bluuebunny/crossref_metadata_2025 huggingface dataset:
The Simulation of Crime Control
Authors: de Lint Willem , Virta Sirpa , Deukmedjian John Edward
Published: July 2007

The authors argue that policing by consent is being displaced by policing by information control. This discomfiting adaptation in liberal democracies is possible in the shadow of asymmetrical, border-collapsing exceptionalism. It has also benefited from synoptic effects in which reference to the liberal democratic legacy substitutes for liberal democratic practices. Current technologies, as demonstrated in watch-listing, public relations operations, and fourth-generation training, exemplify ironic homage to a consent and democracy. These take for granted the loss of innocence: There is no “real” (democracy, order, control) but rather impressions, which require effective simulations. The article concludes with the contention that today it is control, not justice, that must be “seen to be done.”
Public Attitudes Toward Urban Trees and Supporting Urban Tree Programs
Authors: Yaoqi Zhang  , Hussain Anwar , Jinyang Deng  , Letson Neil
Published: July 2007

In this article, we analyze survey responses regarding Alabama urban residents' attitudes toward urban trees and the provision and maintenance of urban forest by federal, state, and local governments, as well as personal willingness to volunteer and donate money in support of urban tree programs and activities. Using ordered probit analysis, our results showed that individuals who are aware of forestry-related programs, hold a full-time job, belong in the age group of younger than 56 years, and earn an annual income greater than U.S. $75,000, have a positive relationship with willingness of donating money and voluntarily contributing time toward urban forestry programs and activities. Individual characteristics such as race, gender, and residence were not statistically significant factors in explaining attitudes toward urban forestry programs. In addition, with few exceptions, attitudes toward government financing of urban forestry programs and activities were influenced by similar factors.
Mystery and Preference in Within-Forest Settings
Authors: Herzog Thomas R. , Bryce Anna G.
Published: July 2007

Recent studies have found negative correlations between mystery and preference for forest settings. Our reanalysis of earlier data suggested that those findings may have stemmed from a failure to examine setting categories within the forest domain. In the current study of 70 within-forest settings, factor analysis of preference ratings revealed two setting categories corresponding to high- and low-visual-access settings. In the high-access category, preference was positively correlated with mystery but uncorrelated with visual access. In the low-access category, preference was uncorrelated with mystery but positively correlated with visual access. We also examined an expanded definition of mystery that made explicit the distinction between mystery and surprise. The expanded definition produced results identical to the standard definition in the high-access category, but in the low-access category, expanded mystery was positively correlated with preference. We conclude that when properly understood, mystery tends to be positively related to preference.
The Healing Power of Symbolization in the Aftermath of Massive War Atrocities: Examples From Liberian and Sierra Leonean Survivors
Authors: Stepakoff Shanee
Published: July 2007

In the aftermath of war atrocities, symbolization—a process whereby an experience or emotion that has been unexpressed is given form—can provide survivors with a sense of relief and solace and can attenuate isolation by permitting traumatic experiences to be shared with and acknowledged by others. This article focuses on creative methods of symbolization used in a trauma counseling program for Liberian and Sierra Leonean refugees in the refugee camps of Guinea. The program, developed by the Center for Victims of Torture, integrated contemporary expressive therapy techniques with indigenous healing practices (e.g., songs, cultural stories, drama, drawing, dance/movement, letter-writing, rituals). A case example of the treatment of a war-traumatized Liberian boy is presented. The psychological harm of war atrocities is exacerbated by silence. Conversely, as victims find ways of giving form to their experiences—verbally, nonverbally, or via a combination of the two—psychological and social repair become possible.
Lung Deposition of Radiolabeled Tiotropium in Healthy Subjects and Patients With Chronic Obstructive Pulmonary Disease
Authors: Brand Peter , Meyer Thomas , Weuthen Thomas , Timmer Wolfgang , Berkel Erhard , Wallenstein Gudrun , Scheuch Gerhard
Published: July 2007

Lung deposition of 18 μg tiotropium administered via a dry‐powder inhaler was investigated in 5 healthy subjects and patients with mild (n = 4), moderate (n = 6), and severe (n = 5) chronic obstructive pulmonary disease after 14 days of treatment with 18 μg tiotropium. On day 15, subjects inhaled 2 capsules of radiolabeled tiotropium, and lung deposition was assessed using γ scintigraphy. Repeated plasma and urine collections were performed on days 14 and 15. Mean delivered dose from the dry‐powder inhaler was 45.1%. Mean lung deposition relative to the delivered dose was 42% (19%, relative to nominal dose) with low intersubject variability (20%). Mean extrathoracic deposition was 57.5% (25.8%, relative to nominal dose). There were no significant differences in deposition among the subgroups. No significant correlation between individual tiotropium deposition and lung function was observed. These results suggest that all stages of chronic obstructive pulmonary disease may gain full therapeutic benefit from the drug.
Research on Organizations and the Natural Environment, 1992-Present: A Review
Authors: Etzion Dror
Published: July 2007

The literature on organizations and the natural environment, published since 1992, is reviewed, with the purpose of determining if and what the contributions have been to strategy and organizational theory. The author performs the review at three levels—firm, industry, and organizational environment. Subsequently, he discusses empirical and conceptual constraints on the production of quality research and highlights research that successfully overcomes these barriers.
Indigenous knowledge and western science: the possibility of dialogue
Authors: Bala Arun , Gheverghese Joseph George
Published: July 2007

In recent years, a number of scientific bodies and development agencies have called for indigenous and traditional systems of knowledge to be recognised as valuable reservoirs of learning - a move inspired, in part, by the prospect of multinational biotechnology corporations exploiting traditional non-western medical, agricultural and ecological knowledge. But recognising the legitimacy of indigenous knowledge, albeit partially, has profound implications for conceptions of science. First, the relationship between science and bodies of knowledge hitherto repudiated as myth and superstition needs to be rethought so that indigenous knowledge is demarcated from both science and pseudo-science. Second, the histories of science and mathematics need to recognise consistent criteria for establishing the existence of cross-cultural transmissions. Third, strategies need to be found to legitimise, where possible, indigenous theoretical and methodological discoveries. Fourth, a multicultural idea of science needs to be developed that is distinct from a postmodern, anti-science stance.
Detained: foreign children in Europe
Authors: Fekete Liz
Published: July 2007

The EU's target-driven and draconian deportation policy towards asylum seekers and undocumented migrant workers has a shocking but little heeded impact on minors, whether the children of asylum-seeking families, separated/unaccompanied minors seeking refuge or the children of sans papiers. The detention of children whose only crime is their parentage is now commonplace across Europe and often in contravention of international law. The harm done to children, as documented here, is incalculable.
Welfare Reform and Black Women's Economic Development
Authors: Alfred Mary V.
Published: July 2007

In 1996, the United States Congress passed the Personal Responsibility and Work Opportunity Reconciliation Act, placing emphasis on individuals to take responsibility for separating themselves from governmental dependence by becoming economically self-sufficient through employment. Using a qualitative approach, this study explored the experiences of 15 African American women as they transitioned from welfare to determine the extent to which they were developing economic sufficiency as a result of their labor force participation. It also sought the perspectives of employers on the work-first approach to economic development among former recipients and their chances of becoming self-sufficient through employment. The study found three systems of barriers to impede the participants' economic progress: the “work-first” philosophy, labor market conditions and employment practices, and personal history and individual responsibility. These findings suggest that a more integrative approach is necessary, one that addresses both the personal and structural dimensions of women's economic development.
Assessing Mechanisms of Recovery During Robot-Aided Neurorehabilitation of the Upper Limb
Authors: Colombo R. , Pisano F. , Micera S. , Mazzone A. , Delconte C. , Carrozza M.C. , Dario P. , Minuco G.
Published: July 2007

Objective. The present study aimed to qualify and quantify the different components of motor recovery in a group of stroke patients treated by robot-aided techniques. In addition, the learning model of each motor recovery component was analyzed. Methods . Two groups of poststroke patients were treated with the use of an elbow-shoulder manipulator, respectively, within (recent) and after (chronic) the first 6 months of their cerebrovascular accident. Both groups were evaluated by means of standard clinical assessment scales and a robot-measured evaluation method. Results. These findings confirm that motor training consisting of voluntary movements assisted by the robot device led to significant improvements in motor performance in terms of the kinematic and dynamic components of the arm movements. This corresponded to improvement of impairment as confirmed by the clinical scale results. Conclusions. Knowledge of the recovery components and of the associated performance acquisition model may be useful in assessing and training stroke patients and should make it possible to precisely plan and, if necessary, modify the rehabilitation strategies.
Effects of morphology and granularity distribution of ferrite powder on fume formation rate of flux cored wire
Authors: Jiang J. M. , Li X. B. , Wang Z. H. , He D. Y. , Wu Y. L.
Published: July 2007

In this study the fume formation rate (FFR) of the flux cored wire for mild steel produced by three different plants was investigated. The fume chemical composition analysis was obtained by inductively coupled mass spectroscopy (ICP) and X-ray diffraction (XRD). The morphology and granularity of ferrite powder produced by different production processes were obtained by scanning electron microscope (SEM) analysis, and their effects on the FFR of the wire and explanation are also included. In the present paper, results demonstrate that the welding fume contains mainly the oxides of ferrite and manganese (∼50%) with remained evaporations of slag. The ferrite powders produced by different production processes have different morphologies. The morphology of ferrite powders has limited effect on the FFR which fluctuates orderly on a small scale with various granularity distributions of ferrite powders. The FFR is lowered when the granularity of ferrite powders retains between 80 and 120 meshes (−210+ 130 μm).
Temperature dependence of deformation mechanism in bonding zone of TLP joint of nickel base single crystal superalloy after tensile test
Authors: Liu J. D. , Jin T. , Zhao N. R. , Wang Z. H. , Sun X. F. , Guan H. R. , Hu Z. Q.
Published: July 2007

A nickel base single crystal superalloy was transient liquid phase (TLP) bonded using Ni–Cr–B amorphous foil at 1230°C for 4 h. Tensile tests of the TLP joint were carried out at different temperatures under constant strain rate. The microstructures and the deformation substructures in the bonding zone of the joint were investigated. The results show that the deformation mechanism of bonding zone depends on test temperature greatly. At low temperatures, the deformation is dominated by γ′ shearing; at high temperatures, the deformation occurs by means of γ′ bypass; at intermediate temperatures, the deformation exhibits a transitional behaviour. The deformation mechanism of different parts of TLP joint is identical.
Online quality inspection of resistance spot welded joint based on electrode indentation using servo gun
Authors: Zhang Y. S. , Zhang X. Y. , Lai X. M. , Chen G. L.
Published: July 2007

Resistance spot welding is one of the major joining techniques widely used for car body assembly. Weld quality may significantly influence the durability and reliability of the automobile body. Automotive manufacturers often rely on destructive testing and monitoring variables which indirectly reflected weld quality to assess the weld quality and control the welding process. However, these approaches have inherent limitations and are difficult to be implemented in plant environments. Therefore, it is imperative to develop an online inspection method to evaluate weld quality. In the present study, a method of producing a series of substantially uniform spot welds between two metal parts using a servomotor driven movable electrode and an axially opposing fixed electrode is proposed. The indentation in the workpiece surface is suitably measured by the displacement of the movable electrode as it applies an electrode force and welding current is passed through the weld site of the workpiece. The optimal indentation range is determined by peel test and metallographic examinations with respect to various sheet gages and grades. Consequently, online weld quality inspection results are achieved based on developed optimal indentation range.
Theoretical study of Marangoni convection and weld penetration under influence of high oxygen content in base metal
Authors: Zhao Y. Z. , Zhao H. Y. , Lei Y. P. , Shi Y. W.
Published: July 2007

A 3D mathematical model is developed to simulate the weld pool development in a moving weld pool of 304 stainless steels with different oxygen concentrations. It is shown that the oxygen can cause significant changes in fluid flow patterns and temperature fields. When oxygen content is <280 ppm, the weld penetration and depth/width ratios increase sharply with increasing oxygen content; positive and negative temperature coefficients of surface tension coexist and cause shallow and wide weld pool. When oxygen content is in the range of 280–500 ppm, positive temperature coefficient of surface tension dominates the flow patterns and causes deep and narrow weld pool. The weld penetration and depth/width ratios remain nearly constant. When oxygen content is >500 ppm, the weld penetration and depth/width ratios decrease again. Vortexes that have different positions, strength and directions may be found in the pool. The vortexes with opposite directions caused by positive temperature coefficient of surface tension can efficiently transfer the thermal energy from the arc, creating a deep weld pool.
Processing and banding in AA2524 and AA2024 friction stir welding
Authors: Yan J. H. , Sutton M. A. , Reynolds A. P.
Published: July 2007

An attempt has been made to clarify the relationship between the periodicity of process parameters and that of the micro-/mesostructural banding in friction stir welding (FSW). The oscillation of FSW parameters was measured and analysed during baseline experiments without welding and during a series of FSW of AA2524 and AA2024 aluminium alloys; the banded structures in all the welds were also characterised. It is found that independent of the tool runout, there are well defined periodic variations in the process forces, the translational resistance force F x) and Z axis force F z of the welding tool in all joints. The measured band spacing is closely correlated with the oscillation period of process forces F x and F z, exerted on and by the welding tool. The direct and consistent relationship observed between periodicity in variation of F x and F z and the metallurgical structure, e.g. grain size, particle distribution, band width and microhardness, indicate that the formation of banded structures in FSW joints is related to the periodic variation of welding parameters.
Development of new low transformation temperature welding consumable to prevent cold cracking in high strength steel welds
Authors: Zenitani S. , Hayakawa N. , Yamamoto J. , Hiraoka K. , Morikage Y. , Kubo T. , Yasuda K. , Amano K.
Published: July 2007

A low transformation temperature (LTT) welding consumable has been developed to prevent cold cracking in high strength steel welded joints without preheating. In the LTT welded joint, the residual tensile stress is reduced by martensitic expansion of weld metal formed by the LTT consumable. In the weld cracking tests, cold cracking in the LTT weld metal is successfully prevented under high restraint conditions, but cold cracking occurs at very low joint restraint strength in case the weld metal is fully martensitic. Chemical compositions of the consumable are designed to retain austenite in martensite in the newly developed weld metal to absorb the diffusible hydrogen into the austenite to prevent cold cracking. In the newly developed LTT weld metal, cold cracking is almost fully suppressed without preheating under every joint restraint condition.
Damage and fracture behaviours of 5A06 aluminium alloy welded joint under thermal cycling condition
Authors: Jin C. , Niu J. T. , He S. Y.
Published: July 2007

The 5A06 aluminium alloy is widely used in the aerospace industry, owing to its good corrosion resistance and excellent weldability. The tensile strength of this material welded joint can reach 90% of that of the base alloy. However, when used in aerospace applications, thermal cycling conditions can affect the mechanical performance of the alloy. In this paper, the deterioration of mechanical properties and damage mechanism of 5A06 aluminium alloy welded joint under thermal cycling conditions were investigated. The tensile performance was examined after the thermal cycling test. The microstructural changes and fracture mechanism were analysed. Results show that the thermal cycling can induce more severe damage in the welded joint than in the base 5A06 aluminium alloy. The particles formed in the weld heat affected zone are the source of local damage during thermal cycling. The thermal mismatch stress plus the external stress can cause debonding between the particles and the base alloy. Microvoid nucleation and evolution around the particles cause the mechanical properties deterioration of the welded joint during thermal cycling.
Diffusion bonding between high chromium white iron and austenitic stainless steel
Authors: Kurt B. , Eroglu M.
Published: July 2007

In the present study, a high chromium white iron was diffusion bonded to an austenitic stainless steel, AISI 316L. The effects of bonding temperature and holding time at the reached temperature on microstructural developments across the joint region were investigated. After diffusion bonding, microstructural analysis including metallographic examination, energy dispersive X-ray (EDX), X-ray, microhardness measurements and shear strength was performed. From the results, it was seen that bonding temperature with holding time was effective on the formation of carbide (M3C) and width of the diffusion zone that affected the shear strength of the bonds.
Arc heating hot wire assisted arc welding technique for low resistance welding wire
Authors: Lv S. X. , Tian X. B. , Wang H. T. , Yang S. Q.
Published: July 2007

An assistant arc was used to preheat the wire for hot wire tungsten inert gas (TIG) welding which was independent on the resistance of the welding wires and avoided the drawbacks of the traditional hot wire preheating method. The new method is suitable for low resistance wire such as copper and aluminium. The experimental results showed that the wire temperature varied linearly with preheating current and hyperbolically with wire feeding speed. The temperature of wires achieved 60% of their melting points when LF6, H90, HS201 and H08Mn2Si welding wires were used at a current less than 50 A. With arc assisted hot wire, the welding deposition efficiency of the HS201 wire was increased by 96% compared with the traditional TIG welding method, while its microstructure was similar to that of the cold wire welding.
Numerical studies of preheating time effect on temperature and material behaviours in friction stir welding process
Authors: Zhang Z. , Zhang H. W.
Published: July 2007

The effect of preheating time on friction stir welding (FSW) is analysed in the current work by using a fully coupled thermomechanical model. Results indicate that the preheating time is very important for a successful FSW. Insufficient temperature rise and insufficient plastic deformation lead to the failure of FSW when the preheating time is very short. But excessive preheating time leads to the tool penetration in FSW. The rotating time of the material particles under the shoulder becomes longer when the preheating time is increased. Moreover, some of the material particles at the retreating side can enter into the advancing side when the preheating time is longer but this is not obvious when the preheating time is shorter. Based on this fact, it can be concluded that the decrease in the preheating time can lead to the decrease in the stirring effect of the welding tool, which may be the reason for the formation of the weld flaw when the preheating time is very short.
Chromosomal abnormalities in Philadelphia chromosome–negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase
Authors: Jabbour Elias , Kantarjian Hagop M. , Abruzzo Lynne V. , O'Brien Susan , Garcia-Manero Guillermo , Verstovsek Srdan , Shan Jianqin , Rios Mary Beth , Cortes Jorge
Published: July 2007

The development of chromosomal abnormalities (CAs) in the Philadelphia chromosome (Ph)–negative metaphases during imatinib (IM) therapy in patients with newly diagnosed chronic myecloid leukemia (CML) has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CAs in Ph-negative cells; excluding −Y, this incidence was 5%. Sixteen (70%) of all CAs were observed in 2 or more metaphases. The median time from start of IM to the appearance of CAs was 18 months. The most common CAs were −Y and + 8 in 9 and 3 patients, respectively. CAs were less frequent in young patients (P = .02) and those treated with high-dose IM (P = .03). In all but 3 patients, CAs were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with − 7). At last follow-up, 3 patients died from transplantation-related complications, myocardial infarction, and progressive disease and 2 lost cytogenetic response. CAs occur in Ph-negative cells in a small percentage of patients with newly diagnosed CML treated with IM. In rare instances, these could reflect the emergence of a new malignant clone.
β3-Adrenergic receptor Trp64Arg polymorphism and increased body mass index in sleep apnoea
Authors: Piérola J. , Barceló A. , de la Peña M. , Barbé F. , Soriano J. B. , Sánchez Armengol A. , Martínez C. , Agustí A.
Published: July 2007

Obesity is an important risk factor for obstructive sleep apnoea syndrome (OSAS), insulin resistance and cardiovascular disease. The substitution of tryptophan 64 with arginine (Trp64Arg) polymorphism (Arg variant) of the β3-adrenergic receptor (ADRB3) has been associated with obesity. In this study, the prevalence of the Trp64Arg ADRB3 polymorphism in a large group of patients with OSAS and its association with body mass index (BMI), insulin resistance and hypertension were evaluated.

ADRB3 genotype was determined in 387 patients with OSAS and 137 healthy subjects recruited from three Spanish tertiary hospitals.

The distributions of the ADRB3 genotypes were similar in OSAS and controls, and, in a multivariate model, the risk of OSAS was not associated with the presence of the Arg variant of the ADRB3 gene. However, BMI was higher in those patients with OSAS who carried this genetic variant than in those with the Trp variant. Furthermore, a linear trend for higher BMI was found in those with the Arg variant (56, 75 and 100% for Trp/Trp, Trp/Arg and Arg/Arg, respectively). Insulin resistance, blood pressures and serum levels of lipids and glucose were not associated with the presence of the Arg variant of the ADRB3 gene.

The presence of the arginine 64 allele of the β3-adrenergic receptor gene does not increase the risk of obstructive sleep apnoea syndrome, but is associated with the development of obesity in those patients who suffer obstructive sleep apnoea syndrome.
Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea
Authors: Beecroft J. M. , Hoffstein V. , Pierratos A. , Chan C. T. , McFarlane P. A. , Hanly P. J.
Published: July 2007

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea.

An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index ≥10 events·h−1).

The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04±0.84versus3.46±0.80 cm2for the functional residual capacity and 1.99±0.51versus2.14±0.58 cm2for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function.

In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.
An analysis of expression patterns of genes encoding proteins with catalytic activities
Authors: Cankaya Murat , Hernandez Ana Martinez , Ciftci Mehmet , Beydemir Sukru , Ozdemir Hasan , Budak Harun , Gulcin Ilhami , Comakli Veysel , Emircupani Tufan , Ekinci Deniz , Kuzu Muslum , Jiang Qiuhong , Eichele Gregor , Kufrevioglu Omer Irfan
Published: July 2007

Background

In situ hybridization (ISH) is a powerful method for visualizing gene expression patterns at the organismal level with cellular resolution. When automated, it is capable of determining the expression of a large number of genes.

Results

The expression patterns of 662 genes that encode enzymes were determined by ISH in the mid-gestation mouse embryo, a stage that models the complexity of the adult organism. Forty-five percent of transcripts encoding metabolic enzymes (n = 297) showed a regional expression pattern. A similar percentage was found for the 190 kinases that were also analyzed. Many mRNAs encoding glycolytic and TCA cycle enzymes exhibited a characteristic expression pattern. The annotated expression patterns were deposited on the Genepaint database and are retrievable by user-defined queries including gene name and sites of expression.

Conclusion

The 662 expression patterns discussed here comprised gene products with activities associated with catalysis. Preliminary analysis of these data revealed that a significant number of genes encoding housekeeping functions such as biosynthesis and catabolism were expressed regionally, so they could be used as tissue-specific gene markers. We found no difference in tissue specificity between mRNAs encoding housekeeping functions and those encoding components of signal transduction pathways, as exemplified by the kinases.
The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulations
Authors: McInnes Fiona , Baillie Alan J , Stevens Howard N E
Published: July 2007

A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration. Vapour sorption analysis demonstrated substantial weight gain of the lyophilisates on exposure to 95% relative humidity, ranging from 38% to 66%. Agar was used as a synthetic mucosal model designed to provide a standardised quantity of water available for rehydration of the formulations in in-vitro tests. A dynamic adhesion test and a texture analyser sliding test were designed to quantify different aspects of the spreading and adhesion of the hydrating formulations on the synthetic mucosal surface. Examination of the lyophilised formulations using confocal microscopy allowed visualisation and quantification of the initial rate of water ingress into the lyophilisates, which was found to consist of an initial rapid phase, followed by a slower steady-state phase. The results demonstrated that the use of a combination of methods representing the dynamic conditions of the nasal cavity is advisable in order to evaluate a formulation fully and to avoid misleading conclusions.
Development of a robust once-a-day glipizide matrix system
Authors: Jamzad Shahla , Fassihi Reza
Published: July 2007

The robustness of a new hydroxypropylmethylcellulose (HPMC) based modified release glipizide (10 mg) formulation was studied. The tablet formulations were prepared by dry blending the ingredients and direct compression, incorporating a range of release modifying agents up to ± 20% w/w relative to an optimized formulation. The dissolution was assessed in 900 mL pH 6.8 buffer at 75 rev min−1 paddle speed. Calculated difference and similarity factors (f1 and f2) and results of analysis of variance suggest that the overall release profiles were similar. Compositional changes up to ± 20% w/w and a reduction of drug dose to half did not change the general release pattern of this low dose/pH-dependent drug in a significant way. It is concluded that the drug release from the developed matrix systems is highly dependent on the kinetics of hydration and erosion, and that the proposed compositional changes within ± 20% w/w did not alter this relationship. The particulate systems used were characterized by determining the Carr index, Hausner ratio and the rheological properties using a texture analyser. Results indicate that the release is reproducible and the system has potential for successful scale-up operation, while complying with recommended Food and Drug Administration guidelines “Scale Up and Post Approval Changes”.
Large molecules as anti-adhesive compounds against pathogens
Authors: Wittschier N , Lengsfeld C , Vorthems S , Stratmann U , Ernst J F , Verspohl E J , Hensel A
Published: July 2007

Anti-adhesive compounds are potential prophylactic tools in alternative treatment regimes against bacterial infection, as bacterial adhesion is commonly mediated by carbohydrate-protein interactions between surface adhesions of microorganisms and the host cell. The use of exogenous polyvalent, high-molecular carbohydrates and tannin-like plant-derived compounds should antagonize the adhesive interaction. A range of carbohydrates and carbohydrate- and proanthocyanidin-enriched plant extracts were screened for potential anti-adhesive effects against Helicobacter pylori, Campylobacter jejuni, Porphyromonas gingivalis and Candida albicans in different in-situ assays on primary tissue. The adhesion of H. pylori on human stomach tissue was effectively blocked by glucuronic acid-enriched polysaccharides from immature okra fruits (Abelmoschus esculentus). These compounds also had strong in-vitro effects against C. jejuni (inhibition up to 80%), but were ineffective in an in-vivo study in infected chicken broilers due to metabolism in the gastrointestinal system. Polysaccharides from Glycyrrhizia glabra, also enriched with glucuronic acid, showed strong anti-adhesive properties against H. pylori and P. gingivalis (inhibition 60–70%). Pelargonium sidoides extract, containing mainly polymeric proanthocyanidins, was effective against H. pylori in a dose-dependent manner. Due to the multifunctional adhesive strategy of C. albicans, no effective compounds were detected against this yeast. Structure-activity relationships are presented and the potential in-vivo use of carbohydrate-based anti-adhesives is discussed.
Pharmacokinetics of letrozole in male and female rats: influence of complexation with hydroxybutenyl-β-cyclodextrin
Authors: Wempe Michael F , Buchanan Charles M , Buchanan Norma L , Edgar Kevin J , Hanley Gregory A , Ramsey Michael G , Skotty Jennifer S , Rice Peter J
Published: July 2007

Cyclodextrins (CDs) are one of the most successful solutions to the problem of poor drug solubility. In this study, we examined the in-vitro effects of three CDs on the solubility of letrozole, a breast cancer drug that is practically insoluble in water. The most promising, hydroxybutenyl-β-cyclodextrin (HBenβCD), was used for in-vivo studies in male and female Sprague-Dawley rats. Letrozole is a drug with dramatic gender-based differences in pharmacokinetics. For example, the terminal half-life (t1/2) of letrozole following intravenous administration in male rats was 11.5 ± 1.8 h (n = 3), while in female rats it was 42.3 ± 2.9 h (n = 3). HBenβCD increased the solubility and enhanced the dissolution rate of letrozole. Complexation of letrozole with HBenβCD improved oral absorption in male rats and maximized absorption in female rats. Regardless of gender, the presence of HBenβCD in the formulation increased the in-vivo rate of absorption. When administered in a capsule formulation with letrozole, HBenβCD resulted in a higher Cmax (61% in male rats, 42% in female), shorter Tmax values (8.4 to 6.3 h in male, 16.4 h to 5.4 h in female) and increased absolute oral bioavailability (46 ± 2 vs 38 ± 3 in male, 101 ± 3 vs 95 ± 2 in female). Thus, solubility limits both rate and extent of letrozole absorption in male rats, but limits only the rate of absorption in female rats.
Prediction of human pharmacokinetics—evaluation of methods for prediction of hepatic metabolic clearance
Authors: Fagerholm Urban
Published: July 2007

Methods for prediction of hepatic clearance (CLH) in man have been evaluated. A physiologically-based in-vitro to in-vivo (PB-IVIV) method with human unbound fraction in blood (fu,bl) and hepatocyte intrinsic clearance (CLint)-data has a good rationale and appears to give the best predictions (maximum ∼2-fold errors; < 25% errors for half of CL-predictions; appropriate ranking). Inclusion of an empirical scaling factor is, however, needed, and reasons include the use of cryopreserved hepatocytes with low activity, and inappropriate CLint- and fu,bl-estimation methods. Thus, an improvement of this methodology is possible and required. Neglect of fu,bl or incorporation of incubation binding does not seem appropriate. When microsome CLint-data are used with this approach, the CLH is underpredicted by 5- to 9-fold on average, and a 106-fold underprediction (attrition potential) has been observed. The poor performance could probably be related to permeation, binding and low metabolic activity. Inclusion of scaling factors and neglect of fu,bl for basic and neutral compounds improve microsome predictions. The performance is, however, still not satisfactory. Allometry incorrectly assumes that the determinants for CLH relate to body weight and overpredicts human liver blood flow rate. Consequently, allometric methods have poor predictability. Simple allometry has an average overprediction potential, > 2-fold errors for ∼1/3 of predictions, and 140-fold underprediction to 5800-fold overprediction (potential safety risk) range. In-silico methodologies are available, but these need further development. Acceptable prediction errors for compounds with low and high CLH should be ∼50 and ∼10%, respectively. In conclusion, it is recommended that PB-IVIV with human hepatocyte CLint and fu,bl is applied and improved, limits for acceptable errors are decreased, and that animal CLH-studies and allometry are avoided.
Montelukast reduces ischaemia/reperfusion-induced bladder dysfunction and oxidant damage in the rat
Authors: Şener Göksel , Şehirli Ozer , Toklu Hale , Ercan Feriha , Alican Inci
Published: July 2007

The present study aimed to investigate the possible beneficial effects of the cysteinyl leukotriene-1 receptor antagonist montelukast on contractility and oxidant damage after ischaemia/reperfusion (I/R) of rat urinary bladder. The abdominal aorta of Sprague-Dawley rats was occluded to induce I/R. Montelukast (10 mg kg−1) or saline was administered intraperitoneally before I/R. In the sham-operated group, the abdominal aorta was left intact and the animals were treated with montelukast or saline. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for biochemical assays. In the I/R group, the isometric contractile responses of the bladder strips to carbachol (10−8-10−4 M) were lower than those of the control group and were reversed by treatment with montelukast. Lipid peroxidation and myeloperoxidase activity of the bladder tissues in the I/R group were greater than in the sham-operated group. Montelukast treatment in the I/R group decreased these parameters compared with I/R alone. Similarly, the significant decrease in tissue glutathione level in the I/R group compared with controls was also prevented by montelukast. Treatment with montelukast almost completely reversed the low contractile responses of rat urinary bladder to carbachol and prevented oxidative tissue damage following I/R.
Decursinol and decursin protect primary cultured rat cortical cells from glutamate-induced neurotoxicity
Authors: Kang So Young , Kim Young Choong
Published: July 2007

We previously reported six neuroprotective decursinol derivatives, coumarins from Angelica gigas (Umbelliferae) roots. To elucidate the action patterns of decursinol derivatives, we investigated the neuroprotective effects of decursinol and decursin, which showed highly significant activity and were major constituents of A. gigas, using primary cultures of rat cortical cells in-vitro. At concentrations of 0.1–10.0 μM, both decursinol and decursin exerted a significant neuroprotective activity pretreatment and throughout treatment. In addition, decursin had a neuroprotective impact in the post-treatment paradigm implying that decursin might possess different action mechanisms from that of decursinol in the protection of neurons against glutamate injury. Both decursinol and decursin effectively reduced the glutamate-induced increased intracellular calcium ([Ca2+]i) in cortical cells, suggesting that these two coumarins may exert neuroprotection by reducing calcium influx by overactivation of glutamate receptors. This suggestion was supported by the result that decursinol and decursin protected neurons against kainic acid (KA)-induced neurotoxicity better than against that induced by N-methyl-D-aspartate (NMDA). Moreover, both decursinol and decursin significantly prevented glutamate-induced decreases in glutathione, a cellular antioxidant, and glutathione peroxidase activity. In addition, both compounds efficiently reduced the overproduction of cellular peroxide in glutamate-injured cortical cells. These results suggested that both decursinol and decursin protected primary cultured rat cortical cells against glutamate-induced oxidative stress by both reducing calcium influx and acting on the cellular antioxidative defence system. Moreover, decursin is considered to probably have a different action mechanism from that of decursinol in protecting cortical cells against glutamate injury.
An extract of Apium graveolens var. dulce leaves: structure of the major constituent, apiin, and its anti-inflammatory properties
Authors: Mencherini T , Cau A , Bianco G , Loggia R Della , Aquino R P , Autore G
Published: July 2007

Flavonoids, natural compounds widely distributed in the plant kingdom, are reported to affect the inflammatory process and to possess anti-inflammatory as well as immunomodulatory activity in-vitro and in-vivo. Since nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is one of the inflammatory mediators, the effects of the ethanol/water (1:1) extract of the leaves of Apium graveolens var. dulce (celery) on iNOS expression and NO production in the J774.A1 macrophage cell line stimulated for 24 h with Escherichia coli lipopolysaccharide (LPS) were evaluated. The extract of A. graveolens var. dulce contained apiin as the major constituent (1.12%, w/w, of the extract). The extract and apiin showed significant inhibitory activity on nitrite (NO) production in-vitro (IC50 0.073 and 0.08 mg mL−1 for the extract and apiin, respectively) and iNOS expression (IC50 0.095 and 0.049 mg mL−1 for the extract and apiin, respectively) in LPS-activated J774.A1 cells. The croton-oil ear test on mice showed that the extract exerted anti-inflammatory activity in-vivo (ID50 730 μg cm−2), with a potency seven-times lower than that of indometacin (ID50 93 μg cm−2), the non-steroidal anti-inflammatory drug used as reference. Our results clearly indicated the inhibitory activity of the extract and apiin in-vitro on iNOS expression and nitrite production when added before LPS stimulation in the medium of J774.A1 cells. The anti-inflammatory properties of the extract demonstrated in-vivo might have been due to reduction of iNOS enzyme expression.
Regulation of theArabidopsisroot vascular initial population byLONESOME HIGHWAY
Authors: Ohashi-Ito Kyoko , Bergmann Dominique C.
Published: July 2007

Complex organisms consist of a multitude of cell types arranged in a precise spatial relation to each other. Arabidopsis roots generally exhibit radial tissue organization; however, within a tissue layer, cells are not identical. Specific vascular cell types are arranged in diametrically opposed longitudinal files that maximize the distance between them and create a bilaterally symmetric (diarch) root. Mutations in the LONESOME HIGHWAY (LHW) gene eliminate bilateral symmetry and reduce the number of cells in the center of the root, resulting in roots with only single xylem and phloem poles. LHW does not appear to be required for the creation of any specific cell type, but coordinately controls the number of all vascular cell types by regulating the size of the pool of cells from which they arise. We cloned LHW and found that it encodes a protein with weak sequence similarity to basic helix-loop-helix (bHLH)-domain proteins. LHW is a transcriptional activator in vitro. In plants, LHW is nuclear-localized and is expressed in the root meristems, where we hypothesize it acts independently of other known root-patterning genes to promote the production of stele cells, but might also indirectly feed into established regulatory networks for the maintenance of the root meristem.
Effect of strain hardening on residual stress distribution in beams determined using the crack compliance method
Authors: Urriolagoitia-Sosa G , Durodola J. F , Fellows N. A
Published: July 2007

This work used the crack compliance method for the determination of residual stresses in beams subjected to prior straining before the introduction of residual stresses through bending. The paper also introduces a support system that allows free movement of specimens during cutting by electric discharge machining. The experimental testing and verification procedure considered factors such as different materials and strain hardening levels. The results obtained provide a quantitative demonstration of the effect of prior strain hardening on residual stress distribution in beams.
Numerical and experimental investigation of three-dimensional strains in adhesively bonded joints
Authors: Ruiz P D , Jumbo F , Seaton A , Huntley J. M , Ashcroft I. A , Swallowe G. M
Published: July 2007

Strain distributions within adhesively bonded double-lap shear joints under tensile load have been investigated experimentally using the complementary experimental techniques of neutron diffraction (ND) and moire interferometry (MI). ND provides three-dimensional strain values within the samples, whereas MI gives high-resolution maps of the in-plane strain components at the surface. The resulting comprehensive datasets obtained from both aluminium and steel joints were compared against finite element (FE) predictions. The importance of a range of factors (e.g. two-dimensional versus three-dimensional geometry, sample asymmetry, residual strains) was assessed through development of the FE model and detailed comparison with the experimental data. The main conclusions were that FEA can be used accurately to predict strains in the adherends of bonded lap joints and that many of the simplifications of the joints commonly used in the analysis of bonded joints are justified as including them results in relatively small differences compared with sample-to-sample variation and the safety factors used in designing bonded joints.
Neutron diffraction measurements of stress in an austenitic butt weld
Authors: Suzuki H , Holden T. M
Published: July 2007

In this study, the residual stress distribution in a double-V butt weld plate of 304-type austenitic stainless steel was measured using the neutron diffraction technique with the diffractometer for residual stress analysis (RESA) located in the JRR-3 (Japan research reactor number 3) at the Japan Atomic Energy Agency. Coupon samples were cut from the weld plate in order to follow the changes in chemical and microstructure or effects from type-2 intergranular strains. The residual stresses were measured using the {111}, {002}, and {220} reflections. The residual stress derived from {002} reflection is sensitive to intergranular effects, so that when the analysis ignored intergranular effects, the stress variation for the {002} reflection was different from the stresses derived from the other reflections. However, the stress distributions evaluated from the lattice strains for all the reflections were in good agreement, within the error bar of ± 35 MPa, after correcting the measured strains by subtracting the intergranular strains derived from the coupon measurements. The consideration of intergranular effects thus improves the accuracy of neutron stress measurements of weldments.
The effect of Poisson's ratio on stress concentrations
Authors: Grant R J , Lorenzo M , Smart J
Published: July 2007

In design, it is common to use values for stress concentration factors (SCFs) obtained from textbooks. These textbook values have generally been obtained from photoelastic experiments for which Poisson's ratio will probably have a value greater than 0.3 and for frozen stress analysis a value approaching 0.5. However, when designing machine parts made from other isotropic materials, e.g. metals and structural ceramics, Poisson's ratio will probably have a lower value, which will affect the value of the SCF.

In this paper, various stress-raising features have been analysed using the finite element method to determine the stress concentration factor. It is shown that Poisson's ratio can have a significant effect on the SCF.