bluuebunny/crossref_metadata_2025 huggingface dataset:
Densification and Grain Growth of Fe‐Doped and Fe/Y Codoped Alumina: Effect of Fe Valency
Authors: Drahus M. D. , Chan H. M. , Rickman J. M. , Harmer M. P.
Published: December 2005

The effect of iron and iron/yttrium codoping on the densification and grain growth of ultra high‐purity (99.995%) fine‐grained alumina has been studied. The experiments were carried out under both oxidizing (flowing air) and reducing conditions (N2/H2 mixture, pO2∼5.1 × 10−14). For studies carried out in air, relative to undoped alumina, the addition of 1000 ppm Fe was found to reduce the densification rate by a factor of 5 and also retard the grain growth rate. This result, which was consistent with tensile creep data obtained in a separate study, was attributed to the retardation of grain‐boundary diffusive processes by segregating Fe(III) ions. In contrast, under reducing conditions the 1000 ppm Fe‐ doped samples exhibited an increase in the densification rate of 2.5 orders of magnitude over that of the undoped samples. In the case of the codoped compositions (1000 ppm Fe/1000 ppm Y), for heat treatment in air, the densification behavior did not differ significantly from that of samples singly doped with Y (1000 ppm). However, under reducing conditions, the presence of the Fe2+ in the samples appeared to compensate for the retarding effect of the yttrium, such that the densification rate of the codoped samples was comparable with that of the undoped material. A mechanism based on compensating point defects is invoked to rationalize the more rapid kinetics under reducing conditions.
Visual impairment in Finnish Usher syndrome type III
Authors: Plantinga Rutger F. , Pennings Ronald J. E. , Huygen Patrick L. M. , Sankila Eeva‐Marja , Tuppurainen Kaija , Kleemola Leenamaija , Cremers Cor W. R. J. , Deutman August F.
Published: December 2005

Purpose:  To evaluate visual impairment in Finnish Usher syndrome type 3 (USH3) and compare this with visual impairment in Usher syndrome types 1b (USH1b) and 2a (USH2a).

Methods:  We carried out a retrospective study of 28 Finnish USH3 patients, 24 Dutch USH2a patients and 17 Dutch USH1b patients. Cross‐sectional regression analyses of the functional acuity score (FAS), functional field score (FFS*) and functional vision score (FVS*) related to age were performed for all patients. The FFS* and FVS* were calculated using the isoptre V‐4 test target instead of the usual III‐4 target. Statistical tests relating to regression lines and Student's t‐test were used to compare between USH3 patients and the other genetic subtypes of Usher syndrome.

Results:  Cross‐sectional analyses revealed significant deterioration in the FAS (1.3% per year), FFS* (1.4% per year) and FVS* (1.8% per year) with advancing age in the USH3 patient group. At a given age the USH3 patients showed significantly poorer visual field function than the USH2a patients.

Conclusions:  The rate of deterioration in visual function in Finnish USH3 patients was fairly similar to that in Dutch USH1b or USH2a patients. At a given age, visual field impairment in USH3 patients was similar to that in USH1b patients but poorer than in USH2a patients.
Behavioral motor dysfunction in Kv3‐type potassium channel‐deficient mice
Authors: Joho R. H. , Street C. , Matsushita S. , Knöpfel T.
Published: November 2005

The voltage‐gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3‐null allele‐dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657–6665, Genes, Brain Behav 3, 90–100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317–3327). Here, we describe two sensitive and non‐invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3‐mutant mice. In contrast to wildtype and Kv3.1‐single mutants, Kv3.3‐single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3‐null allele‐dependent gait alterations. Although the Kv3‐null allele‐dependent gait changes correlate with reduced motor performance, they appear to not affect the training‐induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.
Why do People Believe Weird Things?
Authors: Matthews Robert
Published: November 2005

From claims that NASA faked the moon landings to creationist rejections of evolution, many people hold views that fl y in the face of evidence. By refusing to be swayed by hard facts, such people are clearly irrational—or are they? Robert Matthews argues that the frustration of scientists over the persistence of “irrational” beliefs highlights their own misconceptions about the process of inference.
Comprehensive screening of CREB‐binding protein gene mutations among patients with Rubinstein‐Taybi syndrome using denaturing high‐performance liquid chromatography
Authors: Udaka Toru , Samejima Hazuki , Kosaki Rika , Kurosawa Kenji , Okamoto Nobuhiko , Mizuno Seiji , Makita Yoshio , Numabe Hironao , Toral Joaquín Fernández , Takahashi Takao , Kosaki Kenjiro
Published: November 2005

ABSTRACT  Mutations in the CREBBP (CREB‐binding protein gene) cause Rubinstein‐Taybi syndrome (RSTS). At present, however, genetic testing of CREBBP is not commonly applied in clinical settings because the currently available assays are technically and financially demanding, mainly because of the size of the gene. In the present study, we took advantage of a highly sensitive and specific, automated denaturing high‐performance liquid chromatography (DHPLC) technique. First, we developed a DHPLC‐based protocol to analyze the entire coding region of CREBBP. Second, we analyzed genetic samples from 21 RSTS patients using DHPLC. The coding region was amplified by 41 primer pairs, all of which have the same cycling conditions, aliquoted on a 96‐well format PCR plate. In this manner, all the exons were simultaneously amplified using a single block in a PCR machine. We then wrote a computer script to analyze all the PCR amplicons generated from various portions of the CREBBP gene in a serial manner at optimized conditions determined individually for each amplicon. Heterozygous CREBBP mutations were identified in 12 of the 21 patients: five frameshift mutations, three nonsense mutations, two splice‐site mutations, and two missense mutations. The resulting detection rate of 57% was comparable to the outcome of previous studies. The relatively high detection rate in the present study demonstrates the enhanced sensitivity of the DHPLC‐based mutation analysis, as exemplified by mutation analyses of other genes. The implementation of similar methodologies for other dysmorphic syndromes will help medical geneticists to confirm their clinical impressions and to provide accurate genetic counseling for patients and their families.
Elevated susceptibility of newborn as compared with young rats to 2‐tert‐butylphenol and 2,4‐di‐tert‐butylphenol toxicity
Authors: Hirata‐Koizumi Mutsuko , Hamamura Masao , Furukawa Hiromi , Fukuda Naemi , Ito Yoshihiko , Wako Yumi , Yamashita Kotaro , Takahashi Mika , Kamata Eiichi , Ema Makoto , Hasegawa Ryuichi
Published: November 2005

ABSTRACT  In order to determine the susceptibility of newborn rats to 2‐tert‐butylphenol (2TBP) and 2,4‐di‐tert‐butylphenol (DTBP) toxicity, studies were conducted with oral administration from postnatal days (PND) 4 to 21 and the findings were compared with results for young rats exposed from 5 or 6 weeks of age for 28 days. In the newborn rats, specific effects on physical and sexual development and reflex ontogeny were not observed. While there were no clear differences in toxicological profiles between newborn and young rats, the no‐observed‐adverse‐effect levels (NOAELs) differed markedly. For 2TBP, clinical signs such as ataxic gait, decrease in locomotor activity and effects on liver, such as increase in organ weight, were observed and the NOAELs were concluded to be 20 and 100 mg/kg/day in newborn and young rats, respectively. Based on hepatic and renal toxicity (histopathological changes and increase in organ weight with blood biochemical changes), the respective NOAELs for DTBP were concluded to be 5 and 20 mg/kg/day. Therefore, the susceptibility of newborn rats to 2TBP and DTBP was found to be 4–5 times higher than that of young rats.
Acute Renal Effects of Intravenous Bisphosphonates in the Rat
Authors: Pfister Thomas , Atzpodien Elke , Bohrmann Bernd , Bauss Frieder
Published: December 2005

Abstract:Bisphosphonates are potent osteoclast inhibitors that have been associated with renal toxicity following rapid intravenous administration of high doses, which was hypothesised to be due to precipitation of bisphosphonate aggregates or complexes in the kidney. Five studies were conducted in rats investigating the characteristics of bisphosphonate‐related acute renal effects. These studies included single intravenous injections of the nitrogen‐containing bisphosphonates (1) ibandronate (1–20 mg/kg), or (2) zoledronate (1–10 mg/kg); (3) a single nephrotoxic dose of the non‐nitrogen‐containing bisphosphonate, clodronate (2×200 mg/kg intraperitoneal injection); (4) a single low dose of ibandronate (1 mg/kg); (5) a single high dose of zoledronate (10 mg/kg). Clinical biochemistry and kidney histopathology were performed 1 and/or 4 days after bisphosphonate dosing. The proximal convoluted tubules were the primary target for renal injury. Tubular degeneration and single cell necrosis of the these tubules were observed with all three bisphosphonates on the fourth, but not the first day after dosing. Differences between the bisphosphonates in the type and/or localisation of the lesions were apparent. Granular deposits in the lumen of distal tubules were apparent with the highest dose of zoledronate (10 mg/kg). However, intraluminal debris was proteinaceous with no evidence of any precipitation of bisphosphonate, or formation of aggregates or complexes in the kidney. Generally, biochemical parameters of renal safety and urinary enzymes did not differ significantly from controls. In summary, bisphosphonate‐related renal changes did not appear to be due to the precipitation, aggregation or complexation of bisphosphonate, and biochemical parameters of renal safety did not reliably detect this renal injury.
36 kDa Glycoprotein Isolated from Rhus verniciflua Stokes Inhibits G/GO‐Induced Mitochondrial Apoptotic Signal Pathways in BNL CL.2 Cells
Authors: Lee Sei‐Jung , Oh Phil‐Sun , Lim Kwang , Lim Kye‐Taek
Published: December 2005

Abstract: Rhus verniciflua Stokes is one of the medicinal plants traditionally used to heal and treat hepatic and inflammatory diseases. We found that a glycoprotein isolated from the fruit has a molecular weight of 36 kDa and consists of a carbohydrate component (38.75%) and a protein (61.25%), and that the glycoprotein has a strong scavenging activity against hydroxyl radicals without any pro‐oxidant activity in the cell‐free system. In glucose/glucose oxidase (G/GO)‐induced BNL CL.2 cells, the results showed that Rhus verniciflua Stokes glycoprotein has dose‐dependent blocking activities against G/GO‐induced cytotoxicity and apoptosis, increasing the glutathione (GSH) peroxidase activity. In the activity of the mitochondrial apoptotic mediators (cytochrome c, caspases and poly(ADP‐ribose)polymerase (PARP)), the glycoprotein (100 μg/ml) showed an inhibitory effect on cytochrome c release, caspase‐9/3 activation, and PARP cleavage. Moreover, Rhus verniciflua Stokes glycoprotein has a stimulating effect on the nitric oxide production. Here, we speculate that this glycoprotein is one of the natural antioxidants and of the modulators of apoptotic signal pathways in BNL CL.2 cells.
Effects of Concurrent Exposure to Tributyltin and 1,1‐Dichloro‐2,2 bis (p‐chlorophenyl) ethylene (p,p′‐DDE) on Immature Male Wistar Rats
Authors: Makita Yuji , Omura Minoru , Tanaka Akiyo , Kiyohara Chikako
Published: December 2005

Abstract: Tributyltin and 1, 1‐dichloro‐2, 2 bis (p‐chlorophenyl) ethylene (p,p′‐DDE) have been ubiquitously distributed over the world. In Japan, p,p′‐DDE and tributyltin are ingested through marine products, in which these substances are accumulated through bio‐concentration and the food chain. However, the consequence of potential combined hazards of these substances remains unknown. Therefore, the effects of concurrent exposure to 125 ppm p,p′‐DDE and 25 ppm tributyltin were investigated in immature male Wistar rats by oral administration during puberty. In this study, tributyltin promoted the growth of pubertal male rats, while p,p′‐DDE itself did not affect the growth but inhibited the growth enhancement by tributyltin. Furthermore, tributyltin reduced thymus weight but p,p′‐DDE also prevented this weight reduction. Neither development of male sexual accessory organs nor sexual maturation was affected even by concurrent exposure to p,p′‐DDE and tributyltin. No significant changes of serum testosterone, luteinizing hormone, follicle‐stimulating hormone concentrations, and epididymal sperm numbers were observed with the administration of p,p′‐DDE and/or tributyltin. These results indicate that sexual maturation, male reproductive organ development and sperm production is scarcely affected in immature male Wistar rats even by concurrent exposure to p,p′‐DDE and tributyltin at a daily dose of ca. 2 mg/kg tributyltin and 10 mg/kg p,p′‐DDE. Moreover, the simultaneous administration of p,p′‐DDE with tributyltin counterbalanced the effects that were attributed to tributyltin alone.
Prooxidant Action of Hinokitiol: Hinokitiol‐Iron Dependent Generation of Reactive Oxygen Species
Authors: Murakami Keiko , Ohara Yoshihiro , Haneda Miyako , Tsubouchi Ryoko , Yoshino Masataka
Published: December 2005

Abstract: Hinokitiol (α‐thujaplicin, 2‐hydroxy‐4‐isopropyl‐2,4,6‐cycloheptatrien‐1‐one), one of the tropolone compounds purified from the woods of Chamaecyparis and Thujopsis (hinoki and hiba), produced reactive oxygen species as a complex with transition metals. Hinokitiol/iron complex inactivated aconitase, the most sensitive enzyme to reactive oxygen, whereas it did not affect aldolase and glyceraldehyde 3‐phosphate dehydrogenase. The inactivation of aconitase was iron‐dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species and superoxide dismutase, suggesting that the hinokitiol/iron‐mediated generation of superoxide anion is responsible for the inactivation of aconitase. Addition of hinokitiol effectively enhanced the ascorbate/copper‐mediated formation of 8‐hydroxy‐2′‐deoxyguanosine in DNA. Cytotoxic effect of hinokitiol can be explained by its prooxidant properties: hinokitiol/transition metal complex generates reactive oxygen species causing inactivation of aconitase and production of hydroxyl radical resulting in the formation of DNA base adduct.
Pathophysiology and Treatment of Acute Pancreatitis: New Therapeutic Targets – A Ray of Hope?
Authors: Felderbauer Peter , Müller Christophe , Bulut Kerem , Belyaev Orlin , Schmitz Frank , Uhl Waldemar , Schmidt Wolfgang E.
Published: December 2005

Abstract: Acute pancreatitis is a life‐threatening disease with putatively high mortality rates, particularly in the setting of systemic inflammatory response and multiple organ failure when superinfection of necrosis occurs. Although the APACHE II and Ranson score are widely accepted as clinical scores to predict the prognosis, current medical treatment is still based upon state of the art intensive care treatment largely unrelated to the pathogenesis of the disease. The mechanisms by which premature enzyme activation and autodigestion of the pancreatic gland is triggered and maintained are still ill‐defined. It is well known that activation of chemokines, cytokines and pancreatic enzymes characterize the cause of the disease, but disease‐phase specific treatment attempts have thus far not resulted in successful molecular based medical treatments. The current summary describes the novel understanding in the pathophysiology of acute pancreatitis with special emphasis on specific disease phases. It outlines promising and novel experimental and medical therapeutic approaches which might become clinical targets and successful strategies to significantly reduce pancreatitis‐associated mortality rates.
Transgenic Paulownia Expressing shiva‐1 Gene Has Increased Resistance to Paulownia Witches' Broom Disease
Authors: DU Tao , WANG Yao , HU Qin‐Xue , CHEN Jie , LIU Sheng , HUANG Wen‐Jin , LIN Mu‐Lan
Published: December 2005

Abstract: Stem segments from diseased Paulownia tomentosa ×P. fortunei and leaves from healthy control were transformed with the expression vector p438PRSI via Agrobacterium tumefaciens. The p43 8PRSI vector contained shiva‐1 gene, which encodes an antibacterial peptide under the control of a CaMV35S promoter. The regenerated plants from transformed explants were planted in a greenhouse and nursery. PCR and Southern blotting analysis showed that the shiva‐1 gene was successfully integrated into the Paulownia genome. Transcription of the integrated shiva‐1 gene was confirmed by RT‐PCR. Bioassay in the green house and phytoplasma DNA‐dot blotting demonstrated that resistance to Paulownia witch's broom disease (PWB) increased significantly in shiva‐1 ‐transgenic Paulownia. Further investigations indicated that higher Shiva‐1 expression correlated with fewer phytoplasma and less symptoms in diseased transgenic Paulownia. Together, our findings strongly suggest that breeding shiva‐1‐Paulownia is an effective strategy to control PWB disease.

(Managing editor: Li‐Hui ZHAO)
SPINNING DISC MEASUREMENT OF TWO‐STAGE CLEANING OF HEAT TRANSFER FOULING DEPOSITS OF MILK
Authors: MORISON KEN R. , LARSEN SUSAN
Published: December 2005

The efficient and effective cleaning of milk protein – based deposits from heat transfer equipment is essential in the dairy industry. The aim of this study was to evaluate the effectiveness of two‐stage cleaning using acid and caustic. Stainless steel discs were fouled during heat transfer by skimmed milk and whey protein. The discs were then cleaned with acid and sodium hydroxide solutions under controlled mass transfer conditions using spinning disc techniques. The use of 0.5% nitric acid, and a commercial acid known as Triplex, as a rinse before caustic cleaning increased the cleaning rate by 2.5 times. The foulant was found to swell about 40% and calcium was leached out within 5 min after exposure to acid. The acid treatment is believed to cause a reduction in the viscosity, and hence an increase in dissolution, of the gel layer formed when caustic cleaning takes place.
PREDICTION OF SPRAY‐DRIED PRODUCT QUALITY USING TWO SIMPLE DRYING KINETICS MODELS
Authors: PATEL KAMLESH C. , CHEN XIAO DONG
Published: December 2005

Increasing attention has been given to spray drying because of its popularity in the manufacturing of various powders with prerequisite quality. A large number of theoretical and experimental studies have been published during the last five decades to study spray‐drying operations. Despite this progress, there is still lack of information on the selection of an accurate and simple drying kinetics model to characterize the droplet drying process. This article has particularly focused on the comparison of two simple and effective drying kinetics models: the characteristic drying‐rate curve and reaction‐engineering approach (REA) models. This article reported mathematical models that can be used to design the spray‐drying operation and to predict the particle's characteristics for realistic dryer‐wide situations. Both the physical and biochemical quality attributes were investigated regarding their sensitivity to the model parameters used in the two drying kinetics models. The REA model was found to deliver more realistic predictions during the modeling of the droplet drying process for all the sets of conditions tested.
EXPERIMENTAL AND NEURAL NETWORK PREDICTION OF THE PERFORMANCE OF A SOLAR TUNNEL DRIER FOR DRYING JACKFRUIT BULBS AND LEATHER
Authors: BALA B.K. , ASHRAF M.A. , UDDIN M.A. , JANJAI S.
Published: December 2005

This article presents the field performance of a solar tunnel drier for drying jackfruit bulbs and leather. The drier consists of a transparent plastic‐covered flat‐plate collector and a drying tunnel connected in series to supply hot air directly into the drying tunnel using two direct‐current fans operated by a photovoltaic module. The drier has a loading capacity of 120–150 kg of fruits. Sixteen experimental runs were conducted for drying jackfruit bulbs and leather (eight runs each). The use of a solar tunnel drier led to a considerable reduction in drying time and dried products of better quality in comparison to products dried under the sun. A multilayered neural network approach was used to predict the performance of the solar tunnel drier. Using solar drying data of jackfruit bulbs and leather, the model has been trained using backpropagation algorithm. The prediction of the performance of the drier was found to be excellent after it was adequately trained. It can be used to predict the potential of the drier for different locations, and can also be used in a predictive optimal control algorithm.
Synaptobrevin2‐expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis
Authors: Crippa Debora , Schenk Ursula , Francolini Maura , Rosa Patrizia , Verderio Claudia , Zonta Micaela , Pozzan Tullio , Matteoli Michela , Carmignoto Giorgio
Published: December 2005

The SNARE‐dependent exocytosis of glutamate‐containing vesicles in astrocytes is increasingly viewed as an important signal at the basis of the astrocyte‐to‐neurone communication system in the brain. Here we provide further insights into the molecular features and dynamics of vesicles in cultured astrocytes. We found that immunoisolated synaptobrevin2 vesicles are clear vesicles quite heterogenous in size and contain the vesicular glutamate transporter v‐Glut‐2. Moreover, they are immunopositive for synaptotagmin IV, for AMPA receptor subunits GluR2,3 and, to a lesser extent, for GluR1. We also provide direct evidence for the functional expression of v‐Glut‐2 in astrocytes and demonstrate that synaptobrevin2‐positive vesicles can specifically take up (3H)l‐glutamate via a bafilomycin‐sensitive mechanism. Finally, by time lapse confocal microscopy, we show that a subpopulation of vesicles (tagged with a synaptobrevin2–EGFP chimera) is highly mobile and can fuse with the plasma membrane, preferentially at the level of the astrocyte processes, in a Ca2+‐dependent manner. These latter observations, together with the evidence reported here for the expression of functional v‐Glut‐2 in synaptobrevin2‐positive vesicles, provide a molecular basis for regulated exocytosis in astrocyte.
Synapsin‐regulated synaptic transmission from readily releasable synaptic vesicles in excitatory hippocampal synapses in mice
Authors: Hvalby Øivind , Jensen Vidar , Kao Hung‐Teh , Walaas S. Ivar
Published: December 2005

The effects of synapsin proteins on synaptic transmission from vesicles in the readily releasable vesicle pool have been examined by comparing excitatory synaptic transmission in hippocampal slices from mice devoid of synapsins I and II and from wild‐type control animals. Application of stimulus trains at variable frequencies to the CA3‐to‐CA1 pyramidal cell synapse suggested that, in both genotypes, synaptic responses obtained within 2 s stimulation originated from readily releasable vesicles. Detailed analysis of the responses during this period indicated that stimulus trains at 2–20 Hz enhanced all early synaptic responses in the CA3‐to‐CA1 pyramidal cell synapse, but depressed all early responses in the medial perforant path‐to‐granule cell synapse. The synapsin‐dependent part of these responses, i.e. the difference between the results obtained in the transgene and the wild‐type preparations, showed that in the former synapse, the presence of synapsins I and II minimized the early responses at 2 Hz, but enhanced the early responses at 20 Hz, while in the latter synapse, the presence of synapsins I and II enhanced all responses at both stimulation frequencies. The results indicate that synapsins I and II are necessary for full expression of both enhancing and decreasing modulatory effects on synaptic transmission originating from the readily releasable vesicles in these excitatory synapses.
A Clonogenic Bone Marrow Progenitor Specific for Macrophages and Dendritic Cells
Authors: Fogg Darin K. , Sibon Claire , Miled Chaouki , Jung Steffen , Aucouturier Pierre , Littman Dan R. , Cumano Ana , Geissmann Frederic
Published: December 2005

Macrophages and dendritic cells (DCs) are crucial for immune and inflammatory responses and belong to a network of cells that has been termed the mononuclear phagocyte system (MPS). However, the origin and lineage of these cells remain poorly understood. Here, we describe the isolation and clonal analysis of a mouse bone marrow progenitor that is specific for monocytes, several macrophage subsets, and resident spleen DCs in vivo. It was also possible to recapitulate this differentiation in vitro by using treatment with the cytokines macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Thus, macrophages and DCs appear to renew from a common progenitor, providing a cellular and molecular basis for the concept of the MPS.
Synthesis of 2-Substituted 6-(Hydroxymethyl)purine Bases and Nucleosides
Authors: Šilhár Peter , Pohl Radek , Votruba Ivan , Hocek Michal
Published: November 2005

A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines or N-protected 2-amino-6-halopurines with (benzoyloxymethyl)zinc iodide followed by deprotection. Regioselective hydroxymethylations of 2,6-dihalopurines were also studied and used for the synthesis of 2-chloro-6-(hydroxymethyl)- or 2,6-bis(hydroxymethyl)purines. The 6-(hydroxymethyl)purine ribonucleoside 5f exerted high cytostatic effect and moderate inhibition of adenosine deaminase, while all the other derivatives were much less effective or entirely inactive.
Formal Total Syntheses of Crocacin A-D
Authors: Besev Magnus , Brehm Christof , Fürstner Alois
Published: November 2005

A concise route to the common polyketide fragment5of crocacin A-D (1-4) is presented which has previously been converted into all members of this fungicidal and cytotoxic family of dipeptidic natural products by various means. Our synthesis features asyn-selective titanium aldol reaction controlled by a valinol-derived auxiliary, a zinc-mediated, palladium-catalyzedanti-selective addition of propargyl mesylate10to the chiral aldehyde9, as well as a comparison of palladium-catalyzed Stille and Suzuki cross-coupling reactions for the formation of the diene moiety of the target.
Toluene Dioxygenase-Mediated Oxidation of Bromo(methylsulfanyl)benzenes. Absolute Configuration of Metabolites and Evaluation of Chemo- and Regioselectivity Trends
Authors: Finn Kevin J. , Pavlyuk Oksana , Hudlický Tomáš
Published: November 2005

A series of 2-, 3-, and 4-bromo-1-(methylsulfanyl)benzenes was subjected to whole-cell fermentation withEscherichia coliJM 109 (pDTG601), a recombinant strain that expresses toluene dioxygenase. New metabolites were isolated and their structure and absolute configuration determined by chemical and spectral methods. Experimental details are provided for all new compounds and directing trends in the enzymatic oxidation of substituted aromatics are discussed along with projected applications of these metabolites in asymmetric synthesis.
Understanding parental motivators and barriers to uptake of child poison safety strategies: a qualitative study
Authors: Gibbs L , Waters E , Sherrard J , Ozanne-Smith J , Robinson J , Young S , Hutchinson A
Published: December 2005

Objectives:To develop an understanding of factors acting as barriers and motivators to parental uptake of child poison safety strategies.

Design:A qualitative study involving semistructured interviews and focus groups. A grounded theory approach was used for the collection and analysis of data.

Participants:Sixty five parents of children under 5 years of age, some of whom had experienced an unintentional child poisoning incident.

Results:A range of knowledge based, environmental, and behavioral barriers to comprehensive parental uptake of poison safety practices were identified. As a result there tended to be only partial implementation of safety initiatives in the home. Selection of safety practices was often guided by the interests and behaviors of the child. This made the child vulnerable to changes in the home environment, inadequate supervision, and/or shifts in their own behavior and developmental ability. Personal or vicarious exposure of a parent to a child poisoning incident was a significant motivator for parental review of safety practices.

Conclusion:Environmental measures targeting child resistant containers, warning labels, and lockable poisons cupboards will support parents’ efforts to maintain poison safety. Additional education campaigns using stories of actual poisoning incidents may help to increase awareness of risk and encourage increased uptake.
Attributable risk of alcohol and other drugs for crashes in the transit industry
Authors: Cunradi C B , Ragland D R , Greiner B , Klein M , Fisher J M
Published: December 2005

Objective:To estimate the impact of employee alcohol and drug use on crashes in the transit industry from 1995–2000.

Design:Secondary analysis of federally mandated post crash and random alcohol and drug testing results.

Setting:The US transit industry.

Subjects:Transit industry employees.

Main outcome measures:Relative risk (RR), population attributable risk (PAR), and population attributable risk percentage (PAR%).

Results:For alcohol testing, the estimated PAR% ranged from 0.02% (1999) to 0.03% (1995). For drug testing, the estimated PAR% ranged from 0.38% (1998) to 0.67% (1997). Based on these calculations, the estimated number of crashes per 1000 crashes attributable to alcohol was less than one during 1995–2000, and the number attributable to drugs ranged from about four to about six. The number of crashes attributable to either alcohol or drugs did not vary greatly from 1995–2000. Estimated rates of crashes attributable to alcohol or drugs were substantially lower in 1995, the first year of testing, than had been projected based on previous estimates, and did not show substantial change from 1995–2000.

Conclusions:Approaches to transit safety based on reducing employee use of alcohol and other drugs have modest potential for reducing number of fatalities, injuries, and crashes.
The global burden of non-conflict related firearm mortality
Authors: Richmond T S , Cheney R , Schwab C W
Published: December 2005

Objective:Understanding global firearm mortality is hindered by data availability, quality, and comparability. This study assesses the adequacy of publicly available data, examines populations for whom firearm mortality data are not publicly available, and estimates the global burden of non-conflict related firearm mortality.

Design:The design is a secondary analysis of existing data. A dataset of countries, populations, economic development, and geographic regions was created, using United Nations 2000 world population data and World Bank classifications of economic development and global regions. Firearm mortality data were obtained from governmental vital statistics reported by the World Health Organization and published survey data. A qualitative review of literature informed estimates for the 15 most populous countries without firearm death data. For countries without data, estimates of firearm deaths were made using quartiles of observed rates and peer reviewed literature.

Main outcome measures:Non-conflict related firearm deaths.

Results:Global non-conflict related firearm deaths were estimated to fall between 196 000 and 229 000, adjusted to the year 2000. 162 800 firearm deaths adjusted for the year 2000 came from countries reporting data and represent 35% of the world’s 186 countries. Public data are not available for 122 of these 186 countries, representing more than three billion (54%) of the world’s population, predominately in lower and lower middle income countries. Estimates of firearm death for those countries without data range from 33 200 to 66 200.

Conclusions:This study provides evidence that the burden of firearm related mortality poses a substantial threat to local and global health.
Injury prevention practices as depicted in G and PG rated movies: the sequel: Table 1
Authors: Ramsey L T , Ballesteros M F , Pelletier A R , Wolf J
Published: December 2005

Objective:To determine whether the depiction of injury prevention practices in children’s movies released during 1998–2002 is different from an earlier study, which found that characters were infrequently depicted practicing recommended safety behaviors.

Methods:The top 25 G (general audience) and PG (parental guidance suggested) rated movies per year from 1998–2002 comprised the study sample. Movies or scenes not set in the present day, animated, documentary, or not in English were excluded; fantasy scenes were also excluded. Injury prevention practices of motor vehicle occupants, pedestrians, bicyclists, and boaters were recorded for characters with speaking roles.

Results:Compared with the first study, the proportion of scenes with characters wearing safety belts increased (27%v35%, p<0.01), the proportion of scenes with characters wearing personal flotation devices decreased (17%v0%, p<0.05), and no improvement was noted in pedestrian behavior or use of bicycle helmets.

Conclusions:Despite a modest increase in safety belt usage, appropriate injury prevention practices are still infrequently shown in top grossing G and PG rated movies. The authors recommend that the entertainment industry incorporate safe practices into children’s movies. Parents should call attention to the depiction of unsafe behaviors in movies and educate children to follow recommended safety practices.
When one is not enough: prevalence and characteristics of homes not adequately protected by smoke alarms
Authors: Peek-Asa C , Allareddy V , Yang J , Taylor C , Lundell J , Zwerling C
Published: December 2005

Objective:The National Fire Protection Association (NFPA) has specific recommendations about the number, location, and type of smoke alarms that are needed to provide maximum protection for a household. No previous studies have examined whether or not homes are completely protected according to these guidelines. The authors describe the prevalence and home characteristics associated with compliance to recommendations for smoke alarm installation by the NFPA.

Design, setting, and subjects:Data are from the baseline on-site survey of a randomized trial to measure smoke alarm effectiveness. The trial was housed in a longitudinal cohort study in a rural Iowa county. Of 1005 homes invited, 691 (68.8%) participated.

Main outcome measures:Information about smoke alarm type, placement, and function, as well as home and occupant characteristics, was collected through an on-site household survey.

Results:Although 86.0% of homes had at least one smoke alarm, only 22.3% of homes (approximately one in five) were adequately protected according to NFPA guidelines. Fourteen percent of homes had no functioning smoke alarms. More than half of the homes with smoke alarms did not have enough of them or had installed them incorrectly, and 42.4% of homes with alarms had at least one alarm that did not operate. Homes with at least one high school graduate were nearly four times more likely to be fully protected. Homes that had multiple levels, a basement, or were cluttered or poorly cleaned were significantly less likely to be fully protected.

Conclusion:These findings indicate that consumers may not be knowledgeable about the number of alarms they need or how to properly install them. Occupants are also not adequately maintaining the alarms that are installed.
Informal medicine: ethical analysis
Authors: Leavitt F J , Peleg R , Peleg A
Published: November 2005

Context:Doctors have been known to treat or give consultation to patients informally, with none of the usual record keeping or follow up. They may wish to know whether this practice is ethical.

Objective:To determine whether this practice meets criteria of medical ethics.

Design:Informal medicine is analysed according to standard ethical principles: autonomy, beneficence and non-maleficence, distributive and procedural justice, and caring.

Setting:Hospital, medical school, and other settings where patients may turn to physicians for informal help.

Conclusion:No generalisation can be made to the effect that informal medicineisoris notethical. Each request for informal consultation must be considered on its own merits.

Guidelines:Informal medicine may be ethical if no payment is involved, and when the patient is fully aware of the benefits and risks of a lack of record keeping. When an informal consultation does not entail any danger to the patient or others, the physician may agree to the request. If, however, any danger to the patient or others is foreseen, then the physician must insist on professional autonomy, and consider refusing the request and persuading the patient to accept formal consultation. If a reportable infectious disease, or other serious danger to the community, is involved, the physician should refuse informal consultation or treatment, or at least make a proper report even if the consultation was informal. If agreeing to the request will result in an unfair drain on the physician’s time or energy, he or she should refuse politely.
Quantitative aspects of informed consent: considering the dose response curve when estimating quantity of information: Figure 1
Authors: Lynöe N , Hoeyer K
Published: November 2005

Information is usually supposed to be a prerequisite for people making decisions on whether or not to participate in a clinical trial. Previously conducted studies and research ethics scandals indicate that participants have sometimes lacked important pieces of information. Over the past few decades the quantity of information believed to be adequate has increased significantly, and in some instances a new maxim seems to be in place: the more information, the better the ethics in terms of respecting a participant’s autonomy. The authors hypothesise that the dose-response curve from pharmacology or toxicology serves as a model to illustrate that a large amount of written information does not equal optimality. Using the curve as a pedagogical analogy when teaching ethics to students in clinical sciences, and also in engaging in dialogue with research institutions, may promote reflection on how to adjust information in relation to the preferences of individual participants, thereby transgressing the maxim that more information means better ethics.
Tobacco document research reporting
Authors: Carter S M
Published: November 2005

Objective:To understand the use of internal tobacco industry documents in the peer reviewed health literature.

Design:Interpretive analysis of published research.

Sample:173 papers indexed in Medline between 1995 and 2004 that cited tobacco industry documents.

Analysis:Information about year published, journal and author, and a set of codes relating to methods reporting, were managed in N*Vivo. This coding formed the basis of an interpretation of tobacco document research reporting.

Results:Two types of papers were identified. The first used tobacco documents as the primary data source (A-papers). The second was dedicated to another purpose but cited a small number of documents (B-papers). In B-papers documents were used either to provide a specific example or to support an expansive contention. A-papers contained information about purpose, sources, searching, analysis, and limitations that differed by author and journal and over time. A-papers had no clear methodological context, but used words from three major traditions—interpretive research, positivist research, and history—to describe analysis.

Interpretation:A descriptive mainstream form of tobacco document reporting is proposed, initially typical but decreasing, and a continuum of positioning of the researcher, from conduit to constructor. Reporting practices, particularly from experienced researchers, appeared to evolve towards researcher as constructor, with later papers showing more complex purposes, diverse sources, and detail of searching and analysis. Tobacco document research could learn from existing research traditions: a model for planning and evaluating tobacco document research is presented.
Use of nicotine replacement therapy and the risk of acute myocardial infarction, stroke, and death
Authors: Hubbard R , Lewis S , Smith C , Godfrey C , Smeeth L , Farrington P , Britton J
Published: November 2005

Objective:To determine whether nicotine replacement therapy (NRT) is associated with an increased risk of acute myocardial infarction, acute stroke, or death.

Design:Self control case series analysis of data from The Health Improvement Network (THIN) to estimate the relative incidence of myocardial infarction and stroke in four 14 day periods before and after the first prescription for NRT.

Setting:THIN is a computerised general practice database.

Subjects:Patients contributing data to THIN.

Interventions:Observational study of NRT.

Main outcomes:Acute myocardial infarction, acute stroke, and death.

Results:33 247 individuals had been prescribed NRT, of whom 861 had had a myocardial infarction and 506 a stroke. There was a progressive increase in the incidence of first myocardial infarction in the 56 days leading up to the first NRT prescription (overall incidence ratio 5.55, 95% confidence interval (CI) 4.42 to 6.98), but the incidence fell after this time and was not increased in the 56 days after starting NRT (incidence ratio 1.27, 95% CI 0.82 to 1.97). The results were similar for second myocardial infarction and stroke, and for subgroups of people with pre-existing angina and hypertension. There were 960 deaths in our cohort during a mean follow up period of 2.6 years after starting NRT, with no evidence of an increased mortality in the 56 days after the NRT prescription (incidence ratio 0.86, 95% CI 0.60 to 1.23).

Conclusions:The use of NRT is not associated with any increase in the risk of myocardial infarction, stroke, or death.
Secondhand smoke exposure and risk following the Irish smoking ban: an assessment of salivary cotinine concentrations in hotel workers and air nicotine levels in bars
Authors: Mulcahy M , Evans D S , Hammond S K , Repace J L , Byrne M
Published: November 2005

Objective:To investigate whether the Irish smoking ban has had an impact on secondhand smoke (SHS) exposures for hospitality workers.

Design, setting, and participants:Before and after the smoking ban a cohort of workers (n  =  35) from a sample of city hotels (n  =  15) were tested for saliva cotinine concentrations and completed questionnaires. Additionally, a random sample (n  =  20) of city centre bars stratified by size (range 400–5000 square feet), were tested for air nicotine concentrations using passive samplers before and after the ban.

Main outcome measures:Salivary cotinine concentrations (ng/ml), duration of self reported exposures to secondhand smoke, air nicotine (μg/cubic metre).

Results:Cotinine concentrations reduced by 69%, from 1.6 ng/ml to 0.5 ng/ml median (SD 1.29; p < 0.005). Overall 74% of subjects experienced decreases (range 16–99%), with 60% showing a halving of exposure levels at follow up. Self reported exposure to SHS at work showed a significant reduction from a median 30 hours a week to zero (p < 0.001). There was an 83% reduction in air nicotine concentrations from median 35.5 µg/m3to 5.95 µg/m3(p < 0.001). At baseline, three bars (16%) were below the 6.8 μg/m3air nicotine significant risk level for lung cancer alone; at follow up this increased to 10 (53%).

Conclusions:Passive smoking and associated risks were significantly reduced but not totally eliminated. Exposure to SHS is still possible for those working where smoking is still allowed and those working where smoke may migrate from outdoor areas. Further research is required to assess the true extent and magnitude of these exposures.
Marketing to the marginalised: tobacco industry targeting of the homeless and mentally ill
Authors: Apollonio D E , Malone R E
Published: November 2005

Objectives:To describe the tobacco industry’s relationships with and influence on homeless and mentally ill smokers and organisations providing services to them.

Methods:Analysis of internal tobacco industry documents and journal articles.

Results:The tobacco industry has marketed cigarettes to the homeless and seriously mentally ill, part of its “downscale” market, and has developed relationships with homeless shelters and advocacy groups, gaining positive media coverage and political support.

Discussion:Tobacco control advocates and public health organisations should consider how to target programmes to homeless and seriously mentally ill individuals. Education of service providers about tobacco industry efforts to cultivate this market may help in reducing smoking in these populations.
BDD-BASED ANALYSIS OF GAPPED q-GRAM FILTERS
Authors: FONTAINE MARC , BURKHARDT STEFAN , KÄRKKÄINEN JUHA
Published: December 2005

Recently, there has been a surge of interest in gapped q-gram filters for approximate string matching. Important design parameters for filters are for example the value of q, the filter-threshold and in particular the shape (aka seed) of the filter. A good choice of parameters can improve the performance of a q-gram filter by orders of magnitude and optimizing these parameters is a nontrivial combinatorial problem. We describe a new method for analyzing gapped q-gram filters. This method is simple and generic. It applies to a variety of filters, overcomes many restrictions that are present in existing algorithms and can easily be extended to new filter variants. To implement our approach, we use an extended version of BDDs (Binary Decision Diagrams), a data structure that efficiently represents sets of bit-strings. In a second step, we define a new class of multi-shape filters and analyze these filters with the BDD-based approach. Experiments show that multi-shape filters can outperform the best single-shape filters, which are currently in use, in many aspects. The BDD-based algorithm is crucial for the design and analysis of these new and better multi-shape filters. Our results apply to the k-mismatches problem, i.e. approximate string matching with Hamming distance.