bluuebunny/crossref_metadata_2025 huggingface dataset:
Productive Replication of Human Papillomavirus 31 Requires DNA Repair Factor Nbs1
Authors: Anacker Daniel C. , Gautam Dipendra , Gillespie Kenric A. , Chappell William H. , Moody Cary A.
Published: May 2014

Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage response (DDR) is necessary for productive replication of human papillomavirus 31 (HPV31). We previously found that DNA repair and homologous recombination (HR) factors localize to sites of HPV replication, suggesting that ATM activity is required to recruit factors to viral genomes that can productively replicate viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex is an essential component of the DDR that is necessary for ATM-mediated HR repair and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7 protein is sufficient to increase levels of the MRN complex and also interacts with MRN components. We have found that Nbs1 depletion blocks productive viral replication and results in decreased localization of Mre11, Rad50, and the principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes to the DDR by acting as an upstream activator of ATM in response to double-strand DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S-phase checkpoint. We have found that phosphorylation of ATM and its downstream target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2 are required for productive replication, our results suggest that Nbs1 contributes to viral replication outside its role as an ATM activator, potentially through ensuring localization of DNA repair factors to viral genomes that are necessary for efficient productive replication.

IMPORTANCE
The mechanisms that regulate human papillomavirus (HPV) replication during the viral life cycle are not well understood. Our finding that Nbs1 is necessary for productive replication even in the presence of ATM (ataxia telangiectasia-mutated kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral replication downstream of facilitating ATM activation. Nbs1 is required for the recruitment of Mre11 and Rad50 to viral genomes, suggesting that the MRN complex plays a direct role in facilitating productive viral replication, potentially through the processing of substrates that are recognized by the key homologous recombination (HR) factor Rad51. The discovery that E7 increases levels of MRN components, and MRN complex formation, identifies a novel role for E7 in facilitating productive replication. Our study not only identifies DNA repair factors necessary for HPV replication but also provides a deeper understanding of how HPV utilizes the DNA damage response to regulate viral replication.
MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal Transduction
Authors: Rodriguez Kenny R. , Bruns Annie M. , Horvath Curt M.
Published: May 2014

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral transcriptional response that provides an initial barrier to replication and impacts both innate and adaptive immune responses. Retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) proteins mediate intracellular virus recognition and are activated by viral RNA ligands to induce antiviral signal transduction. While the mechanisms of RIG-I regulation are already well understood, less is known about the more enigmatic melanoma differentiation-associated 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2). Emerging evidence suggests that these two RLRs are intimately associated as both accomplices and antagonists of antiviral signal transduction.
Evaluation of the Contributions of Individual Viral Genes to Newcastle Disease Virus Virulence and Pathogenesis
Authors: Paldurai Anandan , Kim Shin-Hee , Nayak Baibaswata , Xiao Sa , Shive Heather , Collins Peter L. , Samal Siba K.
Published: May 2014

Naturally occurring Newcastle disease virus (NDV) strains vary greatly in virulence. The presence of multibasic residues at the proteolytic cleavage site of the fusion (F) protein has been shown to be a primary determinant differentiating virulent versus avirulent strains. However, there is wide variation in virulence among virulent strains. There also are examples of incongruity between cleavage site sequence and virulence. These observations suggest that additional viral factors contribute to virulence. In this study, we evaluated the contribution of each viral gene to virulence individually and in different combinations by exchanging genes between velogenic (highly virulent) strain GB Texas (GBT) and mesogenic (moderately virulent) strain Beaudette C (BC). These two strains are phylogenetically closely related, and their F proteins contain identical cleavage site sequences,
112
RRQKR↓F
117
. A total of 20 chimeric viruses were constructed and evaluated
in vitro
, in 1-day-old chicks, and in 2-week-old chickens. The results showed that both the envelope-associated and polymerase-associated proteins contribute to the difference in virulence between rBC and rGBT, with the envelope-associated proteins playing the greater role. The F protein was the major individual contributor and was sometimes augmented by the homologous M and HN proteins. The dramatic effect of F was independent of its cleavage site sequence since that was identical in the two strains. The polymerase L protein was the next major individual contributor and was sometimes augmented by the homologous N and P proteins. The leader and trailer regions did not appear to contribute to the difference in virulence between BC and GBT.

IMPORTANCE
This study is the first comprehensive and systematic study of NDV virulence and pathogenesis. Genetic exchanges between a mesogenic and a velogenic strain revealed that the fusion glycoprotein is the major virulence determinant regardless of the identical virulence protease cleavage site sequence present in both strains. The contribution of the large polymerase protein to NDV virulence is second only to that of the fusion glycoprotein. The identification of virulence determinants is of considerable importance, because of the potential to generate better live attenuated NDV vaccines. It may also be possible to apply these findings to other paramyxoviruses.
Structural Insight into BH3 Domain Binding of Vaccinia Virus Antiapoptotic F1L
Authors: Campbell Stephanie , Thibault John , Mehta Ninad , Colman Peter M. , Barry Michele , Kvansakul Marc
Published: May 2014

Apoptosis is a tightly regulated process that plays a crucial role in the removal of virus-infected cells, a process controlled by both pro- and antiapoptotic members of the Bcl-2 family. The proapoptotic proteins Bak and Bax are regulated by antiapoptotic Bcl-2 proteins and are also activated by a subset of proteins known as BH3-only proteins that perform dual functions by directly activating Bak and Bax or by sequestering and neutralizing antiapoptotic family members. Numerous viruses express proteins that prevent premature host cell apoptosis. Vaccinia virus encodes F1L, an antiapoptotic protein essential for survival of infected cells that bears no discernible sequence homology to mammalian cell death inhibitors. Despite the limited sequence similarities, F1L has been shown to adopt a novel dimeric Bcl-2-like fold that enables hetero-oligomeric binding to both Bak and the proapoptotic BH3-only protein Bim that ultimately prevents Bak and Bax homo-oligomerization. However, no structural data on the mode of engagement of F1L and its Bcl-2 counterparts are available. Here we solved the crystal structures of F1L in complex with two ligands, Bim and Bak. Our structures indicate that F1L can engage two BH3 ligands simultaneously via the canonical Bcl-2 ligand binding grooves. Furthermore, by structure-guided mutagenesis, we generated point mutations within the binding pocket of F1L in order to elucidate the residues responsible for both Bim and Bak binding and prevention of apoptosis. We propose that the sequestration of Bim by F1L is primarily responsible for preventing apoptosis during vaccinia virus infection.

IMPORTANCE
Numerous viruses have adapted strategies to counteract apoptosis by encoding proteins responsible for sequestering proapoptotic components. Vaccinia virus, the prototypical member of the family
Orthopoxviridae
, encodes a protein known as F1L that functions to prevent apoptosis by interacting with Bak and the BH3-only protein Bim. Despite recent structural advances, little is known regarding the mechanics of binding between F1L and the proapoptotic Bcl-2 family members. Utilizing three-dimensional structures of F1L bound to host proapoptotic proteins, we generated variants of F1L that neutralize Bim and/or Bak. We demonstrate that during vaccinia virus infection, engagement of Bim and Bak by F1L is crucial for subversion of host cell apoptosis.
Enhancement of Interferon Induction by ORF3 Product of Hepatitis E Virus
Authors: Nan Yuchen , Ma Zexu , Wang Rong , Yu Ying , Kannan Harilakshmi , Fredericksen Brenda , Zhang Yan-Jin
Published: May 2014

Hepatitis E virus (HEV) causes both the endemic and epidemic spread of acute hepatitis in many parts of the world. HEV open reading frame 3 (ORF3) encodes a 13-kDa multifunctional protein (vp13) that is essential for HEV infection of animals. The exact role of vp13 in HEV infection remains unclear. In this study, vp13 was found to enhance interferon (IFN) production induced by poly(I · C), a synthetic analog of double-stranded RNA. Poly(I · C) treatment induced a higher level of IFN-β mRNA in HeLa cells stably expressing vp13 than in control cells. Using a luciferase reporter construct driven by the IFN-β promoter, we demonstrated that vp13 enhanced retinoic acid-inducible gene I (RIG-I)-dependent luciferase expression. This enhancement was found to be due to both an increased level of RIG-I protein and its activation. The levels of both endogenous and exogenous RIG-I were increased by vp13 by extension of the half-life of RIG-I. Additionally, vp13 interacts with the RIG-I N-terminal domain and enhances its K63-linked ubiquitination, which is essential for RIG-I activation. Analysis of vp13 deletion constructs suggested that the C-terminal domain of vp13 was essential for the enhancement of RIG-I signaling. In HEV-infected hepatoma cells, wild-type HEV led to a higher level of RIG-I and more poly(I · C)-induced IFN-β expression than did ORF3-null mutants. Analysis of vp13 from four HEV genotypes showed that vp13 from genotype I and III strains boosted RIG-I signaling, while vp13 from genotype II and IV strains had a minimal effect. These results indicate that vp13 enhances RIG-I signaling, which may play a role in HEV invasion.

IMPORTANCE
Hepatitis E virus (HEV) is a significant pathogen causing hepatitis in many parts of the world, yet it is understudied compared with other viral hepatitis pathogens. Here we found that the HEV open reading frame 3 product, vp13, enhances interferon induction stimulated by a synthetic analog of double-stranded RNA. This enhancement may play a role in HEV invasion, as vp13 is essential for HEV infection
in vivo
. The results of this study provide insights into virus-cell interactions during HEV infection. In addition to revealing its possible roles in HEV interference with cellular signaling, these results suggest that the second half of the vp13 sequence can be ligated into the genomes of attenuated live viruses to induce an innate immune response for better protective immunity, as well as a marker for differentiation of vaccinated animals from those infected with the corresponding wild-type viruses.
Sepsis-related hypertensive response: friend or foe?
Authors: Saleh Mohamed
Published: May 2014

In daily practice acute arterial hypertension may occur during acute sepsis. No management guidelines concerning this issue figured in the latest sepsis campaign guidelines. Arterial hypertension occurring during sepsis could be an overlooked condition despite its potential haemodynamic harmful consequences. In this paper, a clinical study of acute hypertensive response related to sepsis is detailed. It shows that arterial hypertension, renal salt wasting and glomerular hyperfiltration can occur simultaneously during sepsis. Mechanisms and management options of sepsis-related arterial hypertensive response are also discussed.
Protocol for a prospective neuroimaging study investigating the supraspinal control of lower urinary tract function in healthy controls and patients with non-neurogenic lower urinary tract symptoms
Authors: Walter Matthias , Michels Lars , Kollias Spyros , van Kerrebroeck Philip E , Kessler Thomas M , Mehnert Ulrich
Published: May 2014

Introduction

Lower urinary tract symptoms (LUTS) are highly prevalent, cause an enormous economic burden on healthcare systems and significantly impair the quality of life (QoL) of affected patients. The dependence of the LUT on complex central neuronal circuits makes it unique in comparison to other visceral functions, such as the gastrointestinal tract, but also more vulnerable to neurological diseases.

Methods and analysis

This is a prospective neuroimaging study investigating the supraspinal control of LUT function in healthy controls and in patients with non-neurogenic LUTS. The clinical assessment will include medical history, neuro-urological examination, bladder diary, urine analysis, urodynamic investigations, as well as standardised questionnaires regarding LUTS and QoL. The acquisition of neuroimaging data will include structural assessments (T1-weighted imaging and diffusion tensor imaging) as well as functional investigations using blood-oxygen-level dependent sensitive functional MRI (fMRI) in a 3 T MR scanner. The fMRI will be performed during four different bladder tasks using an automated MR-compatible and MR-synchronised pump system. The first three task-related fMRIs will consist of automated, repetitive filling of 100 mL warm (37°C) saline starting with (1) an empty bladder, (2) a low prefilled bladder volume (100 mL) and (3) a high prefilled bladder volume (persistent desire to void). The fourth task-related fMRI will comprise of automated, repetitive filling of 100 mL cold (4–8°C) saline starting with an empty bladder.

Ethics and dissemination

The local ethics committee approved this study (KEK-ZH-Nr. 2011–0346). The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings.

Trial registration number

This study has been registered at clinicaltrials.gov (http://www.clinicaltrials.gov/ct2/show/NCT01768910).
Axial pile response of bidirectional O-cell loading from modified analytical elastic solution and downhole shear wave velocity
Authors: Niazi Fawad S. , Mayne Paul W.
Published: May 2014

The Osterberg cell (O-cell) type of bidirectional pile load testing is a modern full-scale proofing method in the realm of performance-based pile design. It is done at considerable cost, not possible on small- to medium-size projects. An economical approach of utilizing the flexible and approximate analytical solution proposed by Randolph has frequently been adopted in the past for evaluating pile settlements under static, unidirectional, top-down axial compression loading. To extend this solution for O-cell loadings, the following adaptations are warranted: (i) appropriate modifications to handle the loadings in two directions and (ii) development of a nonlinear stiffness reduction model, derived from the back-analysis of O-cell pile load tests. Accordingly, a modified analytical solution is presented for the two common cases of O-cell loading arrangements. Using these modified sets of solutions and a well-documented database of O-cell load tests on drilled shaft foundations from different sites, two stiffness reduction models have been developed. The shear wave velocity readings obtained from the hybrid geophysical–geotechnical seismic piezocone tests afford the evaluation of fundamental shear stiffness modulus (Gmax) profiles. These profiles together with the re-arranged modified solution were applied to the axial loads versus displacements (Q–w) from the database of load tests to back-calculate the applicable operational shear stiffness (G) values. Additional sensitivity analyses indicate that pile geometry and soil stiffness profile are the two most significant factors affecting the outcome of this solution. A comprehensive set of step-by-step example calculations is included to explain the procedure for implementing the solution.
On submanifolds of highly negatively curved spaces
Authors: Pacelli Bessa G. , Pigola Stefano , Setti Alberto G.
Published: May 2014

We prove spectral, stochastic and mean curvature estimates for complete m-submanifolds φ : M → N of n-manifolds with a pole N in terms of the comparison isoperimetric ratio Im and the extrinsic radius rφ ≤ ∞. Our proof holds for the bounded case rφ < ∞, recovering the known results, as well as for the unbounded case rφ = ∞. In both cases, the fundamental ingredient in these estimates is the integrability over (0, rφ) of the inverse [Formula: see text] of the comparison isoperimetric radius. When rφ = ∞, this condition is guaranteed if N is highly negatively curved.
E-polynomial of SL2(ℂ)-character varieties of free groups
Authors: Cavazos Samuel , Lawton Sean
Published: May 2014

Let 𝖥r be a free group of rank r, 𝔽q a finite field of order q, and let SL n(𝔽q) act on Hom (𝖥r, SL n(𝔽q)) by conjugation. We describe a general algorithm to determine the cardinality of the set of orbits Hom (𝖥r, SL n(𝔽q))/ SL n(𝔽q). Our first main theorem is the implementation of this algorithm in the case n = 2. As an application, we determine the E-polynomial of the character variety Hom (𝖥r, SL 2(ℂ))// SL 2(ℂ), and of its smooth and singular locus. Thus we determine the Euler characteristic of these spaces.
Lift in the 3-sphere of knots and links in lens spaces
Authors: Manfredi Enrico
Published: May 2014

An important geometric invariant of links in lens spaces is the lift in the 3-sphere of a link L in L(p, q), that is the counterimage [Formula: see text] of L under the universal covering of L(p, q). If lens spaces are defined as a lens with suitable boundary identifications, then a link in L(p, q) can be represented by a disk diagram, that is to say, a regular projection of the link on a disk. Starting from this diagram of L, we obtain a diagram of the lift [Formula: see text] in S3. Using this construction, we are able to find different knots and links in L(p, q) having equivalent lifts, that is to say, we cannot distinguish different links in lens spaces only from their lift.
Performance Assessment of a Concrete Gravity Dam at Shenwo Reservoir of China Using Deterministic and Probabilistic Methods
Authors: Gu Quan , Yu Chengyi , Lin Peihui , Ling Xianzhang , Tang Liang , Huang Surong
Published: May 2014

This paper performs degradation assessment and safety evaluation of a concrete gravity dam at Shenwo reservoir in Liaoning province of China by using two methods, i.e. deterministic method and probabilistic method, respectively. The deterministic responses of representative sluice piers are computed through static pushover and dynamic analyses. The probabilistic uncertainty analysis, including time invariant and time variant reliability analyses, is based on finite element (FE) reliability theory. For time invariant case, the material and loading parameters are considered as random variables, including elastic modulus, Poisson's ratio, mass density and pushover forces. For time variant case, the earthquake history is simulated by using random process, and the first-order reliability method (FORM) approximation combined with Koo's analytical solution is used to compute the mean upcrossing rate for given performance functions, through which the failure probabilities are calculated. Based on the analysis results using these two methods, the safety and reliability of the dam is assessed. Furthermore, the performance assessments of the dam in its current state are compared with those in the original state (i.e. when the dam was built) to quantify its performance degradation. Finally, the assessment results of using the deterministic and probabilistic methods are compared, and the discrepancies between them are quantified and explained. The computation is based on a general FE analysis platform for earthquake engineering simulation, OpenSees.
A Cross Weighted-Residual Time Integration Scheme for Structural Dynamics
Authors: Kim Wooram , Park Sang-Shin , Reddy J. N.
Published: May 2014

In this article, we develop a novel stable time integration scheme for the transient analysis of structural dynamics problems. A second-order (in time) differential operator equation (e.g. obtained after finite element discretization in space) is written as a pair of first-order equations in terms of displacements and velocities. Then the solution is sought by minimizing the inner product of the residuals in the two equations (an unconventional approach) over typical time interval to obtain a symmetric set of algebraic equations involving displacements and velocities at two subsequent intervals. The new time integration scheme is termed the cross weighted-residual (CWR) time integration scheme because each of the two residuals takes the other one as a weight function in the minimization. The CWR time integration scheme is developed by using a uniform linear time approximation of the displacement and velocity fields to yield only a single step time integration scheme, which is comparable to the Newmark family of time integration scheme. A reduced integration technique is used to prevent velocity locking, which is caused by linear approximation of both the displacement and velocity fields. For the verification of the consistency and the stability, the CWR time integration scheme is tested with single-degree as well as multi-degree of freedom problems. The scheme performs extremely well compared with those of the well-known Newmark family of time integration schemes.
Some remarks on graded nilpotent Lie algebras and the Toral Rank Conjecture
Authors: Ames Guillermo , Cagliero Leandro , Cruz Mónica
Published: May 2014

If 𝔫 is a [Formula: see text]-graded nilpotent finite-dimensional Lie algebra over a field of characteristic zero, a well-known result of Deninger and Singhof states that dim H*(𝔫) ≥ L(p) where p is the polynomial associated to the grading and L(p) is the sum of the absolute values of the coefficients of p. From this result they derived the Toral Rank Conjecture (TRC) for 2-step nilpotent Lie algebras. An algebraic version of the TRC states that dim H*(𝔫) ≥ 2 dim (ℨ) for any finite-dimensional nilpotent Lie algebra 𝔫 with center ℨ. The TRC is more than 25 years old and remains open even for [Formula: see text]-graded 3-step nilpotent Lie algebras. Investigating to what extent the bound given by Deninger and Singhof could help to prove the TRC in this case, we considered the following two questions regarding a nilpotent Lie algebra 𝔫 with center ℨ: (A) If 𝔫 admits a [Formula: see text]-grading [Formula: see text], such that its associated polynomial p satisfies L(p) > 2 dim ℨ, does 𝔫 admit a ℤ+-grading [Formula: see text] such that its associated polynomial p′ satisfies L(p′) > 2 dim ℨ? (B) If 𝔫 is r-step nilpotent admitting a grading 𝔫 = 𝔫1 ⊕ 𝔫2 ⊕ ⋯ ⊕ 𝔫k such that its associated polynomial p satisfies L(p) > 2 dim ℨ, does 𝔫 admit a grading [Formula: see text] such that its associated polynomial p′ satisfies L(p′) > 2 dim ℨ? In this paper we show that the answer to (A) is yes, but the answer to (B) is no.
Emergent quantum mechanics as a thermal ensemble
Authors: De Córdoba P. Fernández , Isidro J. M. , Perea Milton H.
Published: May 2014

It has been argued that gravity acts dissipatively on quantum-mechanical systems, inducing thermal fluctuations that become indistinguishable from quantum fluctuations. This has led some authors to demand that some form of time irreversibility be incorporated into the formalism of quantum mechanics. As a tool toward this goal, we propose a thermodynamical approach to quantum mechanics, based on Onsager's classical theory of irreversible processes and Prigogine's nonunitary transformation theory. An entropy operator replaces the Hamiltonian as the generator of evolution. The canonically conjugate variable corresponding to the entropy is a dimensionless evolution parameter. Contrary to the Hamiltonian, the entropy operator is not a conserved Noether charge. Our construction succeeds in implementing gravitationally-induced irreversibility in the quantum theory.
Rosa Beta granite (Sardinian Pink Granite): a heritage stone of international significance from Italy
Authors: Careddu N. , Grillo S.
Published: May 2014

‘Rosa Beta’ or ‘Sardinian Pink granite’, an Hercynian granitoid from the Italian island of Sardinia, is formally here nominated as a Global Heritage Stone Resource. Rosa Beta is sourced from the Gallura region of northern Sardinia and has been associated with human heritage since prehistoric times. Notably it can be found in construction ranging from prehistoric Tomba dei Giganti, the 1st century Pantheon in Rome and the Renaissance Cathedral in Pisa to early 20th century monuments in Brazil and Egypt. Most importantly, it has also been used very extensively in the late 20th century for significant construction in countries as wide ranging as the USA, Saudi Arabia, Hong Kong, Singapore and Australia.
The ‘Global Heritage Stone Resource’ designation: past, present and future
Authors: Cooper Barry J.
Published: May 2014

The proposal to designate those natural stones that have achieved widespread utilization in human culture was first mooted in late 2007, and first presented in a public forum at the 33rd International Geological Congress in July 2008. Over the next four years, a network of international correspondents was created, circulars were distributed, a website was established and formal rules were adopted, all with the focus of establishing the ‘Global Heritage Stone Resource’ designation. During the 34th International Geological Congress in July 2012, the Heritage Stone Task Group was formally established under the auspices of the International Union of Geological Sciences, in association with the International Association of Engineering Geology and the Environment, Commission C-10 Building Stones and Ornamental Rocks, and with a formal Board of Management. It has now been recognized that the new designation has value both in offering a mechanism to promote the safeguarding of stone resources, as well as in the formal definition of stone types within sufficiently tight parameters that it can facilitate name protection. For the future, the Board of Management needs to encourage and approve nominations for the new designation. As well, an annual conference needs to be organized.
Mucin 3 is involved in intestinal epithelial cell apoptosis via N-(3-oxododecanoyl)-l-homoserine lactone-induced suppression of Akt phosphorylation
Authors: Taguchi Ryoko , Tanaka Shinya , Joe Ga-Hyun , Maseda Hideaki , Nomura Nobuhiko , Ohnishi Junji , Ishizuka Satoshi , Shimizu Hidehisa , Miyazaki Hitoshi
Published: May 2014

N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL). A low concentration of 3-oxo-C12-HSL (30 μM) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C12-HSL. 3-Oxo-C12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens.
Modeling glucose and free fatty acid kinetics during insulin-modified intravenous glucose tolerance test in healthy humans: role of counterregulatory response
Authors: Thomaseth Karl , Brehm Attila , Pavan Alessandra , Pacini Giovanni , Roden Michael
Published: May 2014

Insulin administration during insulin-modified intravenous glucose tolerance test (IM-IVGTT) can induce transient hypoglycemia in healthy insulin-sensitive subjects. This triggers counterregulatory reflex (CRR) responses, which influence the kinetics of glucose and nonesterified fatty acids (NEFA), and undermines the accuracy of mathematical modeling methods that do not explicitly account for CRR. The aim of this study is to evaluate mathematical models of glucose and NEFA kinetics against experimental data in the presence or absence of CRR. Thirteen healthy nondiabetic subjects underwent a standard IM-IVGTT and a modified test (GC-IM-IVGTT) with a variable glucose infusion preventing hypoglycemia. While model predictions fit very well with glucose and NEFA data from GC-IM-IVGTT, they lagged behind observations from IM-IVGTT during recovery from hypoglycemia, independently of insulinemia, which did not differ significantly between protocols. A modification to the glucose minimal model, using the glucose concentration below a threshold as a signal for CRR, improves model predictions for both glucose and NEFA. The associated increase in endogenous glucose production correlates, among various CRR hormones, mainly with the dynamics of glucagon concentration. The modified minimal models introduce new parameters that quantify strength and duration of CRR following hypoglycemia. Although CRR represents an unwanted side-effect in IM-IVGTT occurring only in insulin-sensitive subjects, this study provides new insights leading to improved procedures for estimating insulin sensitivity from IM-IVGTT, which may also allow for assessing the individual capacity of recovery from hypoglycemic events in patients treated with insulin or insulin-releasing drugs.
Na+-K+-ATPase trafficking induced by heat shock pretreatment correlates with increased resistance to anoxia in locusts
Authors: Hou Nicholas , Armstrong Gary A. B. , Chakraborty-Chatterjee Munmun , Sokolowski Marla B. , Robertson R. Meldrum
Published: May 2014

The sensitivity of insect nervous systems to anoxia can be modulated genetically and pharmacologically, but the cellular mechanisms responsible are poorly understood. We examined the effect of a heat shock pretreatment (HS) on the sensitivity of the locust ( Locusta migratoria) nervous system to anoxia induced by water immersion. Prior HS made locusts more resistant to anoxia by increasing the time taken to enter a coma and by reducing the time taken to recover the ability to stand. Anoxic comas were accompanied by surges of extracellular potassium ions in the neuropile of the metathoracic ganglion, and HS reduced the time taken for clearance of excess extracellular potassium ions. This could not be attributed to a decrease in the activity of protein kinase G, which was increased by HS. In homogenates of the metathoracic ganglion, HS had only a mild effect on the activity of Na+-K+-ATPase. However, we demonstrated that HS caused a threefold increase in the immunofluorescent localization of the α-subunit of Na+-K+-ATPase in metathoracic neuronal plasma membranes relative to background labeling of the nucleus. We conclude that HS induced trafficking of Na+-K+-ATPase into neuronal plasma membranes and suggest that this was at least partially responsible for the increased resistance to anoxia and the increased rate of recovery of neural function after a disturbance of K+homeostasis.
Painful cutaneous laser stimuli induce event-related oscillatory EEG activities that are different from those induced by nonpainful electrical stimuli
Authors: Chien J. H. , Liu C. C. , Kim J. H. , Markman T. M. , Lenz F. A.
Published: May 2014

The non-phase-locked EEG response to painful stimuli has usually been characterized as decreased oscillatory activity (event-related desynchronization, ERD) in the alpha band. Increased activity (event-related synchronization, ERS) in the gamma band has been reported more recently. We have now tested the hypothesis that the non-phase-locked responses to nonpainful electric cutaneous stimuli are different from those to painful cutaneous laser stimuli when the baseline salience of the two stimuli is the same and the salience during the protocol is modulated by count laser and count electric tasks. Both of these stimuli were presented in random order in a single train at intensities that produced the same baseline salience in the same somatic location. The response to the laser stimulus was characterized by five windows (designated windows I–V) in the time-frequency domain: early (200–400 ms) and late (600–1,400 ms) delta/theta ERS, 500–900 ms alpha ERD, 1,200–1,600 ms beta ERS (rebound), and 800–1,200 ms gamma ERS. Similar ERS/ERD windows of activity were found for the electric stimulus. Individual participants very commonly had activity in windows consistent with the overall analysis. Linear regression of ERS/ERD for parietal channels was most commonly found for sensory (pain or unpleasantness)- or attention (salience)-related measures. Overall, the main effect for modality was found in window I-delta/theta and window V-gamma, and the Modality with Task interaction was found in all five windows. All significant interaction terms included Modality as a factor. Therefore, Modality was the most common factor explaining our results, which is consistent with our hypothesis.
Contribution of auditory nerve fibers to compound action potential of the auditory nerve
Authors: Bourien Jérôme , Tang Yong , Batrel Charlène , Huet Antoine , Lenoir Marc , Ladrech Sabine , Desmadryl Gilles , Nouvian Régis , Puel Jean-Luc , Wang Jing
Published: May 2014

Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude.
Cav1.2 and Cav1.3 L-type calcium channels regulate dopaminergic firing activity in the mouse ventral tegmental area
Authors: Liu Yudan , Harding Meghan , Pittman Andrea , Dore Jules , Striessnig Jörg , Rajadhyaksha Anjali , Chen Xihua
Published: May 2014

Dopaminergic projections from the ventral tegmental area (VTA) constitute the mesolimbocortical system that underlies addiction and psychosis primarily as a result of increased dopaminergic transmission. Dopamine release is spike dependent. L-type calcium channels (LTCCs) play an important role in regulating firing activities, but the contribution of specific subtypes remains unclear. This article describes different functions of Cav1.2 and Cav1.3 subtypes in regulating firing properties with two transgenic mouse strains. For basal firing, Cav1.3-deficient (Cav1.3−/−) mice had a lower basal firing frequency. The dihydropyridine (DHP) channel blocker nifedipine reduced single-spike firing in mice expressing DHP-insensitive Cav1.2 channels (Cav1.2DHP−/−mice), confirming the significant contribution from the Cav1.3 subtype in basal firing. Moreover, the DHP channel activator ( S)-(−)-Bay K8644 and the non-DHP channel activator FPL 64176 converted firing patterns from single spiking to bursting in Cav1.2DHP−/−mice. Nifedipine inhibited burst firing induced by both activators, suggesting that Cav1.3 also serves an essential role in burst firing. However, FPL 64176 also induced bursting in Cav1.3−/−mice. These results indicate that the Cav1.3 subtype is crucial to regulation of basal single-spike firing, while activation of both Cav1.2 and Cav1.3 can support burst firing of VTA neurons.
Low‐Loss Polymer‐Based Ring Resonator for Resonant Integrated Optical Gyroscopes
Authors: Qian Guang , Tang Jie , Zhang Xiao-Yang , Li Ruo-Zhou , Lu Yu , Zhang Tong
Published: May 2014

Waveguide ring resonator is the sensing element of resonant integrated optical gyroscope (RIOG). This paper reports a polymer‐based ring resonator with a low propagation loss of about 0.476 dB/cm for RIOG. The geometrical parameters of the waveguide and the coupler of the resonator were optimally designed. We also discussed the optical properties and gyroscope performance of the polymer resonator which shows a high quality factor of about 105. The polymer‐based RIOG exhibits a limited sensitivity of less than 20 deg/h for the low and medium resolution navigation systems.
Cardiac Arrest after Connecting Negative Pressure to the Subgaleal Drain during Craniotomy Closure
Authors: Yadav Monu , Nikhar Sapna A. , Kulkarni Dilip Kumar , Gopinath R.
Published: May 2014

A one-year-old child operated on for arachnoid cyst in right frontoparietotemporal region had sudden bradycardia followed by cardiac arrest leading to death after connecting negative pressure to the subgaleal drain during craniotomy closure. The surgical procedure was uneventful. It is a common practice to place epidural or subgaleal drains connected to a vacuum system towards the end of craniotomy to prevent accumulation of intracranial and extracranial blood. The phenomenon of bradycardia with hypotension is known to occur following negative pressure application to the epidural, epicranial, or subgaleal space after craniotomy closure. However cardiac arrest as a complication of negative pressure suction drain in neurosurgical patients is not described in the literature.
Low-Profile Dual-Wideband MIMO Antenna with Low ECC for LTE and Wi-Fi Applications
Authors: Jeong Gye-Taek , Choi Sunho , Lee Kyoung-hak , Kim Woo-Su
Published: May 2014

This paper presents a low-profile dual-wideband multiple input multiple output (MIMO) antenna with low envelop correlation coefficient (ECC) for long-term evolution (LTE) and wireless fidelity (Wi-Fi) applications. The antenna covers LTE band 7 and Wi-Fi as well as wireless broadband (Wibro) and Worldwide Interoperability for Microwave Access (WiMax) (except for the 3.5-GHz band). To aid with integration of a practical mobile terminal, the MIMO antenna elements are placed at appropriate locations by analyzing the surface current distribution and without using any additional isolation techniques. The measured bandwidths with reflection coefficients of <−10 dB are 36.8% in the range 2.02–2.93 GHz and 23.4% in the range 5.10–6.45 GHz. Isolation is satisfied to be >20 dB in the operating frequency ranges of both LTE band 7 and Wi-Fi. Additionally, the calculated ECC is in the range0.005<ρ<0.025, which is considerably lower than theρ<0.5required for MIMO applications. The measured radiation patterns are appropriate for mobile terminals, and omnidirectional radiation patterns are obtained.
Numerical Investigation of Periodically Unsteady Pressure Field in a High Power Centrifugal Diffuser Pump
Authors: Pei Ji , Wang Wenjie , Yuan Shouqi , Mao Jieyun
Published: May 2014

Pressure fluctuations are the main factors that can give rise to reliability problems in centrifugal pumps. The periodically unsteady pressure characteristics caused by rotor-stator interaction have been investigated by CFD calculation in a residual heat removal pump. Side chamber flow effect is also considered for the simulation to accurately predict the flow in whole flow passage. The pressure fluctuation results in time and frequency domains were considered for several typical monitoring points in impeller and diffuser channels. In addition, the pressure fluctuation intensity coefficient (PFIC) based on standard deviation was defined on each grid node for entire space and impeller revolution period. The results show that strong pressure fluctuation intensity can be found in the gap between impeller and diffuser. As a source, the fluctuation can spread to the upstream and downstream flow channels as well as the side chamber channels. Meanwhile, strong pressure fluctuation intensity can be found in the discharge tube of the circular casing. In addition, the obvious influence of operational flow rate on the PFIC distribution can be found. The analysis indicates that the pressure fluctuations in the aspects of both frequency and intensity can be used to comprehensively evaluate the unsteady pressure characteristics in centrifugal pumps.
Research of Electrosurgical Ablation with Antiadhesive Functionalization on Thermal and Histopathological Effects of Brain Tissues In Vivo
Authors: Hsiao Wen-Tien , Kung Chun-Ming , Chu Jan-Show , Ou Keng-Liang , Peng Pei-Wen
Published: May 2014

Thermal injury and tissue sticking are two major concerns in the electrosurgery. In the present study, the effect of lateral thermal injury caused by different electrosurgical electrodes on wound healing was investigated. An electrosurgical unit equipped with untreated (SS) and titanium oxide layer-coated (TiO2-coated) stainless steel needle-type electrodes was used to create lesions on the rat brain tissue. TiO2layers were produced by radiofrequency plasma and magnetron sputtering in the form of amorphous (TO-SS-1), anatase (TO-SS-2), and rutile (TO-SS-3) phase. Animals were sacrificed for evaluations at 0, 2, 7, and 28 days postoperatively. TO-SS-3 electrodes generated lower levels of sticking tissue, and the thermographs showed that the recorded highest temperature in brain tissue from the TO-SS-3 electrode was significantly lower than in the SS electrode. The total injury area of brain tissue caused by TO-SS-1 and TO-SS-3 electrodes was significantly lower than that caused by SS electrodes at each time point. The results of the present study reveal that the plating of electrodes with a TiO2film with rutile phases is an efficient method for improving the performance of electrosurgical units and should benefit wound healing.
Qualitative and Quantitative Analysis for Facial Complexion in Traditional Chinese Medicine
Authors: Zhao Changbo , Li Guo-zheng , Li Fufeng , Wang Zhi , Liu Chang
Published: May 2014

Facial diagnosis is an important and very intuitive diagnostic method in Traditional Chinese Medicine (TCM). However, due to its qualitative and experience-based subjective property, traditional facial diagnosis has a certain limitation in clinical medicine. The computerized inspection method provides classification models to recognize facial complexion (including color and gloss). However, the previous works only study the classification problems of facial complexion, which is considered as qualitative analysis in our perspective. For quantitative analysis expectation, the severity or degree of facial complexion has not been reported yet. This paper aims to make both qualitative and quantitative analysis for facial complexion. We propose a novel feature representation of facial complexion from the whole face of patients. The features are established with four chromaticity bases splitting up by luminance distribution on CIELAB color space. Chromaticity bases are constructed from facial dominant color using two-level clustering; the optimal luminance distribution is simply implemented with experimental comparisons. The features are proved to be more distinctive than the previous facial complexion feature representation. Complexion recognition proceeds by training an SVM classifier with the optimal model parameters. In addition, further improved features are more developed by the weighted fusion of five local regions. Extensive experimental results show that the proposed features achieve highest facial color recognition performance with a total accuracy of 86.89%. And, furthermore, the proposed recognition framework could analyze both color and gloss degrees of facial complexion by learning a ranking function.
Prediction on the Inhibition Ratio of Pyrrolidine Derivatives on Matrix Metalloproteinase Based on Gene Expression Programming
Authors: Li Yuqin , You Guirong , Jia Baoxiu , Si Hongzong , Yao Xiaojun
Published: May 2014

Quantitative structure-activity relationships (QSAR) were developed to predict the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase via heuristic method (HM) and gene expression programming (GEP). The descriptors of 33 pyrrolidine derivatives were calculated by the software CODESSA, which can calculate quantum chemical, topological, geometrical, constitutional, and electrostatic descriptors. HM was also used for the preselection of 5 appropriate molecular descriptors. Linear and nonlinear QSAR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient (R2) of 0.93 and 0.94. The two QSAR models are useful in predicting the inhibition ratio of pyrrolidine derivatives on matrix metalloproteinase during the discovery of new anticancer drugs and providing theory information for studying the new drugs.
Success and High Predictability of Intraorally Welded Titanium Bar in the Immediate Loading Implants
Authors: Fogli Vaniel , Camerini Michele , Lauritano Dorina , Carinci Francesco
Published: May 2014

The implants failure may be caused by micromotion and stress exerted on implants during the phase of bone healing. This concept is especially true in case of implants placed in atrophic ridges. So the primary stabilization and fixation of implants are an important goal that can also allow immediate loading and oral rehabilitation on the same day of surgery. This goal may be achieved thanks to the technique of welding titanium bars on implant abutments. In fact, the procedure can be performed directly in the mouth eliminating possibility of errors or distortions due to impression. This paper describes a case report and the most recent data about long-term success and high predictability of intraorally welded titanium bar in immediate loading implants.