhibitory concentrations of the drug. Ro 31-8959-resistant HIV-1 obtained after five passages in the presence of the drug was capable of replicating, as measured by infectious virus yield, in the presence of concentrations of Ro 31-8959 able to inhibit completely the replication of the parental HIV-IIIB. Cloning of the Ro 31–8959-resistant viral preparations revealed that a number of different strains of HIV-1 with various degrees of sensitivity to Ro 31–8959 emerged during propagation of HIV-IIIB in C8166 cells in the presence of the drug. The most resistant strain shows an ID50 value of 21.8 nM that is 13.2 fold higher than the value observed in HIV-IIIB infected C8166 cells.
Protective Effect of Carrageenan against Murine Cytomegalovirus Infection in Mice
Authors: Hamasuna R. , Eizuru Y. , Shishime Y. , Minamishima Y. 
Published: May 2015

The protective effect of iota-carrageenan (CAR) was evaluated against murine cytomegalovirus (MCMV) infection in mice. Female ICR mice were challenged intraperitoneally (i.p.) with 3 LD50 of salivary gland-passaged MCMV. More than 0.5 mg of CAR showed a protective effect on mice only when CAR was administered i.p. and then MCMV was inoculated i.p. The protective effect of CAR was evidenced by an increase in plaque-forming unit per LD50 and a decrease in the titre of infectious viruses in the target organs. Neither a virucidal nor a virustatic effect on MCMV was evidenced for CAR. The protective effect of CAR seemed to be host-mediated. Pretreatment of mice with CAR augmented natural killer (NK) activity of the spleen cells without elevating the serum interferon level. However, administration of anti-asialo GM1 antibody did not nullify the inhibitory effect of CAR on virus replication in the target organs. MCMV infection induced leukopenia including neutropenia and lymphopenia in saline-treated mice. Pretreatment with CAR protected mice from those signs, except for slight lymphopenia. Administration of cyclophosphamide induced severe leukopenia including neutropenia and lymphopenia even in CAR-treated mice. Under such conditions, the protective effect of CAR against MCMV infection was abrogated by cyclophosphamide. Thus, the protective effect of CAR seems to be non-NK-mediated.
[Melle4]Cyclosporin, a Novel Natural Cyclosporin with anti-HIV Activity: Structural Elucidation, Biosynthesis and Biological Properties
Authors: Traber R. , Kobel H. , Loosli H.-R. , Senn H. , Rosenwirth B. , Lawen A. 
Published: May 2015

From fermentations of Tolypocladium niveum supplemented with D-threonine, a novel natural cyclosporin, [Melle4]cyclosporin, was isolated. Its structural elucidation is based on amino acid analysis and spectroscopic data; the amino acid sequence was deduced from two-dimensional NMR investigations applied to the iso-derivative of [Melle4]cyclosporin which, in contrast to the natural product, is present as one homogenous conformation in solution. We show that one of the four N-methyl-L-leucine units of cyclosporin A, namely that in position 4, is replaced by N-methyl-L-isoleucine. The putative mechanism by which D-threonine induces in vivo biosynthesis of [Melle4]cyclosporin is discussed. In vitro biosynthesis of [Melle4]cyclosporin was achieved using the previously described enzymatic system [Lawen and Traber (1993) J Biol Chem268: 20452–20465], thereby demonstrating the high affinity of cyclosporin synthetase for isoleucine in position 4. In a long series of cyclosporins obtained by in vitro and in vivo biosynthesis, [Melle4]cyclosporin represents the first example that is devoid of immunosuppressive efficacy while retaining strong binding to cyclophilin. It exerts potent in vitro anti-HIV-1 activity.
A Proposal that Herpesviruses are Co-Factors of HIV Disease
Authors: Griffiths P. D. 
Published: May 2015

There is now extensive evidence that herpesviruses can interact with human immunodeficiency virus (HIV) in vitro. To determine if such interactions could be operative in vivo, evidence from AIDS autopsy series are reviewed. Using basic histopathological techniques, cytomegalovirus (CMV) and HIV coinfection of various individual ceils has been demonstrated. Using cell culture, CMV has been detected in 66% and herpes simplex virus in 11% of patients. Using immunocytochemistry, human herpesvirus type 6 (HHV-6) has been found in virtually all tissue sections. The hypothesis that these viruses contribute to the death of individuals with AIDS is supported by the results of two double-blind, placebo-controlled randomized trials of high-dose aciclovir and an observational study of the same drug. All three studies have shown improved survival. Thus, the case is made that herpesviruses act as co-factors of HIV disease, and that inhibition of such infections represents a potential way of reducing mortality in those with AIDS. This paper was presented as the case for in a debate on ‘Herpesviruses as co-factors of HIV disease’. The case against was made by Don Jeffries (see page 22)