bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory Failures and Regulatory Solutions: A Characteristic Analysis of the Aftermath of Disaster
Authors: Haines Fiona
Published: February 2009

This article analyzes the regulatory reform and implementation process in Australia following three event clusters: an industrial explosion, recent terrorist attacks, and a corporate collapse. The research employed a characteristic analysis where the compliance challenge on the ground is understood as affected not only by the enforcement efforts of the regulator, but also the reform process and the structure of the industry concerned. In each of the cases studied, preferred reforms could be understood as “metaregulatory” and framed around outcomes, principles, and processes rather than a preoccupation with adherence to prescriptive rules. Metaregulation was seen as the most appropriate regulatory framework to maintain the integrity between regulatory goal, regulatory regime, and compliance behavior. Yet, reform pressures that shaped the causal narrative associated with the particular risk, the emotional work involved in compliance, and success strategies of sites all affected what risks were actually reduced and hence the likelihood of a repeat disaster.
Judicial Culture and the Politicolegal Opportunity Structure: Explaining Bill of Rights Legal Impact in New Zealand
Authors: Erdos David
Published: February 2009

This article argues that the cultural self‐understandings of the judiciary can exert a profound effect on legal outcomes under a bill of rights. Utilizing the case of New Zealand, it demonstrates that confinement of expansive case law under the New Zealand Bill of Rights (NZBOR) to the criminal law and freedom of expression arenas is most significantly explained by a British‐descended judicial culture that prioritizes, first, those civil liberty values already cognizable by the common law and, second, rights connected with the policing of parliamentary and legal processes. Nevertheless, judicial culture does not operate in a vacuum. Rather, the opportunity structure facing potential public interest litigants under NZBOR depends also on their politicolegal resource set including the attitude of the political branches (legislature and executive) to the claim being forwarded.
Prevention, detection and intervention with delirium in an acute care hospital: a feasibility study
Authors: Benedict Lynn , Hazelett Susan , Fleming Eileen , Ludwick Ruth , Anthony Mary , Fosnight Sue , Holder Carolyn , Zeller Rich , Allen Kyle , Zafirau William
Published: February 2009

Background.  The prevalence of delirium in acute care hospitals ranges from 5–86%. Delirious patients are at greater risk of negative health outcomes and their care is often more costly.

Aim.  To determine the feasibility of a full‐scale trial to test the effectiveness of an intervention designed to improve delirium prevention, detection and intervention in an acute care hospital.

Design.  A delirium prevention protocol was designed by an interdisciplinary group of clinicians and implemented on intervention unit patients who passed a mental status screen, were at high risk for delirium according to the modified NEECHAM scale, and met other eligibility criteria. These patients were reviewed at daily interdisciplinary team meetings and team recommendations were placed in the patient’s chart. On the usual care unit, physicians were notified if their patients were at high risk, but the delirium protocol was not implemented.

Methods.  The delirium protocol was pilot tested with 35 high risk patients on an Acute Care for Elders (ACE) unit. Outcomes were compared to 35 high risk patients on a similar medical unit without the delirium protocol.

Results.  The main outcome examined whether there is a difference in average day 3 modified NEECHAM scores comparing the intervention and control groups. The mean modified NEECHAMs on day 3 were not statistically significantly different (intervention group 3.76 and control group 3.24) (P= 0.368). Baseline NEECHAM scores did not correlate well with development of delirium (P = 0.204). A history of confusion during a previous hospitalization was the strongest predictor of developing delirium during the current hospitalization.

Conclusion.  This pilot study was not powered to detect an effect of the intervention, however, feasibility for a fully powered trial was established.

Relevance to clinical practice.  Completion of the NEECHAM screen every shift was not considered burdensome for either nurses or patients and may help identify acute delirium.
Overview of Imaging in Inflammatory Arthritis
Authors: Katz James D. , Nayyar Geeta , Noeth Erinn
Published: February 2009

Whether magnetic resonance imaging (MRI) or ultrasound (US) are chosen for the purposes of musculoskeletal interrogation depends upon a variety of factors ranging from the anatomy targeted to cost considerations and the time of acquisition. Newer technologies such as higher‐strength MRI or 3D‐US promise to help overcome some of the disadvantages of each option. Improving technical proficiency is the thrust of efforts to support more widespread application of sonographic assessment in various clinical arenas. Finally, these technologies offer the opportunity to diagnose inflammatory conditions at early stages of their disease progression.
MRI for Assessing Erosion and Joint Space Narrowing in Inflammatory Arthropathies
Authors: Momeni Mahnaz , Brindle Kathleen
Published: February 2009

The superior soft tissue contrast and multiplanar capability of magnetic resonance imaging has contributed to earlier diagnosis and implementation of effective treatment for a variety of arthropathies. Owing to overlapping clinical signs and symptoms, MRI plays a role in delineating the features and stages of these conditions. With the advent of disease‐modifying therapies, it is important to diagnose inflammatory arthropathy as early as possible. In this chapter, we discuss the pathophysiology of bone erosion and joint space narrowing, as well as the role of MRI in the imaging of the seropositive and seronegative inflammatory arthropathies.
Peptide‐YY Is Released by the Intestinal Cell Line STC‐1
Authors: Geraedts M.C.P. , Troost F.J. , Saris W.H.M.
Published: February 2009

ABSTRACT:  Dietary modulation of the response of gut satiety hormones, which partly regulate food intake, provides a promising treatment for overweight and obesity. Gut‐derived cell lines such as STC‐1 are widely used to investigate these hormonal responses to nutrients. To date, no peptide‐YY (PYY) secreting cell line has been identified. The aim of this study was to investigate whether STC‐1 cells are able to secrete PYY and if so, whether dietary compounds can modulate PYY secretion. The effects of fatty acid types C4:0, C12:0, C14:0, C16:0, and C18:0 on PYY release were investigated by measuring PYY in the supernatant after 30, 60, 90, and 120 min of incubation, respectively, using RIA assays. The STC‐1 cells were able to secrete PYY in a time‐dependent manner. It was shown that after 30 min, C4:0, C12:0, C16:0, and C18:0 caused increased PYY levels compared to the control. At time points 60 and 90 min, C4:0 and C18:0 induced elevated PYY levels compared to the control. After 120 min, C4:0, C14:0, and C18:0 caused elevated levels compared to the control. We are the first to show that the STC‐1 cells are also able to secrete PYY next to cholecystokinin (CCK) and glucagon‐like peptide 1 (GLP‐1). Addition of fatty acids resulted in increased levels of PYY, which is consistent with the literature describing human studies. We conclude that the STC‐1 cell line provides an appropriate cell line for screening the effects of ingredients on the release of the satiety‐related gut hormones CCK, GLP‐1, and PYY.
Influence of Storage Temperature on the Kinetics of the Changes in Anthocyanins, Vitamin C, and Antioxidant Capacity in Fresh‐Cut Strawberries Stored under High‐Oxygen Atmospheres
Authors: Odriozola‐Serrano I. , Soliva‐Fortuny R. , Martín‐Belloso O.
Published: February 2009

ABSTRACT:  Changes in the main antioxidant properties of fresh‐cut strawberries stored under high‐oxygen atmospheres (80 kPa O2) were studied at selected temperatures (5 to 20 °C). The suitability of zero‐ and 1st‐order kinetics as well as a model based on Weibull distribution function to describe changes in experimental data is discussed. A non‐Arrhenius approach was used to determine the temperature dependence of the estimated rate constants. A Weibull kinetic model most accurately (R2adj≥ 0.800) estimated changes in anthocyanins and antioxidant capacity of fresh‐cut strawberries throughout the storage period, whereas a 1st‐order model adequately fitted (R2adj≥ 0.982) the variation of vitamin C. The temperature dependency of the kinetic rate constants for each antioxidant property was successfully modeled through the non‐Arrhenius approach (R2adj≥ 0.709). The Tc obtained for anthocyanins, vitamin C, and antioxidant capacity degradation were 290, 284, and 289 K, respectively, indicating the temperature at which a marked acceleration of the losses in the antioxidant potential of strawberry wedges occurs. These findings will help to describe the variation of the antioxidant potential of fresh‐cut strawberries upon storage time and temperature.
Chemistry and Quality of Hibiscus (Hibiscus sabdariffa) for Developing the Natural‐Product Industry in Senegal
Authors: Juliani H. R. , Welch C. R. , Wu Q. , Diouf B. , Malainy D. , Simon J. E.
Published: February 2009

ABSTRACT:  The objectives of this study were to assess and improve the quality of the hibiscus calyces from Senegal over 2 production seasons (2004 to 2005), to develop and adapt new procedures for the determination of hibiscus anthocyanins and analysis of the 2 major ones, delphinidin‐3‐sambubioside and cyanidin‐3‐sambubioside. The foreign matter, total ashes, and acid insoluble ashes showed that the calyces harvested in 2005 were produced following hygienic practices, while the color assessment of the calyces and analysis of hibiscus active principles also showed higher amounts of anthocyanins in 2005. A protocol to measure anthocyanins by pH‐differential UV‐Vis spectrophotometry was adapted to measure the hibiscus anthocyanins from a water extract. The spectrophotometric method for quantitation of total anthocyanins showed a close correlation (r2= 0.82) when compared with the HPLC method, suggesting the use of the colorimetric method in quality control programs as an affordable alternative method to assess anthocyanin content in hibiscus. New and raised standards for the cleanliness and active principle content in hibiscus are also proposed. This study demonstrated that the implementation of a quality control program and the application of agricultural good practices in the production and processing of hibiscus calyces can lead to higher quality natural plant products.
Cyclopropane fatty acids are involved in organic solvent tolerance but not in acid stress resistance in Pseudomonas putida DOT‐T1E
Authors: Pini Cecilia‐Vanesa , Bernal Patricia , Godoy Patricia , Ramos Juan‐Luis , Segura Ana
Published: February 2009

Bacterial membranes constitute the first physical barrier against different environmental stresses. Pseudomonas putida DOT‐T1E accumulates cyclopropane fatty acids (CFAs) in the stationary phase of growth. In this strain the cfaB gene encodes the main cyclopropane synthase responsible of the synthesis of CFAs, and its expression is mediated by RNA polymerase with sigma factor σ38. We generated a cfaB mutant of P. putida DOT‐T1E and studied its response to solvents, acid pH and other stress conditions such as temperature changes, high osmolarity and the presence of antibiotics or heavy metals in the culture medium. A CfaB knockout mutant was more sensitive to solvent stress than the wild‐type strain, but in contrast to Escherichia coli and Salmonella enterica, the P. putida cfaB mutant was as tolerant to acid shock as the wild‐type strain. The cfaB mutant was also as tolerant as the parental strain to a number of drugs, antibiotics and other damaging agents.
Molecular and biochemical characterization of the tetralin degradation pathway in Rhodococcus sp. strain TFB
Authors: Tomás‐Gallardo Laura , Santero Eduardo , Camafeita Emilio , Calvo Enrique , Schlömann Michael , Floriano Belén
Published: February 2009

The tetralin biodegradation pathway in Rhodococcus sp. strain TFB, a Gram‐positive bacterium resistant to genetic manipulation, was characterized using a proteomic approach. Relative protein expression in cell free extracts from tetralin‐ and glucose‐grown cells was compared using the 2D‐DIGE technique. Identification of proteins specifically expressed in tetralin‐grown cells was used to characterize a complete set of genes involved in tetralin degradation by reverse genetics. We propose a tetralin degradation pathway analogous to that described for Sphingomonas macrogolitabida strain TFA. TFB thn genes are organized into three operons; two contain all of the structural genes and are transcribed in the same direction, while the third operon, thnST, is transcribed in the opposite direction and encodes a two‐component regulatory system, whose transcription is higher in tetralin‐grown cells. In addition to tetralin induction, TFB thn structural genes are subject to glucose repression. Primer extension assays and translational thnA1::gfp and thnS::gfp fusions were used to characterize putative promoter regions. A mutational analysis of the thnA1 promoter region allowed us to define nucleotides within the cis regulatory elements that are important for the control of thn gene expression.
Coupling a genome‐scale metabolic model with a reactive transport model to describe in situ uranium bioremediation
Authors: Scheibe Timothy D. , Mahadevan Radhakrishnan , Fang Yilin , Garg Srinath , Long Philip E. , Lovley Derek R.
Published: February 2009

The increasing availability of the genome sequences of microorganisms involved in important bioremediation processes makes it feasible to consider developing genome‐scale models that can aid in predicting the likely outcome of potential subsurface bioremediation strategies. Previous studies of the in situ bioremediation of uranium‐contaminated groundwater have demonstrated that Geobacter species are often the dominant members of the groundwater community during active bioremediation and the primary organisms catalysing U(VI) reduction. Therefore, a genome‐scale, constraint‐based model of the metabolism of Geobacter sulfurreducens was coupled with the reactive transport model HYDROGEOCHEM in an attempt to model in situ uranium bioremediation. In order to simplify the modelling, the influence of only three growth factors was considered: acetate, the electron donor added to stimulate U(VI) reduction; Fe(III), the electron acceptor primarily supporting growth of Geobacter; and ammonium, a key nutrient. The constraint‐based model predicted that growth yields of Geobacter varied significantly based on the availability of these three growth factors and that there are minimum thresholds of acetate and Fe(III) below which growth and activity are not possible. This contrasts with typical, empirical microbial models that assume fixed growth yields and the possibility for complete metabolism of the substrates. The coupled genome‐scale and reactive transport model predicted acetate concentrations and U(VI) reduction rates in a field trial of in situ uranium bioremediation that were comparable to the predictions of a calibrated conventional model, but without the need for empirical calibration, other than specifying the initial biomass of Geobacter. These results suggest that coupling genome‐scale metabolic models with reactive transport models may be a good approach to developing models that can be truly predictive, without empirical calibration, for evaluating the probable response of subsurface microorganisms to possible bioremediation approaches prior to implementation.
Magnesium Isotope Compositions of Natural Reference Materials
Authors: Bolou‐Bi Emile B. , Vigier Nathalie , Brenot Agnès , Poszwa Anne
Published: February 2009

This study presents a chemical protocol for the separation of Mg that is particularly adapted to alkali‐rich samples (granite, soil, plants). This protocol was based on a combination of two pre‐existing methods: transition metals were first removed from the sample using an AG‐MP1 anion‐exchange resin, followed by the separation of alkalis (Na, K) and bivalent cations (Ca2+, Mn2+ and Sr2+) using a AG50W‐X12 cation‐exchange resin. This procedure allowed Mg recovery of ∼ 10 0 ± 8%. The [Σcations]/[Mg] molar ratios in all of the final Mg fractions were lower than 0.05. The Mg isotope ratios of eleven reference materials were analysed using two different MC‐ICP‐MS instruments (Isoprobe and Nu Plasma). The long‐term reproducibility, assessed by repeated measurements of Mg standard solutions and natural reference materials, was 0.14‰. The basalt (BE‐N), limestone (Cal‐S) and seawater (BCR‐403) reference materials analysed in this study yielded δ26Mg mean values of −0.28 ± 0.08‰, −4.37 ± 0.11‰ and −0.89 ± 0.10‰ respectively, in agreement with published data. The two continental rocks analysed, diorite (DR‐N) and granite (GA), yielded δ26Mg mean values of −0.50 ± 0.08‰ and −0.75 ± 0.14‰, respectively. The weathering products, soil (TILL‐1) and river water (NIST SRM 1640), gave δ26Mg values of −0.40 ± 0.07‰ and −1.27 ± 0.14‰, respectively. We also present, for the first time, the Mg isotope composition of bulk plant and organic matter. Rye flour (BCR‐381), sea lettuce (Ulva lactuva) (BCR‐279), natural hairgrass (Deschampsia flexuosa) and lichen (BCR‐482) reference materials gave δ26Mg values of −1.10 ± 0.14‰, −0.90 ± 0.19‰, −0.50 ± 0.22‰ and −1.15 ± 0.27‰ respectively. Plant δ26Mg values fell within the range defined by published data for chlorophylls.
Accuracy of Laser Ablation U‐Pb Zircon Dating: Results from a Test Using Five Different Reference Zircons
Authors: Klötzli Urs , Klötzli Eva , Günes Zekeriya , Kosler Jan
Published: February 2009

Using a state‐of‐the‐art 193 nm‐LA‐MC‐ICP‐MS system and with careful control of analytical procedures, the long term external reproducibility and accuracy of the ages Phanerozoic zircons measured over a period of months using calibrator bracketing for the 206Pb/238U and 207Pb/206Pb ages were ca. 1% (2 RSD) if a single reference zircon was used for the matrix‐matched calibration. When different reference zircons were used for the calibration, suspicious systematic shifts in the obtained ages were observed and thus a reduction in the overall accuracy of the dating method became obvious. Such shifts were within a few percent range of the U‐Pb and Pb/Pb ages and seemed to vary independently of zircon age and composition. A “test of accuracy” experiment was conducted reducing instrumental effects as far as possible by analysing five different reference zircons mounted on a single mount eight times during the same session. An identical protocol was used for all analyses, with unchanged instrument parameters and with ion beam intensities kept as identical as possible. For data reduction, every zircon served consecutively as the reference zircon for calibration, with the others in the batch treated as unknowns. The known reference age and the four calculated ages obtained using the four other RMs for calibration were then compared. Even using such a strict analytical protocol, shifts in 206Pb/238U, 207Pb/235U and 207Pb/206Pb ratios were still present. They varied non‐systematically and ranged from −4.35% to 3.08% for the investigated age range (1065 Ma to 226 Ma). Assuming the absence of instrumental effects (i.e., memory, dead‐time correction, non‐linearity of ion counters and interdetector calibration, crystallographic orientation, ablation cell geometry and setup, gas flows), the observed shifts were attributed to matrix and/or ablation related effects. It is proposed that non‐spectral matrix effects in the Ar plasma torch resulted in non‐uniform signal enhancement (or depression?) leading to shifts both in elemental and Pb isotopic ratios. Additionally, the ablated particle size distribution could be an important factor controlling plasma conditions and thus mass bias and fractionation. Until such effects are well understood and controlled, it would seem that any LA‐ICP‐MS zircon U‐Pb and 207Pb/206Pb age determination cannot be meaningfully interpreted at below a ca. 3% to 4% (2 RSD) confidence level.
Beyond biological control: non‐pest insects and their pathogens in a changing world
Authors: ROY HELEN E. , HAILS ROSEMARY S. , HESKETH HELEN , ROY DAVID B. , PELL JUDITH K.
Published: February 2009

Abstract.

Over the last few decades, there have been considerable advances in the fields of insect pathology and insect conservation but the two disciplines rarely meet. The potential of entomopathogens as biological control agents of pest insects is widely recognised but information on the role of pathogens in insect population regulation, more generally, is limited. For example, the role of pathogens as natural enemies of non‐pest insects, including those of conservation value, is seldom considered beyond their context as ‘non‐targets’ of microbial control agents.

Entomopathogens are prevalent in natural systems and should receive greater attention in life‐history studies. There is no doubt that viruses, bacteria and fungi are major mortality agents of insects but their significance tends to be overshadowed by the attention given to predators and parasitoids.

We highlight the critical function that entomopathogens could have in insect population dynamics with particular reference fragmented habitats as illustrated by the theoretical literature. However, we emphasise that there are few empirical studies to test theoretical predictions.

We suggest that since an increase in the incidence of disease is predicted in most environmental change scenarios, it is more important than ever to turn our attention to insect pathology when we consider insect population dynamics.
Alterations in Hematopoietic Microenvironment in Patients with Aplastic Anemia
Authors: Shipounova Irina N. , Petrova Tatiana V. , Svinareva Daria A. , Momotuk Kira S. , Mikhailova Elena A. , Drize Nina I.
Published: February 2009

Mechanisms of hematopoietic failure in patients with aplastic anemia (AA) are obscure. We investigate alterations in the hematopoietic microenvironment in AA patients. We present the results of studying mesenchymal stromal cells (MSC), fibroblastic colony‐forming units (CFU‐F), and adherent cell layers (ACL) of long‐term bone marrow cultures (LTBMC) from bone marrow (BM) samples of AA patients. MSC of AA patients proliferated longer than those of donors. In half of the patients’ MSC cultures, adipogenesis was impaired. Osteogenic differentiation was not achieved in 36% of AA MSC. CFU‐F formed enlarged colonies, and their concentration in the BM of AA patients was significantly increased. Our data suggest that the physiological activation of the stromal microenvironment is characteristic of AA. We detected a decrease in the expression of the angiopoetin‐1 (ANG‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) genes, together with an increase in the expression of vascular endothelial growth factor (VEGF) in ACL of AA patients. This ndicates abnormal regulatory patterns in both osteoblastic and vascular contexts. Addition of AA patients’ serum to donors’ LTBMCfor 3 weeks induced similar gene expression alterations. The addition of parathyroid hormone (PTH) resulted in the expression levels of analyzed genes returning to normal, in both AA LTBMC and donor cultures treated with AA serum. The physiologic status of the BM stromal microenvironment (MSC, CFU‐F, and ACL of LTBMC) of AA patients was altered.
Verbascum eskisehirensis sp. nov. (Scrophulariaceae) from central Anatolia, Turkey
Authors: Ahmet Karavelioğulları Faik , Ocak Atilla , Ekici Murat , Cabi Evren
Published: February 2009

Verbascum eskisehirensis Karavel., Ocak & Ekici sp. nov. (sect. Bothrosperma Murb.) is described and illustrated from Turkey. This new species is confined to B3 Eskisehir in central Anatolia. A morphological comparison is made with the closely related species; V. oreophilum K. Koch and V. pyramidatum M. Bieb. In addition, a cluster analysis was conducted and a distribution map of the new species and the related species is also given.
Semistable reduction for overconvergentF-isocrystals, III: Local semistable reduction at monomial valuations
Authors: Kedlaya Kiran S.
Published: February 2009

We resolve the local semistable reduction problem for overconvergentF-isocrystals at monomial valuations (Abhyankar valuations of height 1 and residue transcendence degree zero). We first introduce a higher-dimensional analogue of the generic radius of convergence for ap-adic differential module, which obeys a convexity property. We then combine this convexity property with a form of thep-adic local monodromy theorem for so-called fake annuli.
Desingularized fiber products of semi-stable elliptic surfaces with vanishing third Betti number
Authors: Schoen Chad
Published: February 2009

Desingularized fiber products of semi-stable elliptic surfaces withHetale3=0 are classified. Such varieties may play a role in the study of supersingular threefolds, of the deformation theory of varieties with trivial canonical bundle, and of arithmetic degenerations of rigid Calabi–Yau threefolds.
Novel Inhibitor of
Plasmodium
Histone Deacetylase That Cures
P. berghei-
Infected Mice
Authors: Agbor-Enoh S. , Seudieu C. , Davidson E. , Dritschilo A. , Jung M.
Published: February 2009

Histone deacetylases (HDAC) are potential targets for the development of new antimalarial drugs. The growth of
Plasmodium falciparum
and other apicomplexans can be suppressed in the presence of potent HDAC inhibitors in vitro and in vivo; however, in vivo parasite suppression is generally incomplete or reversible after the discontinuation of drug treatment. Furthermore, most established HDAC inhibitors concurrently show broad toxicities against parasites and human cells and high drug concentrations are required for effective antimalarial activity. Here, we report on HDAC inhibitors that are potent against
P. falciparum
at subnanomolar concentrations and that have high selectivities; the lead compounds have mean 50% inhibitory concentrations for the killing of the malaria parasite up to 950 times lower than those for the killing of mammalian cells. These potential drugs improved survival and completely and irreversibly suppressed parasitemia in
P. berghei-
infected mice.
Relative Contributions of the
Candida albicans
ABC Transporters Cdr1p and Cdr2p to Clinical Azole Resistance
Authors: Tsao Sarah , Rahkhoodaee Fariba , Raymond Martine
Published: February 2009

Candida albicans
frequently develops resistance to treatment with azole drugs due to the acquisition of gain-of-function mutations in the transcription factor Tac1p. Tac1p hyperactivation in azole-resistant isolates results in the constitutive overexpression of several genes, including
CDR1
and
CDR2
, which encode two homologous transporters of the ATP-binding cassette family. Functional studies of Cdr1p and Cdr2p have been carried out so far by heterologous expression in the budding yeast
Saccharomyces cerevisiae
and by gene deletion or overexpression in azole-sensitive
C. albicans
strains in which
CDR1
expression is low and
CDR2
expression is undetectable. Thus, the direct demonstration that
CDR1
and
CDR2
overexpression causes azole resistance in clinical strains is still lacking, as is our knowledge of the relative contribution of each transporter to clinical azole resistance. In the present study, we used the
SAT1
flipper system to delete the
CDR1
and
CDR2
genes from clinical isolate 5674. This strain is resistant to several azole derivatives due to a strong hyperactive mutation in Tac1p and expresses high levels of Cdr1p and Cdr2p. We found that deleting
CDR1
had a major effect, reducing resistance to fluconazole (FLC), ketoconazole (KTC), and itraconazole (ITC) by 6-, 4-, and 8-fold, respectively. Deleting
CDR2
had a much weaker effect, reducing FLC or KTC resistance by 1.5-fold, and had no effect on ITC resistance. These results demonstrate that Cdr1p is a major determinant of azole resistance in strain 5674 and potentially in other clinical strains overexpressing Cdr1p and Cdr2p, while Cdr2p plays a more minor role.
Penetration of Moxifloxacin into Bone Evaluated by Monte Carlo Simulation
Authors: Landersdorfer Cornelia B. , Kinzig Martina , Hennig Friedrich F. , Bulitta Jürgen B. , Holzgrabe Ulrike , Drusano George L. , Sörgel Fritz , Gusinde Johannes
Published: February 2009

Moxifloxacin is a fluoroquinolone with a broad spectrum of activity and good penetration into many tissues, including bone. Penetration of moxifloxacin into bone has not yet been studied using compartmental modeling techniques. Therefore, we determined the rate and extent of bone penetration by moxifloxacin and evaluated its pharmacodynamic profile in bone via Monte Carlo simulation. Twenty-four patients (10 males, 14 females) undergoing total hip replacement received 400 mg moxifloxacin orally 2 to 7 h prior to surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen by a cryogenic mill, including an internal standard. Drug concentrations were analyzed by high-performance liquid chromatography. We used ADAPT II (results reported), NONMEM, and WinBUGS for pharmacokinetic analysis. Monte Carlo simulation was performed to reverse engineer the necessary area under the free concentration-time curve
f
AUC
SERUM
/MIC in serum and total AUC
BONE
/MIC in bone for a successful clinical or microbiological outcome. The median (10% to 90% percentile for between-subject variability) of the AUC in bone divided by the AUC in serum (AUC
BONE
/AUC
SERUM
) was 80% (51 to 126%) for cortical bone and 78% (42 to 144%) for cancellous bone. Equilibration between serum and bone was rapid. Moxifloxacin achieved robust (≥90%) probabilities of target attainment (PTAs) in serum, cortical bone, and cancellous bone up to MICs of ≤0.375 mg/liter based on the targets
f
AUC
SERUM
/MIC ≥ 40 and AUC
BONE
/MIC ≥ 33. Moxifloxacin showed high bone concentrations and a rapid equilibrium between bone and serum. The favorable PTAs compared to the 90%-inhibitory MIC of
Staphylococcus aureus
warrant future clinical trials on the effectiveness of moxifloxacin in the treatment of bone infections.
Experimental Bacteriophage Therapy Increases Survival of
Galleria mellonella
Larvae Infected with Clinically Relevant Strains of the
Burkholderia cepacia
Complex
Authors: Seed Kimberley D. , Dennis Jonathan J.
Published: February 2009

The
Burkholderia cepacia
complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterpillar infection model, we show that BCC phage therapy is an alternative treatment possibility and is highly effective under specific conditions.
Apricitabine Does Not Select Additional Drug Resistance Mutations in Tissue Culture in Human Immunodeficiency Virus Type 1 Variants Containing K65R, M184V, or M184V plus Thymidine Analogue Mutations
Authors: Oliveira Maureen , Moisi Daniela , Spira Bonnie , Cox Susan , Brenner Bluma G. , Wainberg Mark A.
Published: February 2009

Human immunodeficiency virus type 1 containing the reverse transcriptase mutation M184V or K65R or mutations M41L, M184V, and T215Y did not accumulate additional resistance mutations in the reverse transcriptase when increasing amounts of apricitabine drug pressure were applied. The original mutations were maintained by the presence of apricitabine but were lost when cultured without drug pressure.
A Redox Basis for Metronidazole Resistance in
Helicobacter pylori
Authors: Kaakoush N. O. , Asencio C. , Mégraud F. , Mendz G. L.
Published: February 2009

Metronidazole resistance in
Helicobacter pylori
has been attributed to mutations in
rdxA
or
frxA
. Insufficient data correlating RdxA and/or FrxA with the resistant phenotype, and the emergence of resistant strains with no mutations in either
rdxA
or
frxA
, indicated that the molecular basis of
H. pylori
resistance to metronidazole required further characterization. The
rdxA
and
frxA
genes of four matched pairs of metronidazole-susceptible and -resistant strains were sequenced. The resistant strains had mutations in either
rdxA
,
frxA
, neither gene, or both genes. The reduction rates of five substrates suggested that metabolic differences between susceptible and resistant strains cannot be explained only by mutations in
rdxA
and/or
frxA
. A more global approach to understanding the resistance phenotype was taken by employing two-dimensional gel electrophoresis combined with tandem mass spectrometry analyses to identify proteins differentially expressed by the matched pair of strains with no mutations in
rdxA
or
frxA
. Proteins involved in the oxireduction of ferredoxin were downregulated in the resistant strain. Other redox enzymes, such as thioredoxin reductase, alkyl hydroperoxide reductase, and superoxide dismutase, showed a pI change in the resistant strain. The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance.
Activity Profile In Vitro of Micafungin against Spanish Clinical Isolates of Common and Emerging Species of Yeasts and Molds
Authors: Cuenca-Estrella Manuel , Gomez-Lopez Alicia , Mellado Emilia , Monzon Araceli , Buitrago Maria J. , Rodriguez-Tudela Juan L.
Published: February 2009

A collection of 2,278 isolates belonging to 86 different fungal species was tested with micafungin and eight other drugs using the EUCAST procedures. Micafungin was active against species of
Candida
and
Aspergillus
(even azole-resistant species) as well as
Penicillium
spp.,
Scedosporium apiospermum
, and
Acremonium
spp. It was inactive for species of
Basidiomycota
and
Mucorales
and for multiresistant species such as those of
Fusarium
.
Frequency and Domain Specificity of Toxin-Neutralizing Paratopes in the Human Antibody Response to Anthrax Vaccine Adsorbed
Authors: Reason Donald , Liberato Justine , Sun Jinying , Keitel Wendy , Zhou Jianhui
Published: February 2009

Protective antigen (PA) is the cell surface recognition unit of the binary anthrax toxin system and the primary immunogenic component in both the current and proposed “next-generation” anthrax vaccines. Several studies utilizing animal models have indicated that PA-specific antibodies, acquired by either active or passive immunization, are sufficient to protect against infection with
Bacillus anthracis
. To investigate the human antibody response to anthrax immunization, we have established a large panel of human PA-specific monoclonal antibodies derived from multiple individuals vaccinated with the currently approved anthrax vaccine BioThrax. We have determined that although these antibodies bind PA in standard binding assays such as enzyme-linked immunosorbent assay, Western blotting, capture assays, and dot blots, less than 25% are capable of neutralizing lethal toxin (LT) in vitro. Nonneutralizing antibodies also fail to neutralize toxin when present in combination with other nonneutralizing paratopes. Although neutralizing antibodies recognize determinants throughout the PA monomer, they are significantly less common among those paratopes that bind to the immunodominant amino-terminal portion of the molecule. These findings demonstrate that PA binding alone is not sufficient to neutralize LT and suggest that for an antibody to effectively block PA-mediated toxicity, it must bind to PA such that one of the requisite toxin functions is disrupted. A vaccine design strategy that directed a higher percentage of the antibody response toward neutralizing epitopes may result in a more efficacious vaccine for the prevention of anthrax infection.
Interleukin-18-Related Genes Are Induced during the Contraction Phase but Do Not Play Major Roles in Regulating the Dynamics or Function of the T-Cell Response toListeria monocytogenesInfection
Authors: Haring Jodie S. , Harty John T.
Published: February 2009

Proinflammatory cytokines, such as gamma interferon (IFN-γ), impact aspects of T-cell responses after infection, including expansion, contraction, and memory formation. Interleukin-18 (IL-18) functions as a proinflammatory cytokine by stimulating the production of IFN-γ from multiple cell types and accentuating the development of Th1 CD4 T-cell responses. Focused microarray analyses revealed upregulation of IL-18 and IL-18 receptor genes in CD8 T cells during the contraction phase. Based on these findings we investigated if and how signaling through the IL-18 receptor influences the development and kinetics of antigen (Ag)-specific CD8 and CD4 T-cell responses following infection. IL-18Rα−/−and IL-18−/−mice developed frequencies and total numbers of Ag-specific CD8 T cells afterListeria monocytogenesinfection that were similar to those of wild-type C57BL/6 mice. The kinetics of expansion, contraction, and memory CD8 T-cell maintenance were also similar. When IL-18Rα deficiency was isolated to Ag-specific CD8 T cells, the kinetics of the expansion and contraction phases were also normal. These basic findings were confirmed by examining the response to vaccinia virus infection. In contrast, the expansion of Ag-specific CD4 T cells was slightly curtailed by the absence of IL-18Rα; however, contraction and the maintenance of memory were not altered. Importantly, both memory Ag-specific CD8 and CD4 T cells generated in the absence of IL-18Rα expanded appropriately after secondary antigen exposure and were protective, indicating that signaling through the IL-18 receptor is not required for normal T-cell response kinetics and survival of immunized mice challenged with a lethalL. monocytogenesinfection.
Hfq, a Novel Pleiotropic Regulator of Virulence-Associated Genes in
Francisella tularensis
Authors: Meibom Karin L. , Forslund Anna-Lena , Kuoppa Kerstin , Alkhuder Khaled , Dubail Iharilalao , Dupuis Marion , Forsberg Åke , Charbit Alain
Published: February 2009

Francisella tularensis
is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the
Francisella
pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in
F. tularensis
involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in
F. tularensis
and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the
F. tularensis
vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of
F. tularensis
, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in
F. tularensis
, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.
Chiral recognition in bicyclic guanidines
Authors: Donovan Daniel H. O’ , Rozas Isabel , Blanco Fernando , Alkorta Ibon , Elguero José
Published: February 2009

A theoretical study of chiral recognition in bicyclic guanidines has been carried out by means of B3LYP/6-31+G(d,p) DFT calculations. A series of complexes between protonated 4,8-dimethyl-1,5,7-triazabicyclodecene (DTBD) and 2,5-disubtituted chiral cyclopentanones have been evaluated for chiral recognition, both in the gas phase and in benzene solution as per the polarizable continuum model (PCM) and analyzed by AIM and NBO methodologies. An inversion in the sense of chiral recognition has been observed between gas phase and solvated results for cyclopentanone complexes. Among the different correlations found (i.e. between electron density, hydrogen bond distance, second-order perturbation energy), a linear correlation has been established between the chiral recognition energy and different molecular parameters.
SHORT CHANNEL, FLOATING BODY, AND 3D COUPLING EFFECTS IN TRIPLE-GATE MOSFET
Authors: NA KYOUNG-IL , LEE JUNG-HEE , CRISTOLOVEANU SORIN , BAE YOUNG-HO , PATRUNO PAUL , XIONG WADE
Published: February 2009

We have investigated the short-channel effect (SCE), floating-body effect, and three-dimensional coupling effect in triple-gate MOSFET with various fin widths, gate lengths and number of fins. It is found that the SCE of these devices is alleviated as the fin width shrinks and does not depend on the number of fins. The gate-induced floating-body effect (GIFBE) is visible even in fully depleted (FD) triple-gate transistors when the film-buried oxide (BOX) interface is swept from depletion to accumulation by the back-gate bias. The 3-D coupling effect in vertical, lateral, and longitudinal directions was investigated for different channel geometries. The biasing condition which enables the simultaneous activation of all channels and gives rise to volume inversion is discussed.
ANALOG AND DIGITAL PERFORMANCE OF THE SCREEN-GRID FIELD EFFECT TRANSISTOR (SGRFET)
Authors: FOBELETS K. , DING P.W. , SHADROKH Y. , VELAZQUEZ-PEREZ J.E.
Published: February 2009

The Screen-Grid Field Effect Transistor (SGrFET) is a planar MOSFET-type device with a gating configuration consisting of metal cylindrical fingers inside the channel perpendicular to the current flow. The SGrFET operates in a MESFET mode using oxide insulated gates. The multi-gate configuration offers advantages for both analog and digital applications, whilst the gate cylinder holes can be exploited for bio-applications. In this manuscript TCAD results are presented on the analog and digital performance of the Screen-Grid Field Effect Transistor. The results are compared to the operation of an SOI-MOSFET and a finFET.
BIOMOLECULAR SENSING USING CARBON NANOTUBES: A SIMULATION STUDY
Authors: ABADIR G.B. , WALUS K. , TURNER R.F.B. , PULFREY D.L.
Published: February 2009

A simulation study using molecular dynamics and the density-functional-theory/non-equilibrium-Green's-function approach has been carried out to investigate the potential of carbon nanotubes (CNT) as molecular-scale biosensors. Single molecules of each of two amino acids (isoleucine and asparagine) were used as the target molecules in two separate simulations. The results show a significant suppression of the local density of states (LDOS) in both cases, with a distinct response for each molecule. This is promising for the prospect of CNT-based single-molecule sensors that might depend on the LDOS, e.g., devices that respond to changes in either conductance or electroluminescence.
AlGaN/GaN HEMTs: RECENT DEVELOPMENTS AND FUTURE DIRECTIONS
Authors: RAJAN SIDDHARTH , MISHRA UMESH K. , PALACIOS TOMÁS
Published: February 2009

This paper provides an overview of recent work and future directions in Gallium Nitride transistor research. We discuss the present status of Ga -polar AlGaN / GaN HEMTs and the innovations that have led to record RF power performance. We describe the development of N -polar AlGaN / GaN HEMTs with microwave power performance comparable with state-of-art Ga -polar AlGaN / GaN HEMTs. Finally we will discuss how GaN -based field effect transistors could be promising for a less obvious application: low-power high-speed digital circuits.
IMPREGNATED SEMICONDUCTOR SCINTILLATOR
Authors: LURYI SERGE
Published: February 2009

A semiconductor scintillation-type gamma radiation detector is discussed in which the gamma-ray absorbing semiconductor body is impregnated with multiple small direct-gap semiconductor inclusions of bandgap slightly narrower than that of the body. If the typical distance between them is smaller than the diffusion length of carriers in the body material, the photo-generated electrons and holes will recombine inside the impregnations and produce scintillating radiation to which the wide-gap body is essentially transparent. In this way it is possible to implement a semiconductor scintillator of linear dimensions exceeding 10 cm.
OPTICAL MEMS TECHNOLOGIES FOR ELECTRICALLY TUNABLE MULTI-SPECTRAL SHORT-WAVE INFRARED SENSORS AND ARRAYS
Authors: MILNE JASON S. , DELL JOHN M. , KEATING ADRIAN J. , FARAONE LORENZO
Published: February 2009

Optical MEMS technology combined with broadband infrared sensor technology is used to realize wavelength-tunable infrared sensors. This paper describes the ongoing research into one such sensor design based on an electrically tunable Fabry-Pérot cavity. Theory, measured results and future research directions are presented and discussed for the single-sensor design currently being developed, in the context of the intended application of this technology; the development of lightweight, portable and robust multi-spectral imaging systems.
NANOCRYSTALLINE SILICON THIN FILM TRANSISTORS FOR HIGH PERFORMANCE LARGE AREA ELECTRONICS
Authors: ESMAEILI-RAD MOHAMMAD R. , LEE HYUN JUNG , SAZONOV ANDREI , NATHAN AROKIA
Published: February 2009

Nanocrystalline silicon ( nc - Si ) thin film transistors (TFTs) have potential for high-performance applications in large area electronics, such as next generation of flat panel displays and medical x-ray imagers, for pixel drivers, readout circuits, as well as complementary channel logic circuits for system-on-panel integration. This potential stems from reduced threshold voltage shift and higher transconductance, compared to amorphous silicon counterpart. In this paper, we discuss various TFT structures, their associated design and performance considerations, including leakage current and threshold voltage stability mechanisms.
A HIGH INPUT IMPEDANCE VOLTAGE-MODE ALL-PASS/NOTCH FILTER USING A SINGLE VARIABLE GAIN CURRENT CONVEYOR
Authors: YUCE ERKAN , PAL KIRAT , MINAEI SHAHRAM
Published: February 2009

In this paper, a novel circuit for realizing voltage-mode first-order and second-order all-pass filter responses as well as second-order notch filter response depending on the passive component choice, is presented. This circuit has high input impedance; thus, it is easy to cascade the introduced filter with other voltage-mode topologies. Also, it uses a single Variable Gain Current Conveyer — VGCCII and only grounded capacitors. SPICE simulation results based on 0.35 μm TSMC CMOS technology parameters are given to confirm the theory.