bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of gallbladder interstitial Cajal‐like cells in patients with cholelithiasis
Authors: Pasternak Artur , Gil Krzysztof , Matyja Andrzej , Gajda Mariusz , Sztefko Krystyna , Walocha Jerzy A. , Kulig Jan , Thor Piotr
Published: November 2012

Background  Interstitial cells of Cajal (ICCs) play an important role in the regulation of gut motility. There is growing evidence that interstitial Cajal‐like cells (ICLCs) are present in the gallbladder wall. We hypothesize that changes in the density of ICLCs in the gallbladder wall may lead to the development of cholelithiasis due to the impairment of the gallbladder motility. The purpose of this study was to identify ICLCs in the gallbladders of patients with gallstones and to assess their densities.

Methods  Data from 30 patients with gallstones and 25 individuals without gallstones were compared. Tissue samples were obtained during surgery, embedded in paraffin, and cut into sections. Following staining for CD117 and mast cell tryptase, the number of ICLCs and mast cells was determined using image analysis.

Key Results  Cells positive for the c‐Kit receptor (CD117) were detected in the gallbladder wall in all cases examined. Interstitial Cajal‐like cells were most frequently observed in the muscularis propria. The density of ICLCs in the muscularis propria was significantly lower in the patients with gallstones than the density observed in the controls (26.24 ± 10.89 vs 56.29 ± 13.35 cells/mm2). In contrast, the number of mast cells in the gallbladder was increased in the patients with gallstones when compared with the controls (143 ± 24 vs 112 ± 19 cells/mm2).

Conclusions & Inferences  The histopathological differences observed in this study may help elucidate the pathophysiology of gallstones. Gallbladder motility may be affected by the decreased number of ICLCs in patients with cholelithiasis.
New allelic variants found in key rice salt‐tolerance genes: an association study
Authors: Negrão Sónia , Cecília Almadanim M. , Pires Inês S. , Abreu Isabel A. , Maroco João , Courtois Brigitte , Gregorio Glenn B. , McNally Kenneth L. , Margarida Oliveira M.
Published: November 2012

Salt stress is a complex physiological trait affecting plants by limiting growth and productivity. Rice, one of the most important food crops, is rated as salt‐sensitive. High‐throughput screening methods are required to exploit novel sources of genetic variation in rice and further improve salinity tolerance in breeding programmes. To search for genotypic differences related to salt stress, we genotyped 392 rice accessions by EcoTILLING. We targeted five key salt‐related genes involved in mechanisms such as Na+/K+ ratio equilibrium, signalling cascade and stress protection, and we found 40 new allelic variants in coding sequences. By performing association analyses using both general and mixed linear models, we identified 11 significant SNPs related to salinity. We further evaluated the putative consequences of these SNPs at the protein level using bioinformatic tools. Amongst the five nonsynonymous SNPs significantly associated with salt‐stress traits, we found a T67K mutation that may cause the destabilization of one transmembrane domain in OsHKT1;5, and a P140A alteration that significantly increases the probability of OsHKT1;5 phosphorylation. The K24E mutation can putatively affect SalT interaction with other proteins thus impacting its function. Our results have uncovered allelic variants affecting salinity tolerance that may be important in breeding.
Effects of the Gpc‐B1 locus on high grain protein content introgressed into Argentinean wheat germplasm
Authors: Tabbita Facundo , Lewis Silvina , Vouilloz Juan P. , Ortega María A. , Kade Mariana , Abbate Pablo E. , Barneix Atilio J.
Published: November 2012

Wheat grain protein content (GPC) is important for human nutrition and has a strong influence on the quality of pasta and bread. The objective of this study was to analyse the introduction of the Gpc‐B1 allele into two Argentinean bread wheat cultivars. Near‐isogenic lines were developed in ‘ProINTA Oasis’ and ‘ProINTA Granar’ using marker‐assisted selection. Gpc‐B1 lines showed a significant (P = 0.01) increase in GPC and a significant (P = 0.001) decrease in grain weight in comparison with control lines without Gpc‐B1. Differences in yield were not significant (P = 0.49) between lines. Gpc‐B1 lines significantly reduced (P = 0.02) straw nitrogen concentration at maturity and significantly increased (P = 0.02) the nitrogen harvest index. When data were analysed by genotype and environment, differences in some analysed parameters were found, indicating that Gpc‐B1 expression may be affected by different genetic backgrounds and environmental conditions. These results suggest that the introgression of the Gpc‐B1 allele into Argentinean wheat germplasm could be a valuable resource for improving GPC with no detrimental effect on grain yield.
Cross‐sectional epidemiological survey of asthma in Jinan, China
Authors: WANG DEXIANG , XIAO WEI , MA DEDONG , ZHANG YUKE , WANG QIN , Wang CHUAN , JI XIULI , HE BAOLONG , WU XIA , CHEN HONGLI , ZHANG YI , JIANG YUANYUAN , YIN JIA
Published: November 2012

Background and objective

The prevalence and control of asthma in all ages are seldom known in Jinan, China. This study aims to determine the prevalence, related factors and control of asthma in populations of all ages in Jinan, China.

Methods

A cross‐sectional epidemiological questionnaire survey was performed with all members from approximately 4500 randomly selected families from 60 communities in the urban area and in 40 villages in the rural area. The completed questionnaires were focused on asthma, asthma‐like respiratory symptoms and asthma control.

Results

A total of 13 645 individuals were interviewed in the survey, and the number of effective questionnaires reached 13 419. The asthma prevalence of all ages in Jinan was 1.1%. Atopy, asthma family history, household size and age were independent factors related to asthma. The control of asthma in Jinan was suboptimal in a high proportion of patients and even worse in the rural area.

Conclusions

The asthma prevalence for all ages in Jinan was relatively low compared with that in western countries; however, local asthma control fell markedly short from the goals of the Global Initiative for Asthma (GINA) criteria for asthma management, which may be attributed to the poor adherence to GINA guidelines, especially the underuse of preventative medication of inhaled corticosteroids.
Faced with a dilemma: Danish midwives' experiences with and attitudes towards late termination of pregnancy
Authors: Vinggaard Christensen Anne , Christiansen Anne Hjøllund , Petersson Birgit
Published: November 2012

Background

The introduction of prenatal screening for all pregnant women in Denmark in 2004 has lead to an increase in the number of late terminations of pregnancy after the 12th week of pregnancy. Midwives' experiences with late termination of pregnancy (TOP) are still poorly described in the scientific literature.

Aim

To explore Danish midwives' experiences with and attitudes towards late TOP. Focus was on how midwives perceive their own role in late TOP, and how their professional identity is influenced by working with late TOP in a time where prenatal screening is rapidly developing.

Method

A qualitative study consisting of ten individual interviews with Danish midwives, all of whom had taken part in late TOP.

Results

Current practice of late TOP resembles the practice of normal deliveries and is influenced by a growing personalisation of the aborted foetus. The midwives strongly supported women's legal right to choose TOP and considerations about the foetus' right to live were suppressed. Midwives experienced a dilemma when faced with aborted foetuses that looked like newborns and when aborted foetuses showed signs of life after a termination. Furthermore, they were critical of how physicians counsel women/couples after prenatal diagnosis.

Conclusions

The midwives' practice in relation to late TOP was characterised by an acknowledgement of the growing ethical status of the foetus and the emotional reactions of the women/couples going through late TOP. Other professions as well as structural factors at the hospital highly influenced the midwives' ability to organize their work with late terminations. There is a need for more thorough investigation of how to secure the best possible working conditions for midwives, and how to optimise the care for women/couples going through late TOP.
Comparison of anticipatory grief reaction between fathers and mothers of premature infants in neonatal intensive care unit
Authors: Valizadeh Leila , Zamanzadeh Vahid , Rahiminia Elaheh
Published: November 2012

Objectives

Premature birth of neonates leads to anticipatory grief (AG) reaction in parents and make them vulnerable to mental health disorders. The present study aimed to determine and compare the AG reaction in mothers and fathers of premature infants hospitalized in the neonatal intensive care unit.

Methods

This comparative descriptive design was conducted among 40 pairs of mothers and fathers selected by convenience sampling method. The study was performed in 2011 using the Anticipatory Grief Scale. Data were analysed with ‘Wilcoxon ranks test’ using SPSS.

Results

The AG mean scores of fathers and mothers were 1.55 ± 0.55 and 1.68 ± 0.63, respectively. The Wilcoxon test did not show any statistically significant difference between mothers' and fathers' AG reaction (p = 0.12).

Conclusion

Despite expectations, the AG reaction in mothers and fathers showed no difference in this study. It seems necessary to pay more attention to the fathers in addition to mothers to be supported and consulted by the healthcare providers.
Isokinetic rotator muscles fatigue in glenohumeral joint instability before and after Latarjet surgery A pilot prospective study
Authors: Edouard P. , Bankolé C. , Calmels P. , Beguin L. , Degache F.
Published: November 2012

We aimed to analyze the changes in isokinetic internal (IR) and external (ER) rotator muscles fatigue (a) in patients with non‐operated recurrent anterior instability, and (b) before and after shoulder surgical stabilization with the Bristow–Latarjet procedure. Thirty‐seven patients with non‐operated unilateral recurrent anterior post‐traumatic instability (NG) were compared with 12 healthy subjects [control group (CG)]. Twenty patients with operated recurrent anterior instability group (OG) underwent isokinetic evaluation before and 3, 6, and 21 months after Bristow–Latarjet surgery. IR and ER muscles strength was evaluated with Con‐Trex® dynamometer, with subjects seated and at a 45° shoulder abduction angle in scapular plane. IR and ER muscle fatigue was determined after 10 concentric repetitions at 180°·s−1 through the fatigue index, the percent decrease in performance (DP), and the slope of peak torque decrease. There were no differences in rotator muscles fatigue between NG and CG. In OG, 3 months post‐surgery, IR DP of operated shoulder was significantly (P < 0.001) higher than presurgery and 6 and 21 months post‐surgery. Rotator muscles fatigability was not associated with recurrent anterior instability. After surgical stabilization, there was a significantly higher IR fatigability in the operated shoulder 3 months post‐surgery, followed by recovery evidenced 6 months post‐surgery and long‐term maintenance over 21 months.
Shy but Getting By? An Examination of the Complex Links Among Shyness, Coping, and Socioemotional Functioning in Childhood
Authors: Kingsbury Mila , Coplan Robert J. , Rose‐Krasnor Linda
Published: November 2012

The purpose of the current study was to test a conceptual model of the mediated and moderated associations among shyness, coping strategies, and socioemotional functioning in middle childhood. Participants were 358 children (177 boys) aged 9–13 years (M = 10.16 years, SD =.95). Children completed self‐report assessments of shyness, coping style in response to a social stressor, internalizing problems, and peer difficulties. Among the results, shyness was positively associated with internalizing symptoms and negatively related to perceptions of peer difficulties. However, both of these associations were partially mediated by internalizing coping styles. Moreover, problem‐solving coping moderated these mediated pathways: among children who reported higher levels of problem‐solving coping, the associations between internalizing coping and outcomes were attenuated. Several gender differences also emerged, suggesting that problem‐solving coping may be particularly useful for shy boys. Results are discussed in terms of the complex but potentially critical role of coping in shy children's socioemotional functioning.
Paternal and Maternal Mind‐mindedness and Preschoolers' Theory of Mind: The Mediating Role of Interactional Attunement
Authors: Lundy Brenda L.
Published: November 2012

The present investigation explored (1) fathers' contributions to children's theory of mind (ToM) development, (2) the similarity between maternal and paternal mind‐mindedness (MM) in relation to children's ToM, and (3) the relative predictive strength of two concurrently administered measures of MM (an online and an interview assessment) in relation to children's ToM. Thirty‐nine fathers, mothers, and their four‐year‐olds participated. Paternal MM was positively correlated with children's ToM performance. In addition, the two groups of parents performed similarly on both measures of MM. The findings also suggest that mothers and fathers who scored higher on the MM interview were more attuned to their children's mental processes during the online interaction measure of MM. The online measure of MM was found to mediate the relationship between the interview measure of MM and children's ToM for the maternal–child data only.
Subsoil compaction from tractor traffic in an olive (Olea europea L.) grove in Almería, Spain
Authors: Tolón‐Becerra A. , Botta G. F. , Lastra‐Bravo X. , Tourn M. , Rivero D.
Published: November 2012

This study was in an olive (Olea europea L.) grove in the Vélez Blanco District of Almería, Spain, where the soil is a typical Aridisol. The aim was to evaluate subsoil compaction caused by three different tractors currently used in olive groves. Measurements were made of (i) the cone index (CI), (ii) hydraulic conductivity (HC) and (iii) rut depth after passage of a light tractor (LT = 22.50 kN), a heavy tractor (HT = 42.60 kN) and a medium tractor (MT = 33.30 kN). The CI differed for the topsoil (0–200 mm) for each type of tractor after up to five passes. In this depth soil level, the CI was greatest for LT because the ground pressure (by narrow tyres) was greater than under the MT and HT. For deeper layers, there was a strong positive relationship between number of tractor passes and CI values, and the CI was greater for passes by the HT than the LT or MT. The HT resulted in shallower ruts up to the fifth pass, and the CI values were smaller because there was less ground pressure from this tractor than the others. In all treatments, tractor traffic caused varying decreases in HC in the 0–600 mm depth range. The main conclusion is that subsoil compaction is related directly to tractor weight. For the three tractors, topsoil compaction is caused by ground pressure and not on total axle load.
On the center of the ring of differential operators on a smooth variety over ℤ/pnℤ
Authors: Stewart Allen , Vologodsky Vadim
Published: November 2012

We compute the center of the ring of PD differential operators on a smooth variety over ℤ/pnℤ, confirming a conjecture of Kaledin (private communication). More generally, given an associative algebraA0over ℤpand its flat deformationAnover ℤ/pn+1ℤ, we prove that under a certain non-degeneracy condition, the center ofAnis isomorphic to the ring of length-(n+1) Witt vectors over the center ofA0.
Quivers with potentials associated to triangulated surfaces, Part III: tagged triangulations and cluster monomials
Authors: Cerulli Irelli Giovanni , Labardini-Fragoso Daniel
Published: November 2012

To each tagged triangulation of a surface with marked points and non-empty boundary we associate a quiver with potential in such a way that whenever we apply a flip to a tagged triangulation the Jacobian algebra of the quiver with potential (QP) associated to the resulting tagged triangulation is isomorphic to the Jacobian algebra of the QP obtained by mutating the QP of the original one. Furthermore, we show that any two tagged triangulations are related by a sequence of flips compatible with QP-mutation. We also prove that, for each of the QPs constructed, the ideal of the non-completed path algebra generated by the cyclic derivatives is admissible and the corresponding quotient is isomorphic to the Jacobian algebra. These results, which generalize some of the second author’s previous work for ideal triangulations, are then applied to prove properties of cluster monomials, like linear independence, in the cluster algebra associated to the given surface by Fomin, Shapiro and Thurston (with an arbitrary system of coefficients).
Elliptic curves with a given number of points over finite fields
Authors: David Chantal , Smith Ethan
Published: November 2012

Given an elliptic curve E and a positive integer N, we consider the problem of counting the number of primes p for which the reduction of E modulo p possesses exactly N points over 𝔽p. On average (over a family of elliptic curves), we show bounds that are significantly better than what is trivially obtained by the Hasse bound. Under some additional hypotheses, including a conjecture concerning the short-interval distribution of primes in arithmetic progressions, we obtain an asymptotic formula for the average.
Identifying supersingular elliptic curves
Authors: Sutherland Andrew V.
Published: November 2012

Given an elliptic curve E over a field of positive characteristic p, we consider how to efficiently determine whether E is ordinary or supersingular. We analyze the complexity of several existing algorithms and then present a new approach that exploits structural differences between ordinary and supersingular isogeny graphs. This yields a simple algorithm that, given E and a suitable non-residue in 𝔽p2, determines the supersingularity of E in O(n3log 2n) time and O(n) space, where n=O(log p) . Both these complexity bounds are significant improvements over existing methods, as we demonstrate with some practical computations.
Heat Transfer in an Oblique Jet Impingement Configuration With Varying Jet Geometries
Authors: Schueren Simon , Hoefler Florian , Wolfersdorf Jens von , Naik Shailendra
Published: November 2012

The experimental and numerical heat transfer results in a trapezoidal duct with two staggered rows of inclined impingement jets are presented. The influence of changes in the jet bore geometry on the wall heat transfer is examined. The goal of this project is to minimize the thermal load in an internal gas turbine blade channel and to provide sufficient cooling for local hot spots. The dimensionless pitch is varied between p/djet=3 − 6. For p/djet=3, cylindrical and conically narrowing bores with a cross section reduction of 25% and 50%, respectively, are investigated. The studies are conducted at 10,000≤Re≤75,000. Experimental results are obtained using a transient thermochromic liquid crystal technique. The numerical simulations are performed solving the RANS equations with FLUENT using the low- Re k- ω -SST turbulence model. The results show that for a greater pitch, the decreasing interaction between the jets leads to diminished local wall heat transfer. The area averaged Nusselt numbers decrease by up to 15% for p/djet=4.5, and up to 30% for p/djet=6, respectively, if compared to the baseline pitch of p/djet=3. The conical bore design accelerates the jets, thus increasing the area-averaged heat transfer for identical mass-flow by up to 15% and 30% for the moderately and strongly narrowing jets, respectively. A dependency of the displacement between the Nu maximum and the geometric stagnation point from the jet shear layer is shown.
Stability Improvement of High-Pressure-Ratio Turbocharger Centrifugal Compressor by Asymmetrical Flow Control—Part II: Nonaxisymmetrical Self-Recirculation Casing Treatment
Authors: Zheng Xinqian , Zhang Yangjun , Yang Mingyang , Bamba Takahiro , Tamaki Hideaki
Published: November 2012

This is part II of a two-part paper involving the development of an asymmetrical flow control method to widen the operating range of a turbocharger centrifugal compressor with high-pressure ratio. A nonaxisymmetrical self-recirculation casing treatment (SRCT) as an instance of asymmetrical flow control method is presented. Experimental and numerical methods were used to investigate the impact of nonaxisymmetrical SRCT on the surge point of the centrifugal compressor. First, the influence of the geometry of a symmetric SRCT on the compressor performance was studied by means of numerical simulation. The key parameter of the SRCT was found to be the distance from the main blade leading edge to the rear groove (Sr). Next, several arrangements of a nonaxisymmetrical SRCT were designed, based on flow analysis presented in part I. Then, a series of experiments were carried out to analyze the influence of nonaxisymmetrical SRCT on the compressor performance. Results show that the nonaxisymmetrical SRCT has a certain influence on the performance and has a larger potential for stability improvement than the traditional symmetric SRCT. For the investigated SRCT, the surge flow rate of the compressor with the nonaxisymmetrical SRCTs is about 10% lower than that of the compressor with symmetric SRCT. The largest surge margin (smallest surge flow rate) can be obtained when the phase of the largest Sr is coincident with the phase of the minimum static pressure in the vicinity of the leading edge of the splitter blades.
Performance of a Multiple-Injection Dry Low NOx Combustor With Hydrogen-Rich Syngas Fuels
Authors: Dodo Satoschi , Asai Tomohiro , Koizumi Hiromi , Takahashi Hirokazu , Yoshida Shouhei , Inoue Hiroshi
Published: November 2012

An oxygen-blown integrated coal gasification combined cycle (IGCC) plant with precombustion carbon dioxide capture and storage (CCS) is one of the most promising means of zero-emission generation of power from coal. In an IGCC plant with CCS, hydrogen-rich syngas with a wide variation of hydrogen contents is supplied to a gas turbine. Such hydrogen-rich syngas poses a great challenge to a low NOx combustor based on premixed combustion technology, because its high flame speed, low ignition energy, and broad flammability limits can cause flashback and/or autoignition. On the contrary, a diffusion combustor suffers from the high flame temperature of syngas and the resulting high NOx emission. The authors applied a “multi-injection burner” concept to a preliminary burner for hydrogen-rich syngas simulating that from IGCC with CCS. In a preliminary experiment under atmospheric pressure, the multi-injection burner worked without any flashback or any blowout. A prototype multicluster combustor based on the results of that preliminary study was made to be a dry low NOx combustor for hydrogen-rich syngas of IGCC with CCS. It was tested in experiments, which were carried out under medium pressure (0.6 MPa) using test fuels simulating syngas from IGCC with a 0% carbon capture rate, a 30% carbon capture rate, and a 50% carbon capture rate. The test fuels contained hydrogen, methane, and nitrogen, and had a hydrogen content ranging from 40% to 65%.The following conclusions were drawn from the test results: (1) the tested combustor allows the stable combustion of fuels simulating 0%, 30%, and 50% CCS, (2) a convex perforated plate swirler is effective to suppress combustion oscillation, which allows NOx emissions to be less than 10 ppm through the variation of fuel simulating 0%, 30%, and 50% CCS, (3) the extended stable combustion region and enhanced entrainment and mixing due to the convex perforated plate improves the cooling of the combustor liner metal to be less than the liner metal temperature criterion.
Issues in Polycrystalline Diamond Compact Cutter–Rock Interaction From a Metal Machining Point of View—Part II: Bit Performance and Rock Cutting Mechanics
Authors: Che Demeng , Han Peidong , Guo Ping , Ehmann Kornel
Published: November 2012

In Part I of this paper, the issues related to temperature, stress and force were reviewed and parallels were drawn between both metal machining and rock cutting. Part II discusses the issues more directly related to polycrystalline diamond compact (PDC) bit performance and rock mechanics. However, relevant issues in various metal cutting processes will continue to be presented to clarify the gaps and similarities between these two classes of processes.
Metal artifact reduction in computed tomography using local models in an image block‐iterative scheme
Authors: Van Slambrouck Katrien , Nuyts Johan
Published: November 2012

Purpose:

In iterative reconstruction, metal artifacts can be reduced by applying more accurate reconstruction models that are usually also more computationally demanding. The hypothesis of this work is that these complex models only need to be applied in the vicinity of the metals and that a less complex model can be used for the remainder of the reconstruction volume.

Methods:

A method is described that automatically divides the reconstruction volume into metal and nonmetal regions. The different regions are called patches. A different energy and resolution model can be assigned to each of the patches. The patches containing metals are reconstructed with a fully polychromatic spectral model (IMPACT) and if necessary with an increased resolution model. The patch without metals is reconstructed with a simple polychromatic model (MLTRC) that only includes the spectral behavior of water attenuation. Comparing the computational complexity of IMPACT and MLTRC gives a ratio of 8:3. The different patches are updated sequentially as in a grouped coordinate algorithm. Two phantoms were simulated and measured: a circular phantom containing small metal cylinders and a body phantom representing a human pelvis with two femoral implants. As a first test, the sequential update of the patches was applied while using the same energy model for all patches. Second, the local model approach was applied using MLTRC for nonmetal regions and IMPACT for metal regions. The results of different iterative reconstruction schemes are compared to the results of projection completion, another important method for the reduction of metal artifacts.

Results:

Reconstruction schemes including the sequential update of the patches result in images with less streak artifacts compared to a regular reconstruction. The sequential update of each of the metal regions improves the relative convergence of the metals (edges and attenuation values) against the rest of the image, which leads to an improved artifact reduction. Using the combined IMPACT+MLTRC model results in a similar image quality as using IMPACT everywhere, while providing an important benefit regarding computational complexity. Some streak and shadow artifacts were still present, but all structures present in the phantom could be observed. Projection completion results in reconstructions with less obvious streak and shadow artifacts but tends to deform or erase structures lying close to or in between metallic structures.

Conclusions:

Metal artifact reduction with iterative reconstruction can be achieved by using complex models only locally without losing image quality. Separately updating metal regions leads to reduced streak artifacts. Structures lying close to or in between metals are often better reconstructed, compared to projection completion results, because all available information is used.
Trade-Offs of Chemotactic Foraging in Turbulent Water
Authors: Taylor John R. , Stocker Roman
Published: November 2012

Ocean Monarchs

It is hard to grasp that the unseen microorganisms of the oceans are the most productive on the planet, at orders of magnitude greater than sharks and whales or even terrestrial forests. The plankton is thus a major contributor to the geochemical cycles that are currently under pressure from climate change.
Stocker
(p.
628
) reviews the state of knowledge of the web of myriad ephemeral microenvironments within the ocean's bulk and how microorganisms respond to the ever-shifting chemical spectrum. To this end,
Taylor and Stocker
(p.
675
) report experiments on the effects of turbulence on nutrient uptake by chemotactic marine bacteria. They propose that turbulence favors motile bacteria that adopt an optimal foraging strategy, which trades off the relative high cost of motility to gain the benefits of plumes of nutrients by zipping between them at optimized speeds. Scaled up, such apparently “micro” behavior will influence the rate of remineralization of dissolved organic matter and in turn will feed into global patterns of geochemical cycling.
Comment on “Multiyear Prediction of Monthly Mean Atlantic Meridional Overturning Circulation at 26.5°N”
Authors: Vecchi Gabriel A. , Msadek Rym , Delworth Thomas L. , Dixon Keith W. , Guilyardi Eric , Hawkins Ed , Karspeck Alicia R. , Mignot Juliette , Robson Jon , Rosati Anthony , Zhang Rong
Published: November 2012

Matei
et al
. (Reports, 6 January 2012, p. 76) claim to show skillful multiyear predictions of the Atlantic Meridional Overturning Circulation (AMOC). However, these claims are not justified, primarily because the predictions of AMOC transport do not outperform simple reference forecasts based on climatological annual cycles. Accordingly, there is no justification for the “confident” prediction of a stable AMOC through 2014.
Response to Comment on “Multiyear Prediction of Monthly Mean Atlantic Meridional Overturning Circulation at 26.5°N”
Authors: Matei Daniela , Baehr Johanna , Jungclaus Johann H. , Haak Helmuth , Müller Wolfgang A. , Marotzke Jochem
Published: November 2012

Vecchi
et al
. question the skill of our initialized multiyear predictions of Atlantic Meridional Overturning Circulation (AMOC), arguing that our predictions do not outperform their suggested climatological reference forecast—using a single measure of skill. We show that our initialized AMOC predictions do outperform the climatological reference forecast, using both measures of hindcast performance that were presented in our original paper.
Mice Lacking a
Myc
Enhancer That Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors
Authors: Sur Inderpreet Kaur , Hallikas Outi , Vähärautio Anna , Yan Jian , Turunen Mikko , Enge Martin , Taipale Minna , Karhu Auli , Aaltonen Lauri A. , Taipale Jussi
Published: November 2012

From Man to Mouse

Genome-wide association studies of humans have identified single-nucleotide polymorphisms (SNPs) that increase an individual's risk of developing common diseases like cancer. Most of these SNPs have only a modest effect on risk, and many map to noncoding regions of the genome.

Sur
et al.

(p.
1360
, published online 1 November; see the Perspective by
Lewis and Tomlinson
) used a mouse model to study the functional impact of a particular SNP that resides 300 kilobases upstream of the
MYC
oncogene on human chromosome 8q24 and has been linked to cancer risk in humans. When a sequence encompassing this SNP was deleted in mice that were predisposed to develop intestinal tumors, the mice displayed fewer tumors than control mice. This SNP may thus play a causal role in human cancer, presumably through altered regulation of
MYC.
Quantum Procrastination
Authors: Lloyd Seth
Published: November 2012

Entangling two photons allows the wave and particle nature of light to be interchanged even after the light has already been detected.
Getting Moore from Solar Cells
Authors: Norris David J. , Aydil Eray S.
Published: November 2012

Exploring alternative device designs and component materials will be crucial in improving solar cell performance.
Healing Through Heredity
The Science of Human Perfection
How Genes Became the Heart of American Medicine

by Nathaniel Comfort

Yale University Press, New Haven, CT, 2012. 334 pp. $35, £25. ISBN 9780300169911.
Authors: Creager Angela N. H.
Published: November 2012

Exploring the roots of medical genetics, Comfort illuminates neglected connections between eugenics and medicine during the first half of the 20th century.
A New Direction for Gene Loops
Authors: Hampsey Michael
Published: November 2012

Genes adopt a loop conformation to focus the direction of transcription and block the production of noncoding RNAs.
Chloroplast Delivery by UPS
Authors: Kessler Felix
Published: November 2012

Identification of a membrane-anchored E3 ligase in plants reveals a role for the ubiquitin proteasome system in chloroplast development.
The Scientist as World Citizen
Authors: King Mary-Claire
Published: November 2012

In early 2011, listening on U.S. public radio to reports from Tahrir square, I looked forward particularly to those from Mona Seif, a young citizen journalist from Cairo. Her reports were rich in detail, and even when difficult to hear over gunfire, they were clear and informative to a listener on the other side of the world.
Immune Reactions Help Reprogram Cells
Authors: Vogel Gretchen
Published: November 2012

A cell's defensive reaction to viruses seems to make it more open to expressing genes that are usually shut down—whether they are those that trigger inflammation or those that are active in stem cells.
Flying Dinos and Baby Birds Offer New Clues About How Avians Took Wing
Authors: Balter Michael
Published: November 2012

At a meeting of vertebrate paleontologists last month, researchers pondered fresh clues about the origins of flight from studies of feathered dinosaurs and baby birds.
18β-Glycyrrhetinic Acid Inhibits Methicillin-Resistant Staphylococcus aureus Survival and Attenuates Virulence Gene Expression
Authors: Long Danyelle R. , Mead Julia , Hendricks Jay M. , Hardy Michele E. , Voyich Jovanka M.
Published: November 2012

Methicillin-resistant
Staphylococcus aureus
(MRSA) has become a major source of infection in hospitals and in the community. Increasing antibiotic resistance in
S. aureus
strains has created a need for alternative therapies to treat disease. A component of the licorice root
Glycyrrhiza
spp., 18β-glycyrrhetinic acid (GRA), has been shown to have antiviral, antitumor, and antibacterial activity. This investigation explores the
in vitro
and
in vivo
effects of GRA on MRSA pulsed-field gel electrophoresis (PFGE) type USA300. GRA exhibited bactericidal activity at concentrations exceeding 0.223 μM. Upon exposure of
S. aureus
to sublytic concentrations of GRA, we observed a reduction in expression of key virulence genes, including
saeR
and
hla
. In murine models of skin and soft tissue infection, topical GRA treatment significantly reduced skin lesion size and decreased the expression of
saeR
and
hla
genes. Our investigation demonstrates that at high concentrations GRA is bactericidal to MRSA and at sublethal doses it reduces virulence gene expression in
S. aureus
both
in vitro
and
in vivo
.
Functional Analysis of Pneumococcal Drug Efflux Pumps Associates the MATE DinF Transporter with Quinolone Susceptibility
Authors: Tocci Nadia , Iannelli Francesco , Bidossi Alessandro , Ciusa Maria Laura , Decorosi Francesca , Viti Carlo , Pozzi Gianni , Ricci Susanna , Oggioni Marco Rinaldo
Published: November 2012

The pneumococcal chromosome encodes about 140 transporters, many of which are predicted to be involved in efflux. In order to critically evaluate pneumococcal efflux, a series of transporter mutants were constructed, and their phenotypes were assayed by disk diffusion, microdilution drug susceptibility testing (MIC testing), growth of cultures at sub-MIC concentrations, and phenotype microarray analysis. Mutants with mutations in seven ATP binding cassette (ABC) transporters, three multiantimicrobial extrusion (MATE) family efflux pumps, and one major facilitator superfamily (MFS) transporter were obtained in
Streptococcus pneumoniae
strain DP1004. The susceptibility of these 11 mutants to over 250 different substances was compared to that of the parent strain. Of the tested transporters, only the ABC transporter PatAB (SP2073-5) presented a clear multidrug resistance (MDR) profile, as the mutant showed significantly increased susceptibility to ethidium bromide, acriflavine, and berberine. Among the other transporters analyzed, the mutants devoid of the MATE efflux pump SP2065 exhibited reduced susceptibility to novobiocin, and those with mutations of the MATE family DinF transport system (SP1939) exhibited increased susceptibility to moxifloxacin, ciprofloxacin, and levofloxacin. This change in quinolone MIC was found to be independent from the competence-mediated effect of quinolones on the
cinA-recA-dinF
operon. Furthermore, the
dinF
mutant, in contrast to the parental strain, allowed selection for quinolone-resistant mutants when exposed to moxifloxacin. These data confirm the clear MDR profile of the PatAB ABC transporter and suggest for the MATE DinF a phenotype associated with quinolone susceptibility, particularly for moxifloxacin.
Pharmacokinetics and Pharmacodynamics of Anidulafungin for Experimental Candida Endophthalmitis: Insights into the Utility of Echinocandins for Treatment of a Potentially Sight-Threatening Infection
Authors: Livermore J. L. , Felton T. W. , Abbott J. , Sharp A. , Goodwin J. , Gregson L. , Warn P. A. , Howard S. J. , Hope W. W.
Published: November 2012

Candidachorioretinitis and endophthalmitis are relatively common manifestations of disseminated candidiasis. Anidulafungin is increasingly used for the treatment of disseminated candidiasis, but its efficacy forCandidaendophthalmitis is not known. A nonneutropenic model of hematogenousCandidaendophthalmitis was used. Anidulafungin at 5, 10, and 20 mg/kg was initiated at 48 h postinoculation. The fungal densities in the kidney and vitreous humor were determined. Anidulafungin concentrations in the plasma and vitreous humor were measured using high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic model was used to link anidulafungin concentrations with the observed antifungal effect. The area under the concentration-time curve (AUC) associated with stasis was determined in the both the kidney and the vitreous humor. The results were bridged to humans to identify likely dosages that are associated with significant antifungal activity within the eye. Inoculation ofCandida albicansresulted in logarithmic growth in both the vitreous humor and the kidney. The pharmacokinetics of anidulafungin were linear. There was dose-dependent penetration of the anidulafungin into the vitreous humor. The exposure-response relationships in the kidney and vitreous were completely discordant. AUCs of 270 and 100 were required for stasis in the eye and kidney, respectively. The currently licensed regimen results in an AUC for an average patient that is associated with stasis in the kidney but minimal antifungal activity in the eye. We conclude that anidulafungin penetrates the eye in a dose-dependent manner and that dosages higher than those currently licensed are required to achieve significant antifungal activity in the eye.
Interaction of Platelets and Anidulafungin against Aspergillus fumigatus
Authors: Perkhofer Susanne , Striessnig Barbara , Sartori Bettina , Hausott Barbara , Ott Helmut W. , Lass-Flörl Cornelia
Published: November 2012

The combination of platelets and anidulafungin at 0.03 μg/ml significantly (
P
< 0.05) reduced the germination rate and hyphal elongation in
Aspergillus fumigatus
compared to those with either anidulafungin only or an untreated control. Platelets decreased the expression of the
fks
gene, which plays an important role in cell wall synthesis. Our results suggest that human platelets plus anidulafungin might contribute to defense against
A. fumigatus
.
Rapid Isolation and Susceptibility Testing of Leptospira spp. Using a New Solid Medium, LVW Agar
Authors: Wuthiekanun Vanaporn , Amornchai Premjit , Paris Daniel H. , Langla Sayan , Thaipadunpanit Janjira , Chierakul Wirongrong , Smythe Lee D. , White Nicholas J. , Day Nicholas P. J. , Limmathurotsakul Direk , Peacock Sharon J.
Published: November 2012

Pathogenic
Leptospira
spp., the causative agents of leptospirosis, are slow-growing Gram-negative spirochetes. Isolation of
Leptospira
from clinical samples and testing of antimicrobial susceptibility are difficult and time-consuming. Here, we describe the development of a new solid medium that facilitates more-rapid growth of
Leptospira
spp. and the use of this medium to evaluate the Etest's performance in determining antimicrobial MICs to drugs in common use for leptospirosis. The medium was developed by evaluating the effects of numerous factors on the growth rate of
Leptospira interrogans
strain NR-20157. These included the type of base agar, the concentration of rabbit serum (RS), and the concentration and duration of CO
2
incubation during the initial period of culture. The highest growth rate of NR-20157 was achieved using a Noble agar base supplemented with 10% RS (named LVW agar), with an initial incubation at 30°C in 5% CO
2
for 2 days prior to continuous culture in air at 30°C. These conditions were used to develop the Etest for three species,
L. interrogans
(NR-20161),
L. kirschnerii
(NR-20327), and
L. borgpetersenii
(NR-20151). The MICs were read on day 7 for all samples. The Etest was then performed on 109 isolates of pathogenic
Leptospira
spp. The MIC
90
values for penicillin G, doxycycline, cefotaxime, ceftriaxone, and chloramphenicol were 0.64 units/ml and 0.19, 0.047, 0.5, and 2 μg/ml, respectively. The use of LVW agar, which enables rapid growth, isolation of single colonies, and simple antimicrobial susceptibility testing for
Leptospira
spp., provides an opportunity for new areas of fundamental and applied research.
Tigecycline Displays
In Vivo
Bactericidal Activity against Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae after 72-Hour Exposure Period
Authors: Tessier Pamela R. , Nicolau David P.
Published: November 2012

Progressively enhanced activity of a humanized tigecycline (TGC) regimen was noted over 3 days against an extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
isolate and an ESBL-producing
Klebsiella pneumoniae
isolate. Bacterial density reduction approximated 3 log
10
approaching bactericidal activity at 72 h. This level of activity has not been previously noted for compounds such as tetracyclines, normally considered bacteriostatic antimicrobials. Extended regimen studies
in vivo
may aid in better delineation of antimicrobial effects, producing improved correlation with clinical outcomes.
FIM-1, a New Acquired Metallo-β-Lactamase from a Pseudomonas aeruginosa Clinical Isolate from Italy
Authors: Pollini Simona , Maradei Simona , Pecile Patrizia , Olivo Giuseppe , Luzzaro Francesco , Docquier Jean-Denis , Rossolini Gian Maria
Published: November 2012

Acquired metallo-β-lactamases (MBLs) are resistance determinants of increasing clinical importance in Gram-negative bacterial pathogens, which confer a broad-spectrum β-lactam resistance, including carbapenems. Several such enzymes have been described since the 1990s. In the present study, a novel acquired MBL, named FIM-1, was identified and characterized. The
bla
FIM-1
gene was cloned from a multidrug-resistant
Pseudomonas aeruginosa
clinical isolate (FI-14/157) cultured from a patient with a vascular graft infection in Florence, Italy. The isolate belonged in the sequence type 235 epidemic clonal lineage. The FIM-1 enzyme is a member of subclass B1 and, among acquired MBLs, exhibited the highest similarity (ca. 40% amino acid identity) with NDM-type enzymes. In
P. aeruginosa
FI-14/157, the
bla
FIM-1
gene was apparently inserted into the chromosome and associated with IS
CR19
-like elements that were likely involved in the capture and mobilization of this MBL gene. Transfer experiments of the
bla
FIM-1
gene to an
Escherichia coli
strain or another
P. aeruginosa
strain by conjugation or electrotransformation were not successful. The FIM-1 protein was produced in
E. coli
and purified by two chromatography steps. Analysis of the kinetic parameters, carried out with the purified enzyme, revealed that FIM-1 has a broad substrate specificity, with a preference for penicillins (except the 6α-methoxy derivative temocillin) and carbapenems. Aztreonam was not hydrolyzed. Detection of this novel type of acquired MBL in a
P. aeruginosa
clinical isolate underscores the increasing diversity of such enzymes that can be encountered in the clinical setting.
The Target of Daptomycin Is Absent from Escherichia coli and Other Gram-Negative Pathogens
Authors: Randall Christopher P. , Mariner Katherine R. , Chopra Ian , O'Neill Alex J.
Published: November 2012

Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like
Escherichia coli
owing to the permeability barrier presented by the outer membrane and/or the action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such agents almost invariably demonstrate antibacterial activity against Gram negatives. Here we show that this is not the case for the antibiotic daptomycin, whose target appears to be absent from
E. coli
and other Gram-negative pathogens.
Measurement of Anti-Erythropoiesis-Stimulating Agent IgG4 Antibody as an Indicator of Antibody-Mediated Pure Red Cell Aplasia
Authors: Weeraratne Dohan K. , Kuck Andrew J. , Chirmule Narendra , Mytych Daniel T.
Published: November 2012

Patients treated with erythropoietin-based erythropoiesis-stimulating agents (ESAs) can develop a rare but life-threatening condition called antibody-mediated pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology patient with amPRCA include high antibody concentrations with neutralizing activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples and antibody-positive non-PRCA patients. Therefore, we validated a highly sensitive immunoassay on the ImmunoCAP 100 instrument to quantitate anti-ESA IgG4 antibodies using a human recombinant anti-epoetin alfa (EPO) IgG4 antibody as a calibrator. The biotinylated ESA was applied to a streptavidin ImmunoCAP, and bound anti-ESA IgG4 antibodies were detected using a β-galactosidase-conjugated mouse anti-human IgG4 antibody. The validated assay was used to detect anti-ESA IgG4 in amPRCA and non-PRCA patients. The immunoassay detected 15 ng/ml of human anti-EPO IgG4 antibody in the presence of a 200 M excess of human anti-ESA IgG1, IgG2, or IgM antibody and tolerated 2 μg/ml of soluble erythropoietin. All patient samples with confirmed amPRCA had measurable anti-ESA IgG4 antibodies. In addition, 94% (17/18) of non-PRCA patient samples were antibody negative or had below 15 ng/ml of anti-ESA IgG4 antibodies. This novel immunoassay can measure low-nanogram quantities of human anti-ESA IgG4 antibodies in the presence of other anti-ESA antibodies. An increased concentration of anti-ESA IgG4 antibody is associated with the development of amPRCA. We propose that the measurement of anti-ESA specific IgG4 antibodies may facilitate early detection of amPRCA in patients receiving all ESAs structurally related to human erythropoietin.