bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceleration of electrons in Titan's ionosphere
Authors: Zaitsev V. V. , Shaposhnikov V. E. , Khodachenko M. L. , Rucker H. O. , Panchenko M.
Published: March 2010

A consideration of the acceleration mechanism which supplies the fast electrons to the source of Saturnian kilometric radiation (SKR) and an interpretation of the recently reported observational indications of the influence of Titan on the SKR are presented. The proposed mechanism operates by the effect of the different magnetization of the electrons and ions in Titan's ionosphere which in the course of Titan's motion through the Saturnian magnetic field causes the creation of a charge‐separation electric field. This field has a component parallel to the magnetic field and accelerates part of the ionospheric electrons (called “runaway electrons”). The performed estimates show that the mechanism accelerates the runaway electrons up to an energy of ∼5 keV. The power of the acceleration mechanism is sufficient for SKR generation and also for the ultraviolet luminescence of Titan's atmosphere. The weakening of the SKR when Titan passes on the dayside of Saturn is due to a decrease of the magnetic field strength near the dayside magnetopause, when the Moon escapes the Saturnian magnetosphere, as well as due to the break in the magnetic connection between the electron acceleration region on Titan and the SKR sources. The latter prevents the penetration of the accelerated electrons into the radiation generation region. When Titan is on the nightside of Saturn, it enters into shell L∼14, which is stretched owing to the ring current. In this case, the electrons that accelerated in the ionosphere of Titan can reach the nightside SKR sources and activate them and therefore being the reason for the Titan influence on the SKR.
Modeling disturbed stratospheric chemistry during solar‐induced NOx enhancements observed with MIPAS/ENVISAT
Authors: Reddmann T. , Ruhnke R. , Versick S. , Kouker W.
Published: March 2010

Energetic particle precipitation during solar active periods induces enhancements of NOx (N, NO, NO2) in the lower thermosphere/mesosphere which can be transported to the stratosphere within the polar vortex. The quantitative contribution of these NOx intrusions to ozone chemistry in the stratosphere is still under discussion. Here we present simulations with a three‐dimensional model of the middle atmosphere where NOx enhancements in the lower mesosphere have been taken from the observations of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument on the European Space Agency satellite ENVISAT. Covering the period from July 2002 to March 2004 these observations include the strong solar proton event in fall 2003 and intrusions connected to auroral events during the Arctic and Antarctic winters. The comparison of the disturbed run with the undisturbed model run allows a quantitative assessment of the long‐term influence of NOx intrusions on stratospheric chemistry in general and the ozone concentration in particular. From the model simulation, we estimate for the period from July 2002 to March 2004 that in total, an additional 5.4 Gigamol NOy has been brought into the middle atmosphere. This represents in early 2004 about 5% of the global NOy mass in the middle atmosphere. A 2 year decay time for such enhancements is estimated from the model. Persistent reduction of ozone concentration in the stratosphere caused by the NOx intrusions can be followed in the simulation for several months. This reduction is restricted to high latitudes and amounts to several Dobson units in the total ozone column.
Quantification of surface water and groundwater flows to open‐ and closed‐basin lakes in a headwaters watershed using a descriptive oxygen stable isotope model
Authors: Stets Edward G. , Winter Thomas C. , Rosenberry Donald O. , Striegl Robert G.
Published: March 2010

Accurate quantification of hydrologic fluxes in lakes is important to resource management and for placing hydrologic solute flux in an appropriate biogeochemical context. Water stable isotopes can be used to describe water movements, but they are typically only effective in lakes with long water residence times. We developed a descriptive time series model of lake surface water oxygen‐18 stable isotope signature (δL) that was equally useful in open‐ and closed‐basin lakes with very different hydrologic residence times. The model was applied to six lakes, including two closed‐basin lakes and four lakes arranged in a chain connected by a river, located in a headwaters watershed. Groundwater discharge was calculated by manual optimization, and other hydrologic flows were constrained by measured values including precipitation, evaporation, and streamflow at several stream gages. Modeled and observed δL were highly correlated in all lakes (r = 0.84–0.98), suggesting that the model adequately described δL in these lakes. Average modeled stream discharge at two points along the river, 16,000 and 11,800 m3 d−1, compares favorably with synoptic measurement of stream discharge at these sites, 17,600 and 13,700 m3 d−1, respectively. Water yields in this watershed were much higher, 0.23–0.45 m, than water yields calculated from gaged streamflow in regional rivers, approximately 0.10 m, suggesting that regional groundwater discharge supports water flux through these headwaters lakes. Sensitivity and robustness analyses also emphasized the importance of considering hydrologic residence time when designing a sampling protocol for stable isotope use in lake hydrology studies.
The Rac activator STEF (Tiam2) regulates cell migration by microtubule‐mediated focal adhesion disassembly
Authors: Rooney Claire , White Gavin , Nazgiewicz Alicja , Woodcock Simon A , Anderson Kurt I , Ballestrem Christoph , Malliri Angeliki
Published: March 2010

Focal adhesion (FA) disassembly required for optimal cell migration is mediated by microtubules (MTs); targeting of FAs by MTs coincides with their disassembly. Regrowth of MTs, induced by removal of the MT destabilizer nocodazole, activates the Rho‐like GTPase Rac, concomitant with FA disassembly. Here, we show that the Rac guanine nucleotide exchange factor (GEF) Sif and Tiam1‐like exchange factor (STEF) is responsible for Rac activation during MT regrowth. Importantly, STEF is required for multiple targeting of FAs by MTs. As a result, FAs in STEF‐knockdown cells have a reduced disassembly rate and are consequently enlarged. This leads to reduced speed of migration. Together, these findings suggest a new role for STEF in FA disassembly and cell migration through MT‐mediated mechanisms.
The ribosome‐bound initiation factor 2 recruits initiator tRNA to the 30S initiation complex
Authors: Milon Pohl , Carotti Marcello , Konevega Andrey L , Wintermeyer Wolfgang , Rodnina Marina V , Gualerzi Claudio O
Published: March 2010

Bacterial translation initiation factor 2 (IF2) is a GTPase that promotes the binding of the initiator fMet‐tRNAfMet to the 30S ribosomal subunit. It is often assumed that IF2 delivers fMet‐tRNAfMet to the ribosome in a ternary complex, IF2·GTP·fMet‐tRNAfMet. By using rapid kinetic techniques, we show here that binding of IF2·GTP to the 30S ribosomal subunit precedes and is independent of fMet‐tRNAfMet binding. The ternary complex formed in solution by IF2·GTP and fMet‐tRNA is unstable and dissociates before IF2·GTP and, subsequently, fMet‐tRNAfMet bind to the 30S subunit. Ribosome‐bound IF2 might accelerate the recruitment of fMet‐tRNAfMet to the 30S initiation complex by providing anchoring interactions or inducing a favourable ribosome conformation. The mechanism of action of IF2 seems to be different from that of tRNA carriers such as EF‐Tu, SelB and eukaryotic initiation factor 2 (eIF2), instead resembling that of eIF5B, the eukaryotic subunit association factor.
The activities of MMP‐9 and total gelatinase respond differently to substrate coating and cyclic mechanical stretching in fibroblasts and myoblasts
Authors: Cha Ming C. , Purslow Peter P.
Published: March 2010

The current study was designed to investigate whether the activities of TGC (total gelatinase and collagenase) as well as MMP‐9 (matrix metalloproteinase‐9, gelatinase B) secreted by the cultured fibroblasts and myoblasts were influenced by the specific extracellular substrates and by cyclic mechanical strain. Fibroblasts (Rat 2) and myoblasts (C2C12) were cultured with either fibronectin, laminin or collagen type I for 24 h and applied with or without a biaxial deformation at 1 Hz using the Flexcell FX‐4000 system. MMP‐9 activity was increased in fibroblasts when the cells were in contact with fibronectin and laminin, while in myoblasts, enhanced activity of the secreted enzyme was only observed when collagen was present. TGC activity expressed from myoblasts was increased in cells growing on all three types of extracellular proteins in response to the mechanical stimulation, but in fibroblasts, such an increase was only observed in cells grown on the laminin coating. In summary, our data demonstrate that the activities of MMP‐9 synthesized by fibroblasts tend to be regulated by the specific extracellular protein the cells are in contact with, whereas the gelatinolytic actions of proteases produced by myoblasts are more responsive to the mechanical deformation.
A New Classification Based on the Kaban's Modification for Surgical Management of Craniofacial Microsomia
Authors: Madrid Jose Rolando Prada , Montealegre Giovanni , Gomez Viviana
Published: March 2010

In medicine, classifications are designed to describe accurately and reliably all anatomic and structural components, establish a prognosis, and guide a given treatment. Classifications should be useful in a universal way to facilitate communication between health professionals and to formulate management protocols. In many situations and particularly with craniofacial microsomia, there have been many different classifications that do not achieve this goal. In fact, when there are so many classifications, one can conclude that there is not a clear one that accomplishes all these ends and defines a treatment protocol. It is our intent to present a new classification based on the Pruzansky's classification, later modified by Kaban, to determine treatment protocols based on the degree of osseous deficiency present in the body, ramus, and temporomandibular joint. Different mandibular defects are presented in two patients with craniofacial microsomia type III and IV according to our classification with the corresponding management proposed for each type and adequate functional results.
Traumatic Superior Orbital Fissure Syndrome: Current Management
Authors: Chen Chien-Tzung , Chen Yu-Ray
Published: March 2010

Traumatic superior orbital fissure syndrome is an uncommon complication of craniomaxillofacial trauma with an incidence of less than 1%. The syndrome is characterized by ophthalmoplegia, ptosis, proptosis of eye, dilation and fixation of the pupil, and anesthesia of the upper eyelid and forehead. This article describes a detailed anatomy of the superior orbital fissure as it related to pathophysiology and clinical findings. Etiology and diagnosis are established after detailed physical and radiographic examination. On the basis of our clinical experience in the management of superior orbital fissure syndrome and from the data reported previously in the literature, an algorithm for treatment of traumatic superior orbital fissure syndrome including use of steroid, surgical decompression of superior orbital fissure, and reduction of concomitant facial fracture is presented and its rationale discussed.
Revisiting Orthodromic Temporalis Transfer in Treating Long-Standing Facial Paralysis
Authors: Elbarbary Amir S. , Hemeda Mostafa , Amr Adel H.
Published: March 2010

The treatment of long-standing facial paralysis through temporalis muscle transfer has stood the test of time. Herein, we present a modification in temporalis muscle transfer for lower facial reanimation. Instead of the traditional stripping of the temporalis muscle from its origin, its insertion is stripped from the coronoid process through an intraoral approach. The detached fibers were then sutured to a fascia lata graft, which was passed and secured to the orbicularis oris to reanimate the corner of the mouth. The procedure is less extensive and provides a direct “orthodromic” line of pull with good muscular excursion and power. This simple procedure has been applied to 12 consecutive cases with long-standing complete facial paralysis presenting to the Plastic and Reconstructive Surgery Clinic at the Ain-Shams University Hospital over the past 2 years. In addition to symmetry at rest, this easy procedure allowed for good movement of the corner of the mouth with restoration of a balanced smile.
Principles of Implant-Based Reconstruction and Rehabilitation of Craniofacial Defects
Authors: Thimmappa Brinda , Girod Sabine C.
Published: March 2010

The final stages of reconstruction following craniofacial trauma or tumor resection often involve the fitting of prostheses. Development of osseointegrated implants for retention of prostheses has improved function and aesthetic outcome. Placement of osseointegrated implants requires coordinated care from multiple specialists and a lifetime commitment of the patient. The workup and surgical treatment algorithms for placement of intraoral compared with extraoral implants are discussed. The quality and quantity of bone available are the most important factors influencing design and placement. The long-term retention of implants is influenced by implant site, local tissue bed preparation, and hygiene. Osseointegrated implants are a part of the complete rehabilitation of patients with craniomaxillofacial defects. Although final fitting and maintenance of prostheses is completed by prosthodontists and patients, successful placement and preservation of implants is affected largely by the plan set forth by the reconstructive surgeon.
Orbital Floor Fractures: A Retrospective Review of 45 Cases at a Tertiary Health Care Center
Authors: Rhim Chun H. , Scholz Thomas , Salibian Ara , Evans Gregory R.D
Published: March 2010

The purpose of this retrospective study was to investigate treatment options for orbital floor fractures at a Level 1 Trauma Center in Southern California. A review of 45 cases of isolated orbital floor fractures treated at the University of California at Irvine between February 2004 and April 2007 was done. Patients were retrospectively analyzed for gender, age, mechanism of injury, associated facial injuries, presenting symptoms, method of treatment, and postoperative complications. Thirty-six male patients and nine female patients were treated. Motor vehicle collision (26/45) was the most common cause of injury, and the mean age of the patients was 35.5 years (range: 15—81 years). Ecchymosis surrounding the orbital tissue was the most common presentation (38/45). Diplopia was present in 8 of 45 patients, with 1 patient requiring urgent decompression for retrobulbar hematoma. Forty-three patients underwent surgical repair; 40 underwent transconjunctival approach with lateral canthotomy; 17 underwent reconstruction with porous polyethylene Medpor (Porex Surgical, Inc., College Park, GA.); and 26 underwent reconstruction with a titanium mesh plate. Immediate postoperative complications included 12 patients with infraorbital numbness, 3 with diplopia, 1 with cellulitis, and 1 with ectropion with a subcilliary approach. Average timing of surgery of our study was 4.94 days (range, 1—20 days). Orbital floor fracture management has changed significantly over the past few decades with the introduction of new internal fixation methods and new materials for reconstructing orbital floor defects. Recommendations for surgical intervention on orbital floor fractures mostly depend on clinical examination and imaging studies. Consequences of inadequate repair of orbital floor fractures can lead to significant facial asymmetry and visual problems. Both porous polyethylene and titanium plates are effective tools for reconstructing the orbital floor. Our review demonstrates that orbital floor fractures can be repaired safely with minimal postoperative complications and confirms that transconjunctival approach to orbital floor is an effective way for exposure and prevention of ectropion that can be seen with other techniques.
Development of sensitivity to phonological context in learning to spell in English
Authors: Dich Nadya
Published: March 2010

The study attempts to investigate factors underlying the development of spellers’ sensitivity to phonological context in English. Native English speakers and Russian speakers of English as a second language (ESL) were tested on their ability to use information about the coda to predict the spelling of vowels in English monosyllabic nonwords. In addition, the study assessed the participants’ spelling proficiency as their ability to correctly spell commonly misspelled words (Russian participants were assessed in both Russian and English). Both native and non-native English speakers were found to rely on the information about the coda when spelling vowels in nonwords. In both native and non-native speakers, context sensitivity was predicted by English word spelling; in Russian ESL speakers this relationship was mediated by English proficiency. L1 spelling proficiency did not facilitate L2 context sensitivity in Russian speakers. The results speak against a common factor underlying different aspects of spelling proficiency in L1 and L2 and in favor of the idea that spelling competence comprises different skills in different languages.
Consonant deletion, obligatory synharmony, typical suffixing
Authors: Mora-Marín David
Published: March 2010

The Pre-Columbian Mayan hieroglyphic script utilized logograms, representing CVC roots or CVCVC stems, and CV syllabograms. Starting with Knorozov’s (1952 etc.) initial breakthroughs in applying a Mayan linguistic model to account for the script’s spelling practices, most scholars have assumed that ‘synharmonic’ spellings of roots or stems, those in which the final consonant is ‘complemented’ by means of a CV syllabogram whose vowel is identical in quality to that of the root (e.g. C1V1C2 — C2(V1)), exhibited a linguistically ‘fictitious’ (or silent) vowel; such synharmonic spellings were commonly assumed to be default. Efforts were then aimed at determining the motivation of spellings in which the final syllabogram is instead ‘disharmonic’ (e.g. C1V1C2 — C2(V2)). Recently, it has been proposed that the vowels of disharmonic spellings were utilized as diacritics applied to the vowels of the preceding syllables in order to convey that such vowels were complex, while maintaining, generally, that synharmonic spellings were default. The present paper offers a thorough review of these proposals and gives arguments against their persuasiveness, abiding instead by four phonological contexts that call for the insertion of fictitious synharmonic vowels, supplemented by morphological conditioning and consonant deletion that account for additional cases of synharmonic spellings, and the vast majority of disharmonic spellings. These principles allow for a major refinement of the definition of ‘conventionalized’ and ‘default’ spellings, a new avenue for determining the nature of ‘pseudologographic’ or ‘morphosyllabic’ signs based on common syllabograms, and a new cognitive framework for addressing the question of the nature of logograms and syllabograms, as well as the origin and development of Mayan spelling practices.
Prevalence of USA300 Strain Type of Methicillin-Resistant Staphylococcus aureus among Patients with Nasal Colonization Identified with Active Surveillance
Authors: Freitas Eduardo A. F. , Harris Rebecca M. , Blake Ruth K. , Salgado Cassandra D.
Published: March 2010

Background.

USA300 is the most prevalent strain type of community-acquired methicillin-resistantStaphylococcus aureus(MRSA), but the proportion of patients colonized with USA300 strains and their risk for infection are largely unknown.

Objective.

To determine the prevalence of USA300 strains among MRSA nasal colonizing isolates in our hospital, to identify risks for USA300 nasal colonization, and to determine risks of developing infection for nasally colonized patients.

Methods.

Retrospective cohort study of patients found to be nasally colonized with MRSA through active surveillance at a tertiary care hospital from January 2005 through December 2007. MRSA isolates were identified as USA300 or non-USA300. Risks for colonization and infection were identified with logistic regression.

Results.

Among 1,306 MRSA nasal isolates, 307 (24%) were USA300 strains, and this proportion significantly increased over time (17.4% in 2005 and 26.7% in 2007;P= .003). African American race was an independent risk for USA300 nasal colonization (odds ratio [OR], 1.81 [95% confidence ratio {CI}, 1.38-2.38]). Older age (OR, 0.97 [95% CI, 0.96-0.98]) and female sex (OR, 0.74 [95% CI, 0.56-0.97]) decreased risk. Among nasally colonized patients, 238 (18.2%) developed infection. Increased length of stay (OR, 1.03 [95% CI, 1.01-1.06]) independently increased risk for infection among patients nasally colonized with USA300 MRSA, and female sex decreased risk (OR, 0.48 [95% CI, 0.24-0.95]). Increased length of stay (OR, 1.03 [95% CI, 1.02-1.04]) and treatment in an intensive care unit (OR, 1.64 [95% CI, 1.10-2.44]) independently increased risk for infection among patients nasally colonized with non-USA300 MRSA, and female sex decreased risk (OR, 0.67 [95% CI, 0.47-0.94]).

Conclusion.

The proportion of MRSA nasally colonized patients with USA300 strains significantly increased during the study, and risks included African American race. Strain type had no significant effect on the proportion of patients who developed infection, and risk factors for infection were similar.
Bayesian assessment of uncertainty in metrology: a tutorial
Authors: Lira I , Grientschnig D
Published: March 2010

The publication of theGuide to the Expression of Uncertainty in Measurement(GUM), and later of its Supplement 1, can be considered to be landmarks in the field of metrology. The second of these documents recommends a general Monte Carlo method for numerically constructing the probability distribution of a measurand given the probability distributions of its input quantities. The output probability distribution can be used to estimate the fixed value of the measurand and to calculate the limits of an interval wherein that value is expected to be found with a given probability. The approach in Supplement 1 is not restricted to linear or linearized models (as is the GUM) but it is limited to a single measurand.

In this paper the theory underlying Supplement 1 is re-examined with a view to covering explicit or implicit measurement models that may include any number of output quantities. It is shown that the main elements of the theory are Bayes' theorem, the principles of probability calculus and the rules for constructing prior probability distributions. The focus is on developing an analytical expression for the joint probability distribution of all quantities involved. In practice, most times this expression will have to be integrated numerically to obtain the distribution of the output quantities, but not necessarily by using the Monte Carlo method. It is stressed that all quantities are assumed to have unique values, so their probability distributions are to be interpreted as encoding states of knowledge that are (i) logically consistent with all available information and (ii) conditional on the correctness of the measurement model and on the validity of the statistical assumptions that are used to process the measurement data. A rigorous notation emphasizes this interpretation.
Preference Variable Impacts in Direct and Inverse Differential Demand Systems
Authors: Brown Mark G. , Lee Jonq-Ying
Published: March 2010

Preference variables are included in the inverse Rotterdam model based on the Tintner‐Ichimura‐Basmann relationship linking preference effects on quantities demanded to price effects and preference effects on marginal utilities. Restrictions are placed on the effects of the preference variables on the marginal utilities, resulting in reductions in the parameter space for the preference variables in both direct and inverse demand systems. The model is used to analyze impacts of product quality on fresh citrus demand.
Localized motif discovery in gene regulatory sequences
Authors: Narang Vipin , Mittal Ankush , Sung Wing-Kin
Published: March 2010

Motivation: Discovery of nucleotide motifs that are localized with respect to a certain biological landmark is important in several appli-cations, such as in regulatory sequences flanking the transcription start site, in the neighborhood of known transcription factor binding sites, and in transcription factor binding regions discovered by massively parallel sequencing (ChIP-Seq).

Results: We report an algorithm called LocalMotif to discover such localized motifs. The algorithm is based on a novel scoring function, called spatial confinement score, which can determine the exact interval of localization of a motif. This score is combined with other existing scoring measures including over-representation and relative entropy to determine the overall prominence of the motif. The approach successfully discovers biologically relevant motifs and their intervals of localization in scenarios where the motifs cannot be discovered by general motif finding tools. It is especially useful for discovering multiple co-localized motifs in a set of regulatory sequences, such as those identified by ChIP-Seq.

Availability and Implementation: The LocalMotif software is available at http://www.comp.nus.edu.sg/~bioinfo/LocalMotif

Contact:  ksung@comp.nus.edu.sg

Supplementary information:  Supplementary data are available at Bioinformatics online.
Day–night differences in Cunene horse mackerel (Trachurus trecae) acoustic relative densities off Angola
Authors: Vaz Velho Filomena , Barros Pedro , Axelsen Bjørn Erik
Published: March 2010

Vaz Velho, F., Barros, P., and Axelsen, B. E. 2010. Day–night differences in Cunene horse mackerel (Trachurus trecae) acoustic relative densities off Angola. – ICES Journal of Marine Science, 67: 1004–1009. The assessment and the management of the Cunene horse mackerel in Angola rely heavily on abundance estimates from hydroacoustic surveys. Acoustic data collected from 1994 to 1999 were analysed to quantify diurnal variation in relative acoustic densities at 38 kHz. The nautical-area scattering coefficient (sA, m2 nautical mile−2) was characterized by clear day–night differences: sA values recorded during the day were significantly higher (mean sA: 135 m2 nautical mile−2) than the corresponding night-time values (mean sA 83 m2 nautical mile−2). This pattern is associated with differences in behaviour and horizontal and vertical distributions between day and night: by day, the fish school near the seabed, and by night, they move into the pelagic zone and disperse into widespread scattering layers. More than 40% of the total backscatter by day originated from the bottom 10 m, but at night this proportion decreased to <10%. The findings demonstrate considerable influences of behaviour and aggregation dynamics on acoustic measurements. Possible implications for the estimates of acoustic abundance are discussed in the light of the differences.
TOP2 gene disruption reduces drug susceptibility by increasing intracellular ergosterol biosynthesis in Candida albicans
Authors: Zheng Hao , Jiang Yuan-Ying , Wang Yan , Jia Xin-Ming , Yan Tian-Hua , Gao Ping-Hui , Yan Lan , Jiang Ling-Huo , Ji Hui , Cao Yong-Bing
Published: March 2010

In this study the role of theTOP2gene in fungal drug susceptibility was investigated by disrupting and overexpressing the gene inCandida albicans. MIC determination and a spot assay showed that atop2Δ/Δ null mutant (strain T2bc) was more resistant to the antifungals tested than the wild-type (strain CAI4). Real-time RT-PCR and rhodamine 6G efflux examination showed thatTOP2 did not influence the activity of drug efflux pumps. Sterol analysis with GC/high-resolution MS indicated that the intracellular ergosterol composition of thetop2Δ/Δ mutant was significantly increased. Subsequently, fluorescence polarization measurements also revealed that Top2-deprived cells displayed a decrease in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Quantitative real-time RT-PCR analysis further confirmed that theERG11gene, an essential gene in ergosterol biosynthesis, was upregulated. These results demonstrate a close relationship between theTOP2gene and drug susceptibility inC. albicans.
RpoE2 of Sinorhizobium meliloti is necessary for trehalose synthesis and growth in hyperosmotic media
Authors: Flechard Maud , Fontenelle Catherine , Blanco Carlos , Goude Renan , Ermel Gwennola , Trautwetter Annie
Published: March 2010

Adaptation to osmotic stress can be achieved by the accumulation of compatible solutes that aid in turgor maintenance and macromolecule stabilization. The genetic regulation of solute accumulation is poorly understood, and has been described well at the molecular level only in enterobacteria. In this study, we show the importance of the alternative sigma factor RpoE2 inSinorhizobium melilotiosmoadaptation. Construction and characterization of anS. meliloti rpoE2mutant revealed compromised growth in hyperosmotic media. This defect was due to the lack of trehalose, a minor carbohydrate osmolyte normally produced in the initial stages of growth and in stationary phase. We demonstrate here that all three trehalose synthesis pathways are RpoE2 dependent, but only the OtsA pathway is important for osmoinducible trehalose synthesis. Furthermore, we confirm that the absence of RpoE2-dependent induction ofotsAis the cause of the osmotic phenotype of therpoE2mutant. In conclusion, we have highlighted that, despite its low level, trehalose is a crucial compatible solute inS. meliloti, and the OtsA pathway induced by RpoE2 is needed for its accumulation under hyperosmotic conditions.
Establishment of an indicator cell system for hepatitis C virus
Authors: Tanaka Yoshinori , Mori Yoshio , Tani Hideki , Abe Takayuki , Moriishi Kohji , Kojima Hirotatsu , Nagano Tetsuo , Okabe Takayoshi , Suzuki Tetsuro , Tatsumi Masashi , Matsuura Yoshiharu
Published: March 2010

Although a cell culture system for HCV JFH‐1 strain has been developed, no robust cell culture system for serum‐derived HCV is available. In this study, we have established systems capable of monitoring infection with JFH‐1 virus based on specific reporter gene expression through proteolysis of chimeric transcription factors by HCV NS3/4A protease. We utilized a transcriptional factor Gal4‐TBP that synergistically enhances transcription of the GAL4UAS and HIV‐1 LTR tandem promoter with the Tat protein. We constructed chimeric Tat and Gal4‐TBP transcription factors containing the HCV NS3/4A cleavage sequence of a mitochondria‐resident IPS‐1, but not those of the HCV polyprotein, and manipulated them to localize in the ER. Upon infection with JFH‐1 virus, the transcription factors were efficiently cleaved by HCV protease, migrated into the nucleus and activated the reporter gene under the tandem promoter. Upon infection with JFH‐1 virus, the Huh7OK1/TG‐Luc cell line carrying the transcription factors and a luciferase gene under the promoter expressed luciferase in a dose‐dependent manner in close correlation with HCV RNA replication. Huh7OK1/TG‐LNGFR cells carrying the transcription factors and a cDNA of human low affinity nerve growth factor receptor under the promoter were selectively concentrated by immunomagnetic cell sorting upon infection with JFH‐1 virus. These results indicate that the chimeric constructs bearing the ER‐resident IPS‐1 sequence are specifically recognized and efficiently cleaved by HCV protease and are harnessed for detection of HCV replication and for recovery of HCV‐infected cells. This strategy may be applicable for the establishment of cell culture systems for the isolation of serum‐derived HCV.
BRCA1 and XRCC1 polymorphisms associated with survival in advanced gastric cancer treated with taxane and cisplatin
Authors: Shim Hyun Jeong , Yun Joo Young , Hwang Jun Eul , Bae Woo Kyun , Cho Sang Hee , Lee Ji Hee , Kim Hee Nam , Shin Min Ho , Kweon Sun Seog , Lee Jae Hyuk , Kim Hyeoung Joon , Chung Ik Joo
Published: March 2010

This study evaluated the influence of genetic polymorphism influencing drug metabolism on survival in taxane‐ and cisplatin‐treated advanced gastric cancer (AGC). Peripheral blood samples from 207 AGC patients treated with first‐line chemotherapy of taxane and cisplatin were used. We investigated polymorphisms that influenced the metabolism of taxane (ATP‐binding cassette transporter B1 (ABCB1)), cisplatin (glutathione S‐transferase M1 (GSTM1), glutathione S‐transferase P1 (GSTP1), glutathione S‐transferase T1 (GSTT1), excision repair cross complementing 1 (ERCC1), X‐ray Cross Complementing group 3 (XRCC3), X‐ray Cross Complementing group 4 (XRCC4), X‐ray Cross Complementing group 1 (XRCC1), breast cancer (BRCA1)), and 5‐fluorouracil (methylene tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS)). A total of 207 patients were enrolled between May 2004 and Dec 2008, and 200 patients were analyzed. The overall response rate was 38.5%. Time to progression and overall survival time were 4.3 ± 0.19 months and 11.9 ± 1.05 months, respectively. There was no significant association between genetic polymorphism and response rate. However, the BRCA1 mutant TT homozygote was associated with significant prolongation of overall survival (hazard ratio [HR] = 0.43; 95% confidence interval [CI], 0.20–0.92; P = 0.03) and progression‐free survival (HR = 0.51; 95% CI, 0.26–1.00; P = 0.05). Also, the XRCC1 194 CT genotype was associated with inferior overall survival, relative to the XRCC1 194 CC homozygotes (HR = 1.49; 95% CI, 0.11–2.07; P = 0.018).These findings suggest that BRCA1 TT and XRCC1 194 CT genotypes could be modest prognostic markers of AGC response in taxane‐ and cisplatin‐treated patients.

(Cancer Sci 2010; 101: 1247–1254)
The epidemiology of cannabis use and cannabis‐related harm in Australia 1993–2007
Authors: Roxburgh Amanda , Hall Wayne D. , Degenhardt Louisa , McLaren Jennifer , Black Emma , Copeland Jan , Mattick Richard P.
Published: March 2010

Aims To examine trends in patterns of cannabis use and related harm in the Australian population between 1993 and 2007.

Design Analysis of prospectively collected data from: (1) the National Drug Strategy Household Survey (NDSHS) and Australian Secondary Student Alcohol and Drug Survey (ASSADS); (2) the National Hospital Morbidity Database (NHMD); and (3) the Alcohol and Other Drug Treatment Services National Minimum Dataset (AODTS‐NMDS).

Participants Australians aged 14 years and over from the general population; students aged 12–17 years; public and private hospital in‐patients; public and private in‐patients and out‐patients attending for drug treatment.

Measurement Prevalence of 12‐month cannabis use among the general population and secondary students. Proportions in the general population by age group reporting: daily cannabis use; difficulties in controlling cannabis use; and heavy cannabis use on each occasion. Number of hospital and treatment presentations for cannabis‐related problems.

Findings Prevalence of past‐year cannabis use has declined in the Australian population since the late 1990s. Among those reporting past‐year use, daily use is prevalent among 40–49‐year‐olds, while heavy patterns of use are prevalent among 14–19‐year‐olds. Hospital presentations for cannabis‐related problems reflect similar trends. Past‐year cannabis use has decreased among the 10–19‐year age group, but those who are daily users in this age group report using large quantities of cannabis.

Conclusions Despite declines in the prevalence of cannabis use, continued public health campaigns warning of the harms associated with cannabis use are essential, aimed particularly at users who are already experiencing problems. The increasing demand for treatment for cannabis problems in Australia suggests the need for more accessible and more effective interventions for cannabis use disorders.
Flashblood: blood sharing among female injecting drug users in Tanzania
Authors: McCurdy Sheryl A. , Ross Michael W. , Williams Mark L. , Kilonzo Gad P. , Leshabari Melkizedek T.
Published: March 2010

Aims This study examined the association between the blood‐sharing practice of ‘flashblood’ use and demographic factors, human immunodeficiency virus (HIV) status and variables associated with risky sex and drug behaviors among female injecting drug users. Flashblood is a syringe‐full of blood passed from someone who has just injected heroin to someone else who injects it in lieu of heroin.

Design A cross‐sectional study.

Setting Dar es Salaam, Tanzania.

Participants One hundred and sixty‐nine female injecting drug users (IDUs) were recruited using purposive sampling for hard‐to‐reach populations.

Measurements The association between flashblood use, demographic and personal characteristics and risky sex and drug use variables was analyzed by t‐test and χ2 test. The association between flashblood use and residential neighborhood was mapped.

Findings Flashblood users were more likely to: be married (P = 0.05), have lived in the current housing situation for a shorter time (P < 0.000), have been forced as a child to have sex by a family member (P = 0.007), inject heroin more in the last 30 days (P = 0.005), smoke marijuana at an earlier age (P = 0.04), use contaminated rinse‐water (P < 0.03), pool money for drugs (P < 0.03) and share drugs (P = 0.000). Non‐flashblood users were more likely to live with their parents (P = 0.003). Neighborhood flashblood use was highest near downtown and in the next two adjoining suburbs and lowest in the most distant suburbs.

Conclusions These data indicate that more vulnerable women who are heavy users and living in shorter‐term housing are injecting flashblood. The practice of flashblood appears to be spreading from the inner city to the suburbs.
Predicting the life‐time benefit of school‐based smoking prevention programmes
Authors: Jit Mark , Aveyard Paul , Barton Pelham , Meads Catherine A.
Published: March 2010

Aim School‐based smoking prevention programmes may delay the age of smoking initiation, but do not appear to achieve lasting reductions in smoking prevalence beyond school‐leaving age. We explored whether delaying the age at which someone initiates smoking may have life‐time benefits by increasing the likelihood of quitting in later life.

Design and setting Data from the General Household Survey of Great Britain were used in a logistic regression model to examine the association between age at which someone initiates regular smoking and the probability that the person will quit smoking later in life. The effect of confounding variables (sex, ethnicity, socio‐economic class, education and geographical location) was taken into account. The predicted relationship was used in a cohort model to estimate the life‐time reduction in smoking prevalence and all‐cause mortality of a school‐based smoking prevention programme.

Results Age of regular smoking initiation was associated strongly with the probability of quitting later in life (coefficient −0.103, P < 0.001). The strength of the association was slightly reduced but still significant when confounding variables were included (coefficient −0.075, P < 0.001). An intervention that delays smoking initiation without decreasing smoking prevalence at age 18 may reduce adult smoking prevalence by 0.13–0.32% (depending on age) and all‐cause mortality by 0.09% over the life‐time of the sample.

Conclusion School‐based smoking prevention programmes have potential for a beneficial effect over the life‐time of the participants even if they have no apparent effect at school‐leaving age.
Monitoring heparin anticoagulation in the acute phase response
Authors: Uprichard James , Manning Richard A. , Laffan Michael A.
Published: March 2010

The anticoagulant effect of unfractionated heparin (UFH) is monitored using the activated partial thromboplastin time (APTT). An APTT of 1·5–2·5 times the control is usually taken as the therapeutic range and assumed to reflect an anti‐activated factor X (anti‐Xa) level of 0·35–0·7 u/ml. However, in some cases, despite administration of sufficient heparin to achieve a therapeutic anti‐Xa assay level, the APTT remains sub‐therapeutic. This ‘apparent heparin resistance’ is commonly due to high levels of factor VIII (FVIII). In these situations, the anti‐Xa is usually preferred for monitoring in order to avoid, what might be, dangerously high levels of heparin. We hypothesized that at high FVIII levels, the heparin resistance encountered may be genuine rather than apparent and that higher doses of heparin may indeed be needed for an equivalent anticoagulant effect. The relationship between heparin level, APTT and anticoagulant effect at different FVIII concentrations was determined using thrombelastography and the thrombin generation assay. Thromboelastographic and thrombin generation parameters concurred with APTT, demonstrating a genuine heparin resistance in the presence of high FVIII levels. This suggests that APTT may be a more accurate measure of anticoagulant effect in vivo than anti‐Xa.
A United Kingdom Haemophilia Centre Doctors’ Organization guideline approved by the British Committee for Standards in Haematology: guideline on the use of prophylactic factor VIII concentrate in children and adults with severe haemophilia A
Authors: Richards Michael , Williams Michael , Chalmers Elizabeth , Liesner Ri , Collins Peter , Vidler Vicky , Hanley John
Published: March 2010

Consensus‐based guidelines supported by the literature are presented on the role of prophylactic administration of factor VIII concentrate in children and adults with severe haemophilia A. The timing of initiation of prophylaxis, the choice of prophylactic regimen, monitoring, management of breakthrough bleeding and education of the patient and family are discussed.
Advances in the understanding of myeloma bone disease and tumour growth
Authors: Yaccoby Shmuel
Published: March 2010

Advances in multiple myeloma support the notion that the associated bone disease, characterized by increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and necessity of tumour progression. Osteoblastogenesis is suppressed by secreted inhibitors and dysregulation of cell‐surface ‘coupling’ factors on osteogenic cells. Osteoclastogenesis is increased as a consequence of osteoblast deactivation and of production of osteoclast‐activating factors. Osteoclasts express soluble and cell‐surface factors that stimulate myeloma growth, while osteoblasts produce bone‐building factors that restrain growth of myeloma cells that are dependent on the microenvironment; detailed molecular mechanisms are discussed. Experimental and clinical findings indicate that pharmacological and experimental osteoblast‐activating agents that effectively promote bone formation also reduce growth of myeloma cells within bone, seemingly by simultaneously stimulating osteoblastogenesis and restraining osteoclastogenesis. Unravelling mechanisms of myeloma bone disease expands horizons for developing novel interventions and also facilitates better understanding of the association between induction of osteolysis and disease progression.
The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A
Authors: WANG X. F. , ZHAO Y. Q. , YANG R. C. , WU J. S. , SUN J. , ZHANG X. S. , DING Q. L. , GE H. L. , WANG H. L.
Published: March 2010

Summary.  The prevalence of inhibitors in Chinese haemophiliacs has not yet been reported. The aim of this study was to identify the prevalence of factor VIII (FVIII) inhibitors among haemophiliacs who are treated only with plasma‐derived FVIII (pdFVIII), cryoprecipitate or fresh frozen plasma (FFP), and tried to explore the relationship between the generation of inhibitors and particular FVIII deficiency genotypes. Clinical information and blood samples of 1435 patients with haemophilia A (HA) were collected by six haemophilia centres in China. The Nijmegen modification of the Bethesda assay was used to detect inhibitors. Multiplex PCR, long‐range PCR and direct sequencing were performed for genotyping. The overall prevalence of inhibitors in Chinese HA patients was 3.9% and the prevalence of severe haemophiliacs was 4.3%; 18 of the 56 patients with inhibitors had high titres. A total of 38 different mutations were identified in the 55 patients with inhibitors, including 15 intron 22 and 3 intron 1 inversions, seven large deletions, 14 small deletion/insertions, seven nonsense mutations, one splice site mutations and eight missense mutations. Of 38 mutations, 28 were novel. Patients with large deletions and nonsense mutations were prone to have high titre inhibitors, with incidence rates of 57.1% (4/7) and 42.9% (3/7), respectively. In conclusion, the prevalence of inhibitors in Chinese HA patients is much lower than that reported for other ethnic groups and the large deletion and nonsense mutations are high risk factors for high titre inhibitor development.
Therapeutic effects of an indoor gardening programme for older people living in nursing homes
Authors: Tse Mimi Mun Yee
Published: March 2010

Aims.  To explore the activities of daily living and psychological well‐being of older people living in nursing homes and also to examine the effectiveness of a gardening programme in enhancing socilaisation and life satisfaction, reducing loneliness and promoting activities of daily living for older people living in nursing homes.

Background.  Life in nursing homes can mean very limited physical and social activity, leading to further decline in function for many older people.

Design.  This was a quasi‐experimental pre and posttest control group design.

Methods.  Older people from nursing homes were invited to join the eight week indoor gardening programme (experimental group), while older people in other nursing homes were treated as the control group; they received regular care without the eight week indoor gardening programme. There were 26 older people (25 female and one male; mean age 85 years) in the experimental group and 27 (20 female and seven male; mean age 82 years) in the control group. Demographic data including age, gender, educational level and financial situation were collected, in addition to information regarding life satisfaction, loneliness, physical activity and social network situation, before and after the eight week indoor gardening programme for both the experimental and control groups. Also, details of experimental group subjects’ experience of the indoor gardening programme were elicited using open‐ended questions.

Results.  There were significant improvements in life satisfaction and social network and a significant decrease in perception of loneliness for older people in the experimental group after the eight week indoor gardening programme, while the activities of daily living were unchanged for both groups after the programme.

Relevance to clinical practice.  Given the positive effects of gardening activities, it is suggested that they be promoted more widely among nursing home residents.