bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of a serrated trailing edge on sound radiation from nearby quadrupoles
Authors: Karimi Mahmoud , Croaker Paul , Kinns Roger , Kessissoglou Nicole
Published: May 2017

A periodic boundary element technique is implemented to study the noise reduction capability of a plate with a serrated trailing edge under quadrupole excitation. It is assumed for this purpose that the quadrupole source tensor is independent of the trailing edge configuration and that the effect of the trailing edge shape is to modify sound radiation from prescribed boundary layer sources. The flat plate is modelled as a continuous structure with a finite repetition of small spanwise segments. The matrix equation formulated by the periodic boundary element method for this 3D acoustic scattering problem is represented as a block Toeplitz matrix. The discrete Fourier transform is employed in an iterative algorithm to solve the block Toeplitz system. The noise reduction mechanism for a serrated trailing edge in the near field is investigated by comparing contour plots obtained from each component of the quadrupole for unserrated and serrated trailing edge plate models. The noise reduction due to the serrated trailing edge is also examined as a function of the source location.
Papers of note in
Science Immunology
2
(10)
Authors: Foley John F.
Published: May 2017

This month’s articles show that cholesterol-based ligands position splenic dendritic cells near T cells; how synovial fibroblasts and neutrophils promote inflammation in arthritis; that type I interferon activates liver T cells in obese mice; and how the alternative complement pathway plays a role in antibacterial immunity.
Phenotypic and Molecular Evaluation of Echinocandin Susceptibility of Candida glabrata, Candida bracarensis, and Candida nivariensis Strains Isolated during 30 Years in Argentina
Authors: Morales-López Soraya , Dudiuk Catiana , Vivot Walter , Szusz Wanda , Córdoba Susana B. , Garcia-Effron Guillermo
Published: May 2017

The echinocandin susceptibilities of 122
Candida glabrata
complex strains (including 5
Candida nivariensis
and 3
Candida bracarensis
strains) were evaluated by microdilution and compared with the results from a molecular tool able to detect FKS mutations. No echinocandin resistance was detected. The PCR results coincide with the MIC data in 99.25% of the cases (1
C. glabrata
strain was misidentified as resistant) but were 20 h faster.
C. nivariensis FKS
genes were sequenced and showed differences with
C. glabrata
FKS
genes.
Impaired Inhibition by Avibactam and Resistance to the Ceftazidime-Avibactam Combination Due to the D
179
Y Substitution in the KPC-2 β-Lactamase
Authors: Compain Fabrice , Arthur Michel
Published: May 2017

The ceftazidime-avibactam antibiotic combination was recently shown to be at risk for the emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a
Klebsiella pneumoniae
carbapenemase type 2 (KPC-2) β-lactamase harboring the D
179
Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for the resistance. In contrast, the D
179
Y substitution abolished the hydrolysis of aztreonam and imipenem, indicating that these drugs might provide therapeutic alternatives.
NDM-5 and OXA-181 Beta-Lactamases, a Significant Threat Continues To Spread in the Americas
Authors: Rojas Laura J. , Hujer Andrea M. , Rudin Susan D. , Wright Meredith S. , Domitrovic T. Nicholas , Marshall Steven H. , Hujer Kristine M. , Richter Sandra S. , Cober Eric , Perez Federico , Adams Mark D. , van Duin David , Bonomo Robert A.
Published: May 2017

Among Gram-negative bacteria, carbapenem-resistant infections pose a serious and life-threatening challenge. Here, the CRACKLE network reports a sentinel detection and characterization of a carbapenem-resistant
Klebsiella pneumoniae
ST147 isolate harboring
bla
NDM-5
and
bla
OXA-181
from a young man who underwent abdominal surgery in India.
bla
NDM-5
was located on an IncFII plasmid of ≈90 kb, whereas
bla
OXA-181
was chromosomally encoded. Resistome and genome analysis demonstrated multiple copies of the transposable element IS
26
and a “hot-spot region” in the IncFII plasmid.
Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity
Authors: Hargrove Tatiana Y. , Garvey Edward P. , Hoekstra William J. , Yates Christopher M. , Wawrzak Zdzislaw , Rachakonda Girish , Villalta Fernando , Lepesheva Galina I.
Published: May 2017

Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus
Aspergillus fumigatus
. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/
A. fumigatus
CYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis of
A. fumigatus
CYP51/voriconazole and
Candida albicans
CYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using two
A. fumigatus
strains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-
A. fumigatus
potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent.
Population Pharmacokinetic Modeling as a Tool To Characterize the Decrease in Ciprofloxacin Free Interstitial Levels Caused by Pseudomonas aeruginosa Biofilm Lung Infection in Wistar Rats
Authors: Torres Bruna G. S. , Helfer Victória E. , Bernardes Priscila M. , Macedo Alexandre José , Nielsen Elisabet I. , Friberg Lena E. , Dalla Costa Teresa
Published: May 2017

Biofilm formation plays an important role in the persistence of pulmonary infections, for example, in cystic fibrosis patients. So far, little is known about the antimicrobial lung disposition in biofilm-associated pneumonia. This study aimed to evaluate, by microdialysis, ciprofloxacin (CIP) penetration into the lungs of healthy and
Pseudomonas aeruginosa
biofilm-infected rats and to develop a comprehensive model to describe the CIP disposition under both conditions.
P. aeruginosa
was immobilized into alginate beads and intratracheally inoculated 14 days before CIP administration (20 mg/kg of body weight). Plasma and microdialysate were sampled from different animal groups, and the observations were evaluated by noncompartmental analysis (NCA) and population pharmacokinetic (popPK) analysis. The final model that successfully described all data consisted of an arterial and a venous central compartment and two peripheral distribution compartments, and the disposition in the lung was modeled as a two-compartment model structure linked to the venous compartment. Plasma clearance was approximately 32% lower in infected animals, leading to a significantly higher level of plasma CIP exposure (area under the concentration-time curve from time zero to infinity, 27.3 ± 12.1 μg · h/ml and 13.3 ± 3.5 μg · h/ml in infected and healthy rats, respectively). Despite the plasma exposure, infected animals showed a four times lower tissue concentration/plasma concentration ratio (lung penetration factor = 0.44 and 1.69 in infected and healthy rats, respectively), and lung clearance (CL
lung
) was added to the model for these animals (CL
lung
= 0.643 liters/h/kg) to explain the lower tissue concentrations. Our results indicate that
P. aeruginosa
biofilm infection reduces the CIP free interstitial lung concentrations and increases plasma exposure, suggesting that plasma concentrations alone are not a good surrogate of lung concentrations.
Propofol Sedation Exacerbates Kidney Pathology and Dissemination of Bacteria during Staphylococcus aureus Bloodstream Infections
Authors: Visvabharathy Lavanya , Freitag Nancy E.
Published: May 2017

Methicillin-resistantStaphylococcus aureus(MRSA) is responsible for large numbers of postsurgical nosocomial infections across the United States and worldwide. Propofol anesthesia is widely used in surgery and in intensive care units, and recent evidence indicates that even brief exposure to propofol can substantially increase host susceptibility to microbial infection. Here, we delineate the impact of propofol sedation on MRSA bloodstream infections in mice in the presence and absence of prophylactic antibiotic treatment. Consistent with previous reports, brief periods of anesthesia with propofol were sufficient to significantly increase bacterial burdens and kidney pathology in mice infected with MRSA. Propofol exposure increased neutrophilic infiltrates into the kidney and enhanced bacterial dissemination throughout kidney tissue. Propofol sedation reduced populations of effector phagocytes and mature dendritic cells within the kidney and led to the apparent expansion of myeloid-derived suppressor cell-like populations. When propofol was coadministered with vancomycin prophylaxis, it dramatically increased kidney abscess formation and bacterial dissemination throughout kidney tissue at early times post-S. aureusinfection compared to antibiotic-treated but nonsedated animals. Taken together, our data indicate that short-term sedation with propofol significantly increases the severity of bloodstream MRSA infection, even when administered in conjunction with vancomycin prophylaxis.
Infection of Hysterectomized Mice with Chlamydia muridarum and Chlamydia trachomatis
Authors: Yang Chunfu , Whitmire William M. , Sturdevant Gail L. , Bock Kevin , Moore Ian , Caldwell Harlan D.
Published: May 2017

We studied infection and immunity of hysterectomized mice infected withChlamydia muridarumandChlamydia trachomatisto determine if there were differences between these species in their ability to infect vaginal squamous epithelial cellsin vivoindependently of proximal upper genital tract tissues. We found thatC. muridarumreadily colonized and infected vaginal squamous epithelial cells, whereasC. trachomatisdid not. Primary infection of the vaginal epithelium withC. muridarumproduced infections of a duration longer than that reported for normal mice. Infection resulted in an inflammatory response in the vagina characterized by neutrophils and infiltrating submucosal plasma cells consisting primarily of T cells. Despite the delayed clearance, rechallengedC. muridarum-infected mice were highly immune. Mice vaginally infected withC. muridarumproduced serum and vaginal wash antibodies and an antigen-specific gamma interferon-dominated Th1-biased T cell response. By comparison, mice vaginally infected withC. trachomatisexhibited transient low-burden infections, produced no detectable tissue inflammatory response, and failed to seroconvert. We discuss how these marked differences in the biology of vaginal infection between these otherwise genetically similar species are possibly linked to pathogen-specific virulence genes and how they may influence pathology and immunity in the upper genital tract.
Phase-Variable Changes in the Position of
O
-Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance
Authors: Pequegnat Brittany , Laird Renee M. , Ewing Cheryl P. , Hill Christina L. , Omari Eman , Poly Frederic , Monteiro Mario A. , Guerry Patricia
Published: May 2017

Campylobacter jejuni
polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric
O
-methyl phosphoramidate (MeOPN) modifications. The lack of stoichiometry is due to phase variation at homopolymeric tracts within the MeOPN transferase genes.
C. jejuni
strain 81-176 contains two MeOPN transferase genes and has been shown previously to contain MeOPN modifications at the 2 and 6 positions of the galactose (Gal) moiety in the CPS. We demonstrate here that one of the two MeOPN transferases, encoded by CJJ81176_1435, is bifunctional and is responsible for the addition of MeOPN to both the 2 and the 6 positions of Gal. A new MeOPN at the 4 position of Gal was observed in a mutant lacking the CJJ81176_1435 transferase and this was encoded by the CJJ81176_1420 transferase. During routine growth of 81-176, the CJJ81176_1420 transferase was predominantly in an off configuration, while the CJJ81176_1435 transferase was primarily on. However, exposure to normal human serum selected for cells expressing the CJJ81176_1420 transferase. MeOPN modifications appear to block binding of naturally occurring antibodies to the 81-176 CPS. The absence of MeOPN-4-Gal resulted in enhanced sensitivity to serum killing, whereas the loss of MeOPN-2-Gal and MeOPN-6-Gal resulted in enhanced resistance to serum killing, perhaps by allowing more MeOPN to be put onto the 4 position of Gal.

IMPORTANCE
Campylobacter jejuni
undergoes phase variation in genes encoding surface antigens, leading to the concept that a strain of this organism consists of multiple genotypes that are selected for fitness in various environments. Methyl phosphoramidate modifications on the capsule of
C. jejuni
block access of preexisting antibodies in normal human sera to the polysaccharide chain, thus preventing activation of the classical arm of the complement cascade. We show that the capsule of strain 81-176 contains more sites of MeOPN modifications than previously recognized and that one site, on the 4 position of galactose, is more critical to complement resistance than the others. Exposure to normal human serum selects for variants in the population expressing this MeOPN modification.
Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae
Authors: Yamamoto Shouji , Ohnishi Makoto
Published: May 2017

In
Vibrio cholerae
, the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326–347, 2014,
https://doi.org/10.1111/mmi.12462
). TfoS specifically activates the transcription of
tfoR
, encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned off
tfoR
::
lacZ
expression but possessed intact
chiS
and
tfoS
genes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIA
glc
) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIA
glc
inactivated natural competence and
tfoR
transcription. Chitin-induced expression of the
chb
operon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIA
glc
. Furthermore, the regulation of
tfoR
and
chb
expression by EIIA
glc
was dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIA
glc
. These results define a previously unknown connection between the PTS and chitin signaling pathways in
V. cholerae
and suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.

IMPORTANCE
The EIIA
glc
protein of the PTS coordinates a wide variety of physiological functions with carbon availability. In this report, we describe an unexpected association of chitin-activated signaling pathways in
V. cholerae
with EIIA
glc
. The signaling pathways are governed by the chitin-responsive TCS sensor kinase ChiS and lead to the induction of chitin utilization and natural competence. We show that dephosphorylated EIIA
glc
inhibits both signaling pathways in a ChiS-dependent manner. This inhibition is different from classical catabolite repression that is caused by lowered levels of cyclic AMP. This work represents a newly identified connection between the PTS and chitin signaling pathways in
V. cholerae
and suggests a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.
Impact of permafrost thaw on the turbidity regime of a subarctic river: the Sheldrake River, Nunavik, Quebec
Authors: Jolivel Maxime , Allard Michel
Published: May 2017

In order to assess the impact of seasonal active layer thaw and thermokarst on river flow and turbidity, a gauging station was installed near the mouth of the Sheldrake River in the discontinuous permafrost zone of northern Quebec. The station provided 5 years of water level data and 3 years of turbidity data. The hydrological data for the river showed the usual high water stage occurring at spring snowmelt, with smaller peaks related to rain events in summer. Larger and longer turbidity peaks also occurred in summer in response to warm air temperature spells, suggesting that a large part of the annual suspension load was carried during midsummer turbidity peaks. Supported by geomorphological observations across the catchment area, the most plausible interpretation is that the rapid thawing of the active layer during warm conditions in July led to the activation of frostboils and triggered landslides throughout the river catchment, thus increasing soil erosion and raising sediment delivery into the hydrological network. These results indicate that maximum sediment discharge in a thermokarst-affected region may be predominantly driven by the rate of summer thawing and associated activation of erosion features in the catchment.
Evaluation of alternative modelling approaches to account for spatial effects due to age-based movement
Authors: Lee Hui-Hua , Piner Kevin R. , Maunder Mark N. , Taylor Ian G. , Methot Richard D.
Published: May 2017

Spatial patterns due to age-specific movement have been a source of unmodelled process error. Modeling movement in spatially explicit stock assessments is feasible, but hampered by a paucity of data from appropriate tagging studies. This study uses simulation analyses to evaluate alternative model structures that either explicitly or implicitly account for the process of time-varying age-based movement in a population dynamics model. We simulated synthetic populations using a two-area stochastic population dynamics operating model. Simulated data were fit in seven different estimation models. Only the model that includes the correct spatial dynamic results in unbiased and precise estimates of derived and management quantities. In a single-area assessment model, using the fleets-as-area (FAA) approach may be the second best option to estimate both length-based and time-varying age-based selectivity to implicitly account for the contact selectivity and annual availability. An FAA approach adds additional observation error performed nearly as well. Future research could evaluate which stock assessment method is robust to uncertainty in movement and is more appropriate for achieving intended management objectives.
Micromagnetic simulation study of magnetization reversal in torus-shaped permalloy nanorings
Authors: Mishra Amaresh Chandra , Giri R.
Published: May 2017

Using micromagnetic simulation, the magnetization reversal of soft permalloy rings of torus shape with major radius R varying within 20–100 nm has been investigated. The minor radius r of the torus rings was increased from 5 nm up to a maximum value r[Formula: see text] such that R- r[Formula: see text] = 10 nm. Micromagnetic simulation of in-plane hysteresis curve of these nanorings revealed that in the case of very thin rings (r [Formula: see text] 10 nm), the remanent state is found to be an onion state, whereas for all other rings, the remanent state is a vortex state. The area of the hysteresis loop was found to be decreasing gradually with the increment of r. The normalized area under the hysteresis loops (A[Formula: see text]) increases initially with increment of r. It attains a maximum for a certain value of r = r0 and again decreases thereafter. This value r0 increases as we decrease R and as a result, this peak feature is hardly visible in the case of smaller rings (rings having small R).
Frequency hopping signal detection based on wavelet decomposition and Hilbert–Huang transform
Authors: Zheng Yang , Chen Xihao , Zhu Rui
Published: May 2017

Frequency hopping (FH) signal is widely adopted by military communications as a kind of low probability interception signal. Therefore, it is very important to research the FH signal detection algorithm. The existing detection algorithm of FH signals based on the time-frequency analysis cannot satisfy the time and frequency resolution requirement at the same time due to the influence of window function. In order to solve this problem, an algorithm based on wavelet decomposition and Hilbert–Huang transform (HHT) was proposed. The proposed algorithm removes the noise of the received signals by wavelet decomposition and detects the FH signals by Hilbert–Huang transform. Simulation results show the proposed algorithm takes into account both the time resolution and the frequency resolution. Correspondingly, the accuracy of FH signals detection can be improved.
Artificial bee colony algorithm with dynamic multi-population
Authors: Zhang Ming , Ji Zhicheng , Wang Yan
Published: May 2017

To improve the convergence rate and make a balance between the global search and local turning abilities, this paper proposes a decentralized form of artificial bee colony (ABC) algorithm with dynamic multi-populations by means of fuzzy C-means (FCM) clustering. Each subpopulation periodically enlarges with the same size during the search process, and the overlapping individuals among different subareas work for delivering information acting as exploring the search space with diffusion of solutions. Moreover, a Gaussian-based search equation with redefined local attractor is proposed to further accelerate the diffusion of the best solution and guide the search towards potential areas. Experimental results on a set of benchmarks demonstrate the competitive performance of our proposed approach.
A High Bandwidth (DC-40 GHz) Pseudo Differential Distributed Amplifier in 0.18-μm RF CMOS
Authors: Babaeinik Majid , Dousti Massoud , Tavakoli Mohammad Bagher
Published: May 2017

This study presents a CMOS distributed amplifier (DA) with pseudo differential amplifying that achieves DC-40[Formula: see text]GHz bandwidth (BW) in 0.18-[Formula: see text]m RF CMOS process. The DA with three-stage amplifying cells was proposed to improve the DA performance. The inter-stage was composed of pseudo differential amplifying for bandwidth extension.

By incorporating the pseudo differential amplifier configuration and capacitor-less circuit in the stages, the DA provides average gain and high bandwidth. The simulation results showed that the DA has a S[Formula: see text] of 6.4[Formula: see text]dB, 3-dB BW from DC up to 40[Formula: see text]GHz. It also has a minimum noise figure (NF) of 4.27[Formula: see text]dB, one dB compression point (P[Formula: see text] of [Formula: see text]3.5[Formula: see text]dBm, a high reverse isolation S[Formula: see text] of less than [Formula: see text]15[Formula: see text]dB, an input return loss S[Formula: see text] and output return loss S[Formula: see text] of less than [Formula: see text]16 and [Formula: see text]12[Formula: see text]dB, respectively. It consumes 115[Formula: see text]mW and occupies a total active area of 0.27[Formula: see text]mm2.
A generalization of co-Hopfian abelian groups
Authors: Chekhlov Andrey , Danchev Peter
Published: May 2017

We define the concept of an [Formula: see text]-co-Hopfian abelian group, which is a nontrivial generalization of the classical notion of a co-Hopfian group. A systematic and comprehensive study of these groups is given in very different ways. Specifically, a representation theorem for [Formula: see text]-co-Hopfian groups is established as well as it is shown that there exists an [Formula: see text]-co-Hopfian group which is not co-Hopfian.
Quasimolecular nuclear potential and its application to 12C +16O reaction near and above the Coulomb barrier
Authors: Khan Sohail A. , Rasheed Haroon , Ali Khuram
Published: May 2017

The quasimolecular potential in the sudden approximation is used both near and above the Coulomb barrier (CB) for the [Formula: see text] system. It is found that the resonances associated with the dinuclear configuration are well produced in energy above the CB. Near and below the CB where adiabatic potential is appropriate, it was found that the potential can also be used, provided the potential parameters are varied and the range parameter of the Yukawa term is increased. Resonance positions for [Formula: see text] and 11 agree with experimental findings. The [Formula: see text] resonance energy and width very near 9[Formula: see text]MeV and not at 8.8[Formula: see text]MeV is also reproduced thus supporting experimental results.
Stable manifolds for perturbations of exponential dichotomies in mean
Authors: Barreira Luis , Valls Claudia
Published: May 2017

We establish the existence of stable invariant manifolds for any sufficiently small perturbation of a cocycle with an exponential dichotomy in mean. The latter notion corresponds to replace the exponential behavior in the classical notion of an exponential dichotomy by an exponential behavior in average with respect to an invariant measure. We consider both perturbations of a cocycle over a map and over a flow that can be defined on an arbitrary Banach space. Moreover, we obtain an upper bound for the speed of the nonlinear dynamics along the stable manifold as well as a lower bound when the exponential dichotomy in mean is strong (this means that we have lower and upper bounds along the stable and unstable directions of the dichotomy).
A note on approximation efficiency and partial quotients of Engel continued fractions
Authors: Hu Hui , Yu Yueli , Zhao Yanfen
Published: May 2017

We consider the efficiency of approximating real numbers by their convergents of Engel continued fractions (ECF). Specifically, we estimate the Hausdorff dimension of the set of points whose ECF-convergents are the best approximations infinitely often. We also obtain the Hausdorff dimensions of the Jarnik-like set and the related sets defined by some growth rates of partial quotients in ECF expansions.
The realization of the degree zero part of the motivic polylogarithm on abelian schemes in Deligne–Beilinson cohomology
Authors: Scarponi Danny
Published: May 2017

In 2014, Kings and Rössler showed that the realization of the degree zero part of the abelian polylogarithm in analytic Deligne cohomology can be described in terms of a class of currents which was previously defined by Maillot and Rössler and strongly related to the Bismut–Köhler higher torsion form of the Poincaré bundle. In this paper we show that, if the base of the abelian scheme is proper, Kings and Rössler’s result can be refined to hold already in Deligne–Beilinson cohomology. More precisely, by means of Burgos’ theory of arithmetic Chow groups, we prove that the class of currents defined by Maillot and Rössler has a representative with logarithmic singularities at the boundary and therefore defines an element in Deligne–Beilinson cohomology. This element coincides with the realization of the degree zero part of the motivic polylogarithm on abelian schemes in Deligne–Beilinson cohomology.
QM/MM Geometry Optimization on Extensive Free-Energy Surfaces for Examination of Enzymatic Reactions and Design of Novel Functional Properties of Proteins
Authors: Hayashi Shigehiko , Uchida Yoshihiro , Hasegawa Taisuke , Higashi Masahiro , Kosugi Takahiro , Kamiya Motoshi
Published: May 2017

Many remarkable molecular functions of proteins use their characteristic global and slow conformational dynamics through coupling of local chemical states in reaction centers with global conformational changes of proteins. To theoretically examine the functional processes of proteins in atomic detail, a methodology of quantum mechanical/molecular mechanical (QM/MM) free-energy geometry optimization is introduced. In the methodology, a geometry optimization of a local reaction center is performed with a quantum mechanical calculation on a free-energy surface constructed with conformational samples of the surrounding protein environment obtained by a molecular dynamics simulation with a molecular mechanics force field. Geometry optimizations on extensive free-energy surfaces by a QM/MM reweighting free-energy self-consistent field method designed to be variationally consistent and computationally efficient have enabled examinations of the multiscale molecular coupling of local chemical states with global protein conformational changes in functional processes and analysis and design of protein mutants with novel functional properties.
Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese
Authors: Fujii Chikako , Kawai Toshihide , Azuma Koichiro , Oguma Yuko , Katsukawa Fuminori , Hirose Hiroshi , Tanaka Kumiko , Meguro Shu , Matsumoto Hideo , Itoh Hiroshi
Published: April 2017

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese.Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally.Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r=−0.411,p<0.0001), fasting glucose (r=−0.330,p<0.0001), HbA1c (r=−0.231,p=0.0146), and systolic blood pressure (r=−0.224,p=0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r=−0.416,p<0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects.Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.
Myxedema Crisis Presenting with Seizures: A Rare Life-Threatening Presentation—A Case Report and Review of the Literature
Authors: Gunatilake Sonali Sihindi Chapa , Bulugahapitiya Uditha
Published: May 2017

Myxedema crisis is a life-threatening extreme form of hypothyroidism with a high mortality rate if left untreated. Myxedema crisis is commonly seen in older patients, especially in women, and is associated with signs of hypothyroidism, hypothermia, hyponatraemia, hypercarbia, and hypoxemia. Patients might present with different organ specific symptoms. Seizures are a recognized but rare manifestation of myxedema with a very high mortality rate. Prompt diagnosis and appropriate management may improve the prognosis. Many contributory factors may involve development of seizures in a patient with myxedema. Hyponatraemia is one such cause, which is seen in moderate-severe form in the background of myxedema. We report an elderly male who presented with generalized tonic clonic seizure preceded by memory impairment and drowsiness. He had moderate hyponatraemia and very high thyroid stimulatory hormone levels in association with low free thyroxin levels. Diagnosis of myxedema crisis was made and patient was successfully treated with sodium correction and thyroid hormone replacement.
Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium
Authors: Ilicic Marina , Zakar Tamas , Paul Jonathan W.
Published: May 2017

Background. Regulation of myometrial progesterone receptor (PR) expression is an unresolved issue central to understanding the mechanism of functional progesterone withdrawal and initiation of labor in women. Objectives. To determine whether pregnant human myometrium undergoes culture-induced changes in PR isoform expression ex situ and, further, to determine if conditions approaching the in vivo environment stabilise PR isoform expression in culture. Methods. Term nonlaboring human myometrial tissues were cultured under specific conditions: serum supplementation, steroids, stretch, cAMP, PMA, PGF2α, NF-κB inhibitors, or TSA. Following 48 h culture, PR-T, PR-A, and PR-B mRNA levels were determined using qRT-PCR. PR-A/PR-B ratios were calculated. Results. PR-T and PR-A expression and the PR-A/PR-B ratio significantly increased in culture. Steroids prevented the culture-induced increase in PR-T and PR-A expression. Stretch blocked the effects of steroids on PR-T and PR-A expression. PMA further increased the PR-A/PR-B ratio, while TSA blocked culture-induced increases of PR-A expression and the PR-A/PR-B ratio. Conclusion. Human myometrial tissue in culture undergoes changes in PR gene expression consistent with transition toward a laboring phenotype. TSA maintained the nonlaboring PR isoform expression pattern. This suggests that preserving histone and/or nonhistone protein acetylation is critical for maintaining the progesterone dependent quiescent phenotype of human myometrium in culture.
Rational Combination Immunotherapy: Understand the Biology
Authors: Kaufman Howard L.
Published: May 2017

Selecting rational treatment combinations remains a major challenge for improving immunotherapy outcomes. In this issue of Cancer Immunology Research, Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway. By also targeting autophagy, the therapeutic response improved, highlighting the importance of understanding the biology beneath antitumor immunity. Cancer Immunol Res; 5(5); 355–6. ©2017 AACR.

See article by Zhang et al., p. 363.
Minimum Volume Discussion in the Treatment of Colon and Rectal Cancer: A Review of the Current Status and Relevance of Surgeon and Hospital Volume regarding Result Quality and the Impact on Health Economics
Authors: Link Karl-Heinrich , Coy Peter , Roitman Mark , Link Carola , Kornmann Marko , Staib Ludger
Published: May 2017

Background: To answer the question whether minimum caseloads need to be stipulated in the German S3 (or any other) guidelines for colorectal cancer, we analyzed the current representative literature. The question is important regarding medical quality as well as health economics and policy. Methods: A literature research was conducted in PubMed for papers concerning ‘colon cancer' (CC), ‘rectal cancer' (RC), and ‘colorectal cancer' (CRC), with ‘results', ‘quality', and ‘mortality' between the years 2000 and 2016 being relevant factors. We graded the recommendations as ‘pro', ‘maybe', or ‘contra' in terms of a significant correlation between hospital volume (HV) or surgeon volume (SV) and treatment quality. We also listed the recommended numbers suggested for HV or SV as minimum caseloads and calculated and discussed the socio-economic impact of setting minimum caseloads for CRC. Results: The correlations of caseloads of hospitals or surgeons turned out to be highly controversial concerning the influence of HV or SV on short- and long-term surgical treatment quality of CRC. Specialized statisticians made the point that the reports in the literature might not use the optimal biometrical analytical/reporting methods. A Dutch analysis showed that if a decision towards minimum caseloads, e.g. >50 for CRC resections, would be made, this would exclude a lot of hospitals with proven good treatment quality and include hospitals with a treatment quality below average. Our economic analysis envisioned that a yearly loss of EUR <830,000 might ensue for hospitals with volumes <50 per year. Conclusions: Caseload (HV, SV) definitely is an inconsistent surrogate parameter for treatment quality in the surgery of CC, RC, or CRC. If used at all, the lowest tolerable numbers but the highest demands for structural, process and result quality in the surgical/interdisciplinary treatment of CC and RC must be imposed and independently controlled. Hospitals fulfilling these demands should be medically and socio-economically preferred concerning the treatment of CC and RC patients.
Dexamethason-Implantat: Eine gute Alternative bei behandlungsnaivem diabetischem Makulaödem
Authors: Omri Wafa
Published: May 2017

Ziel: Ziel dieser Studie war die Beurteilung der Wirksamkeit eines einzelnen intravitrealen Dexamethason-Implantats (IDI) über 6 Monate in Augen mit chronischem diabetischem Makulaödem (DME), die auf eine intravitreale Behandlung mit Ranibizumab (IR) nicht angesprochen hatten. Methoden: Diese retrospektive Studie wurde an der Universitätsklinik Ondokuz Mayis in Samsun, Türkei, durchgeführt. Als Wirksamkeitsendpunkte wurden die Veränderung der besten korrigierten Sehschärfe (Visus c.c.) und der zentralen Makuladicke (CMT) untersucht. Ergebnisse: 30 Augen von 20 Patienten im mittleren Alter von 61,6 ± 8,8 (45-85) Jahren wurden in die Studie eingeschlossen. Der mittlere Visus c.c verbesserte sich signifikant von 0,68 ± 0,27 auf 0,56 ± 0,30 logMAR (p = 0,001) bzw. 0,57 ± 0,30 logMAR (p = 0,002) nach 1 bzw. 2 Monaten. Der Anteil der Patienten, deren Visus c.c. sich um 3 Zeilen oder mehr verbesserte, betrug 20%. Die mittlere CMT verringerte sich signifikant von 578,93 ± 17,95 µm zu Studienbeginn auf 282,10 ± 21,42, 292,26 ± 19,69, 371,70 ± 21,23 bzw. 463,60 ± 23,16 µm nach 1, 2, 3 bzw. 4 Monaten (p = 0,001). Der intraokulare Druck stieg in 5 Augen (16,7%). Bei 3 von 23 phaken Augen (13%) wurde eine Kataraktoperation erforderlich. Schlussfolgerung: IDI bietet signifikanten Nutzen im Hinblick auf die Verbesserung der Sehschärfe und Anatomie bei IR- resistentem chronischem DME. Es kann bei IDI-behandelten Patienten zu IOD-Erhöhungen und Kataraktprogression kommen. Das Sicherheitsprofil ist jedoch akzeptabel.
Optische Kohärenztomographie-Angiographie mit dem Optovue-System
Authors: Huang David , Jia Yali , Gao Simon S. , Lumbroso Bruno , Rispoli Marco
Published: May 2017

Die AngioVue-Technologie von Optovue für die optische Kohärenztomographie-Angiographie (OCT-A) basiert auf dem Bildgebungssystem AngioVue (Optovue Inc., Freemont, CA, USA) unter Verwendung des SSADA(split-spectrum amplitude-decorrelation angiography)-Algorithmus. Dieser Algorithmus ist darauf ausgelegt, die Dauer des Scan-Vorgangs zu minimieren. Er erkennt Bewegung im Blutgefäßlumen durch die Messung der Veränderungen in der reflektierten OCT-Signalamplitude bei aufeinanderfolgenden Querschnitt-Scans. Die Besonderheit der SSADA liegt in der Art, wie das OCT-Signal weiterverarbeitet wird, um die Flussmessung zu verbessern und das Signalrauschen der axialen Grundbewegung zu eliminieren. Konkret trennt der Algorithmus die OCT-Aufnahme in einzelne Spektralbänder auf und steigert dadurch die Anzahl verwertbarer Bild-Frames. Jeder neue Frame hat eine geringere axiale Auflösung, die weniger empfindlich gegenüber axialen Augenbewegungen infolge des pulsierenden Blutstroms ist. Die Technologie des AngioVue-Systems von Optovue ermöglicht eine quantitative Analyse. Sie liefert nummerische Daten über durchströmte sowie nicht durchströmte Areale und kann Flussdichtekarten erstellen. Diese aufbereiteten Messdaten könnten als Biomarker sowohl für die Diagnose als auch für die Überwachung des Krankheitsverlaufs und des Ansprechens auf eine Therapie dienen. Durchströmte Areale: Die Software berechnet das eingezeichnete Areal und das Gefäßareal in mm2. Sie ermöglicht auch den Vergleich aller Messungen einer Person. Nicht durchströmte Areale: Die Software zeigt die nicht durchbluteten Areale per Mausklick an. Ischämische Areale werden in Gelb dargestellt. Diese Areale können abgespeichert und mit anderen in der Studie abgeglichen werden. Mit dem Flussdichte-Tool lässt sich der prozentuale Anteil von vaskulären Arealen in En-Face-Angiogrammen messen. Die Analyse beruht auf einem ETDRS(Early Treatment Diabetic Retinopathy Study)-Raster, das wie die Dickenkarte auf die Makula zentriert ist. Das Tool ist sowohl für den inneren als auch für den äußeren Gefäßplexus geeignet. Übersetzung aus Dev Ophthalmol. Basel, Karger, 2016, vol 56, pp 6-12 (DOI:10.1159/000442770)
Intravitreal Sustained-Release Steroid Implants for the Treatment of Macular Edema following Surgical Removal of Epiretinal Membranes
Authors: Hattenbach Lars-Olof , Springer-Wanner Christina , Hoerauf Hans , Callizo Josep , Jungmann Stephanie , Brauns Thomas , Fulle Gergana , Eichel Sebastian , Koss Michael Janusz , Kuhli-Hattenbach Claudia
Published: May 2017

Purpose: To evaluate the efficacy of intravitreal dexamethasone implant for the treatment of postoperative persistent cystoid macular edema (CME) following macular pucker surgery. Methods: In this multicenter study, we retrospectively reviewed the data of 37 patients (39 eyes) who had been treated with intravitreal dexamethasone implant (Ozurdex®) for persistent CME following macular pucker surgery. Main outcome measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Results: All eyes underwent spectral domain optical coherence tomography examination within 130 days after implantation. We observed a significant decrease in mean CRT from 519.9 to 392.9 µm (p < 0.0001). By this time, mean BCVA had improved from 0.60 to 0.43 logMAR (p = 0.003). Seventeen eyes (43.6%) required at least 1 repeat injection of dexamethasone. Of these, 8 (47%) eyes received a total number of 3 or more dexamethasone injections. Conclusion: Intravitreal dexamethasone implant injection is an effective treatment option for persistent CME following macular pucker surgery.
Skin Pigmentation Genetics for the Clinic
Authors: Ainger Stephen A. , Jagirdar Kasturee , Lee Katie J. , Soyer H. Peter , Sturm Richard A.
Published: May 2017

Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma. These same polymorphisms have been under selective pressure leading towards lighter pigmentation in Europeans in the last 5,000-20,000 years that have driven the increase in frequency in modern populations. Although pigmentation is a polygenic trait, due to interactive and quantitative gene effects, strong phenotypic associations are readily apparent for these major genes. However, predictive value and utility are increased when considering gene polymorphism interactions. In melanoma, an increased penetrance is found in cases when pigmentation gene risk alleles such as MC1R variants are coincident with mutation of higher-risk melanoma genes including CDKN2A, CDK4 and MITF E318K, demonstrating an interface between the pathways for pigmentation, naevogenesis and melanoma. The clinical phenotypes associated with germline changes in pigmentation and naevogenic genes must be understood by clinicians, and will be of increasing relevance to dermatologists, as genomics is incorporated into the delivery of personalised medicine.
Outcomes of Endovascular Thrombectomy with and without Thrombolysis for Acute Large Artery Ischaemic Stroke at a Tertiary Stroke Centre
Authors: Wee Chee-Keong , McAuliffe William , Phatouros Constantine C. , Phillips Timothy J. , Blacker David , Singh Tejinder P. , Baker Ellen , Hankey Graeme J.
Published: May 2017

Background and Purpose: Endovascular thrombectomy (EVT) improves the functional outcome when added to best medical therapy, including alteplase, in patients with acute ischaemic stroke secondary to large vessel occlusion (LVO) in the anterior circulation. However, the evidence for EVT in alteplase-ineligible patients is less compelling. It is also uncertain whether alteplase is necessary in patients with successful recanalization by EVT, as the treatment effect of EVT may be so powerful that bridging alteplase may not add to efficacy and may compromise safety by increasing bleeding risks. We aimed to survey the proportion of patients suitable for EVT who are alteplase-ineligible and to compare the safety and effectiveness of standard care of acute large artery ischaemic stroke by EVT plus thrombolysis with that of EVT alone in a tertiary hospital clinical stroke service. Methods: We performed a retrospective analysis of acute ischaemic stroke patients treated with EVT at our centre between October 2013 and April 2016, based on a registry with prospective and consecutive patient collection. Individual patient records were retrieved for review. Significant early neurological improvement was defined as a NIHSS score of 0–1, or a decrease from baseline of ≤8, at 24 h after stroke onset. Results: Fifty patients with acute ischaemic stroke secondary to LVO in the anterior circulation received EVT in this period, of whom 21 (42%) received concurrent alteplase and 29 (58%) EVT alone. The 2 groups had similar baseline characteristics and similar outcomes. Significant neurological improvement at 24 h occurred in 47.6% of the patients with EVT and bridging alteplase and in 51.7% of the patients with EVT alone (p = 0.774). Mortality during acute hospitalization was 20% for the bridging alteplase group versus 7.1% for EVT alone (p = 0.184). Intracranial haemorrhage rates were 14.3% for bridging alteplase versus 20.7% for EVT alone (p = 0.716). Local complications, groin haematoma (23.8 vs. 10.3%) and groin pseudoaneurysms (4.8 vs. 0%) (p = 0.170), were not significantly different. Conclusion: Our study highlights the relatively large proportion of patients suitable for EVT who have a contraindication to alteplase and raises the hypothesis that adding alteplase to successful EVT may not be necessary to optimize functional outcome. The results are consistent with observational data from other endovascular centres and support a randomised controlled trial of EVT versus EVT with bridging alteplase.