bluuebunny/crossref_metadata_2025 huggingface dataset:
The Agmatine-Containing Poly(Amidoamine) Polymer AGMA1 Binds Cell Surface Heparan Sulfates and Prevents Attachment of Mucosal Human Papillomaviruses
Authors: Cagno Valeria , Donalisio Manuela , Bugatti Antonella , Civra Andrea , Cavalli Roberta , Ranucci Elisabetta , Ferruti Paolo , Rusnati Marco , Lembo David
Published: June 2015

The agmatine-containing poly(amidoamine) polymer AGMA1 was recently shown to inhibit the infectivity of several viruses, including human papillomavirus 16 (HPV-16), that exploit cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The aim of this work was to assess the antiviral activity of AGMA1 and its spectrum of activity against a panel of low-risk and high-risk HPVs and to elucidate its mechanism of action. AGMA1 was found to be a potent inhibitor of mucosal HPV types (i.e., types 16, 31, 45, and 6) in pseudovirus-based neutralization assays. The 50% inhibitory concentration was between 0.34 μg/ml and 0.73 μg/ml, and no evidence of cytotoxicity was observed. AGMA1 interacted with immobilized heparin and with cellular heparan sulfates, exerting its antiviral action by preventing virus attachment to the cell surface. The findings from this study indicate that AGMA1 is a leading candidate compound for further development as an active ingredient of a topical microbicide against HPV and other sexually transmitted viral infections.
Mutation Landscape of Acquired Cross-Resistance to Glycopeptide and β-Lactam Antibiotics in Enterococcus faecium
Authors: Sacco Emmanuelle , Cortes Mélanie , Josseaume Nathalie , Bouchier Christiane , Dubée Vincent , Hugonnet Jean-Emmanuel , Mainardi Jean-Luc , Rice Louis B. , Arthur Michel
Published: June 2015

Bypass of the
d
,
d
-transpeptidase activity of penicillin-binding proteins by an
l
,
d
-transpeptidase (Ldt
fm
) results in resistance to ampicillin and glycopeptides in
Enterococcus faecium
M9, a mutant obtained by nine consecutive selection steps. Resistance requires activation of a cryptic locus for production of the essential tetrapeptide-containing substrate of Ldt
fm
and impaired activity of protein phosphatase StpA. Here, whole-genome sequencing revealed a high mutation rate for the entire selection procedure (79 mutations in 900 generations). Acquisition of a mutation in the mismatch repair gene
mutL
had little impact on the frequency of rifampin-resistant mutants although the mutation spectrum of M9 was typical of impaired MutL with high transversion to transition (40/11) and substitution to deletion (51/28) ratios. M9 did not mainly accumulate neutral mutations since base substitutions occurred more frequently in coding sequences than expected (χ
2
= 5.0;
P
< 0.05) and silent mutations were underrepresented (χ
2
= 5.72;
P
< 0.02). None of the mutations directly affected recognition of the tetrapeptide substrate of Ldt
fm
by peptidoglycan synthesis enzymes. Instead, mutations appear to remodel regulatory circuits involving two-component regulatory systems and sugar metabolism. The high number of mutations required for activation of the
l
,
d
-transpeptidase pathway may strongly limit emergence of cross-resistance to ampicillin and glycopeptides by this mechanism.
Influenza A(H7N9) Virus Acquires Resistance-Related Neuraminidase I222T Substitution When Infected Mallards Are Exposed to Low Levels of Oseltamivir in Water
Authors: Gillman Anna , Nykvist Marie , Muradrasoli Shaman , Söderström Hanna , Wille Michelle , Daggfeldt Annika , Bröjer Caroline , Waldenström Jonas , Olsen Björn , Järhult Josef D.
Published: June 2015

Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and new human IAVs often contain gene segments originating from avian IAVs. Treatment options for severe human influenza are principally restricted to neuraminidase inhibitors (NAIs), among which oseltamivir is stockpiled in preparedness for influenza pandemics. There is evolutionary pressure in the environment for resistance development to oseltamivir in avian IAVs, as the active metabolite oseltamivir carboxylate (OC) passes largely undegraded through sewage treatment to river water where waterfowl reside. In an
in vivo
mallard (
Anas platyrhynchos
) model, we tested if low-pathogenic avian influenza A(H7N9) virus might become resistant if the host was exposed to low levels of OC. Ducks were experimentally infected, and OC was added to their water, after which infection and transmission were maintained by successive introductions of uninfected birds. Daily fecal samples were tested for IAV excretion, genotype, and phenotype. Following mallard exposure to 2.5 μg/liter OC, the resistance-related neuraminidase (NA) I222T substitution, was detected within 2 days during the first passage and was found in all viruses sequenced from subsequently introduced ducks. The substitution generated 8-fold and 2.4-fold increases in the 50% inhibitory concentration (IC
50
) for OC (
P
< 0.001) and zanamivir (
P
= 0.016), respectively. We conclude that OC exposure of IAV hosts, in the same concentration magnitude as found in the environment, may result in amino acid substitutions, leading to changed antiviral sensitivity in an IAV subtype that can be highly pathogenic to humans. Prudent use of oseltamivir and resistance surveillance of IAVs in wild birds are warranted.
Effective Inhibition of HIV-1 Production by Short Hairpin RNAs and Small Interfering RNAs Targeting a Highly Conserved Site in HIV-1 Gag RNA Is Optimized by Evaluating Alternative Length Formats
Authors: Scarborough Robert J. , Adams Kelsey L. , Daher Aïcha , Gatignol Anne
Published: June 2015

We have previously identified a target site in HIV-1 RNA that was particularly accessible to a ribozyme and a short hairpin RNA (shRNA). To design small interfering RNAs (siRNAs) targeting this site, we evaluated the effects of siRNAs with different lengths on HIV-1 production. The potency and efficacy of these siRNAs were dependent on the length of their intended sense strand with trends for symmetrical and asymmetrical formats that were similar. Although a typical canonical format with a 21-nucleotide (nt) sense strand was effective at inhibiting HIV-1 production, Dicer substrate siRNAs (dsiRNAs) with the longest lengths (27 to 29 nucleotides) were the most effective. Induction of double-stranded RNA immune responses and effects on cell viability were not detected in cells transfected with different siRNAs, suggesting that the differences observed were not related to indirect effects on HIV-1 production. For the corresponding shRNA designs, a different trend in potency and efficacy against HIV-1 production was observed, with the most effective shRNAs having stem lengths from 20 to 27 bp. Our results highlight the importance of evaluating different designs to identify the best siRNA and shRNA formats for any particular target site and provide a set of highly effective molecules for further development as drug and gene therapies for HIV-1 infection.
Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection
Authors: Crepin Valerie F. , Habibzay Maryam , Glegola-Madejska Izabela , Guenot Marianne , Collins James W. , Frankel Gad
Published: June 2015

The hallmarks of enteropathogenic
Escherichia coli
(EPEC) infection are formation of attaching and effacing (A/E) lesions on mucosal surfaces and actin-rich pedestals on cultured cells, both of which are dependent on the type III secretion system effector Tir. Following translocation into cultured cells and clustering by intimin, Tir Y474 is phosphorylated, leading to recruitment of Nck, activation of N-WASP, and actin polymerization via the Arp2/3 complex. A secondary, weak, actin polymerization pathway is triggered via an NPY motif (Y454). Importantly, Y454 and Y474 play no role in A/E lesion formation on mucosal surfaces following infection with the EPEC-like mouse pathogen
Citrobacter rodentium
. In this study, we investigated the roles of Tir segments located upstream of Y451 and downstream of Y471 in
C. rodentium
colonization and A/E lesion formation. We also tested the role that Tir residues Y451 and Y471 play in host immune responses to
C. rodentium
infection. We found that deletion of amino acids 382 to 462 or 478 to 547 had no impact on the ability of Tir to mediate A/E lesion formation, although deletion of amino acids 478 to 547 affected Tir translocation. Examination of enterocytes isolated from infected mice revealed that a
C. rodentium
strain expressing Tir_Y451A/Y471A recruited significantly fewer neutrophils to the colon and triggered less colonic hyperplasia on day 14 postinfection than the wild-type strain. Consistently, enterocytes isolated from mice infected with
C. rodentium
expressing Tir_Y451A/Y471A expressed significantly less CXCL1. These result show that Tir-induced actin remodeling plays a direct role in modulation of immune responses to
C. rodentium
infection.
Neisseria gonorrhoeae Modulates Cell Death in Human Endocervical Epithelial Cells through Export of Exosome-Associated cIAP2
Authors: Nudel Kathleen , Massari Paola , Genco Caroline A.
Published: June 2015

Several bacterial pathogens persist and survive in the host by modulating host cell death pathways. We previously demonstrated that
Neisseria gonorrhoeae
, a Gram-negative pathogen responsible for the sexually transmitted infection gonorrhea, protects against exogenous induction of apoptosis in human cervical epithelial cells. However, induction of cell death by
N. gonorrhoeae
has also been reported in other cell types. The mechanisms by which
N. gonorrhoeae
modulates cell death are not clear, although a role for the inhibitor of apoptosis-2 (cIAP2) has been proposed. In this study, we confirmed that
N. gonorrhoeae
induces production of cIAP2 in human cervical epithelial cells. High levels of intracellular cIAP2 were detected early after
N. gonorrhoeae
stimulation, which was followed by a marked decrease at 24 h. At this time point, we observed increased levels of extracellular cIAP2 associated with exosomes and an overall increase in production of exosomes. Inhibition of cIAP2 in
N. gonorrhoeae
-stimulated epithelial cells resulted in increased cell death and interleukin-1β (IL-1β) production. Collectively these results indicate that
N. gonorrhoeae
stimulation of human endocervical epithelial cells induces the release of cIAP2, an essential regulator of cell death and immune signaling.
Identification of YsaP, the Pilotin of the Yersinia enterocolitica Ysa Type III Secretion System
Authors: Rau Reina , Darwin Andrew J.
Published: June 2015

Secretins are multimeric outer membrane pore-forming proteins found in complex export systems in Gram-negative bacteria. All type III secretion systems (T3SSs) have a secretin, and one of these is the YsaC secretin of the chromosomally encoded Ysa T3SS of
Yersinia enterocolitica
. In some cases, pilotin proteins, which are outer membrane lipoproteins, are required for their cognate secretins to multimerize and/or localize to the outer membrane. However, if secretin multimers mislocalize to the inner membrane, this can trigger the protective phage shock protein (Psp) stress response. During a screen for mutations that suppress YsaC toxicity to a
psp
null strain, we isolated several independent mutations predicted to increase expression of the YE3559 gene within the Ysa pathogenicity island. YE3559, which we have named
ysaP
, is predicted to encode a small outer membrane lipoprotein, and this location was confirmed by membrane fractionation. Elevated
ysaP
expression increased the steady-state level of YsaC but made it less toxic to a
psp
null strain, and it also decreased YsaC-dependent induction of
psp
gene expression. Subsequent experiments showed that YsaP was not required for YsaC multimerization but was required for the multimers to localize to the outer membrane. Consistent with this, a
ysaP
null mutation compromised protein export by the Ysa T3SS. All these observations suggest that YsaP is the pilotin for the YsaC secretin. This is only the second pilotin to be characterized for
Yersinia
and one of only a small number of pilotins described for all bacteria.

IMPORTANCE
Secretins are essential for the virulence of many bacterial pathogens and also play roles in surface attachment, motility, and competence. This has generated considerable interest in understanding how secretins function. However, their fundamental differences from typical outer membrane proteins have raised various questions about secretins, including how they are assembled into outer membrane multimers. Pilotin proteins facilitate the assembly of some secretins, but only a small number of pilotins have been identified, slowing efforts to understand common and distinct features of secretin assembly. This study provides an important advance by identifying a novel member of the pilotin family and also demonstrating a method of pilotin discovery that could be broadly applied.
Functional Dependence between Septal Protein SepJ from Anabaena sp. Strain PCC 7120 and an Amino Acid ABC-Type Uptake Transporter
Authors: Escudero Leticia , Mariscal Vicente , Flores Enrique
Published: June 2015

In the diazotrophic filaments of heterocyst-forming cyanobacteria, two different cell types, the CO
2
-fixing vegetative cells and the N
2
-fixing heterocysts, exchange nutrients, including some amino acids. In the model organism
Anabaena
sp. strain PCC 7120, the SepJ protein, composed of periplasmic and integral membrane (permease) sections, is located at the intercellular septa joining adjacent cells in the filament. The unicellular cyanobacterium
Synechococcus elongatus
strain PCC 7942 bears a gene,
Synpcc7942_1024
(here designated
dmeA
), encoding a permease homologous to the SepJ permease domain.
Synechococcus
strains lacking
dmeA
or lacking
dmeA
and expressing
Anabaena
sepJ
were constructed. The
Synechococcus
dmeA
mutant showed a significant 22 to 32% decrease in the uptake of aspartate, glutamate, and glutamine, a phenotype that could be partially complemented by
Anabaena
sepJ
.
Synechococcus
mutants of an ATP-binding-cassette (ABC)-type transporter for polar amino acids showed >98% decreased uptake of glutamate irrespective of the presence of
dmeA
or
Anabaena
sepJ
in the same strain. Thus,
Synechococcus
DmeA or
Anabaena
SepJ is needed to observe full (or close to full) activity of the ABC transporter. An
Anabaena
sepJ
deletion mutant was significantly impaired in glutamate and aspartate uptake, which also in this cyanobacterium requires the activity of an ABC-type transporter for polar amino acids. SepJ appears therefore to generally stimulate the activity of cyanobacterial ABC-type transporters for polar amino acids. Conversely, an
Anabaena
mutant of three ABC-type transporters for amino acids was impaired in the intercellular transfer of 5-carboxyfluorescein, a SepJ-related property. Our results unravel possible functional interactions in transport elements important for diazotrophic growth.

IMPORTANCE
Membrane transporters are essential for many aspects of cellular life, from uptake and export of substances in unicellular organisms to intercellular molecular exchange in multicellular organisms. Heterocyst-forming cyanobacteria such as
Anabaena
represent a unique case of multicellularity, in which two cell types exchange nutrients and regulators. The SepJ protein located at the intercellular septa in the filaments of
Anabaena
contains a permease domain of the drug/metabolite transporter (DMT) superfamily that somehow contributes to intercellular molecular transfer. In this work, we have found that SepJ stimulates the activity of a polar amino acid uptake transporter of the ATP-binding-cassette (ABC) superfamily, which could itself affect an intercellular transfer activity related to SepJ, thus unraveling possible functional interactions between these different transporters.
Single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery: a meta-analysis of randomised placebo-controlled studies
Authors: Wang Yi-lun , Zeng Chao , Xie Dong-xing , Yang Ye , Wei Jie , Yang Tuo , Li Hui , Lei Guang-hua
Published: June 2015

Objectives

To evaluate the efficacy and safety of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery.

Design

Meta-analysis.

Data sources and study eligibility criteria

A comprehensive literature search, using Medline (1966–2014), the Cochrane Central Register of Controlled Trials and Embase databases, was conducted to identify randomised placebo-controlled trials that used a combination of single-dose intra-articular bupivacaine and morphine for postoperative pain relief.

Results

12 articles were included in this meta-analysis. The mean visual analogue scale (VAS) scores of the bupivacaine plus morphine group were significantly lower than those of the placebo group (weighted mean difference (WMD) −1.75; 95% CI −2.16 to −1.33; p<0.001). The VAS scores at the last follow-up time point (last VAS scores) of the bupivacaine plus morphine group were also significantly lower than those of the placebo group (WMD −1.46; 95% CI −1.63 to −1.29; p<0.001). The number of patients requiring supplementary analgesia was also significantly reduced (RR 0.60; 95% CI 0.39 to 0.93; p=0.02), while there was no significant difference in the time to first analgesic request (WMD 3.46; 95% CI −1.81 to 8.72; p=0.20) or short-term side effects (RR 1.67; 95% CI 0.65 to 4.26; p=0.29).

Conclusions

The administration of single-dose intra-articular bupivacaine plus morphine after knee arthroscopic surgery is effective for pain relief, and its short-term side effects remain similar to saline placebo.
Hybrid short-term freeway speed prediction methods based on periodic analysis
Authors: Zou Yajie , Hua Xuedong , Zhang Yanru , Wang Yinhai
Published: June 2015

Short-term traffic speed forecasting is an important issue for developing Intelligent Transportation Systems applications. So far, a number of short-term speed prediction approaches have been developed. Recently, some multivariate approaches have been proposed to consider the spatial and temporal correlation of traffic data. However, as traffic data often demonstrates periodic patterns, the existing methodologies often fail to take into account spatial and temporal information as well as the periodic features of traffic data simultaneously in the multi-step prediction. This paper comprehensively evaluated the multi-step prediction performance of space time (ST) model, vector autoregression (VAR), and autoregressive integrated moving average (ARIMA) models using the 5 minute freeway speed data collected from five loop detectors located on an eastbound segment of Interstate 394 freeway, in Minnesota. To further consider the cyclical characteristics of freeway speed data, hybrid prediction approaches were proposed to decompose speed into two different components: a periodic trend and a residual part. A trigonometric regression function is introduced to capture the periodic component and the residual part is modeled by the ST, VAR, and ARIMA models. The prediction results suggest that for multi-step freeway speed prediction, as the time step increases, the ST model demonstrates advantages over the VAR and ARIMA models. Comparisons among the ST, VAR, ARIMA, and hybrid models demonstrated that modeling the periodicity and the residual part separately can better interpret the underlining structure of the speed data. The proposed hybrid prediction approach can accommodate the periodic trends and provide more accurate prediction results when the forecasting horizon is greater than 30 min.
Distributed One-Class Support Vector Machine
Authors: Castillo Enrique , Peteiro-Barral Diego , Berdiñas Bertha Guijarro , Fontenla-Romero Oscar
Published: June 2015

This paper presents a novel distributed one-class classification approach based on an extension of the ν-SVM method, thus permitting its application to Big Data data sets. In our method we will consider several one-class classifiers, each one determined using a given local data partition on a processor, and the goal is to find a global model. The cornerstone of this method is the novel mathematical formulation that makes the optimization problem separable whilst avoiding some data points considered as outliers in the final solution. This is particularly interesting and important because the decision region generated by the method will be unaffected by the position of the outliers and the form of the data will fit more precisely. Another interesting property is that, although built in parallel, the classifiers exchange data during learning in order to improve their individual specialization. Experimental results using different datasets demonstrate the good performance in accuracy of the decision regions of the proposed method in comparison with other well-known classifiers while saving training time due to its distributed nature.
Dielectric and impedance spectroscopic studies of 0.8BaTiO3–0.2Bi0.5K0.5TiO3lead-free ceramics
Authors: Ramesh M. N. V. , Ramesh K. V.
Published: June 2015

0.8 BaTiO3–0.2 Bi0.5K0.5TiO3(BT–BKT20) lead-free ceramics were prepared by conventional solid state reaction method followed by high energy ball milling. The formation of a single phase tetragonal structure in the material was confirmed by X-ray diffraction. Frequency and temperature-dependent dielectric studies show relaxor behavior in the BT–BKT20 which was found to obey modified Curie–Weiss law with degree of diffuseness 1.573. Complex impedance and electric modulus spectroscopy studies reveal temperature-dependent relaxation process in the material. The Cole–Cole plots were measured at high temperatures at which grain effect was observed. Impedance and electric modulus spectroscopy studies show non-Debye kind of conductivity relaxation process in the present material. Activation energies were calculated from impedance and electric modulus spectroscopy and the values of activation energy indicated that the conduction is ionic in nature. AC and DC conductivity have been measured and studied at different temperatures.
Limit Cycles in a Class of Quartic Kolmogorov Model with Three Positive Equilibrium Points
Authors: Du Chaoxiong , Liu Yirong , Zhang Qi
Published: June 2015

Limit cycle bifurcation problem of Kolmogorov model is interesting and significant both in theory and applications. In this paper, we will focus on investigating limit cycles for a class of quartic Kolmogorov model with three positive equilibrium points. Perturbed model can bifurcate three small limit cycles near (1, 2) or (2, 1) under a certain condition and can bifurcate one limit cycle near (1, 1). In addition, we have given some examples of simultaneous Hopf bifurcation and the structure of limit cycles bifurcated from three positive equilibrium points. The limit cycle bifurcation problem for Kolmogorov model with several positive equilibrium points are less seen in published references. Our result is good and interesting.
Guess-Work and Reasonings on Centennial Evolution of Surface Air Temperature in Russia: Is it Possible to Build Bifurcation Diagrams Based on Extra-Short Local Observations?
Authors: Kolokolov Yury , Monovskaya Anna
Published: June 2015

Since the bifurcation analysis remains the basic tool to inquire into nonlinear system dynamics, then, theoretically, the bifurcation analysis should be widely used to estimate the evolution of the climate dynamics at a certain geographic point over the last centenary. But it does not occur in practice. A viewpoint how to estimate such evolution is proposed and discussed in the paper. The viewpoint can be briefly formulated as the following: the extra-short timescale, plus the novel conceptual model, plus the modified bifurcation diagrams. So, first, only the data of instrumental measurements (hereafter observations) are used to build the bifurcation diagram, correspondingly, the timescale is restricted by the maximal duration of the reliable observations. In particular, 130-years time series of the land surface air temperature in Russia are analyzed in the paper. Second, the conceptual model (HDS-model) to describe the annual warming–cooling cycle dynamics similar to the dynamics of the hysteresis regulator with double synchronization (HDS-regulator) is introduced. Correspondingly, the local climate dynamics is considered as the dynamics of the system with a variable structure. The main advantage of HDS-model is the possibility to describe quite simply the rich variety of the observable temperature evolution based on the known nonlinear phenomena by the combinations of C-bifurcations (or, in other words, border-collision bifurcations) between three conjugate periodical processes with the same period but different orders of structural changes. Then HDS-hypothesis on the climate dynamics is proposed, where the local temperature evolution is considered under the competition between both amplitude and time quantizations within the Sun–Earth–Moon system. Processing the observations follows the SUC-logic conceptions on the experimental bifurcation analysis that allows to untangle the intricate nonlinear nonstationary behavior of a local climate system by using both special sections (S) and units (U) in a certain consequence (C). As a result, the modified bifurcation diagrams to show the temperature evolution in local climate systems are built under the variation of several bifurcation parameters. The diagrams exhibit intermittency phenomena of high activity in the European part of Russia at least. Generally speaking, HDS-hypothesis gives the good approximation to answer the question whether the observable changes in the local climate dynamics are qualitative and, if yes, in what meaning?
Dynamical Systems with a Codimension-One Invariant Manifold: The Unfoldings and Its Bifurcations
Authors: Saputra Kie Van Ivanky
Published: June 2015

We investigate a dynamical system having a special structure namely a codimension-one invariant manifold that is preserved under the variation of parameters. We derive conditions such that bifurcations of codimension-one and of codimension-two occur in the system. The normal forms of these bifurcations are derived explicitly. Both local and global bifurcations are analyzed and yield the transcritical bifurcation as the codimension-one bifurcation while the saddle-node–transcritical interaction and the Hopf–transcritical interactions as the codimension-two bifurcations. The unfolding of this degeneracy is also analyzed and reveal global bifurcations such as homoclinic and heteroclinic bifurcations. We apply our results to a modified Lotka–Volterra model and to an infection model in HIV diseases.
On ranges of variants of the divisor functions that are dense
Authors: Defant Colin
Published: June 2015

For a real number t, let st be the multiplicative arithmetic function defined by [Formula: see text] for all primes p and positive integers α. We show that the range of a function s-r is dense in the interval (0, 1] whenever r ∈ (0, 1]. We then find a constant ηA ≈ 1.9011618 and show that if r > 1, then the range of the function s-r is a dense subset of the interval [Formula: see text] if and only if r ≤ ηA. We end with an open problem.
On primitivity of Dirichlet characters
Authors: Daileda R. , Jones N.
Published: June 2015

Recall that a Dirichlet character is called imprimitive if it is induced from a character of smaller level, and otherwise it is called primitive. In this paper, we introduce a modification of "inducing to higher level" which causes imprimitive characters to behave primitively, in the sense that the properties of the associated Gauss sum and the functional equation of the attached L-function take on a form usually associated to a primitive character.
The quartic Fermat equation in Hilbert class fields of imaginary quadratic fields
Authors: Lynch Rodney , Morton Patrick
Published: June 2015

It is shown that the quartic Fermat equation x4+ y4= 1 has nontrivial integral solutions in the Hilbert class field Σ of any quadratic field [Formula: see text] whose discriminant satisfies -d ≡ 1 (mod 8). A corollary is that the quartic Fermat equation has no nontrivial solution in [Formula: see text], for p (> 7) a prime congruent to 7 (mod 8), but does have a nontrivial solution in the odd degree extension Σ of K. These solutions arise from explicit formulas for the points of order 4 on elliptic curves in Tate normal form. The solutions are studied in detail and the results are applied to prove several properties of the Weber singular moduli introduced by Yui and Zagier.
A multigroup model for cholera dynamics and control
Authors: Posny Drew , Modnak Chairat , Wang Jin
Published: June 2015

We propose a general multigroup model for cholera dynamics that involves both direct and indirect transmission pathways and that incorporates spatial heterogeneity. Under biologically feasible conditions, we show that the basic reproduction number R0 remains a sharp threshold for cholera dynamics in multigroup settings. We verify the analysis by numerical simulation results. We also perform an optimal control study to explore optimal vaccination strategy for cholera outbreaks.
Interplay between strong Allee effect, harvesting and hydra effect of a single population discrete-time system
Authors: Jana Debaldev , Elsayed Elsayed M.
Published: June 2015

The dynamics of a single population with non-overlapping generations can be described deterministically by a scalar difference equation in this study. A discrete-time Beverton–Holt stock recruitment model with Allee effect, harvesting and hydra effect is proposed and studied. Model with strong Allee effect results from incorporating mate limitation in the Beverton–Holt model. We show that these simple models exhibit some interesting (and sometimes unexpected) phenomena such as the hydra effect, sudden collapses and essential extinction. Along with this, harvesting is a socio-economic issue to continue any system generation after generation. Different dynamical behaviors for these situations have been illustrated numerically also. The biological implications of our analytical and numerical findings are discussed critically.
Unraveling the Tangled Skein: The Evolution of Transcriptional Regulatory Networks in Development
Authors: Rebeiz Mark , Patel Nipam H. , Hinman Veronica F.
Published: June 2015

The molecular and genetic basis for the evolution of anatomical diversity is a major question that has inspired evolutionary and developmental biologists for decades. Because morphology takes form during development, a true comprehension of how anatomical structures evolve requires an understanding of the evolutionary events that alter developmental genetic programs. Vast gene regulatory networks (GRNs) that connect transcription factors to their target regulatory sequences control gene expression in time and space and therefore determine the tissue-specific genetic programs that shape morphological structures. In recent years, many new examples have greatly advanced our understanding of the genetic alterations that modify GRNs to generate newly evolved morphologies. Here, we review several aspects of GRN evolution, including their deep preservation, their mechanisms of alteration, and how they originate to generate novel developmental programs.
(Pro)renin receptor regulates autophagy and apoptosis in podocytes exposed to high glucose
Authors: Li Caixia , Siragy Helmy M.
Published: June 2015

High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62. In contrast, high glucose decreased activation of UNC-51-like kinase-1 (ULK1) by phosphorylating Ser757 and protein levels of microtubule-associated protein-1 light chain 3B (LC3B)-II and Lamp-2. Bafilomycin A1 increased LC3BII and p62 accumulation in high-glucose-treated cells. High glucose reduced the autophagic flux. Confocal microscopy studies showed significant reduction in the protein level of LC3B in response to high glucose. Cyto-ID autophagy staining showed a significant decrease in autophagosome formation with high glucose. In the absence of PRR, activation of Akt with sc-79 or mTOR with MHY-1485 increased p62 accumulation. Caspase-3/7 activity and apoptosis monitored by TUNEL assay were significantly increased in podocytes treated with high glucose. PRR siRNA significantly reversed the effects of high glucose. Based on these data, we conclude that high glucose decreases autophagy and increases apoptosis in mouse podocytes through the PRR/PI3K/Akt/mTOR signaling pathway.
Morbidity and Mortality following Traditional Uvulectomy among Children Presenting to the Muhimbili National Hospital Emergency Department in Dar es Salaam, Tanzania
Authors: Sawe H. R. , Mfinanga J. A. , Ringo F. H. , Mwafongo V. , Reynolds T. A. , Runyon M. S.
Published: June 2015

Background. Traditional uvulectomy is performed as a cultural ritual or purported medical remedy. We describe the associated emergency department (ED) presentations and outcomes.Methods.This was a subgroup analysis of a retrospective review of all pediatric visits to our ED in 2012. Trained abstracters recorded demographics, clinical presentations, and outcomes.Results. Complete data were available for 5540/5774 (96%) visits and 56 (1.0%, 95% CI: 0.7–1.3%) were related to recent uvulectomy, median age 1.3 years (interquartile range: 7 months–2 years) and 30 (54%) were male. Presenting complaints included cough (82%), fever (46%), and hematemesis (38%). Clinical findings included fever (54%), tachypnea (30%), and tachycardia (25%). 35 patients (63%, 95% CI: 49–75%) received intravenous antibiotics, 11 (20%, 95% CI: 10–32%) required blood transfusion, and 3 (5%, 95% CI: 1–15%) had surgical intervention. All were admitted to the hospital and 12 (21%, 95% CI: 12–34%) died. By comparison, 498 (9.1%, 95% CI: 8–10%) of the 5484 children presenting for reasons unrelated to uvulectomy died (p=0.003).Conclusion. In our cohort, traditional uvulectomy was associated with significant morbidity and mortality. Emergency care providers should advocate for legal and public health interventions to eliminate this dangerous practice.
NKG2D and DNAM-1 Ligands: Molecular Targets for NK Cell-Mediated Immunotherapeutic Intervention in Multiple Myeloma
Authors: Fionda Cinzia , Soriani Alessandra , Zingoni Alessandra , Santoni Angela , Cippitelli Marco
Published: June 2015

A pivotal strategy to improve NK cell-mediated antitumor activity involves the upregulation of activating ligands on tumor cells. Enhancement of NK cell-mediated recognition of multiple myeloma cells was reported by us and others showing increased surface expression of NKG2D and DNAM-1 ligands on tumor cells following treatment with a number of chemotherapeutic agents, such as genotoxic drugs or inhibitors of proteasome, histone deacetylases, GSK3, and HSP-90. These compounds have the capability to affect tumor survival but also to activate specific transduction pathways associated with the upregulation of different NK cell activating ligands on the tumor cells. Here, we will summarize and discuss the molecular pathways whereby these drugs can regulate the expression of NK cell activating ligands in multiple myeloma cells.
Method of Integral Equations for the Problem of Electrical Tomography in a Medium with Ground Surface Relief
Authors: Mirgalikyzy Tolkyn , Mukanova Balgaisha , Modin Igor
Published: June 2015

The direct task of the subsurface exploration of a homogeneous medium with surface relief by the resistivity method is analyzed. To calculate the resistivity field for such a medium, the method of integral equations was successfully applied for the first time. The corresponding integral equation for the density of secondary current sources on the surface of the medium was established. The method of computational grid construction, adapted to the characteristics of the surface relief, was developed for the numerical solution of the integral equation. This method enables the calculation of the resistivity field of a point source on a surface that is not smooth and allows for steep ledges. Numerical examples of the calculation of resistivity fields and apparent resistivity are shown. The anomalies of apparent resistivity arising from the deviation of the surface shape from a flat medium were quantitatively established as model examples. Calculations of apparent resistivity for the direct current sounding method were carried out using modifications of the electrical tomography approach.
miR-451a Inhibited Cell Proliferation and Enhanced Tamoxifen Sensitive in Breast Cancer via Macrophage Migration Inhibitory Factor
Authors: Liu Zhenru , Miao Tianyu , Feng Ting , Jiang Zhouhua , Li Mingyuan , Zhou Liming , Li Hong
Published: June 2015

This study aims to investigate the regulative effects of microRNA-451a (miR-451a) on cell proliferation and sensitivity to tamoxifen in breast cancer cells. In cell culture experiments, the lentiviral vectors of pHBLV-miR-451a and pHBLV-miR-451a sponge were constructed and used to transfect MCF-7 and LCC2 cells. The transfection efficiency was tested by fluorescent observation, and cell lines with stable over- or downregulated expression of miR-451a were established. The expression of miR-451a and the target gene macrophage migration inhibitory factor (MIF) were detected by real-time reverse transcriptase polymerase chain reaction and/or western blot. Moreover, MTT assay, colony formation, and Transwell invasion assays were also performed. Data showed that the recombinant lentiviral vectors were constructed correctly, and the virus titer was 1 × 108 CFU/mL. The stable transfected cells were obtained. Overexpression of miR-451a downregulated MIF expression in mRNA and protein levels and inhibited cell proliferation, colony formation, and invasion of breast cancer cells. Downregulation of miR-451a upregulated MIF expression and increased breast cancer cell growth, invasion, and tamoxifen sensitivity. In summary, the miR-451a/MIF pathway may play important roles in the biological properties of breast cancer cells and may be a potential therapeutic target for breast cancer.
Effects of Sheet Resistance on mc-Si Selective Emitter Solar Cells Using Laser Opening and One-Step Diffusion
Authors: Wang Sheng-Shih , Ho Jyh-Jier , Liou Jia-Jhe , Ho Jia-Show , Tsai Song-Yeu , Hung Hsien-Seng , Yeh Chi-Hsiao , Wang Kang L.
Published: June 2015

In order to simplify process procedure and improve conversion efficiency (η), we present new steps of laser opening and one-step POCl3diffusion to fabricate selective emitter (SE) solar cells, in which heavily doped regions (HDR) and lightly doped regions (LDR) were formed simultaneously. For HDR, we divided six cells into two groups for POCl3diffusion with sheet resistance (RS) of 40 Ω/sq (for group A) and 50 Ω/sq (for group B). The dry oxidation duration at a temperature of 850°C was 18, 25, and 35 min for the 3 different cells in each group. This created six SE samples with differentRSpairings for the HDR and LDR. The optimal cell (sample SE2) withRSvalues of 40/81 Ω/Sq in HDR/LDR showed the bestηof 16.20%, open circuit voltage (VOC) of 612.52 mV, and fill factor (FF) of 75.83%. The improvement ratios are 1.57% forηand 14.32% for external quantum efficiency (EQE) as compared with those of the two-step diffusion process of our previous study. Moreover, the one-step laser opening process and omitting the step of removing the damage caused by laser ablation especially reduce chemistry pollution, thus showing ecofriendly process for use in industrial-scale production.
Numerical Solvability and Solution of an Inverse Problem Related to the Gibbs Phenomenon
Authors: Haidar Nassar H. S.
Published: June 2015

We report on the inverse problem for the truncated Fourier series representation of fx∈BV-L,L in a form with a quadratic degeneracy, revealing the existence of the
Gibbs-Wilbraham phenomenon. A new distribution-theoretic proof is proposed for this
phenomenon. The paper studies moreover the iterative numerical solvability and solution of
this inverse problem near discontinuities of fx.
Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients
Authors: Nishimura Yasumitsu , Kumagai-Takei Naoko , Matsuzaki Hidenori , Lee Suni , Maeda Megumi , Kishimoto Takumi , Fukuoka Kazuya , Nakano Takashi , Otsuki Takemi
Published: June 2015

Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme+cells in CD8+lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8+lymphocytes may be stimulated by some kind of “nonself” cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.
MPPT Technique Based on Current and Temperature Measurements
Authors: Vicente Eduardo Moreira , Moreno Robson Luiz , Ribeiro Enio Roberto
Published: June 2015

This paper presents a new maximum power point tracking (MPPT) method based on the measurement of temperature and short-circuit current, in a simple and efficient approach. These measurements, which can precisely define the maximum power point (MPP), have not been used together in other existing techniques. The temperature is measured with a low cost sensor and the solar irradiance is estimated through the relationship of the measured short-circuit current and its reference. Fast tracking speed and stable steady-state operation are advantages of this technique, which presents higher performance when compared to other well-known techniques.
On Global Attractors for a Class of Reaction-Diffusion Equations on Unbounded Domains with Some Strongly Nonlinear Weighted Term
Authors: Zhang Jin , Zhong Chengkui
Published: June 2015

We consider the existence and properties of the global attractor for a class of reaction-diffusion equation∂u/∂t-Δu-u+κ(x)|u|p-2u+f(u)=0,  in  Rn×R+;  u(x,0)=u0(x),  in  Rn. Under some suitable assumptions, we first prove that the problem has a global attractorAinL2(Rn). Then, by using theZ2-index theory, we verify thatAis an infinite dimensional set and it contains infinite distinct pairs of equilibrium points.
Pneumopericarditis: A Case of Acute Chest Pain with ST Segment Elevation
Authors: Argueta Erwin E. , Orellana-Barrios Menfil A. , Nantsupawat Teerapat , Rosales Alvaro , Shurmur Scott
Published: June 2015

Pneumopericarditis describes a clinical scenario where fluid and air are found within the pericardial space. Although infrequent, pneumopericarditis should be considered in patients presenting with acute chest pain as a differential diagnosis. This is relevant in patients with history of upper gastrointestinal (GI) surgery, as this may lead to a fistula communicating the GI tract and the pericardium. We report a 42-year-old man with history of numerous surgical interventions related to a Nissen fundoplication that presented with acute chest pain and inferior lead ST segment elevations. Emergent coronary angiography was negative for coronary vascular disease but fluoroscopy revealed air in the pericardial space. Subsequent radiographic studies helped confirm air in the pericardial space with a fistulous communication to the stomach. Ultimate treatment for this defect was surgical closure.
Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment
Authors: Guo Qiujun , Li Jie , Lin Hongsheng
Published: June 2015

Traditional Chinese medicine (TCM) is an important complementary strategy for treating cancer in China. The mechanism is related to regulating the internal environment and remodeling the tumor immunosuppressive microenvironment (TIM). Herein we illustrate how TIM is reformed and its protumor activity on promoting tumor cell proliferation, angiogenesis and lymphangiogenesis, tumor invasion, and the oncogenicity of cancer stem cells. Furthermore we summarize the effects and mechanism of TCM on regulating TIM via enhancing antitumor immune responses (e.g., regulating the expression of MHC molecules and Fas/FasL, attenuating cancerigenic ability of cancer stem cells) and remolding immunosuppressive cells (e.g., reversing immune phenotypes of T lymphocytes and tumor associated macrophages, promoting dendritic cells mature, restraining myeloid derived suppressor cells function, and regulating Th1/Th2 factors). We also reveal the bidirectional and multitargeting functions of TCM on regulating TIM. Hopefully, it provides new theoretical basis for TCM clinical practice in cancer treatment and prevention.
Dengue Virus Infection Causes the Activation of Distinct NF‐κB Pathways for Inducible Nitric Oxide Synthase and TNF‐α Expression in RAW264.7 Cells
Authors: Cheng Yi-Lin , Lin Yee-Shin , Chen Chia-Ling , Wan Shu-Wen , Ou Yi-Dan , Yu Chia-Yi , Tsai Tsung-Ting , Tseng Po-Chun , Lin Chiou-Feng
Published: June 2015

Infection with dengue virus (DENV) causes an increase in proinflammatory responses, such as nitric oxide (NO) generation and TNF‐α expression; however, the molecular mechanism underlying this inflammatory activation remains undefined, although the activation of the transcription factor NF‐κB is generally involved. In addition to TNF‐α production in DENV‐infected murine macrophage RAW264.7 cells, inducible NO synthase was transcriptionally and posttranslationally elevated and accompanied by NO generation. NF‐κB is known to be activated by DENV infection. Pharmacologically inhibiting NF‐κB activation abolishes iNOS/NO biosynthesis and TNF‐α production. With inhibition, the potential role of NF‐κB in oxidative signaling regulation was prevented during DENV infection. Heat‐inactivated DENV failed to cause the identified inflammatory responses. Pharmacological inhibition of TLR3 partly decreased NF‐κB activation; however, it effectively abolished inducible iNOS/NO biosynthesis but did not inhibit TNF‐α production. In contrast to TLR3, viral protein NS2B3 also independently contributed to NF‐κB activation to regulate TNF‐α production. These results show the distinct pathways for NF‐κB activation caused by DENV infection individually for the regulation of iNOS/NO and TNF‐α expression.
Representing Tactics for Fault Recovery: A Reconfigurable, Modular, and Hierarchical Approach
Authors: Barros Fernando J.
Published: June 2015

We show the advantages of modular and hierarchical design in obtaining fault-tolerant software. Modularity enables the identification of faulty software units simplifying key operations, like software removal and replacement. We describe three approaches to repair faulty software based on replication, namely, Passive Replication, N-Version Replication, and Active Replication, based on modular components. We show that the key construct to represent these tactics is the ability to makead hocchanges in software topologies. We consider hierarchical mobility as a useful operation to introduce new software units for replacing faulty ones. For illustration purposes, we useconnecton, a hierarchical, modular, and self-modifying software specification formalism, and its implementation in theDesmosframework.