bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadband cascading of second-order nonlinearity in randomized nonlinear photonic crystal
Authors: Sheng Yan , Ma Dongli , Ren Mingliang , Chen Baoqin , Roppo Vito , Li Zhiyuan , Koynov Kaloian , Krolikowski Wieslaw
Published: August 2012

We study both experimentally and theoretically optical parametric process in one-dimensional nonlinear photonic crystal with random variation to the sign of the second-order nonlinear coefficient. We demonstrate that the structure randomness enables broadband third-harmonic generation via cascading of two second-order nonlinear parametric wave interactions with the overall conversion efficiency higher than previously recorded in fully disordered media such as the as-grown strontium barium niobate crystal. Furthermore, thanks to the one-dimensional modulation of the second-order nonlinearity, the emitted broadband harmonics preserve well the spatial intensity profile of the incident fundamental light beam, a feature critical for applications of optical frequency conversion but unavailable in two-dimensional fully random media due to the beam divergence caused by the simultaneous emission of noncollinear harmonic.
Removal of strain relaxation induced defects by flushing of InAs quantum dots
Authors: Polojärvi Ville , Schramm Andreas , Aho Arto , Tukiainen Antti , Guina Mircea
Published: August 2012

We report the effect of indium flushing on the electrical and optical properties of strain-relaxed InAs quantum dots (QDs) embedded in GaAs Schottky diodes. The InAs QDs were intentionally grown beyond the critical thickness to induce plastically relaxed QDs. The samples were fabricated by molecular beam epitaxy on GaAs(1 0 0) substrates using continuous and cycled InAs deposition. Deep level transient spectroscopy (DLTS) experiments show broad dislocation-induced defects in non-flushed samples. We show by DLTS that indium flushing after QD deposition decreases remarkably the amount of electron traps in the QD layer and suppresses the defect formation into GaAs capping layer. Using capacitance–voltage measurements we observed that the flushed samples exhibit a recovery of electron confinement in the QD states. Furthermore, we used photoluminescence experiments to analyse the effects of direct versus cycled InAs deposition and indium flushing steps.
Effect of thermal treatment and ageing on IR transmission and visible photoluminescence of nanostructured aluminum oxyhydroxide
Authors: Karlash A Yu , Skryshevsky V A , Khodan A N , Kanaev A V , Gayvoronsky V Ya
Published: August 2012

IR transmission and visible photoluminescence (PL) were studied in raw nanoporous aluminum oxyhydroxide (NOA) and in samples after thermal treatment at different temperatures. Structural and chemical modifications of the NOA sample were related to the water content and adsorption/desorption process at the surface. The differences observed in the FTIR spectra in vacuum and after ageing of the samples can be explained by the effects of molecular water and OH− groups on the stability of the low-temperature phases of NOA. A considerable increase in PL intensity and spectrum expansion to longer wavelengths were observed in all NOA samples after water desorption. This was accompanied by strong changes in the PL decay kinetics. Quenching of the fast luminescent decay and low-energy transitions in aged samples were observed after ageing of the samples. Partial passivation of the NOA surface and defective sites under ambient conditions is discussed.
Every module is an inverse limit of injectives
Authors: Bergman George
Published: August 2012

It is shown that any left moduleAAover a ringRRcan be written as the intersection of a downward directed system of injective submodules of an injective module; equivalently, as an inverse limit of one-to-one homomorphisms of injectives. IfRRis left Noetherian,AAcan also be written as the inverse limit of a system of surjective homomorphisms of injectives. Some questions are raised.
Averages of values of 𝐿-series
Authors: Alkan Emre
Published: August 2012

We obtain an exact formula for the average of values of

L
L

-series over two independent odd characters. The average of any positive moment of values at

s
=
1

s=1

is then expressed in terms of finite cotangent sums subject to congruence conditions. As consequences, bounds on such cotangent sums, limit points for the average of first moment of

L
L

-series at

s
=
1

s=1

and the average size of positive moments of character sums related to the class number are deduced.
Another approach to the thin-film Γ-limit of the micromagnetic free energy in the regime of small samples
Authors: Kreisbeck Carolin
Published: August 2012

The asymptotic behavior of the micromagnetic free energy governing a ferromagnetic film is studied as its thickness gets smaller and smaller compared to its cross section. Here the static Maxwell equations are treated as a Murat’s constant-rank PDE constraint on the energy functional. In contrast to previous work, this approach allows us to keep track of the induced magnetic field without solving the magnetostatic equations. In particular, the mathematical results of Gioia and James [Proc. R. Soc. Lond. A453 (1997), pp. 213–223] regarding convergence of minimizers are recovered by giving a characterization of the correspondingΓ\Gamma-limit.
A Fatou type theorem for complex map germs
Authors: Câmara Leonardo , Scárdua Bruno
Published: August 2012

In this paper we prove a Fatou type theorem for complex map germs. More precisely, we give (generic) conditions assuring the existence of parabolic curves for complex map germs tangent to the identity, in terms of existence of suitable formal separatrices. Such a map cannot have finite orbits.
Les
Réflexions
du marquis d'Argenson sur la liberté des historiens
Authors: Balázs Péter
Published: August 2012

L'article traite d'un ouvrage pratiquement inconnu — publié dans les
Mémoires de littérature, tirés des registres de l'Académie royale des inscriptions et belles-lettres
— du marquis d'Argenson (1694–1757) écrit au sujet de la liberté des historiens au sein de la monarchie française. Son point de départ est une comparaison suivie des grands historiens de l'Antiquité avec les plus illustres des ‘chroniqueurs’ français. Le marquis voit la raison de la supériorité des historiens antiques sur les modernes dans la différence des deux régimes: tandis que les républiques antiques se caractérisaient par la liberté de leurs citoyens, la monarchie française ne réserve que la servitude à ses sujets. Dans ce qui suit j'essaye de contextualiser cette affirmation très catégorique, d'abord en définissant sa place dans les débats contemporains portant sur l'histoire et l'écriture historique, puis en montrant que son auteur, qui s'efforce dans ses ouvrages majeurs de contribuer à la ‘républicanisation de la monarchie’, recourt souvent à des interprétations diamétralement opposées à celle qui est en œuvre dans le texte ici examiné.
Event-related Functional Magnetic Resonance Imaging of a Low Dose of Dexmedetomidine that Impairs Long-term Memory
Authors: Hayama Hiroki R. , Drumheller Kristin M. , Mastromonaco Mark , Reist Christopher , Cahill Lawrence F. , Alkire Michael. T.
Published: August 2012

Background

Work suggests the amnesia from dexmedetomidine (an α2-adrenergic agonist) is caused by a failure of information to be encoded into long-term memory and that dexmedetomidine might differentially affect memory for emotionally arousing material. We investigated these issues in humans using event-related neuroimaging to reveal alterations in brain activity and subsequent memory effects associated with drug exposure.

Methods

Forty-eight healthy volunteers received a computer-controlled infusion of either placebo or low-dose dexmedetomidine (target = 0.15 ng/ml plasma) during neuroimaging while they viewed and rated 80 emotionally arousing (e.g., graphic war wound) and 80 nonarousing neutral (e.g., cup) pictures for emotional arousal content. Long-term picture memory was tested 4 days later without neuroimaging. Imaging data were analyzed for drug effects, emotional processing differences, and memory-related changes with statistical parametric mapping-8.

Results

Dexmedetomidine impaired overall (mean ± SEM) picture memory (placebo: 0.58 ± 0.03 vs. dexmedetomidine: 0.45 ± 0.03, P = 0.001), but did not differentially modulate memory as a function of item arousal. Arousing pictures were better remembered for both groups. Dexmedetomidine had regionally heterogeneous effects on brain activity, primarily decreasing it in the cortex and increasing it in thalamic and posterior hippocampal regions. Nevertheless, a single subsequent memory effect for item memory common to both groups was identified only in the left hippocampus/amygdala. Much of this effect was found to be larger for the placebo than dexmedetomidine group.

Conclusion

Dexmedetomidine impaired long-term picture memory, but did not disproportionately block memory for emotionally arousing items. The memory impairment on dexmedetomidine corresponds with a weakened hippocampal subsequent memory effect.
Modifying Methoxycarbonyl Etomidate Inter-Ester Spacer Optimizes In Vitro Metabolic Stability and In Vivo Hypnotic Potency and Duration of Action
Authors: Husain S. Shaukat , Pejo Ervin , Ge Rile , Raines Douglas E.
Published: August 2012

Background

Methoxycarbonyl etomidate is the prototypical very rapidly metabolized etomidate analog. Initial studies suggest that it may be too short acting for many clinical uses. We hypothesized that its duration of action could be lengthened and clinical utility broadened by incorporating specific aliphatic groups into the molecule to sterically protect its ester moiety from esterase-catalyzed hydrolysis. To test this hypothesis, we developed a series of methoxycarbonyl etomidate analogs (spacer-linked etomidate esters) containing various aliphatic-protecting groups and spacer lengths.

Methods

Spacer-linked etomidate esters were synthesized and their hypnotic potencies and durations of action following bolus administration were measured in rats using a loss-of-righting reflexes assay. Octanol:water partition coefficients and metabolic half-lives in pooled rat blood were determined chromatographically.

Results

All spacer-linked etomidate esters produced hypnosis rapidly and in a dose-dependent manner. ED50s for loss of righting reflexes ranged from 0.69 ± 0.04 mg/kg for cyclopropyl-methoxycarbonyl metomidate to 11.1 ± 0.8 mg/kg for methoxycarbonyl metomidate. The slope of a plot of the duration of loss of righting reflexes versus the logarithm of the dose ranged 12-fold among spacer-linked etomidate esters, implying widely varying brain clearance rates. The in vitro metabolic half-lives of these compounds in rat blood varied by more than two orders of magnitude and were diastereometrically selective.

Conclusions

We created 13 new analogs of methoxycarbonyl etomidate and identified two that have significantly higher potency and potentially address the too-brief duration of action for methoxycarbonyl etomidate. This work may provide a blueprint for optimizing the pharmacological properties of other soft drugs.
D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function
Authors: Sasaki Masato , Knobbe Christiane B. , Itsumi Momoe , Elia Andrew J. , Harris Isaac S. , Chio Iok In Christine , Cairns Rob A. , McCracken Susan , Wakeham Andrew , Haight Jillian , Ten Annick You , Snow Bryan , Ueda Takeshi , Inoue Satoshi , Yamamoto Kazuo , Ko Myunggon , Rao Anjana , Yen Katharine E. , Su Shinsan M. , Mak Tak Wah
Published: August 2012

Isocitratedehydrogenase-1 (IDH1) R132 mutations occur in glioma, but their physiological significance is unknown. Here we describe the generation and characterization of brain-specific Idh1 R132H conditional knock-in (KI) mice. Idh1 mutation results in hemorrhage and perinatal lethality. Surprisingly, intracellular reactive oxygen species (ROS) are attenuated in Idh1-KI brain cells despite an apparent increase in the NADP+/NADPH ratio. Idh1-KI cells also show high levels of D-2-hydroxyglutarate (D2HG) that are associated with inhibited prolyl-hydroxylation of hypoxia-inducible transcription factor-1α (Hif1α) and up-regulated Hif1α target gene transcription. Intriguingly, D2HG also blocks prolyl-hydroxylation of collagen, causing a defect in collagen protein maturation. An endoplasmic reticulum (ER) stress response induced by the accumulation of immature collagens may account for the embryonic lethality of these mutants. Importantly, D2HG-mediated impairment of collagen maturation also led to basement membrane (BM) aberrations that could play a part in glioma progression. Our study presents strong in vivo evidence that the D2HG produced by the mutant Idh1 enzyme is responsible for the above effects.
Complexes with Mixed Primary and Secondary Cellulose Synthases Are Functional in Arabidopsis Plants
Authors: Carroll Andrew , Mansoori Nasim , Li Shundai , Lei Lei , Vernhettes Samantha , Visser Richard G.F. , Somerville Chris , Gu Ying , Trindade Luisa M.
Published: August 2012

In higher plants, cellulose is synthesized by so-called rosette protein complexes with cellulose synthases (CESAs) as catalytic subunits of the complex. The CESAs are divided into two distinct families, three of which are thought to be specialized for the primary cell wall and three for the secondary cell wall. In this article, the potential of primary and secondary CESAs forming a functional rosette complex has been investigated. The membrane-based yeast two-hybrid and biomolecular fluorescence systems were used to assess the interactions between three primary (CESA1, CESA3, CESA6), and three secondary (CESA4, CESA7, CESA8) Arabidopsis (Arabidopsis thaliana) CESAs. The results showed that all primary CESAs can physically interact both in vitro and in planta with all secondary CESAs. Although CESAs are broadly capable of interacting in pairwise combinations, they are not all able to form functional complexes in planta. Analysis of transgenic lines showed that CESA7 can partially rescue defects in the primary cell wall biosynthesis in a weak cesa3 mutant. Green fluorescent protein-CESA protein fusions revealed that when CESA3 was replaced by CESA7 in the primary rosette, the velocity of the mixed complexes was slightly faster than the native primary complexes. CESA1 in turn can partly rescue defects in secondary cell wall biosynthesis in a cesa8ko mutant, resulting in an increase of cellulose content relative to cesa8ko. These results demonstrate that sufficient parallels exist between the primary and secondary complexes for cross-functionality and open the possibility that mixed complexes of primary and secondary CESAs may occur at particular times.
Nitric Oxide-Mediated Maintenance of Redox Homeostasis Contributes to NPR1-Dependent Plant Innate Immunity Triggered by Lipopolysaccharides
Authors: Sun Aizhen , Nie Shengjun , Xing Da
Published: August 2012

The perception of lipopolysaccharides (LPS) by plant cells can lead to nitric oxide (NO) production and defense gene induction. However, the signaling cascades underlying these cellular responses have not yet been resolved. This work investigated the biosynthetic origin of NO and the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) to gain insight into the mechanism involved in LPS-induced resistance of Arabidopsis (Arabidopsis thaliana). Analysis of inhibitors and mutants showed that LPS-induced NO synthesis was mainly mediated by an arginine-utilizing source of NO generation. Furthermore, LPS-induced NO caused transcript accumulation of alternative oxidase genes and increased antioxidant enzyme activity, which enhanced antioxidant capacity and modulated redox state. We also analyzed the subcellular localization of NPR1 to identify the mechanism for protein-modulated plant innate immunity triggered by LPS. LPS-activated defense responses, including callose deposition and defense-related gene expression, were found to be regulated through an NPR1-dependent pathway. In summary, a significant NO synthesis induced by LPS contributes to the LPS-induced defense responses by up-regulation of defense genes and modulation of cellular redox state. Moreover, NPR1 plays an important role in LPS-triggered plant innate immunity.
Randomised clinical trial: low‐volume bowel preparation for colonoscopy ‐ a comparison between two different PEG‐based formulations
Authors: Repici A. , Cestari R. , Annese V. , Biscaglia G. , Vitetta E. , Minelli L. , Trallori G. , Orselli S. , Andriulli A. , Hassan C.
Published: August 2012

Background

Low‐volume bowel preparations with polyethylene glycol (PEG) have been shown to provide an equivalent cleansing with improved tolerability as compared with standard PEG bowel preparation for colonoscopy. A new iso‐osmotic sulphate‐free formulation of PEG‐Citrate‐Simethicone (PEG‐CS) in combination with bisacodyl has been recently developed.

Aim

To compare the quality of bowel cleansing with PEG‐CS with bisacodyl vs. PEG‐Ascorbate (PEG‐ASC) in adult out‐patients undergoing colonoscopy.

Methods

Randomised, observer‐blind, parallel group study in adult out‐patients undergoing colonoscopy in five Italian centres. Both preparations were taken the evening before the procedure. Subjects were instructed to take 2–4 tablets of 5 mg bisacodyl at 16:00 hours and 2 L of PEG‐CS at 20:00 hours or 2 L of PEG‐ASC plus 1 L of additional water the day before colonoscopy. Bowel cleansing was evaluated according to the Boston Bowel Preparation Scale (≥6 scores were considered as ‘clinical success’), and mucosal visibility according to a 3‐point scale. Tolerability, acceptability and compliance were also evaluated.

Results

Four hundred and eight patients were randomly allocated to PEG‐CS and bisacodyl (n = 204, male patient 48%, mean age 59.1 years) or PEG‐ASC (n = 204, male patient 51%, age 59.4 years). In the planned per‐protocol analysis, the rate of successful preparation was 79.1% following PEG‐CS with bisacodyl, and 70% following PEG‐ASC (P < 0.05). Mucosal visibility was evaluated as optimal in 56.1% in the PEG‐CS and bisacodyl and 46.3% in the PEG‐ASC group (P < 0.05). There were no serious adverse events (AE) in each of the two experimental groups. Two subjects in the PEG‐ASC group discontinued the study because of AE.

Conclusions

Polyethylene glycol‐Citrate‐Simethicone in combination with bisacodyl was more effective for bowel cleansing than PEG‐ASC for out‐patient colonoscopy. Tolerability, safety, acceptability and compliance of the two low‐volume bowel preparations were similar.
High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study
Authors: Osunkwo Ifeyinwa , Ziegler Thomas R. , Alvarez Jessica , McCracken Courtney , Cherry Korin , Osunkwo Chinyere E. , Ofori‐Acquah Solomon F. , Ghosh Samit , Ogunbobode Adeolu , Rhodes Jim , Eckman James R. , Dampier Carlton , Tangpricha Vin
Published: August 2012

We report results of a pilot study of high‐dose vitamin D in sickle cell disease (SCD). Subjects were given a 6‐week course of oral high‐dose cholecalciferol (4000–100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high‐dose vitamin D achieved higher serum 25‐hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality‐of‐life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.
Identification, functional analysis, prevalence and treatment of monocarboxylate transporter 8 (MCT8) mutations in a cohort of adult patients with mental retardation
Authors: Visser W. Edward , Vrijmoeth Paul , Visser Frank E. , Arts Willem Frans M. , van Toor Hans , Visser Theo J.
Published: August 2012

Objective

Monocarboxylate transporter 8 (MCT8) is an essential thyroid hormone (TH) transporter as humans with MCT8 mutations have severe neurological and endocrine abnormalities. The objectives are (i) to identify novel MCT8 mutations and (ii) to assess their functional relevance; (iii) to describe the effects of block‐and‐replace treatment in an MCT8 patient.

Design

The TOP‐R study is a cross‐sectional nation‐wide multicentre study.

Patients

Subjects with unexplained mental retardation (MR) were screened for MCT8 mutations.

Results

We identified three mutations: p.F501del (previously described), p.L492P and p.T162T. The F501del and L492P mutants, but not the T162T mutant, showed diminished T3, T4 and rT3 transport in transfected cells. TH transport in T162T fibroblasts was also not affected. One patient was treated with block‐and‐replace therapy to normalize serum TH levels. The results indicated a slow onset of the decrease in serum T4 and T3 by successive treatment with methimazole and PTU, and eventually their complete normalization by administration of LT4 with PTU but not with methimazole. The frequency of MCT8 mutations in males with X‐linked MR approximately 3·9%.

Conclusions

We identified several MCT8 mutations in a cohort of subjects with unexplained MR. We demonstrated the pathogenicity of two missense mutations. The synonymous variant did not affect TH transport. Block‐and‐replace therapy of one patient reversed the TH abnormalities. Our data suggest a decreased TH secretion rate and an increased T4 to T3 conversion by the type I deiodinase in patients with MCT8 mutations. Our study indicates that MCT8 mutations are a relatively frequent cause of X‐linked MR.
Effects of minute misregistrations of prefabricated markers for image‐guided dental implant surgery: an analytical evaluation
Authors: Rußig Lorenz L. , Schulze Ralf K. W.
Published: August 2012

Objectives

The goal of the present study was to develop a theoretical analysis of errors in implant position, which can occur owing to minute registration errors of a reference marker in a cone beam computed tomography volume when inserting an implant with a surgical stent.

Material and methods

A virtual dental‐arch model was created using anatomic data derived from the literature. Basic trigonometry was used to compute effects of defined minute registration errors of only voxel size. The errors occurring at the implant's neck and apex both in horizontal as in vertical direction were computed for mean ±95%‐confidence intervals of jaw width and length and typical implant lengths (8, 10 and 12 mm).

Results

Largest errors occur in vertical direction for larger voxel sizes and for greater arch dimensions. For a 10 mm implant in the frontal region, these can amount to a mean of 0.716 mm (range: 0.201–1.533 mm). Horizontal errors at the neck are negligible, with a mean overall deviation of 0.009 mm (range: 0.001–0.034 mm). Errors increase with distance to the registration marker and voxel size and are affected by implant length.

Conclusion

Our study shows that minute and realistic errors occurring in the automated registration of a reference object have an impact on the implant's position and angulation. These errors occur in the fundamental initial step in the long planning chain; thus, they are critical and should be made aware to users of these systems.
A systematic review of the effectiveness and cost‐effectiveness of bilateral multichannel cochlear implants in adults with severe‐to‐profound hearing loss
Authors: Crathorne L. , Bond M. , Cooper C. , Elston J. , Weiner G. , Taylor R. , Stein K.
Published: August 2012

Clin. Otolaryngol. 2012, 37, 342–354

Background:  In the UK, approximately 10 000 people have cochlear implants, more than 99% with a unilateral implant. Evidence shows that adults implanted bilaterally may benefit from binaural advantages; however, systematic review evidence is limited.

Objectives of the review:  To conduct a systematic review to discover the evidence for effectiveness and cost‐effectiveness of using bilateral cochlear implants in adults with severe‐to‐profound hearing loss by comparing their effectiveness with unilateral cochlear implantation or unilateral cochlear implantation and acoustic hearing aid in the contralateral ear.

Type of review:  Systematic review.

Search strategy:  This examined 16 electronic databases, plus bibliographies and references for published and unpublished studies.

Evaluation method:  Abstracts were independently assessed against inclusion criteria by two researchers, and disagreements were resolved. Selected papers were then retrieved and further independently assessed in a similar way. Included studies had their data extracted by one reviewer and checked by another.

Results:  Searches yielded 2892 abstracts producing 19 includable studies. Heterogeneity between studies precluded meta‐analysis. However, all studies reported that bilateral cochlear implants improved hearing and speech perception: one randomised controlled trial found a significant binaural benefit over the first ear alone for speech and noise from the front (12.6 ± 5.4%, P < 0.001) and when noise was ipsilateral to the first ear (21 ± 6%, P < 0.001); and another found a significant benefit for spatial hearing at 3 and 9 months post‐implantation compared with pre‐implantation [mean difference (sd) scores: 3 months = 1.46 (0.83–2.09), P < 0.01].Quality of life results varied, showing bilateral implantation may improve quality of life in the absence of worsening tinnitus. Limited cost‐effectiveness evidence showed that bilateral implantation is probably only cost‐effective at a willingness‐to‐pay threshold above £62 000 per quality adjusted life year.

Conclusions:  Despite inconsistency in the quality of available evidence, the robustness of systematic review methods gives weight to the positive findings of included studies demonstrating that bilateral implantation is clinically effective in adults but unlikely to be cost‐effective.
PHYLOGENETIC RELATIONSHIPS OF HIPPOLYTID GENERA, WITH AN ASSIGNMENT OF NEW FAMILIES FOR THE CRANGONOIDEA AND ALPHEOIDEA (CRUSTACEA, DECAPODA, CARIDEA)
Authors: CHRISTOFFERSEN MARTIN L.
Published: August 2012

Abstract—

A manual cladistic analysis of the unnamed monophyletic taxon Alpheoidea plus Crangonoidea produced a cladogram containing 36 terminal taxa and 185 characters. The genealogical relationships of most of the 35 genera presently classified under the Hippolytidae have been resolved. Ten of these genera have been transferred, with the Processidae, from the Alpheoidea to the Crangonoidea. The concept of the Hippolytidae Bate, 1888 has been considerably restricted, the available names Lysmatidae Dana, 1852, Thoridae Kingsley, 1878, Hippolytinae Bate, 1888, and Latreutinae Ortmann, 1896 have been invalidated, and the new, family group names Barbouridae, Nauticarididae, Alopidae, and Bythocarididae are proposed. The traditional practice of naming monotypic taxa of suprageneric level has been avoided, yet all genealogical information indicated in the cladogram can be retrieved from the final classification proposed here for the Crangonoidea and Alpheoidea.
Composition of the type VII secretion system membrane complex
Authors: Houben Edith N. G. , Bestebroer Jovanka , Ummels Roy , Wilson Louis , Piersma Sander R. , Jiménez Connie R. , Ottenhoff Tom H. M. , Luirink Joen , Bitter Wilbert
Published: August 2012

Pathogenic mycobacteria require type VII secretion (T7S) systems to transport virulence factors across their complex cell envelope. These bacteria have up to five of these systems, termed ESX‐1 to ESX‐5. Here, we show that ESX‐5 of Mycobacterium tuberculosis mediates the secretion of EsxN, PPE and PE_PGRS proteins, indicating that ESX‐5 is a major secretion pathway in this important pathogen. Using the ESX‐5 system of Mycobacterium marinum and Mycobacterium bovis BCG as a model, we have purified and analysed the T7S membrane complex under native conditions. blue native‐PAGE and immunoprecipitation experiments showed that the ESX‐5 membrane complex of both species has a size of ∼ 1500 kDa and is composed of four conserved membrane proteins, i.e. EccB5, EccC5, EccD5 and EccE5. Subsequent limited proteolysis suggests that EccC5 and EccE5 mostly reside on the periphery of the complex. We also observed that EccC5 and EccD5 expression is essential for the formation of a stable membrane complex. These are the first data on a T7S membrane complex and, given the high conservation of its components, our data can likely be generalized to most mycobacterial T7S systems.
The stepwise acquisition of fluconazole resistance mutations causes a gradual loss of fitness in Candida albicans
Authors: Sasse Christoph , Dunkel Nico , Schäfer Tina , Schneider Sabrina , Dierolf Franziska , Ohlsen Knut , Morschhäuser Joachim
Published: August 2012

The pathogenic yeast Candida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain‐of‐function mutations in the transcription factors Mrr1, Tac1 and Upc2, which result in constitutive overexpression of multidrug efflux pumps and ergosterol biosynthesis genes respectively. It is not known how the permanently changed gene expression program in resistant strains affects their fitness in the absence of drug selection pressure. We have systematically investigated the effects of activating mutations in Mrr1, Tac1 and Upc2, individually and in all possible combinations, on the degree of fluconazole resistance and on the fitness of C. albicans in an isogenic strain background. All combinations of different resistance mechanisms resulted in a stepwise increase in drug resistance, culminating in 500‐fold increased fluconazole resistance in strains possessing mutations in the three transcription factors and an additional resistance mutation in the drug target enzyme Erg11. The acquisition of resistance mutations was associated with reduced fitness under non‐selective conditions in vitro as well as in vivo during colonization of a mammalian host. Therefore, without compensatory mutations, the inability to appropriately regulate gene expression results in a loss of competitive fitness of drug‐resistant C. albicans strains.
Impact of lake‐level changes on the formation of thermogene travertine in continental rifts: Evidence from Lake Bogoria, Kenya Rift Valley
Authors: RENAUT ROBIN W. , OWEN R. BERNHART , JONES BRIAN , TIERCELIN JEAN‐JACQUES , TARITS CORINNE , EGO JOHN K. , KONHAUSER KURT O.
Published: August 2012

Travertine is present at 20% of the ca 60 hot springs that discharge on Loburu delta plain on the western margin of saline, alkaline Lake Bogoria in the Kenya Rift. Much of the travertine, which forms mounds, low terraces and pool‐rim dams, is sub‐fossil (relict) and undergoing erosion, but calcite‐encrusted artefacts show that carbonate is actively precipitating at several springs. Most of the springs discharge alkaline (pH: 8·3 to 8·9), Na‐HCO3 waters containing little Ca (<2 mg l−1) at temperatures of 94 to 97·5°C. These travertines are unusual because most probably precipitated at temperatures of >80°C. The travertines are composed mainly of dendritic and platy calcite, with minor Mg‐silicates, aragonite, fluorite and opaline silica. Calcite precipitation is attributed mainly to rapid CO2 degassing, which led to high‐disequilibrium crystal morphologies. Stratigraphic evidence shows that the travertine formed during several stages separated by intervals of non‐deposition. Radiometric ages imply that the main phase of travertine formation occurred during the late Pleistocene (ca 32 to 35 ka). Periods of precipitation were influenced strongly by fluctuations in lake level, mostly under climate control, and by related changes in the depth of boiling. During relatively arid phases, meteoric recharge of ground water declines, the lake is low and becomes hypersaline, and the reduced hydrostatic pressure lowers the level of boiling in the plumbing system of the hot springs. Any carbonate precipitation then occurs below the land surface. During humid phases, the dilute meteoric recharge increases, enhancing geothermal circulation, but the rising lake waters, which become relatively dilute, flood most spring vents. Much of the aqueous Ca2+ then precipitates as lacustrine stromatolites on shallow firm substrates, including submerged older travertines. Optimal conditions for subaerial travertine precipitation at Loburu occur when the lake is at intermediate levels, and may be favoured during transitions from humid to drier conditions.
Dual effects of hydrogen sulphide on focal cerebral ischaemic injury via modulation of oxidative stress‐induced apoptosis
Authors: Li Guo‐Feng , Luo Hai‐Kun , Li Lan‐Fang , Zhang Qing‐Zeng , Xie Li‐Jun , Jiang Hong , Li Li‐Ping , Hao Na , Wang Wei‐Wei , Zhang Jian‐Xin
Published: August 2012

Hydrogen sulphide (H2S), one of three signalling gasotransmitters, plays an important role in oxidative stress and apoptosis. However, the effects of H2S on oxidative stress‐induced apoptosis in focal cerebral ischaemic injury in rats have not been clarified.

In the present study, sodium hydrosulphide (NaHS) was used as the H2S donor. Eighty‐four Sprague‐Dawley rats were randomly divided into six groups: sham, sham + low‐dose (2.8 mg/kg) NaHS, sham + high‐dose (11.2 mg/kg) NaHS, infarct, infarct + low‐dose NaHS and infarct + high‐dose NaHS. The focal cerebral ischaemic model was created by cranially inserting a nylon thread with a rounded tip into an internal carotid artery. Rats were killed 21 h after administration of NaHS.

In the infarct + low‐dose NaHS compared with infarct group, infarct volume was significantly decreased and injury to the mitochondria in nerve cells was mitigated. Furthermore, significant increases were seen in mitochondrial superoxide dismutase and glutathione peroxidase activity and neuronal bcl‐2 protein levels, whereas mitochondrial malondialdehyde content and neuronal bax and caspase 3 protein levels were significantly decreased, in the infarct + low‐dose NaHS compared with infarct group. The effects seen in the infarct group were significantly aggravated in the infarct + high‐dose NaHS group.

The findings of the present study provide novel evidence for the dual effects of H2S on focal cerebral ischaemic injury via modulation of oxidative stress‐induced apoptosis.
Malignant lymphoma of the spleen in Japan: A clinicopathological analysis of 115 cases
Authors: Shimizu‐Kohno Kei , Kimura Yoshizo , Kiyasu Junichi , Miyoshi Hiroaki , Yoshida Maki , Ichikawa Riko , Niino Daisuke , Ohshima Koichi
Published: August 2012

Primary splenic lymphoma is rare, but malignant lymphoma often produces a lesion in the spleen as part of systemic disease. The frequency of splenic malignant lymphoma in Japan is unknown. We classified 184 specimens of the spleen according to the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition (2008). Of the 184 specimens, 115 were determined to be lymphoid neoplasm (62.5%). The most common subtype of lymphoid neoplasm was diffuse large B‐cell lymphoma (DLBCL) (46 cases), followed by splenic marginal zone lymphoma (SMZL) (28 cases), follicular lymphoma (11 cases), splenic B‐cell lymphoma, unclassifiable (SBL‐U) (6 cases) and peripheral T‐cell lymphoma, not otherwise specified (4 cases). In the SBL‐U subtype, 5 of 6 cases were splenic diffuse red pulp small B‐cell lymphoma, and one case was the hairy cell leukemia variant. Analysis of clinical features revealed that patients with DLBCL had a higher age, high lactate dehydrogenase and tumor formation in the spleen. On the other hand, it was found that patients with SMZL had splenomegaly but no discrete tumor formation. Most of the patients with SBL‐U presented with thrombocytopenia, bone marrow involvement, and advanced stage. Our study revealed the frequency and clinical features of splenic malignant lymphoma in Japan.
Altered expression of microRNA miR‐21, miR‐155, and let‐7a and their roles in pulmonary neuroendocrine tumors
Authors: Lee Hyoun Wook , Lee Eun Hee , Ha Seung Yeon , Lee Chang Hun , Chang Hee Kyung , Chang Sunhee , Kwon Kun Young , Hwang Il Seon , Roh Mee Sook , Seo Jeong Wook
Published: August 2012

MicroRNA (miRNA) has a critical effect on tumorigenesis through post‐transcriptional modification and is considered to be potential biomarkers for cancer diagnosis and treatment monitoring. We evaluated the expression pattern of three selected miRNAs (miR‐21, miR‐155, and let‐7a) to evaluate their potential roles by quantitative reverse transcription‐polymerase chain reaction using formalin‐fixed and paraffin‐embedded tissues of 63 surgically resected pulmonary neuroendocrine (NE) tumors (19 typical carcinoids (TCs), 6 atypical carcinoids (ACs), 19 large cell NE carcinomas (LCNECs), and 19 small cell lung carcinomas (SCLCs). Control amplification for U6 small nuclear RNA (U6) was performed in all samples. Normalized Ct values were calculated (CtExperimental miRNA‐CtU6) for each case and recorded. The expression levels of miR‐21 and miR‐155 were significantly higher in high‐grade NE carcinomas (LCNECs and SCLCs) than in carcinoid tumors (TCs and ACs) (each P < 0.001). The expression level of miR‐21 in carcinoid tumors with lymph node metastasis was significantly higher than in carcinoid tumors without lymph node metastasis (P= 0.010). To the best of our knowledge, the present study is the first to examine the expression patterns of miR‐21 and miR‐155 as an adjunctive diagnostic tool or clinically relevant biomarkers for pulmonary NE tumors.
Clinicopathological study of Japanese patients with genetic iron overload syndromes
Authors: Hattori Ai , Miyajima Hiroaki , Tomosugi Naohisa , Tatsumi Yasuaki , Hayashi Hisao , Wakusawa Shinya
Published: August 2012

In addition to hemochromatosis, aceruloplasminemia and ferroportin disease may be complicated by iron‐induced multiple organ damage. Therefore, clinicopathological features should be evaluated in a wider range of genetic iron disorders. This study included 16 Japanese patients with genetic iron overload syndromes. The responsible genes were CP in four, HAMP in one, HJV in three, TFR2 in five, and SLC40A1 in three patients. No phenotype dissociation was observed in patients with the CP, TFR2, or HAMP genotypes. Two of the three patients with the HJV genotype displayed classic hemochromatosis instead of the juvenile type. Patients with the SLC40A1 genotype were affected by mild iron overload (ferroportin A) or severe iron overload (ferroportin B). Transferrin saturation was unusually low in aceruloplasminemia patients. All patients, except those with ferroportin disease, displayed low serum hepcidin‐25 levels. Liver pathology showed phenotype‐specific changes; isolated parenchymal iron loading in aceruloplasminemia, periportal fibrosis associated with heavy iron overload in both parenchymal and Kupffer cells of ferroportin B, and parenchyma‐dominant iron‐loading cirrhosis in hemochromatosis. In contrast, diabetes occurred in all phenotypes of aceruloplasminemia, hemochromatosis, and ferroportin disease B. In conclusion, clinicopathological features were partially characterized in Japanese patients with genetic iron overload syndromes.
Bilateral, multicenteric metanephric adenoma associated with Wilms' tumor in a child: A rare presentation with important diagnostic and therapeutic implications
Authors: Pasricha Sunil , Gandhi Jatin S , Gupta Gurudutt , Mehta Anurag , Beg Shaham
Published: August 2012

Metanephric adenoma is an uncommon benign renal tumor that occurs predominantly in adult females and rarely in children. On histomorphology it shows a resemblance to Wilms' tumor, nephrogenic rests and papillary renal cell carcinoma. Multifocality along with multicentricity has not been documented in English literature till date. From a diagnostic and therapeutic viewpoint, recognition of this entity is of the utmost importance, because it shows a favorable clinical outcome. We describe a rare case of bilateral, multicentric metanephric adenoma associated with triphasic Wilms' tumor (stage II) of the left kidney in a male child.
Repair of diverse diabetic defects of β‐cells in man and mouse by pharmacological glucokinase activation
Authors: Doliba Nicolai M. , Fenner Deborah , Zelent Bogumil , Bass Joseph , Sarabu Ramakanth , Matschinsky Franz M.
Published: August 2012

Glucokinase activators (GKAs) are being developed and clinically tested for potential antidiabetic therapy. The potential benefits and limitations of this approach continue to be intensively debated. To contribute to the understanding of experimental pharmacology and therapeutics of GKAs, we have tested the efficacy of one of these agents (Piragliatin) in isolated islets from humans with type 2 diabetes mellitus (T2DM), from mice with glucokinase (GK) mutations induced by ethyl‐nitroso‐urea (ENU) as models of Maturity Onset Diabetes of the Young linked to GK and Permanent Neonatal Diabetes Mellitus linked to GK (PNDM‐GK) and finally of islets rendered glucose insensitive by treatment with the sulphonyl urea compound glyburide in organ culture. We found that the GKA repaired the defect in all three instances as manifest in increased glucose‐induced insulin release and elevated intracellular calcium responses. The results show the remarkable fact that acute pharmacological activation of GK reverses secretion defects of β‐cells caused by molecular mechanism that differ vastly in nature, including the little understood multifactorial lesion of β‐cells in T2DM of man, the complex GK mutations in mice resembling GK disease and acute sulphonylurea failure of mouse β‐cells in tissue culture. The implications of these results are to be discussed on the theoretical basis underpinning the strategy of developing these drugs and in light of recent results of clinical trials with GKAs that failed for little understood reasons.
Metabolic stress, IAPP and islet amyloid
Authors: Montane J. , Klimek‐Abercrombie A. , Potter K. J. , Westwell‐Roper C. , Bruce Verchere C.
Published: August 2012

Amyloid forms within pancreatic islets in type 2 diabetes from aggregates of the β‐cell peptide islet amyloid polypeptide (IAPP). These aggregates are toxic to β‐cells, inducing β‐cell death and dysfunction, as well as inciting islet inflammation. The β‐cell is subject to a number of other stressors, including insulin resistance and hyperglycaemia, that may contribute to amyloid formation by increasing IAPP production by the β‐cell. β‐Cell dysfunction, evident as impaired glucose‐stimulated insulin secretion and defective prohormone processing and exacerbated by metabolic stress, is also a likely prerequisite for islet amyloid formation to occur in type 2 diabetes. Islet transplants in patients with type 1 diabetes face similar stressors, and are subject to rapid amyloid formation and impaired proinsulin processing associated with progressive loss of β‐cell function and mass. Declining β‐cell mass is predicted to increase metabolic demand on remaining β‐cells, promoting a feed‐forward cycle of β‐cell decline.
Opioid substitution therapy clients' preferences for targeted versus general primary health‐care outlets
Authors: Islam M. Mofizul , Topp Libby , Conigrave Katherine M. , Day Carolyn A.
Published: August 2012

Introduction and Aims.

Opioid substitution therapy (OST) ideally constitutes a window of opportunity for the provision of essential primary health care (PHC) for OST clients. In the absence of such opportunities, however, OST clients access PHC from existing outlets, either general services or those targeted to specific groups. This study examined OST clients' current main source and preferred future outlets of PHC services and correlates of preferences.

Design and Methods.

Anonymous interviews conducted with n = 257 clients of two public OST clinics in Sydney's inner‐west.

Results.

Overall, 61% (n = 158) of participants reported currently accessing PHC primarily from general outlets (general practitioners or medical centres: 51%, hospital/emergence departments: 10%) and the remainder (39%, n = 99) from outlets that target specific groups (e.g. Aboriginal Medical Services, OST prescriber/clinics, drug user‐targeted PHCs). Twenty‐two percent reported discomfort disclosing drug use to their current PHC providers. However, the majority were satisfied with the care they received and reported a preference to remain with their current PHC providers for a range of reasons, most commonly familiarity with and trust in staff (56%) and not feeling judged about their drug use (49%). Nevertheless, 28% reported that they would access PHC through their OST clinic if it were available.

Discussion and Conclusions.

PHC outlets that target specific groups appear to have an ongoing and important role in providing accessible health care to OST clients.
‘Hang on a Minute, I've Got a Great Idea’: From the Third Way to Mutual Advantage in the Political Economy of the British Labour Party
Authors: Rogers Chris
Published: August 2012

The article considers the reasons why New Labour's political economy failed to insulate Britain from the economic crisis that emerged in 2007, and the characteristics of a political economy platform that would provide Labour with a solid base for a progressive social democratic programme moving forward. The article argues that Third Way political economy failed to appreciate or address the inherent crisis dynamics of market economies, especially the extent to which profit-seeking behaviour tends to contradict social interests more broadly conceived. The article argues that mutual organisation offers an opportunity to mute the crisis dynamics in capital by re-establishing links between production and community, and that the Labour party should seize on this opportunity at a moment of crisis to form the basis of a progressive programme of social democratic reform.
New Labour's ‘Paradox of Responsibility’ and the Unravelling of its Macroeconomic Policy
Authors: Watson Matthew
Published: August 2012

New Labour staked much politically on its ability to enact a trouble-free shift in underlying economic subjectivities so as to nurture responsibly self-sufficient welfare citizens. This policy began merely as the requirement for benefit claimants to become active worker subjects in the interests of enhanced employability. More problematically from the perspective of its own macroeconomic policy, it ended as the requirement for as many people as possible to become much more tension-prone active worker-saver-investor subjects in the interests of enhanced private pension insurance. The article charts the collapse of New Labour's reputation for economic governing competence as these latter subjects’ accumulated asset wealth threatened to implode during the recent financial crisis. In its last days the Brown government inadvertently placed itself in the paradoxical position of being able to defend either the financial interests of responsibly self-sufficient welfare citizens or its own reputation for macroeconomic responsibility, but not both.
The Progressive Dilemmas of British Social Democracy: Political Economy after New Labour
Authors: Diamond Patrick
Published: August 2012

This article traces the roots of ideas currently influencing the Labour party relating to the role of the state in Britain's political economy, exploring the trajectory by which such ideas have entered contemporary debate and how they continue to shape the party's agenda. Subsequent sections explore diverse interpretations of New Labour, the economic legacy of the Blair and Brown governments, the re-imagining of British political economy undertaken by Labour under Miliband's leadership, and the interlinking ‘progressive dilemmas’ that have so far emerged. The article concludes by suggesting that the ambitious rediscovery of interventionism will only be realisable if Labour confronts historical dilemmas relating to the structure and efficacy of the British state. Such a confrontation requires serious engagement between the doctrines of British social democracy and the overlapping and interlinking narratives of liberal political thought.