bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging buildings and building images: from De Kiefhoek to Hageneiland and beyond
Authors: Figueiredo Sérgio Miguel
Published: May 2011

The prompt circulation of images and representations of buildings has not only expanded the audience for architecture, but has also become a critical tool which – quite beyond the architect's reach – is more influential than the ideas, concepts and buildings they represent. Images have become such an important element that they are not only the primary medium through which most architectural works first engage an audience, but their circulation has come to precede the act of building. The mass dissemination of architectural imagery has enabled a consumption of architecture which has not only transformed buildings into culture, but also ensured a significant displacement in architectural reception. While in prior years the dissemination of images took place after the built object, recently, the diffusion of imagery not only precedes the building, but also conditions its reception.
Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain
Authors: Agarwal Sagar , Sane Ramola , Oberoi Rajneet , Ohlfest John R. , Elmquist William F.
Published: May 2011

Glioblastoma multiforme, because of its invasive nature, can be considered a disease of the entire brain. Despite recent advances in surgery, radiotherapy and chemotherapy, current treatment regimens have only a marginal impact on patient survival. A crucial challenge is to deliver drugs effectively to invasive glioma cells residing in a sanctuary within the central nervous system. The blood–brain barrier (BBB) restricts the delivery of many small and large molecules into the brain. Drug delivery to the brain is further restricted by active efflux transporters present at the BBB. Current clinical assessment of drug delivery and hence efficacy is based on the measured drug levels in the bulk tumour mass that is usually removed by surgery. Mounting evidence suggests that the inevitable relapse and lethality of glioblastoma multiforme is due to a failure to effectively treat invasive glioma cells. These invasive cells hide in areas of the brain that are shielded by an intact BBB, where they continue to grow and give rise to the recurrent tumour. Effective delivery of chemotherapeutics to the invasive glioma cells is therefore critical, and long-term efficacy will depend on the ability of a molecularly targeted agent to penetrate an intact and functional BBB throughout the entire brain. This review highlights the various aspects of the BBB, and also the brain–tumour-cell barrier (a barrier due to expression of efflux transporters in tumour cells), that together can significantly influence drug response. It then discusses the challenge of glioma as a disease of the whole brain, which lends emphasis to the need to deliver drugs effectively across the BBB to reach both the central tumour and the invasive glioma cells.
Elastic stress indication in elastically rebounded rock
Authors: Sakaguchi Arito , Sakaguchi Hide , Nishiura Daisuke , Nakatani Masao , Yoshida Shingo
Published: May 2011

It has long been believed impossible to estimate maximum paleo‐elastic stress in rocks, because elastic strain disappears by elastic rebound when a rock is sampled. Plastic strain, on the other hand, leaves a permanent change in rocks even after stress is relaxed. For example, calcite records plastic strain as stress‐dependent intracrystalline deformation by mechanical twinning. What happens if a rock contains a small amount of calcite bounded by silicate‐rich matrix is elastically loaded? To answer this question, we performed a series of triaxial compression tests of sandstones containing calcite particles under the elastic regime. The statistical data show a good correlation between the density of calcite twins in elastically rebounded sandstone specimens and the maximum elastic stress applied. To investigate in detail our experimental results, we used the discrete element method (DEM) to perform a numerical simulation of uni‐axial compression tests on sandstone. Our DEM simulation shows the complex distribution of inter‐particle forces at each stress level. However, its statistical mean corresponds to the overall force load at the boundary. This simulation result confirms that the statistically averaged calcite twin density can be regarded as a good stress indicator in real sandstones.
G–quadruplex RNA structure as a signal for neurite mRNA targeting
Authors: Subramanian Murugan , Rage Florence , Tabet Ricardos , Flatter Eric , Mandel Jean‐Louis , Moine Hervé
Published: May 2011

Targeting of messenger RNAs (mRNAs) in neuron processes relies on cis‐acting regulatory elements, the nature of which is poorly understood. Here, we report that approximately 30% of the best‐known dendritic mRNAs contain a guanine (G)–quadruplex consensus in their 3′‐untranslated region. Among these mRNAs, we show by using RNA structure probing that a G–quadruplex is present in the mRNAs of two key postsynaptic proteins: PSD‐95 and CaMKIIa. The G–quadruplex structure is necessary and sufficient for the potent and fast localization of mRNAs in cortical neurites and this occurs in a metabotropic glutamate receptor‐responsive manner. Thus, G–quadruplex seems to be a common neurite localization signal.
RNA Vaccine: novel approach for cancer treatment
Authors: Dwivedi L K , Goswami Prateeksha , Bhalla Kanika
Published: May 2011

Cancer is still an unsolved puzzle and a major cause of mortality and morbidity in the world. Today, about one in every thousand people is dying due to cancer. No effective agent has yet been found which can cure cancer in its metastatic stage. However, attempts in the shape of chemotherapy, immunotherapy and vaccines are made worldwide to find a remedy through a proper regimen. In continuation, tumor specific mRNA has been introduced as part of vaccines in recent days. It is mostly used in transfection with Dendritic Cells (DCs) for better effectiveness and safety. The DCs are selected for transfection because they are highly potent Antigen Presenting Cells (APCs) with the ability to take up & process tumor antigen in peripheral blood & tissues and can also migrate to the draining lymph nodes to present antigen to naïve T lymphocytes & induce the immune response.Although initially the RNA vaccination was administered alone, due to its unstable and easily degradable nature, it was found to be quite less effective, which led it to be used in combination with some stability enhancers’ viz. RNA packaging in liposomes. They not only increased its stability, but even worked as active immune stimulators as well. RNA could remain stable. Although it showed significant promise in cancer treatment, immune suppression was noticed after vaccination. To enhance the effectiveness it is now being used in combination with few drugs viz. SUNITINIB which can reduce the suppressive effect of suppressor cells. It might be a good choice for combined therapy with RNA vaccine.
Tuberculosis vaccine: pipeline approaches and future prospective
Authors: Dwivedi L K , Singh Ankita , Yadav Poonam
Published: May 2011

Tuberculosis (TB), despite anti-mycobacterial therapies and vaccine, is a deadly infectious disease with about 12 million incident cases worldwide. Existing Bacillus Calmette-Guérin (BCG) vaccine is unquestionably inexpensive, safe and effective against severe forms of childhood TB but appears to be limited in effectiveness against adult pulmonary disease in endemic areas. Genetic variation in the population is the major obstruction inhibiting validation of biomarkers for protective human immunity against TB. Since current TB cases are presenting new challenges with threats of HIV co-infection therefore various attempts at a global platform are being made to develop a new modified vaccine against it. Consequently, Modified Vaccinia Ankara virus (MVA) vectored MPT64 & Ag85A delivery and polyvalent DNA vaccine, expressing an ESAT6–Ag85B fusion protein etc. are preclinically tested for boosted immune effects. However, better vaccine approaches still need to be developed against M. tuberculosis which can be unbeaten in most infected areas.
Considerate Approaches to Achieving Sufficiency for ABC Model Selection
Authors: Barnes Chris , Filippi Sarah , Stumpf Michael , Thorne Tom
Published: May 2011

ABC methods have gained popularity in situations where traditional methods which involve explicit evaluation of likelihoods are either too cumbersome or fail outright. This, almost by definition means that for any interesting real-world scenario we have no or little recourse to sufficient statistics, which had previously been central to ABC approaches and their derivation. In the context of model selection this can have particularly undesirable consequences if we have to compress the data through the use of summary statistics. In this talk we discuss complementary approaches that allow us to address this problem in a principled manner, and outline the scenarios where ABC model selection is unproblematic. We will argue that many of the most interesting applications of ABC do not use summary statistics, and that in other cases it is possible to achieve sufficiency through judicious combination of different statistics, or use of empirical likelihoods.
ABC for Temporally Sampled Genetic Data
Authors: Beaumont Mark
Published: May 2011

ABC for Temporally Sampled Genetic Data
Regulation of virulence in Francisella tularensis by small non-coding RNAs
Authors: Postic Guillaume , Frapy Eric , Dupuis Marion , Dubail Iharilalao , Livny Jonathan , Charbit Alain , Meibom Karin
Published: May 2011

Using a cDNA cloning and sequencing approach we have shown that Francisella tularensis expresses homologues of several small RNAs(sRNAs) that are well-conserved among diverse bacteria. We have also discovered two abundant putative sRNAs that share no sequence similarity or conserved genomic context with any previously annotated regulatory transcripts. Deletion of either of these two loci led to significant changes in the expression of several mRNAs that likely include the cognate target(s) of these sRNAs. Deletion of these sRNAs did not, however, significantly alter F. tularensis growth under various stress conditions in vitro, its replication in murine cells, or its ability to induce disease in a mouse model of F. tularensis infection.
Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling
Authors: Song Kai , Li Qin , Peng Yong-Bo , Li Jie , Ding Kan , Chen Li-Juan , Shao Cheng-Hao , Zhang Li-Jun , Li Ping
Published: May 2011

Many of the ligands involved in developmental processes require HS (heparan sulfate) to modulate signal transduction. hHS6ST2 (human heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2) is a Golgi-resident enzyme that usually acts on GlcA/IdoA(2S)-GlcNAc/NS disaccharide-6-sulfate modifications within the HS sequence. Emerging evidence indicates the importance of 6-O-sulfation in a number of developmental processes. However, any correlation with cancer-related events remains largely unexplored. In the present study, we found that hHS6ST2, but not other variants, was activated in human PC (pancreatic cancer). shRNA (short hairpin RNA)-mediated silencing of endogenous hHS6ST2 expression in the PC cell line PANC-1 inhibited cell invasion and migration. hHS6ST2 knockdown also resulted in markedly reduced tumorigenesis in immunocompromised mice. To specifically explore the molecular alterations resulting from depletion of hHS6ST2-generated 6-O-sulfation, we employed two-dimensional gel electrophoresis technology followed by nano-HPLC–ESI (electrospray ionization)–tandem MS to separate and identify total proteins from PC cells. Our data suggest that hHS6ST2 potentiates Notch signalling in PC cells. We also identified a role for hHS6ST2 in the growth and tumorigenicity of these cells which, at least in part, acts through Notch-mediated EMT (epithelial–mesenchymal transition) and angiogenesis. The results of the present study suggest that hHS6ST2 could be an attractive target for PC therapy.
Triple class experience after initiation of combination antiretroviral treatment in Australia: survival and projections
Authors: Pour Sadaf Marashi , Woolley Ian , Canavan Peter , Chuah John , Russell Darren B. , Law Matthew , Petoumenos Kathy
Published: May 2011

Background Patients who have become triple class experienced (TCE) are at a high risk of exhausting available treatment options. This study aims to investigate factors associated with becoming TCE and to explore the effect of becoming TCE on survival. We also project the prevalence of TCE in Australia to 2012. Methods: Patients were defined as TCE when they stopped a combination antiretroviral treatment (cART) that introduced the third of the three major antiretroviral classes. Cox proportional hazards models were used to investigate factors associated with TCE and the effect of TCE on survival. To project TCE prevalence, we used predicted rates of TCE by fitting a Poisson regression model, together with the estimated number of patients who started cART in each year in Australia, assuming a mortality rate of 1.5 per 100 person-years. Results: Of the 1498 eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE included current CD4 counts below 200 cells μL–1 and earlier calendar periods. No significant difference in survival was observed between those who were TCE and those who were not yet TCE. An increasing number of patients are using cART in Australia and if current trends continue, the number of patients who are TCE is estimated to increase from 2800 in 2003 to 5000 in 2012. Conclusion: Our results suggest that the prevalence of TCE in Australia is estimated to plateau after 2003. However, as an increasing number of patients are becoming TCE, it is necessary to develop new drugs that come from new classes or do not have overlapping resistance.
Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji
Authors: Tabrizi Sepehr N. , Law Irwin , Buadromo Eka , Stevens Matthew P. , Fong James , Samuela Josaia , Patel Mahomed , Mulholland E. Kim , Russell Fiona M. , Garland Suzanne M.
Published: May 2011

Background
There is currently limited information about human papillomavirus (HPV) genotype distribution in women in the South Pacific region. This study’s objective was to determine HPV genotypes present in cervical cancer (CC) and precancers (cervical intraepithelial lesion (CIN) 3) in Fiji. Methods: Cross-sectional analysis evaluated archival CC and CIN3 biopsy samples from 296 women of Melanesian Fijian ethnicity (n = 182, 61.5%) and Indo-Fijian ethnicity (n = 114, 38.5%). HPV genotypes were evaluated using the INNO-LiPA assay in archival samples from CC (n = 174) and CIN3 (n = 122) among women in Fiji over a 5-year period from 2003 to 2007. Results: Overall, 99% of the specimens tested were HPV DNA-positive for high-risk genotypes, with detection rates of 100%, 97.4% and 100% in CIN3, squamous cell carcinoma (SCC) and adenosquamous carcinoma biopsies, respectively. Genotypes 16 and 18 were the most common (77%), followed by HPV 31 (4.3%). Genotype HPV 16 was the most common identified (59%) in CIN3 specimens, followed by HPV 31 (9%) and HPV 52 (6.6%). Multiple genotypes were detected in 12.5–33.3% of specimens, depending on the pathology. Conclusion: These results indicated that the two most prevalent CC-associated HPV genotypes in Fiji parallel those described in other regions worldwide, with genotype variations thereafter. These data suggest that the currently available bivalent and quadrivalent HPV vaccines could potentially reduce cervical cancers in Fiji by over 80% and reduce precancers by at least 60%.
Treatment for prevention of HIV transmission in a localised epidemic: the case for South Australia
Authors: Heymer Kelly-Jean , Wilson David P.
Published: May 2011

Background Discussion is currently taking place among international HIV/AIDS groups around increasing HIV testing and initiating earlier use of antiretroviral therapy (ART) among people diagnosed with HIV as a method to reduce the spread of HIV. In this study, we explore the expected epidemiological impact of this strategy in a small population in which HIV transmission is predominantly confined to men who have sex with men (MSM). Methods: A deterministic mathematical transmission model was constructed to investigate the impacts of strategies that increase testing and treatment rates, and their likely potential to mitigate HIV epidemics among MSM. Our novel model distinguishes men in the population who are more easily accessible to prevention campaigns through engagement with the gay community from men who are not. This model is applied to the population of MSM in South Australia. Results: Our model-based findings suggest that increasing testing rates alone will have minimal impact on reducing the expected number of infections compared to current conditions. However, in combination with increases in treatment coverage, this strategy could lead to a 59–68% reduction in the number of HIV infections over the next 5 years. Targeting men who are socially engaged with the gay community would result in the majority of potential reductions in incidence, with only minor improvements possible by reaching all other MSM. Conclusions: Investing in strategies that will achieve higher coverage and earlier initiation of treatment to reduce infectiousness of HIV-infected individuals could be an effective strategy for reducing incidence in a population of MSM.
Trends of reported chlamydia infections and related complications in New Zealand, 1998 - 2008
Authors: Morgan Jane , Colonne Chanukya , Bell Anita
Published: May 2011

Aim
To compare trends in chlamydia (Chlamydia trachomatis) testing and detection with trends in hospital discharge rates of chlamydia-related diseases in the upper North Island of New Zealand during 1998–2008. Methods: Analysis of trends in chlamydia testing and detection rates and age-specific hospital admission rates per 100 000 females for pelvic inflammatory disease (PID), female infertility and ectopic pregnancy, and per 100 000 males for epididymo-orchitis. Results: Regional laboratory testing volumes increased from 3732 tests per 100 000 population in 1998 to 9801 tests per 100 000 in 2008. Two of three regions had a significant increase in percent test positivity over time. The highest detection rates and greatest increase in reported cases were amongst women aged 15–24 years, at 1992 per 100 000 in 1998, to 5737 per 100 000 in 2008. For women aged 15–24 years, the rate of hospital admissions for PID and chlamydia-related pelvic infections declined during 1998–2004 but rose in 2005–08, the rate of publicly-funded infertility admissions fell and the ectopic pregnancy rate was unchanged. The age-specific rate for epididymo-orchitis admissions amongst 15–44-year-old men remained stable. Conclusion: Chlamydia testing volumes from three New Zealand regions have trebled since 1998, as have reported infection rates, although disease complication rates do not appear to have increased. Test positivity increases may reflect better targeted testing of those more at risk or a rising chlamydia incidence. The recent rise in hospital admissions for PID among women aged 15–24 is a concern; ongoing monitoring of these trends, despite data limitations, is important.
Behavioural surveillance among gay men in Australia: methods, findings and policy implications for the prevention of HIV and other sexually transmissible infections
Authors: Zablotska Iryna B. , Kippax Susan , Grulich Andrew , Holt Martin , Prestage Garrett
Published: May 2011

Background The Australian HIV and sexually transmissible infection (STI) behavioural surveillance system (the repeated cross-sectional Gay Community Periodic Surveys, GCPS) has been conducted since 1998 and covers six main Australian jurisdictions. In this paper, we review its history and methodology, and the available indicators, their trends and their use. Methods:We describe the design and history of GCPS. For analyses of indicators, we use Pearson’s χ2-test and test for trend where appropriate. Results: About 90% of gay men in Australia have been tested for HIV (60% to 70% of men who were not HIV-positive) have been tested as recommended in the preceding 12 months. STI testing levels (~70% in the preceding 12 months) are high, but remain insufficient for STI prevention. In general, unprotected anal intercourse with regular (UAIR) and casual (UAIC) sex partners has increased over time. The prevalence and increasing trends in UAIR were similar across jurisdictions (P-trend <0.01), while trends in UAIC differed across the states: during 2001–08, UAIC declined in NSW (P-trend <0.01) and increased elsewhere (P-trend <0.01). Trends in UAIC were associated with HIV diagnoses. Conclusion: This review of the design, implementation and findings of the Australian HIV/STI behavioural surveillance highlights important lessons for HIV/STI behavioural surveillance among homosexual men, particularly the need for consistent data collection over time and across jurisdictions. Investment in systematic behavioural surveillance appears to result in a better understanding of the HIV epidemic, the availability of a warning system and a better targeted HIV prevention strategy.
The effect of hydrogen iodide on the ignition of Hg-free metal–halide lamps
Authors: Estupiñán E G , Pereyra R , Li Y-M , Lapatovich W P
Published: May 2011

Trace amounts of moisture (e.g. adsorbed on metal–halide salt pellets during lamp fabrication) may react with the salts during initial lamp light-up to form volatile hydrogen iodide (HI). Hg-free lamps are particularly prone to HI formation since the elemental mercury is not included. The Hg-free lamps can develop high ignition voltages due to the HI, which adversely affects lamp operation especially ignition. This work discusses the thermochemistry and spectroscopic measurements which predict and demonstrate that HI is indeed formed in the reaction of salts and moisture. Experimental confirmation of increased breakdown voltage with increasing concentration of HI (at the ppm level) was obtained in discharge cell experiments. Computer simulations of xenon and HI gas mixtures show qualitative agreement with experiments.
Longitudinally mounted light emitting plasma in a dielectric resonator
Authors: Gilliard Richard , DeVincentis Marc , Hafidi Abdeslam , O'Hare Daniel , Hollingsworth Gregg
Published: May 2011

Methods for coupling power from a dielectric resonator to a light-emitting plasma have been previously described (Gilliard et al IEEE Trans. Plasma Sci. at press). Inevitably, regardless of the efficiency of power transfer, much of the emitted light is absorbed in the resonator itself which physically surrounds much if not all of the radiating material. An investigation into a method is presented here for efficiently coupling power to a longitudinally mounted plasma vessel which is mounted on the surface of the dielectric material of the resonator, thereby eliminating significant absorption of light within the resonator structure. The topology of the resonator and its physical properties as well as those of the metal halide plasma are presented. Results of basic models of the field configuration and plasma are shown as well as a configuration suitable as a practical light source.
Detection of DNA of genetically modified maize by a silicon nanowire field-effect transistor
Authors: Pham Van Binh , Tung Pham Xuan Thanh , Duong Dang Ngoc Thuy , Tuyen Le Thi Thanh , Tran Phu Duy , Nguyen Thanh Chien , Nguyen Van Quoc , Dang Mau Chien , van Rijn Cees J M , Tong Duy Hien
Published: May 2011

A silicon nanowire field-effect transistor based sensor (SiNW-FET) has been proved to be the most sensitive and powerful device for bio-detection applications. In this paper, SiNWs were first fabricated by using our recently developed deposition and etching under angle technique (DEA), then used to build up the complete SiNW device based biosensor. The fabricated SiNW biosensor was used to detect DNA of genetically modified maize. As the DNA of the genetically modified maize has particular DNA sequences of 35S promoter, we therefore designed 21 mer DNA oligonucleotides, which are used as a receptor to capture the transferred DNA of maize. In our work, the SiNW biosensor could detect DNA of genetically modified maize with concentrations down to about 200 pM.
Examining changes in Irish fishing practices in response to the cod long-term plan
Authors: Davie Sarah , Lordan Colm
Published: May 2011

Davie, S., and Lordan, C. 2011. Examining changes in Irish fishing practices in response to the cod long-term plan. – ICES Journal of Marine Science, 68: 1638–1646. In 2009, there were marked changes in Irish demersal fishing effort owing to the implementation of a new cod long-term plan (CLTP). This replaced previous top-down cod recovery plans, first implemented in 2002, that set days-at-sea limits for fishing vessels. The new plan specifies a harvest control rule, annual effort ceilings for EU Member States, and rules for adapting fishing effort. It encourages cod avoidance, but leaves Member States to allocate effort between individual vessels. During 2009, effort was allocated through a series of pilot schemes in Ireland. These can be considered as an evolution towards co-management. Industry and state authorities worked closely together to develop strategies for effort management and cod avoidance. The impact of recent effort-management measures on the Irish fleet, fishery, and métiers affected by the CLTP is evaluated. Vessel movements within and between métiers are described and discussed, and unintended impacts resulting from the implementation of management schemes are highlighted. In future, possible fishers' responses to policy initiatives should be considered prior to implementation to minimize potentially adverse consequences.
Comparing demersal fish assemblages between periods of contrasting climate and fishing pressure
Authors: ter Hofstede Remment , Rijnsdorp Adriaan D.
Published: May 2011

ter Hofstede, R., and Rijnsdorp, A. D. 2011. Comparing demersal fish assemblages between periods of contrasting climate and fishing pressure. – ICES Journal of Marine Science, 68: 1189–1198. Fish communities are dynamic and their structure is known to change over time. Traditionally, these changes were considered to be fisheries-induced, but recent analyses also suggest that global warming could affect the distribution, abundance, and assemblage composition of marine fish. However, disentangling the effects of fisheries and those resulting from climate change is difficult, because both potential drivers act simultaneously. In our study, we distinguished between the effects of fisheries and climate change on the fish assemblage of the southern North Sea by comparing survey catch data for that region during four unique periods throughout the past century, characterized by (i) low fishing pressure during a cold period (1902–1908), (ii) low fishing pressure during a warm period (1950–1956), (iii) high fishing pressure during a cold period (1978–1984), and (iv) high fishing pressure during a warm period (2002–2008). Our analysis indicates that the demersal fish community in the southern North Sea has changed in response to changes in both climate and fishing pressure. Our results suggest both a relatively higher richness of Lusitanian (warm-favouring) species compared with boreal (cool-favouring) species, and a lower mean body size of the fish community during times of warming, independent of fishing pressure.
Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats
Authors: Cotten Joseph F. , Le Ge Ri , Banacos Natalie , Pejo Ervin , Husain S. Shaukat , Williams James H. , Raines Douglas E.
Published: May 2011

Background

Etomidate is a sedative-hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model.

Methods

A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague-Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1-24 and measuring serum corticosterone concentrations every 30 min.

Results

The sedative-hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion termination varied (methoxycarbonyl etomidate > carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion.

Conclusions

Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative-hypnotic maintenance agents when hemodynamic stability is desirable.
Melanogenesis in dermatophyte species in vitro and during infection
Authors: Youngchim Sirida , Pornsuwan Soraya , Nosanchuk Joshua D. , Dankai Wiyada , Vanittanakom Nongnuch
Published: May 2011

Dermatophytes are keratinophilic fungi that are the most common cause of fungal skin infections worldwide. Melanin has been isolated from several important human fungal pathogens, and the polymeric pigment is now recognized as an important virulence determinant. This study investigated whether dermatophytes, includingTrichophyton rubrum,Trichophyton mentagrophytes,Epidermophyton floccosumandMicrosporum gypseum,produce melanin or melanin-like compoundsin vitroand during infection. Digestion of the pigmented microconidia and macroconidia of dermatophytes with proteolytic enzymes, denaturant and hot concentrated acid yielded dark particles that retained the size and shape of the original fungal cells. Electron spin resonance spectroscopy revealed that particles derived from pigmented conidia contained a stable free radical signal, consistent with the pigments being a melanin. Immunofluorescence analysis demonstrated reactivity of a melanin-binding mAb with the pigmented conidia and hyphae, as well as the isolate particles. Laccase, an enzyme involved in melanization, was detected in the dermatophytes by an agar plate assay using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. Skin scrapings from patients with dermatophytoses contained septate hyphae and arthrospores that were reactive with the melanin-binding mAb. These findings indicate that dermatophytes can produce melanin or melanin-like compoundsin vitroand during infection. Based on what is known about the function of melanin as a virulence factor of other pathogenic fungi, this pigment may have a similar role in the pathogenesis of dermatophytic diseases.
Characterization of the KstR-dependent promoter of the gene for the first step of the cholesterol degradative pathway in Mycobacterium smegmatis
Authors: Uhía Iria , Galán Beatriz , Medrano Francisco Javier , García José Luis
Published: May 2011

The KstR-dependent promoter of the MSMEG_5228 gene of Mycobacterium smegmatis, which encodes the 3-β-hydroxysteroid dehydrogenase (3-β HSDMS) responsible for the first step in the cholesterol degradative pathway, has been characterized. Primer extension analysis of the P5228
promoter showed that the transcription starts at the ATG codon, thus generating a leaderless mRNA lacking a 5′ untranslated region (5′UTR). Footprint analyses demonstrated experimentally that KstR specifically binds to an operator region of 31 nt containing the quasi-palindromic sequence AACTGGAACGTGTTTCAGTT, located between the −5 and −35 positions with respect to the transcription start site. This region overlaps with the −10 and −35 boxes of the P5228
promoter, suggesting that KstR represses MSMEG_5228 transcription by preventing the binding of RNA polymerase. Using a P5228
–β-galactosidase fusion we have demonstrated that KstR is able to work as a repressor in a heterologous system like Escherichia coli. A 3D model of the KstR protein revealed folding typical of TetR-type regulators, with two domains, i.e. a DNA-binding N-terminal domain and a regulator-binding C-terminal domain composed of six helices with a long tunnel-shaped hydrophobic pocket that might interact with a putative highly hydrophobic inducer. The finding that similar P5228
promoter regions have been found in all mycobacterial strains examined, with the sole exception of Mycobacterium tuberculosis, provides new clues about the role of cholesterol in the pathogenicity of this micro-organism.
Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages
Authors: Jinadasa Rasika N. , Bloom Stephen E. , Weiss Robert S. , Duhamel Gerald E.
Published: May 2011

Cytolethal distending toxin (CDT) is a heterotrimeric AB-type genotoxin produced by several clinically important Gram-negative mucocutaneous bacterial pathogens. Irrespective of the bacterial species of origin, CDT causes characteristic and irreversible cell cycle arrest and apoptosis in a broad range of cultured mammalian cell lineages. The active subunit CdtB has structural homology with the phosphodiesterase family of enzymes including mammalian DNase I, and alone is necessary and sufficient to account for cellular toxicity. Indeed, mammalian cells treated with CDT initiate a DNA damage response similar to that elicited by ionizing radiation-induced DNA double strand breaks resulting in cell cycle arrest and apoptosis. The mechanism of CDT-induced apoptosis remains incompletely understood, but appears to involve both p53-dependent and -independent pathways. While epithelial, endothelial and fibroblast cell lines respond to CDT by undergoing arrest of cell cycle progression resulting in nuclear and cytoplasmic distension that precedes apoptotic cell death, cells of haematopoietic origin display rapid apoptosis following a brief period of cell cycle arrest. In this review, the ecology of pathogens producing CDT, the molecular biology of bacterial CDT and the molecular mechanisms of CDT-induced cytotoxicity are critically appraised. Understanding the contribution of a broadly conserved bacterial genotoxin that blocks progression of the mammalian cell cycle, ultimately causing cell death, should assist with elucidating disease mechanisms for these important pathogens.
Charge-density analysis of 1-nitroindoline: refinement quality using freeRfactors and restraints
Authors: Zarychta Bartosz , Zaleski Jacek , Kyzioł Janusz , Daszkiewicz Zdzisław , Jelsch Christian
Published: May 2011

Nitramines and relatedN-nitro compounds have attracted significant attention owing to their use in rocket fuel and as explosives. The charge density of 1-nitroindoline was determined experimentally and from theoretical calculations. Electron-density refinements were performed using the multipolar atom formalism. In order to design the ideal restraint strategy for the charge-density parameters,R-free analyses were performed involving a series of comprehensive refinements. Different weights were applied to the charge-density restraints, namely the similarity between chemically equivalent atoms and local symmetry. Additionally, isotropic thermal motion and an anisotropic model calculated by rigid-body analysis were tested on H atoms. The restraint weights which resulted in the lowest values of the averagedR-free factors and the anisotropic H-atom model were considered to yield the best charge density and were used in the final refinement. The derived experimental charge density along with intra- and intermolecular interactions was analysed and compared with theoretical calculations, notably with respect to the symmetry of multipole parameters. A comparison of different refinements suggests that the appropriate weighting scheme applied to charge-density restraints can reduce the observed artefacts. The topological bond orders of the molecule were calculated.
Modulated anharmonic ADPs are intrinsic to aperiodic crystals: a case study on incommensurate Rb2ZnCl4
Authors: Li Liang , Wölfel Alexander , Schönleber Andreas , Mondal Swastik , Schreurs Antoine M. M. , Kroon-Batenburg Loes M. J. , van Smaalen Sander
Published: May 2011

A combination of structure refinements, analysis of the superspace MEM density and interpretation of difference-Fourier maps has been used to characterize the incommensurate modulation of rubidium tetrachlorozincate, Rb2ZnCl4, at a temperature of T = 196 K, close to the lock-in transition at T
lock-in = 192 K. The modulation is found to consist of a combination of displacement modulation functions, modulated atomic displacement parameters (ADPs) and modulated third-order anharmonic ADPs. Up to fifth-order Fourier coefficients could be refined against diffraction data containing up to fifth-order satellite reflections. The center-of-charge of the atomic basins of the MEM density and the displacive modulation functions of the structure model provide equivalent descriptions of the displacive modulation. Modulations of the ADPs and anharmonic ADPs are visible in the MEM density, but extracting quantitative information about these modulations appears to be difficult. In the structure refinements the modulation parameters of the ADPs form a dependent set, and ad hoc restrictions had to be introduced in the refinements. It is suggested that modulated harmonic ADPs and modulated third-order anharmonic ADPs form an intrinsic part, however small, of incommensurately modulated structures in general. Refinements of alternate models with and without parameters for modulated ADPs lead to significant differences between the parameters of the displacement modulation in these two types of models, thus showing the modulation of ADPs to be important for a correct description of the displacive modulation. The resulting functions do not provide evidence for an interpretation of the modulation by a soliton model.
DNA damage and repair kinetics after microbeam radiation therapy emulation in living cells using monoenergetic synchrotron X-ray microbeams
Authors: Sprung Carl N. , Cholewa Marian , Usami Noriko , Kobayashi Katsumi , Crosbie Jeffrey C.
Published: May 2011

A novel synchrotron-based approach, known as microbeam radiation therapy (MRT), currently shows considerable promise in increased tumour control and reduced normal tissue damage compared with conventional radiotherapy. Different microbeam widths and separations were investigated using a controlled cell culture system and monoenergetic (5.35 keV) synchrotron X-rays in order to gain further insight into the underlying cellular response to MRT. DNA damage and repair was measured using fluorescent antibodies against phosphorylated histone H2AX, which also allowed us to verify the exact location of the microbeam path. Beam dimensions that reproduced promising MRT strategies were used to identify useful methods to study the underpinnings of MRT. These studies include the investigation of different spatial configurations on bystander effects. γH2AX foci number were robustly induced in directly hit cells and considerable DNA double-strand break repair occurred by 12 h post-10 Gy irradiation; however, many cells had some γH2AX foci at the 12 h time point. γH2AX foci at later time points did not directly correspond with the targeted regions suggesting cell movement or bystander effects as a potential mechanism for MRT effectiveness. Partial irradiation of single nuclei was also investigated and in most cases γH2AX foci were not observed outside the field of irradiation within 1 h after irradiation indicating very little chromatin movement in this time frame. These studies contribute to the understanding of the fundamental radiation biology relating to the MRT response, a potential new therapy for cancer patients.
Automatic loop centring with a high-precision goniometer head at the SLS macromolecular crystallography beamlines
Authors: Pauluhn Anuschka , Pradervand Claude , Rossetti Daniel , Salathe Marco , Schulze-Briese Clemens
Published: May 2011

Automatic loop centring has been developed as part of the automation process in crystallographic data collection at the Swiss Light Source. The procedure described here consists of an optional set-up part, in which the background images are taken, and the actual centring part. The algorithm uses boundary and centre-of-mass detection at two different microscope image magnifications. Micromounts can be handled as well. Centring of the loops can be achieved in 15–26 s, depending on their initial position, and as fast as manual centring. The alignment of the sample is carried out by means of a new flexural-hinge-based compact goniometer head. The device features an electromagnet for robotic wet mounting of samples. The circle of confusion was measured to be smaller than 1 µm (r.m.s.); its bidirectional backlash is below 2 µm.
The YopJ superfamily in plant‐associated bacteria
Authors: LEWIS JENNIFER D. , LEE AMY , MA WENBO , ZHOU HUANBIN , GUTTMAN DAVID S. , DESVEAUX DARRELL
Published: May 2011

Bacterial pathogens employ the type III secretion system to secrete and translocate effector proteins into their hosts. The primary function of these effector proteins is believed to be the suppression of host defence responses or innate immunity. However, some effector proteins may be recognized by the host and consequently trigger a targeted immune response. The YopJ/HopZ/AvrRxv family of bacterial effector proteins is a widely distributed and evolutionarily diverse family, found in both animal and plant pathogens, as well as plant symbionts. How can an effector family effectively promote the virulence of pathogens on hosts from two separate kingdoms? Our understanding of the evolutionary relationships among the YopJ superfamily members provides an excellent opportunity to address this question and to investigate the functions and virulence strategies of a diverse type III effector family in animal and plant hosts. In this work, we briefly review the literature on YopJ, the archetypal member from Yersinia pestis, and discuss members of the superfamily in species of Pseudomonas, Xanthomonas, Ralstonia and Rhizobium. We review the molecular and cellular functions, if known, of the YopJ homologues in plants, and highlight the diversity of responses in different plant species, with a particular focus on the Pseudomonas syringae HopZ family. The YopJ superfamily provides an excellent foundation for the study of effector diversification in the context of wide‐ranging, co‐evolutionary interactions.
Validation of cardiac output measurement with the LiDCOTM pulse contour system in patients with impaired left ventricular function after cardiac surgery*
Authors: Mora B. , Ince I. , Birkenberg B. , Skhirtladze K. , Pernicka E. , Ankersmit H. J. , Dworschak M.
Published: May 2011

After cardiac surgery, patients with low left ventricular ejection fraction probably benefit the most from accurate monitoring of continuous cardiac output. Thirty patients with impaired ventricular function were studied, and intermittent bolus thermodilution and continuous pulse contour (LiDCO plusTM) cardiac output compared. Following lithium dilution calibration, a total of 220 paired results were recorded. Thermodilution and LiDCO measurements ranged from 2.3 to 11.0 and 2.6 to 10.8 l.min−1, respectively. Corresponding means (SD) were 6.1 (1.6) and 6.2 (1.9) l.min−1, with coefficients of variance of 26 and 31%, respectively. The correlation coefficient was 0.82, bias 0.28 l.min−1 with upper and lower limits of agreement 1.96 and −1.41 l.min−1; the percentage error was 27%. LiDCO showed good correlation, marginal bias and acceptable limits of agreement and percentage error. It could therefore potentially replace thermodilution as a means of measuring cardiac output in the ICU, particularly when determination of pulmonary artery pressure is not required.
Comparison of tracheal intubation with the Airway Scope or Clarus Video System in patients with cervical collars
Authors: Kim J. K. , Kim J. A. , Kim C. S. , Ahn H. J. , Yang M. K. , Choi S. J.
Published: May 2011

Tracheal intubations with the Airway Scope or the Clarus Video System, a new rigid fibrescope, were compared in 140 patients whose necks were immobilised by cervical collars. The time for intubation, success rate, number of attempts and number of optimisation manoeuvres were assessed. Mean (SD) intubation time was longer with the Airway Scope (30.4 (16.5) s) than with the Clarus Video System (18.9 (15.2) s; p = 0.003) and the median (IQR [range]) number of optimisation manoeuvres was also marginally different; 0 (0–1 [0–2]) with the Airway Scope, 0 (0–0 [0–2]) with the Clarus Video System; p = 0.004. The tracheas of 67 (95.7%) and 66 (94.3%) patients were successfully intubated with the Airway Scope and the Clarus Video System, respectively (p = 1.0). The number of attempts, vital signs and complications were not different between devices. The Clarus Video System was comparable to the Airway Scope in the success rate for tracheal intubation, but provided faster and easier intubations than the Airway Scope in patients with cervical collars.
Long‐term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome
Authors: Gangale Maria F. , Miele Luca , Lanzone Antonio , Sagnella Francesca , Martinez Daniela , Tropea Anna , Moro Francesca , Morciano Andrea , Ciardulli Andrea , Palla Carola , Pompili Maurizio , Cefalo Consuelo , Grieco Antonio , Apa Rosanna
Published: May 2011

Objective  The objective of this study is to determine the ability of metformin treatment in reducing the prevalence of metabolic syndrome (MS) and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome (PCOS).

Design  Clinical Trial.

Patients  We recruited 140 hyperinsulinaemic overweight women with PCOS in their reproductive age. Metformin treatment (500 mg × 3/die) was prescribed to each patient for twelve months.

Measurements  The primary outcome was to evaluate the prevalence of nonalcoholic fatty liver disease (NAFLD) and MS in hyperinsulinaemic overweight patients with PCOS. The secondary outcome was to evaluate, in the same patients, the effects of metformin therapy on endocrine, metabolic and hepatic parameters.

Results  At basal evaluation, NAFLD was diagnosed in 81 of 140 patients with PCOS (57·85%); MS was present only in the NAFLD group (32·09%vs 0%; P < 0·001). After twelve months, metformin is able to significantly reduce, in the same group, the prevalence of MS (28·9%vs 13·5%; P < 0·01). An improvement of hepatic parameters and a significant decrease in oligomenorrhea (85·7%vs 19%, P < 0·001) were also observed.

Conclusions  Treatment with metformin is indicated in all hyperinsulinaemic overweight patients with PCOS, especially in those with NAFLD. These data appear even more interesting considering their increased risk to develop metabolic and hepatic complications.