bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and Pharmacodynamics of High Doses of Pharmaceutically Prepared Heroin, by Intravenous or by Inhalation Route in Opioid‐Dependent Patients
Authors: Rook Elisabeth J. , Van Ree Jan M. , Van Den Brink Wim , Hillebrand Michel J. X. , Huitema Alwin D. R. , Hendriks Vincent M. , Beijnen Jos H.
Published: January 2006

Abstract: A pharmacokinetic‐pharmacodynamic study was performed in opioid‐dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by “chasing the dragon” method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady‐state heroin treatment for at least 12 months. For safety reasons, there was no crossing‐over between heroin injection or inhalation. In a double‐blind randomised study, 67–100–150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6‐monoacetylmorphine, morphine and morphine‐glucuronides were analysed using LC‐MS‐MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean Cmax of heroin and its metabolites were 2–6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44–61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799–1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661–2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R2 15–19%). Morphine‐glucuronides levels were inversely related to creatinine clearance. After heroin administration, the reaction time was significantly prolonged with 28±5.3 msec. in injecting and 13±4.9 msec. in inhaling patients. Cardiovascular changes were only mild after heroin administration. Craving‐scores declined immediately after heroin administration in both administration groups. Subjective heroin effect was rated more positively in heroin inhaling than in injecting patients, despite the lower Cmax levels following heroin inhalation. In both groups, in this blinded study heroin dose increments were more appreciated than dose reductions. Increments of 50% of the regular heroin dose did not cause any serious side effect.
Up‐Regulation of α1A‐Adrenoceptors in Rat Mesenteric Artery Involves Intracellular Signal Pathways
Authors: Cao Yong‐Xiao , Xu Cang‐Bao , Luo Guo‐Gang , Edvinsson Lars
Published: January 2006

Abstract: The aim of the present study was to investigate if there is an altered expression of α‐adrenoceptors during organ culture of rat mesenteric artery segments by using a sensitive pharmacological method and molecular biological techniques. Noradrenalin (NA) induced contraction via α1‐adrenoceptors. The contraction and α1A‐adrenoceptor mRNA levels were elevated during organ culture. Transcriptional inhibitor actinomycin D, translational inhibitor cycloheximide, protein kinase C inhibitors (staurosporine and RO31‐8220) and mitogen‐activated protein kinase (MAPK) pathway inhibitors (SB386023, U0126 and SB239063) prevented the increase in NA‐induced contractions. The amount of α1A‐adrenoceptor mRNA was significantly lower in the artery segments cultured for 1 day in the presence of specific MAPK extracellular signal‐regulated protein kinase1/2 pathway inhibitor SB386023 than that of the cultured controls. SB386023 did not affect α2‐adrenoceptor mRNA level. Our results suggest that the up‐regulation of α1A‐adrenoceptors involves transcription and intracellular signal transduction via the protein kinase C and the ERK 1/2 pathways.
Predicting Liana Crown Location from Stem Diameter in Three Panamanian Lowland Forests1
Authors: Kurzel Brian P. , Schnitzer Stefan A. , Carson Walter P.
Published: January 2006

In three forests that differed in annual rainfall and seasonality, the probability of a liana with a stem ≥2.0 cm stem diameter reaching the canopy was >50 percent. Lianas reached the canopy at significantly smaller size‐classes (1.5 cm) in the wet aseasonal forest, suggesting that this estimate changes with forest type. Nevertheless, as a general rule, we suggest that 2.0 cm is the minium stem diameter to examine the abundance and diversity of canopy lianas or canopy competition between lianas and trees.
How Decoupled are Decoupled Payments? The Evidence from Ireland
Authors: Hennessy Thia C. , Thorne Fiona S.
Published: January 2006

This article explores the production effects of the EU's system of decoupled payments and the implications for WTO negotiations. We compare survey data on Irish farmers' production plans post decoupling to the optimal outputs predicted by a farm‐level profit maximisation model. The results show that, post decoupling, a significant number of farmers plan to use their decoupled payments to continue or expand economically non‐viable production. An econometric analysis reveals that the decision to maintain or expand production levels post decoupling is not significantly influenced by current or future projected profitability levels. The analysis suggests likely widespread cross subsidisation of unprofitable production post decoupling but that aggregate production is still likely to decline relative to the traditional coupled, but production‐limiting, blue box payments. If the EU wants to claim in the current WTO negotiations that decoupled payments amount to green box support, then the argument must be made that the payments have no, or at most minimal, trade distorting effects or effects on production. If it becomes apparent to members of the WTO that European farmers are using their decoupled income to subsidise market loss production, then the green boxing of the EU's decoupled payment scheme may come up for debate at the negotiations.
Influence of blood donation on O2 uptake on‐kinetics, peak O2 uptake and time to exhaustion during severe‐intensity cycle exercise in humans
Authors: Burnley Mark , Roberts Claire L. , Thatcher Rhys , Doust Jonathan H. , Jones Andrew M.
Published: January 2006

We hypothesized that the reduction of O2‐carrying capacity caused by the withdrawal of ∼450 ml blood would result in slower phase II O2 uptake
kinetics, a lower
and a reduced time to exhaustion during severe‐intensity cycle exercise. Eleven healthy subjects (mean ±s.d. age 23 ± 6 years, body mass 77.2 ± 11.0 kg) completed ‘step’ exercise tests from unloaded cycling to a severe‐intensity work rate (80% of the difference between the predetermined gas exchange threshold and the
) on two occasions before, and 24 h following, the voluntary donation of ∼450 ml blood. Oxygen uptake was measured breath‐by‐breath, and
kinetics estimated using non‐linear regression techniques. The blood withdrawal resulted in a significant reduction in haemoglobin concentration (pre: 15.4 ± 0.9 versus post: 14.7 ± 1.3 g dl−1; 95% confidence limits (CL): −0.04, −1.38) and haematocrit (pre: 44 ± 2 versus post: 41 ± 3%; 95% CL: −1.3, −5.1). Compared to the control condition, blood withdrawal resulted in significant reductions in
(pre: 3.79 ± 0.64 versus post: 3.64 ± 0.61 l min−1; 95% CL: −0.04, − 0.27) and time to exhaustion (pre: 375 ± 129 versus post: 321 ± 99 s; 95% CL: −24, −85). However, the kinetic parameters of the fundamental
response, including the phase II time constant (pre: 29 ± 8 versus post: 30 ± 6 s; 95% CL: 5, −3), were not altered by blood withdrawal. The magnitude of the
slow component was significantly reduced following blood donation owing to the lower
attained. We conclude that a reduction in blood O2‐carrying capacity, achieved through the withdrawal of ∼450 ml blood, results in a significant reduction in
and exercise tolerance but has no effect on the fundamental phase of the
on‐kinetics during severe‐intensity exercise.
Immunomodulatory Effects of a Traditional Chinese Medicine with Potential Antiviral Activity: A Self-Control Study
Authors: Poon P. M. K. , Wong C. K. , Fung K. P. , Fong C. Y. S. , Wong E. L. Y. , Lau J. T. F. , Leung P. C. , Tsui S. K. W. , Wan D. C. C. , Waye M. M. Y. , Au S. W. N. , Lau C. B. S. , Lam C. W. K.
Published: January 2006

Traditional Chinese medicine (TCM) has been used for prevention and treatment of severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in spring 2003. We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases. Thirty-seven healthy volunteers were given the oral TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days 0, 15 and 29 for hematology, biochemistry and immunology tests, including the measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1 and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated in a control study without TCM treatment for the same time course of blood tests. Two volunteers withdrew on day 2, due to headache and dizziness. All others remained well without any side effects. No participants showed significant changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio increased significantly from 1.31 ± 0.50 ( mean ± SD ) on day 0 to 1.41 ± 0.63 on day 15 ( p < 0.02), and reduced to 1.32 ± 0.47 on day 29 ( p < 0.05). In the control study, there were no changes in the CD4/CD8 ratio. The transient increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the administration of the innovative TCM may have beneficial immunomodulatory effects for preventing viral infections including SARS.
Effects of Electrical Acupuncture on Acupoint BL15 Evaluated in Terms of Heart Rate Variability, Pulse Rate Variability and Skin Conductance Response
Authors: Hsu Chih-Chieh , Weng Ching-Sung , Liu Te-Sheng , Tsai Yuh-Show , Chang Yung-Hsien
Published: January 2006

In this research, heart rate variability (HRV), pulse rate variability (PRV) and human skin conductance (SC) of all acupoints on Heart Meridian were used to evaluate the effects of electrical acupuncture (EA) on acupoint BL15 (Bladder Meridian). Ten healthy volunteers (aged 23 ± 6) were selected as the control group on the first day, and then used again as the experimental group on the second day. The control group received sham EA during the study, while subjects of the experimental group were stimulated by 2 Hz EA on acupoint BL15 for 10 minutes. Electrocardiogram (ECG), wrist blood pressure pulse meter and skin conductance response (SCR) device were used to measure and analyze HRV, PRV and SCR for the two groups before and after stimulation. From the spectrum analysis of ECG and pulse pressure graph, we found that the EA applied on BL15 could induce a significant increase in the normalized high frequency power (nHFP) component of HRV and PRV, as well as a significant decrease in the normalized low frequency power (nLFP) part ( p < 0.05). Moreover, both the heart rate and pulse rate were reduced in the analysis of the time domain of ECG and PRV. Furthermore, most of the SCR values at acupoints were decreased after stimulation. These results also indicate that the stimulation of BL15 by EA could cause relaxation, calmness and reduce feeling of tension or distress.
Moxibustion at ST36 Alleviates Pain in Complete Freund's Adjuvant-Induced Arthritic Rats
Authors: Kim Jae-Hyo , Kim Hee-Kee , Park Yong-Il , Sohn In-Churl , Choi Dong-Ok , Kim Min-Sun , Park Byung-Rim
Published: January 2006

This study was to investigate the antinociceptive effects of moxibustion in a complete Freund's adjuvant (CFA)-induced arthritic rat model, and the effects of moxibustion on immunohistochemical changes at the spinal cord level. Moxibustion was applied to the ipsilateral (right) Zusanli (ST36) acupoint to the lesion side for 9 days to CFA-induced arthritic rats. The stepping force was measured as a behavioral test, c-Fos immunohistochemistry, NO production and nNOS Western blots were examined to evaluate antinociceptive effects. Moxibustion at ST36 significantly improved the stepping force in the affected hind limb in CFA-induced arthritis. Moreover, moxibustion at ST36 suppressed the production of NO and the protein expression of c-Fos and nNOS induced by arthritis. These results suggest that moxibustion at ST36 has a potent antinociceptive effect in an arthritic rat model, and modulates neuronal excitability and endogenous NO production by suppressing c-Fos and nNOS protein expression.
Physiological Function of Insoluble Dietary Fiber Prepared from Exploded Oak Wood (Quercus mongolica)
Authors: Yang Jae-Kyung , Choi Myung-Suk , Kim Chang-Joon , Shin Yong-Seung , Han Dae-Yong , Han Sang-Woo , Lim Bu-Kug , Lee Jong-Yoon , Rhee Soon-Jae , Kim Eun-Hee , Kim Gon-Sup
Published: January 2006

This study investigated the production of insoluble dietary fiber using exploded and chemically treated oak wood (Quercus mongolica) and the physiological functions of prepared insoluble dietary fiber in laboratory animals. To produce high quality insoluble dietary fiber, the steam explosion treatment was performed at 25 kg f/ cm 2 pressure for 6 minutes. In the chemical analysis of insoluble dietary fiber, exploded oak wood was pretreated by 1% sodium hydroxide solution. The insoluble dietary fiber contained 7.6% residual lignin and 61.7% of α-cellulose. In order to compare the physiological functions of prepared insoluble dietary fiber with those of commercial insoluble dietary fiber, Sprague-Dawley male rats weighing 100 ± 10 g were randomly assigned to one normal diet and five high cholesterol diets, containing 1% cholesterol. The high cholesterol diet groups were classified as the fiber-free diet (FF group), 5% commercial α-cellulose diet group (5C group), 10% commercial α-cellulose group (10C group), 5% insoluble dietary fiber group (5M group) and 10% insoluble dietary fiber group (10M group). Food intake, weight gain and food efficiency ratio in high cholesterol groups were significantly higher than those of the normal group, but there were no significant differences among the high cholesterol diet groups. In addition, there were no significant differences in the weights of liver, kidney and small intestine in insoluble dietary fiber-supplemented groups. Cecum weights in all insoluble dietary fiber groups were significantly higher than those of the FF group. There were no significant differences in the activities of the glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) among the insoluble dietary fiber-supplemented groups. In conclusion, the prepared insoluble dietary fiber and the commercially available insoluble fiber showed the same physiological effects. Moreover, the preparation method for the insoluble dietary fiber from the exploded oak wood was successful.
Effects of Ginseng on the Proliferation of Human Lung Fibroblasts
Authors: Yoo Hye Hyun , Yokozawa Takako , Satoh Akiko , Kang Ki Sung , Kim Hyun Young
Published: January 2006

In this study, we investigated the effects of methanolic extracts of white ginseng (Panax ginseng C.A. MEYER) and two kinds of heat-treated ginseng made by steaming fresh ginseng at 100°C for 3 hours (HTG-100) or 120°C for 3 hours (HTG-120) on the cell growth of human fibroblasts. All of the tested ginseng extracts stimulated cell growth, although the effect of HTG-120 was weaker than that of the other extracts. However, none of the ginseng extracts exhibited any effect on the growth of old cells with a population doubling level (PDL) of 48.7. Flow cytometric analysis showed that ginseng extracts raised the population of cells in G 0/ G 1 phase after treatment for 24 hours, but did not exert any effect after treatment for 48 hours. These results suggest that ginsengs exert their cell growth-promoting action mainly on younger cells at an early stage of the cell cycle, and that this effect is closely associated with an increase in the population of cells in the G 0/ G 1 phase.
Inhibitory Effects of Anti-SARS Traditional Chinese Medicines on the UV Irradiation of λ-Lysogen
Authors: Li Yaqiong , Li Jing , Fang Chengxiang
Published: January 2006

By using λ-lysogen as a model, the inhibitory effects of anti-severe acute respiratory syndrome (SARS) traditional Chinese medicines (TCMs) prescription I on the UV irradiation were investigated in this present study. It was found that the prescription I possessed obvious inhibitory effects on the UV induction of λ-lysogen, the inhibitory rate reaching 83.87%. Among five medicinal herbs prescribed in that formula, Herba Patriniae, Radix Astragali and Radix Glycyrrhizae played important roles. When these three herbs were eliminated from the recipe separately, the inhibitory effects were prominently decreased. If only one of these five medicinal herbs was added into the medium of λ-lysogen, the inhibitory rates ranged from 27.0% ~ 45.0%. By electron spin resonance (ESR) detection, we found that the prescription I , Herba Patriniae and other main herbs in that recipe, could quench effectively the free radicals generated in the process of λ-lysogenic cells by UV. These results provide a novel idea for further studying the pharmacology of TCM and exploring the mechanism of SARS virus infection.
AN EMPIRICAL EVALUATION OF AUTOMATED THEOREM PROVERS IN SOFTWARE CERTIFICATION
Authors: DENNEY EWEN , FISCHER BERND , SCHUMANN JOHANN
Published: January 2006

We describe a system for the automated certification of safety properties of NASA software. The system uses Hoare-style program verification technology to generate proof obligations which are then processed by an automated first-order theorem prover (ATP). We discuss the unique requirements this application places on the ATPs, focusing on automation, proof checking, traceability, and usability, and describe the resulting system architecture, including a certification browser that maintains and displays links between obligations and source code locations. For full automation, the obligations must be aggressively preprocessed and simplified, and we demonstrate how the individual simplification stages, which are implemented by rewriting, influence the ability of the ATPs to solve the proof tasks. Our results are based on 13 comprehensive certification experiments that lead to 366 top-level safety obligations and ultimately to more than 25,000 proof tasks which have been used to determine the suitability of the high-performance provers DCTP, E-Setheo, E, Gandalf, Otter, Setheo, Spass, and Vampire, and our associated infrastructure. The proofs found by Otter have been checked by Ivy.
MoMM — FAST INTERREDUCTION AND RETRIEVAL IN LARGE LIBRARIES OF FORMALIZED MATHEMATICS
Authors: URBAN JOSEF
Published: January 2006

MoMM (in the narrower sense) is a tool allowing fast interreduction of a high number of clauses, dumping and fast-loading of the interreduced clause sets, and their use for real-time retrieval of matching clauses in an interactive mode. MoMM's main task is now providing these services for the world's largest body of formalized mathematics — the Mizar Mathematical Library (MML), which uses a richer formalism than just pure predicate logic. This task leads to a number of features (strength, speed, memory efficiency, dealing with the richer Mizar logic, etc.) required from MoMM, and we describe the choices taken in its implementation corresponding to these requirements.

An important part of MoMM (in the wider sense) are the tools exporting the richer logic of MML into the clause-like format suitable for fast interreduction, and the tools allowing the use of MoMM as an interactive advisor for the authors of Mizar articles. These tools and choices taken in their implementation are also described here. Next we present some results of the interreduction of MML, which provide an interesting information about subsumption and repetition in the MML and can be used for its refactoring. This interreduction reveals that more than 2 percent of the main MML theorems are subsumed by others, and that for more than 50 percent of the internal lemmas proved by Mizar authors MoMM can provide useful advice for their justification. Finally some problems and possible future work are discussed.
Electrical and electronic waste management in China: progress and the barriers to overcome
Authors: Liu Xianbing , Tanaka Masaru , Matsui Yasuhiro
Published: January 2006

Serious adverse impacts on the environment and human health from e-waste recycling have occurred in the past and continue to occur in China today, due to a lack of national management strategies. China has made great efforts to face the challenges of the approaching peak increase in the domestic generation of e-waste and the illegal shipment of e-waste from other countries. This study examined recent progress and analysed the main problems associated with this issue in China. It was found that the material and the financial flows of e-waste in China had their own specific characteristics. Nearly 60% of the generated e-wastes were sold to private individual collectors and passed into informal recycling processes. More than 90% of Chinese citizens are reluctant to pay for the recycling of their e-waste. This is due to their traditional understanding that there remained value in these end-of-life products. Regulations concerning e-waste in China have been drafted but their deficiencies are obvious. The extended producer responsibilities (EPR) have been introduced but are not well defined. Eight formal facilities have been planned and are under construction or are in operation along the eastern coast of China but it will be difficult for them to compete with the informal processes for the reasons identified during the study.
Evaluation of environmental impacts from municipal solid waste management in the municipality of Aarhus, Denmark (EASEWASTE)
Authors: Kirkeby Janus T. , Birgisdottir Harpa , Hansen Trine Lund , Christensen Thomas H. , Bhander Gurbakhash Singh , Hauschild Michael
Published: January 2006

A new computer based life cycle assessment model (EASE-WASTE) was used to evaluate a municipal solid waste system with the purpose of identifying environmental benefits and disadvantages by anaerobic digestion of source-separated household waste and incineration. The most important processes that were included in the study are optical sorting and pre-treatment, anaerobic digestion with heat and power recovery, incineration with heat and power recovery, use of digested biomass on arable soils and finally, an estimated surplus consumption of plastic in order to achieve a higher quality and quantity of organic waste to the biogas plant. Results showed that there were no significant differences in most of the assessed environmental impacts for the two scenarios. However, the use of digested biomass may cause a potential toxicity impact on human health due to the heavy metal content of the organic waste. A sensitivity analysis showed that the results are sensitive to the energy recovery efficiencies, to the extra plastic consumption for waste bags and to the content of heavy metals in the waste. A model such as EASE-WASTE is very suitable for evaluating the overall environmental consequences of different waste management strategies and technologies, and can be used for most waste material fractions existing in household waste.
Defining Molecular Profiles of Poor Outcome in Patients With Invasive Bladder Cancer Using Oligonucleotide Microarrays
Authors: Sanchez-Carbayo Marta , Socci Nicholas D. , Lozano Juanjo , Saint Fabien , Cordon-Cardo Carlos
Published: January 2006

Purpose

Bladder cancer is a common malignancy characterized by a poor clinical outcome when tumors progress into invasive disease. We sought to define genetic signatures characteristic of aggressive clinical behavior in advanced bladder tumors.

Methods

Oligonucleotide arrays were utilized to analyze the transcript profiles of 105 bladder tumors: 33 superficial, 72 invasive lesions, and 52 normal urothelium. Hierarchical clustering and supervised algorithms were used to classify and stratify bladder tumors on the basis of stage, node metastases, and overall survival. Immunohistochemical analyses on bladder cancer tissue arrays (n = 294 cases) served to validate associations between marker expression, staging and outcome.

Results

Hierarchical clustering classified normal urothelium, superficial, and invasive tumors with 82.2% accuracy, and stratified bladder tumors on the basis of clinical outcome. Predictive algorithms rendered an 89%-correct rate for tumor staging using genes differentially expressed between superficial and invasive tumors. Accuracies of 82% and 90% were obtained for predicting overall survival when considering all patients with bladder cancer or only patients with invasive disease, respectively. A genetic profile consisting of 174 probes was identified in those patients with positive lymph nodes and poor survival. Two independent Global Test runs confirmed the robust association of this profile with lymph node metastases (P = 7.3–13) and overall survival (P = 1.9–14) simultaneously. Immunohistochemical analyses on tissue arrays sustained the significant association of synuclein with tumor staging and clinical outcome (P = .002).

Conclusion

Gene profiling provides a genomic-based classification scheme of diagnostic and prognostic utility for stratifying advanced bladder cancer. Identification of this poor outcome profile could assist in selecting patients who may benefit from more aggressive therapeutic intervention.
Potential for alternative intron–exon pairings in group II intron RmInt1 from Sinorhizobium meliloti and its relatives
Authors: COSTA MARÍA , MICHEL FRANÇOIS , TORO NICOLÁS
Published: January 2006

Ribozyme constructs derived from group II intron RmInt1 of Sinorhizobium meliloti self-splice in vitro when incubated under permissive conditions, but exon ligation is unusually inefficient when the 5′ exon is truncated close to the IBS2 intron-binding site. One plausible explanation for this observation is the presence of an alternative intron–exon pairing between an intron segment that overlaps with the EBS2 exon-binding site and a 5′ exon site located just distal of IBS2 relative to the splice junction. Strikingly, the existence of this pairing is supported by comparative sequence analysis of introns related to RmInt1.
Distal regulation of alternative splicing by splicing enhancer in equine β-casein intron 1
Authors: LENASI TINA , PETERLIN B. MATIJA , DOVC PETER
Published: January 2006

The complexity of cotranscriptional splicing is reflected in the coordinated interplay between various cis-elements and transacting factors. In this report, we demonstrated that a cis-element in intron 1 of the equine β-casein gene (intronic splicing enhancer 1, ISE1) increases the inclusion of all weak exons in its pre-mRNA. The ISE1 also functioned on a hybrid transcript, which was transcribed from the α-globin promoter, where it increased the inclusion of the human fibronectin EDA exon and the β-casein exon 5. The region of ISE1 necessary for its function included the same sequence as is found in some exonic splicing enhancers. Since the ISE1 influenced the splicing of the entire transcript from intron 1, we propose a model for the cotranscriptional splicing of β-casein mRNA, where the 5′ end of the growing transcript remains associated with the C-terminal domain of RNA polymerase II. Thus, the ISE1 remains in close proximity to the mRNA exit groove throughout transcription and influences all weak exons as soon as they are copied.
Morphometric analysis of acetabular dysplasia in cerebral palsy
Authors: Chung C. Y. , Park M. S. , Choi I. H. , Cho T.-J. , Yoo W. J. , Lee K. M.
Published: January 2006

We carried out a morphometric analysis of acetabular dysplasia in patients with cerebral palsy requiring hip surgery using three-dimensional CT. We evaluated 54 hips in 27 patients. The contralateral normal hips of ten patients with unilateral Perthes’ disease were used as a control group. The acetabular defects were assessed qualitatively as anterior, posterior or global. Quantitative assessments were made using three-directional acetabular indices (anterosuperior, superolateral and posterosuperior) and measured by multiplanar reformation, from which we calculated the acetabular volume.

In the qualitative study, posterior defects were most common in the subluxation group whereas global defects predominated in the dislocation group. In the quantitative study, all acetabular indices in both the subluxation and dislocation groups were higher than those in the control group and the superolateral indices showed a tendency to elevation in the dislocation group. The acetabular volume was largest in the control group, smallest in the dislocation group, and intermediate between the two in the subluxation group.
The premature failure of the Charnley Elite-Plus stem
Authors: Hauptfleisch J. , Glyn-Jones S. , Beard D. J. , Gill H. S. , Murray D. W.
Published: January 2006

We performed a clinical and radiological study to determine the rate of failure of the Charnley Elite-Plus femoral component. Our aim was to confirm or refute the predictions of a previous roentgen stereophotogrammetric analysis study in which 20% of the Charnley Elite-Plus stems had shown rapid posterior head migration. It was predicted that this device would have a high early rate of failure.

We examined 118 patients at a mean of nine years after hip replacement, including the 19 patients from the original roentgen stereophotogrammetric study. The number of revision procedures was recorded and clinical and radiological examinations were performed.

The rate of survival of the femoral stems at ten years was 83% when revision alone was considered to be a failure. It decreased to 59% when a radiologically loose stem was also considered to be a failure. All the patients previously shown in the roentgen stereophotogrammetric study to have high posterior head migration went on to failure. There was a highly significant difference (p = 0.002) in posterior head migration measured at two years after operation between failed and non-failed femoral stems, but there was no significant difference in subsidence between these two groups.

Our study has shown that the Charnley Elite-Plus femoral component has an unacceptably high rate of failure. It confirms that early evaluation of new components is important and that roentgen stereophotogrammetric is a good tool for this. Our findings have also shown that rapid posterior head migration is predictive of premature loosening and a better predictor than subsidence.
Ankle arthrodesis and its relationship to ipsilateral arthritis of the hind- and mid-foot
Authors: Sheridan B. D. , Robinson D. E. , Hubble M. J. W. , Winson I. G.
Published: January 2006

It has been suggested that arthrodesis of the ankle leads to osteoarthritis of the joints of the ipsilateral hind- and midfoot. We believe these studies overlooked the presence of osteoarthritic changes in these joints before the arthrodesis.

We reviewed the pre-operative radiographs of 70 patients with osteoarthritis of the ankle who underwent 71 ankle arthrodeses (one was bilateral). The talonavicular, calcaneocuboid, subtalar and naviculocuneiform joints were given an osteoarthritis score according to Kellgren and Lawrence. The mean age at operation was 54.9 years and the most common indication was for post-traumatic osteoarthritis (52 cases). A total of 68 patients showed pre-existing arthritis in either the hind- or mid-foot, with the subtalar joint the most commonly affected.

Ipsilateral hind- and mid-foot arthritis is almost universally present in patients with arthritis of the ankle requiring arthrodesis. The presence of such changes may not be a consequence of this arthrodesis.
Hands-on robotic unicompartmental knee replacement
Authors: Cobb J. , Henckel J. , Gomes P. , Harris S. , Jakopec M. , Rodriguez F. , Barrett A. , Davies B.
Published: January 2006

We performed a prospective, randomised controlled trial of unicompartmental knee arthroplasty comparing the performance of the Acrobot system with conventional surgery. A total of 27 patients (28 knees) awaiting unicompartmental knee arthroplasty were randomly allocated to have the operation performed conventionally or with the assistance of the Acrobot. The primary outcome measurement was the angle of tibiofemoral alignment in the coronal plane, measured by CT. Other secondary parameters were evaluated and are reported.

All of the Acrobot group had tibiofemoral alignment in the coronal plane within 2° of the planned position, while only 40% of the conventional group achieved this level of accuracy. While the operations took longer, no adverse effects were noted, and there was a trend towards improvement in performance with increasing accuracy based on the Western Ontario and McMaster Universities Osteoarthritis Index and American Knee Society scores at six weeks and three months. The Acrobot device allows the surgeon to reproduce a pre-operative plan more reliably than is possible using conventional techniques which may have clinical advantages.
The effect of fixation and location on the stability of the markers in navigated total hip arthroplasty
Authors: Mayr E. , de la Barrera J.-L. Moctezuma , Eller G. , Bach C. , Nogler M.
Published: January 2006

In navigated total hip arthroplasty, the pelvis and the femur are tracked by means of rigid bodies fixed directly to the bones. Exact tracking throughout the procedure requires that the connection between the marker and bone remains stable in terms of translation and rotation. We carried out a cadaver study to compare the intra-operative stability of markers consisting of an anchoring screw with a rotational stabiliser and of pairs of pins and wires of different diameters connected with clamps. These devices were tested at different locations in the femur. Three human cadavers were placed supine on an operating table, with a reference marker positioned in the area of the greater trochanter. K-wires (3.2 mm), Steinman pins (3 and 4 mm), Apex pins (3 and 4 mm), and a standard screw were used as fixation devices. They were positioned medially in the proximal third of the femur, ventrally in the middle third and laterally in the distal portion. In six different positions of the leg, the spatial positions were recorded with a navigation system.

Compared with the standard single screw, with the exception of the 3 mm Apex pins, the two-pin systems were associated with less movement of the marker and could be inserted less invasively. With the knee flexed to 90° and the dislocated hip rotated externally until the lower leg was parallel to the table (figure-four position), all the anchoring devices showed substantial deflection of 1.5° to 2.5°. The most secure area for anchoring markers was the lateral aspect of the femur.
A Statistical Method to Assess the Reliability of Cleanness Measurements for High Quality Bearing Steels
Authors: Hénault E
Published: January 2006

During the past decade, greatly increased in-service demands on finished products such as gears, bearings, and springs have inspired a wish by steel makers to guarantee the highest level of cleanness in their steels. In order to achieve this, it has been necessary to develop methods of characterization of cleanness which can describe all the nonmetallic inclusion populations endogenous and exogenous contained in the steel. These methods are essentially based on quantitative metallography and ultrasonic tests. Statistical tools have also been developed to maximize the accuracy of measurements in relation to the time taken to make them, and to answer the key question: What is the minimum analyzed volume for which a measurement can be expected to yield a reliable estimate of a specific in-service property? For quantitative metallographic methods, smaller inclusion densities necessitate an increase in the surface area analyzed, and the study of a larger surface is time consuming. Extreme value analysis is a further method for prediction of the expected size of the largest inclusion in a volume. Often, however, the amount of material examined is not sufficient to assess the quality of the heat with complete certainty. Other tools that have been developed utilize high frequency ultrasonic tests over a frequency range from 10 to 100 MHz, which make it possible to detect inclusions with diameters ranging from 15 µm to 1 mm. In all cases, in order to obtain accurate estimates of the densities of nonmetallic inclusions, it is important to know the appropriate settings for the measurement method. In particular, it is very important to estimate the diagnosis error when we rate a product on the basis of measurements. For each of these inspection techniques, statistical models have been developed to assess the main statistical properties of the methods. The results are reported here. They give a basis for comparison of steel heats that takes account of knowledge of the confidence level of the various measurement methods.
The requisite path to community policing
Authors: Watson Elizabeth M.
Published: January 2006

This paper describes the author's recent six‐year experience of collaborating with Elliott Jaques in an examination of community policing. It describes how they met, some of the things she learned from him, the findings of the research, and why his work holds such potential for enhancing the effectiveness of policing in democratic societies. Copyright © 2005 John Wiley & Sons, Ltd.
Memories of Dr Elliott Jaques
Authors: King Pearl
Published: January 2006

Elliott Jaques studied medicine, and later became a major in the Canadian Army. He acted as a liaison offier with the Psychiatric Division of the British Army under Brigadier JR Rees, and in this role he made contact with psychoanalysts who worked in the British Army. Several of these officers, along with Jaques and myself, trained as psychoanalysts. Jaques was one of the founder members of the Tavistock Institute of Human Relations. In 1961 Jaques was elected as Scientific Secretary of the British Psychoanalytic Society. In 1965 he was appointed Professor and Head of the School of Social Sciences at Brunel University. In 1967 he asked me to work as a part‐time senior lecturer in the School. Jaques was a prolific writer and became known to organizations world‐wide. He was a consultant to a number of institutions, and later to governments, including the Pentagon. In 1980 he left London for the USA. Copyright © 2005 John Wiley & Sons, Ltd.
Who was Elliott Jaques?
Authors: Kirsner Douglas
Published: January 2006

Douglas Kirsner traces his own collaboration with Elliott Jaques to explain the trajectory of Elliott's life and work, in particular his overall goals of understanding individuals and their social and biological contexts. He describes Elliott's approach as ranging across many disciplines and explores why, given its value, his work has been has been taken up relatively little by others. Kirsner describes who Elliott was and how he approached his stratified systems theory, requisite organization, work. Copyright © 2005 John Wiley & Sons, Ltd.
Einfluss der flüssigen Phase auf Detonationen im zweiphasigen System Methanol/Sauerstoff
Authors: Dengel J. , Hieronymus H.
Published: January 2006

Untersucht werden Detonationen im zweiphasigen System, bestehend aus flüssigem Methanol und gasförmigen Sauerstoff. Bei Detonationen in zweiphasigen Systemen treten im Vergleich zu Gasdetonationen außerordentlich hohe Druckerhöhungsfaktoren auf. Eine sicherheitstechnische Bewertung solcher zweiphasigen Systeme wird dadurch erschwert, dass die von Gasexplosionen bekannten sicherheitstechnischen Kenngrößen, beispielsweise die Explosionsgrenzen, nicht unmittelbar auf zweiphasige Systeme zu übertragen sind. So haben diese Systeme bei bestimmten Prozessparametern die Eigenschaft, dass Detonationen auch dann auftreten können, wenn die Gasphase, bestehend aus dem Oxidationsmittel und dem Lösemitteldampf, nicht explosionsfähig ist. Die Ergebnisse zeigen, dass zweiphasige Systeme höhere Risiken als detonationsfähige Mischungen in der reinen Gasphase aufweisen.
Untersuchung des Verweilzeitverhaltens eines autothermen Vergasungsreaktors bei Drücken bis 70 bar(Ü)
Authors: Zeißler R. , Meyer B. , Seifert P. , Heinzel A. , Jentsch T.
Published: January 2006

Die Hochdrucksynthesegaserzeugung ist eine Schlüsseltechnologie für zukunftsorientierte Energiekonzepte großer Leistung. In dem gemeinsam mit Lurgi vorangebrachten HP‐POX‐Projekt der TU Bergakademie Freiberg sollen Möglichkeiten zur Leistungssteigerung und zur Modellierung einer neuen Vergasergeneration mit Drücken bis 100 bar(Ü) untersucht werden. Strömungstechnische Informationen über diesen messtechnisch schwer zugänglichen Reaktor sind für Modellierungsaufgaben unerlässlich. Es werden Verweilzeitmessungen an dem 5‐MW‐Vergaser bei Drücken von 30 bis 70 bar(Ü) durchgeführt. Es wird gezeigt, dass das Strömungsprofil des Reaktors als eine Schaltung von Idealreaktoren abgebildet werden kann. Dies eröffnet Möglichkeiten, die Modelle für gekoppelte Strömungs‐ und Reaktionsprozesse mit dem tatsächlichen Verweilzeitverhalten abzugleichen.
Untersuchungen an einer Filterschneckenpresse für feindispers mineralische Schlämme
Authors: Dong D. , Schlegel D.
Published: January 2006

Das Konzept einer Filterschneckenpresse für Suspensionen von feindispers mineralischen Teilchen mit Teilchengrößen im μm‐Bereich, z. B. für einen feinkeramischen Schlicker in Wasser, wird in einer Pilotanlage getestet. Dauerversuche zeigen, dass Abrieb und Verstopfungen beherrschbar sind und dass der flächenspezifische Filtratfluss wesentlich größer ist als in einer Kammerfilterpresse. Die Bedingungen für ein optimales Steuer‐ und Regelverhalten werden ermittelt. Mit Modellannahmen werden die gekoppelten Vorgänge von Flüssigkeitsabtrennung und Druckaufbau in der Filterschneckenpresse durch numerische Rechnung simuliert. Rechen‐ und Messergebnisse stimmen für das feinkeramische Material in der Pilotanlage gut überein.
Strukturierung von Oberflächen mit Hilfe polymerer Stempelstrukturen
Authors: Winzer B. , Peukert W.
Published: January 2006

Oberflächen, die hinsichtlich der Benetzungseigenschaften über Microcontact‐Printing vorstrukturiert sind, können in weiteren Experimenten zur geordneten Anlagerung von verschiedensten kolloidalen Partikeln eingesetzt werden. Bei entsprechender Wahl der Stabilitätsbedingungen in der Lösung, der Partikelkonzentration und der Trocknungsbedingungen des Films erhält man geordnete Strukturen von Mikro‐ und Nanopartikeln auf lokal scharf abgegrenzten Oberflächenbereichen.
Untersuchung der Sorption und Reaktion von 1‐Buten an einem technischen VOx‐TiO2‐Katalysator
Authors: Suprun W. , Kießling D. , Staudt R. , Schädlich K. , Papp H.
Published: January 2006

Während die Wirkungsweise von VOx‐TiO2‐Katalysatoren bei der katalytischen Oxidation und bei oxidativen Dehydrierreaktionen intensiv untersucht wurde, liegen zum Adsorptionsverhalten von C4‐Kohlenwasserstoffen an diesen Katalysatoren keine Angaben vor. Ziel der vorliegenden Arbeit war es, die Adsorption von 1‐Buten an einem VOx‐TiO2‐Katalysator unter den technisch relevanten Reaktionsbedingungen der Selektivoxidation von n‐Butan/n‐Buten zu untersuchen. Für die mathematische Beschreibung des Reaktionsablaufes sind neben Kenntnissen reaktionskinetischer Parameter auch die von Adsorptions‐ und Desorptionsprozessen erforderlich.
Herstellung von Kohlenstoff‐Nanotubes und ‐fasern durch Gasphasenabscheidung
Authors: Jess A. , Kern C. , Schrögel K. , Jung A. , Schütz W.
Published: January 2006

Kohlenstoff‐Nanotubes und ‐fasern sind interessante Materialien für viele Anwendungen, angefangen von der Kunststofftechnik bis zur Katalyse. Bisher existiert aber noch kein technischer Herstellungsprozess. Die vorliegende Arbeit soll eine Übersicht über die Grundlagen der Synthese von Kohlenstoff‐Nanotubes und ‐fasern geben. Das Hauptaugenmerk liegt dabei auf der Kinetik und Reaktionstechnik der Herstellung durch katalytische Gasphasenabscheidung aus Kohlenmonoxid und Ethen.
Die Finite‐Elemente‐Methode am Beispiel des Strahlapparates
Authors: Vogel H.‐H.
Published: January 2006

Strahlapparate werden in vielen Bereichen der Vakuum‐, Verfahrens‐ und Energietechnik eingesetzt. Diese Arbeit betrachtet Fluide konstanter und gleicher Dichte, wie sie in Flüssigkeits/Flüssigkeits‐ und in erster Näherung in Gas/Gas‐Strahlapparaten für Unterschallgeschwindigkeiten vorliegen, zur Aufdeckung einfacher Gesetzmäßigkeiten. Die Ergebnisse der Finite‐Elemente‐Methode werden auf ein einfaches eindimensionales Strömungsmodell übertragen, das sich mit Hilfe neu eingeführter Diagramme zur graphischen Inter‐ und Extrapolation der Ergebnisse gut eignet.
Conjugation of a Photosensitizer to an Oligoarginine‐Based Cell‐Penetrating Peptide Increases the Efficacy of Photodynamic Therapy
Authors: Choi Yongdoo , McCarthy Jason R. , Weissleder Ralph , Tung Ching‐Hsuan
Published: January 2006

To improve the efficiency of intracellular delivery of photosensitizers and the efficacy of photodynamic therapy, a membrane‐penetrating arginine oligopeptide (R7) was conjugated to 5‐[4‐carboxyphenyl]‐10,15,20‐triphenyl‐2,3‐dihydroxychlorin (TPC). The resulting conjugate (R7–TPC) enhanced intracellular TPC uptake, which increased proportionally with the incubation time of the conjugate. The water solubility of the highly hydrophobic TPC photosensitizer was also improved after conjugation. Increased phototoxicity of R7–TPC was observed after an incubation time of only 30 min. Tumor cells mainly underwent apoptosis at lower concentrations of the photosensitizer–polyarginine conjugate, whereas necrotic cell damage became prevalent at higher concentrations.
Bisubstrate Inhibitors of CatecholO‐Methyltransferase (COMT): the Crucial Role of the Ribose Structural Unit for Inhibitor Binding Affinity
Authors: Paulini Ralph , Trindler Christian , Lerner Christian , Brändli Lukas , Schweizer W. Bernd , Jakob‐Roetne Roland , Zürcher Gerhard , Borroni Edilio , Diederich François
Published: January 2006

Inhibition of the enzyme catechol O‐methyltransferase offers a therapeutic handle to regulate the catabolism of catecholamine neurotransmitters, providing valuable assistance in the treatment of CNS disorders such as Parkinson's disease. A series of ribose‐modified bisubstrate inhibitors of COMT featuring 2′‐deoxy‐, 3′‐deoxy‐, 2′‐aminodeoxy‐3′‐deoxy‐, and 2′‐deoxy‐3′‐aminodeoxyribose‐derived central moieties and analogues containing the carbocyclic skeleton of the natural product aristeromycin were synthesized and evaluated to investigate the molecular recognition properties of the ribose binding site in the enzyme. Key synthetic intermediates in the ribose‐derived series were obtained by deoxygenative [1,2]‐hydride shift rearrangement of adenosine derivatives; highlights in the synthesis of carbocyclic aristeromycin analogues include a diastereoselective cyclopropanation step and nucleobase introduction with a modified Mitsunobu protocol. In vitro biological evaluation and kinetic studies revealed dramatic effects of the ribose modification on binding affinity: 3′‐deoxygenation of the ribose gave potent inhibitors (IC50values in the nanomolar range), which stands in sharp contrast to the remarkable decrease in potency observed for 2′‐deoxy derivatives (IC50values in the micromolar range). Aminodeoxy analogues were only weakly active, whereas the change of the tetrahydrofuran skeleton to a carbocycle unexpectedly led to a complete loss of biological activity. These results confirm that the ribose structural unit of the bisubstrate inhibitors of COMT is a key element of molecular recognition and that modifications thereof are delicate and may lead to surprises.