bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging
Authors: Hyodo Fuminori , Soule Benjamin P , Matsumoto Ken-ichiro , Matusmoto Shingo , Cook John A , Hyodo Emi , Sowers Anastasia L , Krishna Murali C , Mitchell James B
Published: July 2008

Regulation of tissue redox status is important to maintain normal physiological conditions in the living body. Disruption of redox homoeostasis may lead to oxidative stress and can induce many pathological conditions such as cancer, neurological disorders and ageing. Therefore, imaging of tissue redox status could have clinical applications. Redox imaging employing magnetic resonance imaging (MRI) with nitroxides as cell-permeable redox-sensitive contrast agents has been used for non-invasive monitoring of tissue redox status in animal models. The redox imaging applications of nitroxide electron paramagnetic resonance imaging (EPRI) and MRI are reviewed here, with a focus on application of tumour redox status monitoring. While particular emphasis has been placed on differences in the redox status in tumours compared to selected normal tissues, the technique possesses the potential to have broad applications to the study of other disease states, inflammatory processes and other circumstances where oxidative stress is implicated.
High-throughput screening technologies for drug glucuronidation profiling
Authors: Trubetskoy Olga , Finel Moshe , Trubetskoy Vladimir
Published: July 2008

A significant number of endogenous and exogenous compounds, including many therapeutic agents, are metabolized in humans via glucuronidation, catalysed by uridine diphosphoglucurono-syltransferases (UGTs). The study of the UGTs is a growing field of research, with constantly accumulated and updated information regarding UGT structure, purification, substrate specificity and inhibition, including clinically relevant drug interactions. Development of reliable UGT assays for the assessment of individual isoform substrate specificity and for the discovery of novel isoform-specific substrates and inhibitors is crucial for understanding the function and regulation of the UGT enzyme family and its clinical and pharmacological relevance. High-throughput screening (HTS) is a powerful technology used to search for novel substrates and inhibitors for a wide variety of targets. However, application of HTS in the context of UGTs is complicated because of the poor stability, low levels of expression, low affinity and broad substrate specificity of the enzymes, combined with difficulties in obtaining individual UGT isoforms in purified format, and insufficient information regarding isoform-specific substrates and inhibitors. This review examines the current status of HTS assays used in the search for novel UGT substrates and inhibitors, emphasizing advancements and challenges in HTS technologies for drug glucuronidation profiling, and discusses possible avenues for future advancement of the field.
Effect of oil-in-water lipid emulsions prepared with fish oil or soybean oil on the growth of MCF-7 cells and HepG2 cells
Authors: Ueda Kumiko , Asai Yukiko , Yoshimura Yoshimizu , Iwakawa Seigo
Published: July 2008

The growth of human breast cancer-derived MCF-7 cells was affected by oil-in-water lipid emulsions prepared with fish oil (FO) rich in n-3 fatty acids (FAs) and egg-yolk phosphatides (EYP) (FO-emulsions), but not by lipid emulsions prepared with soybean oil (SO) and EYP (SO-emulsions). On the other hand, the growth of human hepatocarcinoma HepG2 cells was affected by neither SO-emulsions nor FO-emulsions. The growth inhibition of MCF-7 cells in the presence of FO-emulsions was not affected by trolox, but was inhibited by α-lipoic acid, and was even potentiated by ebselen, which works as an antioxidant as well as a lipoxygenase inhibitor. Since prostaglandin E3, generated from n-3 FAs by cyclooxygenases, has a suppressive effect on tumour cell growth, and increases when lipoxygenases are inhibited, these findings suggest that lipid emulsions incorporating triglycerides of n-3 FAs might be effective in suppressing the growth of MCF-7 cells, possibly via oxidative stress and through eicosanoid production with anti-proliferating activity against cancer cells.
Inflammatory factors that contribute to upregulation of ERG and cardiac arrhythmias are suppressed by CPU86017, a class III antiarrhythmic agent
Authors: Du Rong-Hui , Yi Hong-Wei , Dai De-Zai , Tang Wei-Hua , Dai Yin
Published: July 2008

The aim of this study was to verify whether exaggerated arrhythmogenesis is attributed to inflammatory factors actively involving an excess of reactive oxygen species (ROS), transforming growth factor (TGF)-β and endothelin (ET). We hypothesized that CPU86017, derived from berberine, which possesses multi-channel blocking activity, could suppress inflammatory factors, resulting in inhibition of over-expression of ether-a-go-go (ERG) and an augmented incidence of ventricular fibrillation (VF) in ischaemia/reperfusion (I/R). Rats with cardiomyopathy (CMP) induced by thyroxine (0.2 mg−1kg−1 s.c. daily for 10 days) were treated with propranolol (10 mg kg−1 p.o.) or CPU86017 (80 mg kg−1 p.o.) on days 6–10. On the 11th day, arrhythmogenesis of the CMP was evaluated by I/R. In the CMP control group, an increase in VF incidence was found with the I/R episode, accompanied by increased ROS, which manifested as an increased level of malondialdehyde and decreased activities of SOD, glutathione peroxidase and catalase in the myocardium. Levels of inducible nitric oxide synthase and TGF-β mRNA were increased in association with upregulation of preproET-1 and ET- converting enzyme. We found increased levels of ERG, which correlated well with arrhythmogenesis. Treatment with CPU86017 or propranolol reversed these changes. These experiments verified our hypothesis that the inflammatory factors ROS, iNOS, TGF-β and ET-1 are actively involved in upregulation of ERG and arrhythmogenesis. CPU86017 and propranolol reduced VF by suppressing these inflammatory factors in the myocardium.
Adrenergic responses of rat colonic muscularis mucosae
Authors: Percy William H , Keupp Sarah M
Published: July 2008

We have investigated adrenoceptor-mediated responses of muscularis mucosae from the proximal, mid and distal regions of the rat colon. Noradrenaline-induced relaxations of the muscularis mucosae in each region were unaffected by atenolol, butoxamine or propranolol, but they were attenuated by the selective β3-adrenoceptor antagonist cyanopindolol. The β3-adrenoceptor agonist CL216343 elicited concentration-dependent relaxation of the muscularis mucosae in all regions of the colon. Isoprenaline, a non-selective β-adrenoceptor agonist, evoked concentration-dependent relaxations of the muscularis mucosae in all regions, but only in the proximal colon were these significantly larger than the maximum noradrenaline-induced relaxation. The α1-adrenoceptor agonist methoxamine caused large contractions of the proximal colonic muscularis mucosae. When proximal tissue was pretreated with phentolamine, an α1-adrenoceptor antagonist, maximal noradrenaline- and isoprenaline-induced relaxations did not differ significantly. Although the mid colonic muscularis mucosae was also found to possess excitatory α1-adrenoceptors, these were associated with small contractions and did not modify the muscle's inhibitory responses to noradrenaline. Distal colonic muscularis mucosae lacked excitatory adrenoceptors and only responded to noradrenaline with β3-adrenoceptor-mediated relaxations. No evidence was obtained for functional α2-adrenoceptors on the muscularis mucosae in any region of the rat colon. These data demonstrated that noradrenaline-induced relaxation of the rat colonic muscularis mucosae was mediated via β3-adrenoceptors throughout, but in the proximal region this was modified by concurrent excitatory α1-adrenoceptor activation. Based upon these observations it appeared unlikely that noradrenaline-induced relaxation of rat colonic muscularis mucosae would be functionally linked to the secretory responses of the corresponding mucosa during periods of increased sympathetic activity.
Inhibition of H+/K+ ATPase in the gastroprotective effect ofBaccharis illinitaDC
Authors: Freitas Cristina S , Baggio Cristiane H , Finau Jaqueline , Anginoni Margano , Pizzolatti Moacir G , Santos Adair R S , Marques Maria C A
Published: July 2008

Baccharis illinita DC (Compositae) is used in folk medicine to treat gastric disturbances. Preliminary studies with other extracts of B. Illinita showed gastric protection against ethanol-, indometacin- and stress-induced ulcers and the inhibition of gastric secretion. Based on these data, the aim of this study was to verify the pathways involved in the inhibition of gastric secretion. The chloroform extract (CE) of flowers from B. illinita (3, 10, 30 and 100 mg kg−1 i.p.) tested on rats with pylorus ligature reduced the volume and the total acidity of gastric content by approximately 50% (ED50 = 69 mg kg−1). Treatment with CE (100 mg kg−1 i.p.) reduced the gastric total acidity stimulated by histamine, bethanechol and pentagastrin to 42%, 27% and 57% of that in the stimulated control group, respectively. The CE (10, 30 and 100 μM) inhibited H+/K+ ATPase activity in-vitro, with an IC50 of 37 μM. The isolated flavonoid luteolin (1, 3, 10 and 30 μM) also inhibited H+/K+ ATPase activity by 50%, at a dose of 30 μM. Our results suggest that the reduction in gastric secretion occurs through inhibition of H+/K+ ATPase, which is the final step in acid secretion and therefore one of the most important steps.
Consistency study on three cutting force modelling methods for peripheral milling
Authors: Wan M , Zhang W H , Qin G H , Wang Z P
Published: July 2008

Three methods are presented for calibrating the instantaneous cutting force coefficient (ICFC) and the cutter runout parameters in peripheral milling. In the first method, ICFC and the runout parameters are calibrated separately. First, the nominal cutting force components extracted from the measured force data are used to calibrate the ICFC, and then the runout parameters are obtained by optimally selecting those producing the minimum squared difference between the measured and predicted cutting forces. The second method calibrates the cutting force coefficients and the runout parameters simultaneously by choosing those that best maintain the cutting force coefficients constant. The third method was previously proposed by the current authors. Comparisons between the calibrated results from different tests and different methods are made to validate the consistency of the presented methods. Experiments are also conducted for comparison purposes.
Gate positioning design of injection mould using bi-objective micro genetic algorithm
Authors: Lee J , Lee J
Published: July 2008

The use of a micro genetic algorithm (mGA)-based approach to solve a bi-objective optimization of an injection mould design problem is presented. The advantage of the mGA-based approach is that it requires fewer computational resources than a conventional GA because it has a smaller population than a conventional GA. The main drawback of the mGA-based approach is that design diversity is not secured when multi-modal and multi-objective designs are investigated. To implement the mGA-based bi-objective optimization procedure, the present study proposes a memory set, a filtering process, weight control, and reproduction from the memory set in order to explore new optimal solutions, and identify more-evenly distributed Pareto surfaces. A number of mathematical functions and a typical structural optimization problem are tested to verify the proposed strategies. The approach is subsequently applied to the bi-objective injection moulding design problem of minimizing both the maximum injection pressure and maximum pressure difference between the gate positions in the runner system.
Validity and reliability of applying manufacturing excellence frameworks to Indian industries
Authors: Sharma M , Kodali R
Published: July 2008

Manufacturing excellence requires a manufacturer to be the best in its field in each competitive priority and to demonstrate industry best practice. This paper explores the validity and reliability of existing manufacturing excellence/world-class manufacturing frameworks when applied to Indian companies by means of a survey conducted across a wide range of manufacturing companies based in India. The nature of the questionnaire is outlined together with the results from the analysis of the data obtained from the questionnaire. This research has identified that while a majority of the frameworks display a high level of reliability, very few of them display unidimensionality with respect to the construct, i.e. the manufacturing excellence it measures. A frequency analysis shows that the majority of the attributes have a high mean score. As all the frameworks display different elements with some overlap among them, it was found that there is a need for a new framework.
A heuristic for the one-dimensional cutting stock problem with pattern reduction
Authors: Cui Y , Zhao X , Yang Y , Yu P
Published: July 2008

A sequential heuristic algorithm is presented for the one-dimensional cutting stock problem in which a set of items with specified length and demand are cut from the stock rods such that the waste is minimized. The algorithm generates a cutting pattern using items of a selected subset of the unassigned items, determines the frequency (number of times) at which the pattern can be used, deletes from the set of the unassigned items those that are assigned to the current pattern, and repeats until all items have been assigned. The selected subset is determined such that the frequency of the generated pattern can be as large as possible, provided that some constraints are observed to keep reasonable trim loss, and the cutting pattern is obtained from solving a bounded knapsack problem. The computational test on 18 classes of 1800 benchmark instances indicates that the algorithm performs better than two recently published algorithms for pattern reduction.
Shaft diagnostics and prognostics development and evaluation using damaged dynamic simulation
Authors: Wu S , He D
Published: July 2008

This paper presents a shaft damage dynamic simulation methodology for development and evaluation of effective diagnostic and prognostic algorithms. The methodology uses dynamic shaft vibration models to simulate vibration signals with arbitrary shaft and operating conditions. These simulated vibration signals are used to develop and validate different diagnostic and prognostic algorithms. A simulation study to demonstrate the application of the methodology is provided. In comparison with traditional methods that acquire data from test rig or operational machines, the presented methodology has the following three major benefits. (1) It is able to simulate signals under any shaft and operating conditions (crack size, speed, torque), which is important because of the cost and time required to gather comprehensive operational and test bench data for algorithm development and validation. (2) The methodology could capture nuance for tiny faults without the contamination of extraneous variables, such as ambient noise, test stand dynamics, etc., that are not present in the actual case. Accuracy in this regard is crucial when using vibration data to diagnose faults, for instance to distinguish the effect of noise from a minor crack. (3) It may approach the true signatures of naturally occurring and growing faults more closely by comparison with artificially seeded fault tests or highly accelerated fatigue tests.
Fusion of artificial neural networks and genetic algorithms for multi-objective system reliability design optimization
Authors: Zio E , Maio F Di , Martorell S
Published: July 2008

In this work, artificial neural networks (ANNs) are used to include the decision-maker's preference structure within a genetic algorithm (GA) search of the optimal system reliability configuration. For verification, the proposed approach is applied to two literature case studies of increasing complexity concerning the optimization of the reliability design of a series system.
Identifying critical components in technical infrastructure networks
Authors: Jönsson H , Johansson J , Johansson H
Published: July 2008

A new method for identifying and ranking critical components and sets of components in technical infrastructures is presented. The criticality of a component or a set of components is defined as the vulnerability of the system to failure in a specific component, or set of components. The identification of critical components is increasingly difficult when considering multiple simultaneous failures. This is especially difficult when dealing with failures of multiple components with synergistic consequences, i.e. consequences that cannot be calculated by adding the consequences of the individual failures. The proposed method addresses this problem. In exemplifying the method, an analysis of an electric power distribution system in a Swedish municipality is presented. It is concluded that the proposed method facilitates the identification of critical sets of components for large-scale technical infrastructures.
A multi-objective genetic algorithm for RAMS+C optimization with uncertain decision variables
Authors: Martorell S , Sánchez A , Villanueva J F , Carlos S , Serradell V
Published: July 2008

Surveillance requirements applied to safety systems of a nuclear power plant are established by the technical specification (TS). These requirements impose the surveillance test intervals (STIs) performed to ensure that safety-related systems normally in standby are ready to operate on demand. There is a great interest in the optimization of STIs, as they have a great effect on plant risk and also on the resources necessary to implement a certain surveillance test strategy. Operational experience at nuclear power plants shows that tests are not performed at a constant interval. Thus, it is a more realistic choice to consider the STI as a random variable rather than a constant value, as it has usually been considered. This paper focuses on the STI optimization based on risk and cost criteria and considering that the test intervals can be performed within a tolerance range.
Analysis of non-coherent fault trees using ternary decision diagrams
Authors: Remenyte-Prescott R , Andrews J
Published: July 2008

Risk and safety assessments performed on potentially hazardous industrial systems commonly utilize fault tree analysis (FTA) to forecast the probability of system failure. The type of logic for the top event is usually limited to AND and OR gates, which leads to a coherent fault tree structure. In non-coherent fault trees, the working states of components as well as their failures contribute to the failure of the system. The qualitative and quantitative analyses of non-coherent fault trees can introduce further difficulties over and above those seen in the coherent case. It is shown that the binary decision diagram (BDD) method can be used for this type of assessment. The BDD approach can improve the accuracy and efficiency of the quantitative analysis of non-coherent fault trees. This article demonstrates the value of the ternary decision diagram (TDD) method for the qualitative analysis of non-coherent fault trees. Such analysis can be used to provide information to a decision-making process for future actions of an autonomous system, and therefore it must be performed in real time. In these circumstances, fast processing and small storage requirements are very important. The TDD method provides a fast processing capability, and small storage is achieved when a single structure is used for both qualitative and quantitative analyses. The efficiency of the TDD method is discussed and compared with the performance of the established methods for analysis of non-coherent fault trees.
Multistate systems with static performance- dependent fault coverage
Authors: Levitin G , Amari S V
Published: July 2008

The paper suggests a new fault coverage model for the case when the effectiveness of recovery mechanisms in a subsystem depends on the entire performance level of this subsystem. Examples of this effect can be found in computing systems, electrical power distribution networks, communication systems, etc. The paper presents a modification of the generalized reliability block diagram (RBD) method for evaluating reliability and performance indices of complex multistate series-parallel systems with performance-dependent fault coverage under the assumption that the system state cannot change during the task execution. The suggested method based on a universal generating function technique allows the system performance distribution to be obtained using a straightforward recursive procedure. Illustrative examples are presented.
Look Before You Leap: Market Opportunity Identification in Emerging Technology Firms
Authors: Gruber Marc , MacMillan Ian C. , Thompson James D.
Published: July 2008

Entrepreneurs play a fundamental role in bringing new technologies to market. Because technologies are often configurable to serve a variety of different markets, it is possible for entrepreneurs to identify multiple market opportunities prior to the first market entry of their emerging firms, and if they elect to do so, to therefore have a choice of which market to enter first. The empirical results presented in this paper offer three new insights regarding this important early-stage choice in new firm creation. First, they reveal that serial entrepreneurs have learned through prior start-up experience to generate a “choice set” of alternative market opportunities before deciding which one to pursue in their new firm creation. Second, the analysis indicates that entrepreneurs who identify a “choice set” of market opportunities prior to first entry derive performance benefits by doing so. Third, the positive relationship between the number of market opportunities identified prior to first entry and new firm performance is nonlinear and subject to decreasing marginal return. The research literature has yet to acknowledge the notion of multiple opportunity identification prior to entry, and the related idea of selecting the most favorable market opportunity for the creation of a new technology firm.
Sex‐biased ratio of avoidant/ambivalent attachment in middle childhood
Authors: Del Giudice Marco
Published: July 2008

In this study, new evidence is presented of marked sex differences in the distribution of insecure attachment patterns in middle childhood. Attachment was assessed with the Manchester Child Attachment Story Task (MCAST) in a sample of 122 Italian 7‐year‐olds. The four‐way distribution of attachment patterns was significantly unbalanced, with insecure boys more often avoidant (27%) than ambivalent (2%), and insecure girls more often ambivalent (25%) than avoidant (4%). In addition, boys were rated as more severely disorganized than girls on a continuous disorganization score. A survey of previous literature strongly collaborates these findings, showing that similar attachment distributions have been obtained cross‐culturally (US, Canada, and Israel) in nearly all of the (relatively few) studies in which children's sex had been taken into account. It is argued that sex biases in attachment avoidance/ambivalence become apparent starting at about 6–7 years, in contrast with the lack of sex‐related effects in infancy and early childhood, and probably anticipate the pattern of sex differences found in adults with romantic attachment questionnaires.
Children's subjective identification with social groups: A group‐reference effect approach
Authors: Bennett Mark , Sani Fabio
Published: July 2008

A study is reported that seeks to examine 5‐, 7‐, and 10‐year‐old children's internalization of in‐groups within the self‐concept. Methodologically, the study draws upon the self‐reference effect, extending it to the group‐level identity. In particular, it was found that participants' encoding of information with reference to in‐groups (family, age, gender) facilitated recall to the same degree as when information had been encoded with reference to the personal self. Both self‐ and group‐reference encoding were associated with higher levels of recall than were control conditions. These findings suggest that group memberships are integral parts of children's self‐concepts.
Perception and awareness of accents in young children
Authors: Girard Frédérique , Floccia Caroline , Goslin Jeremy
Published: July 2008

This study examines children's metaphonological awareness for accent‐related information in connected speech. In the first experiment, 5‐ to 6‐year‐old French‐speaking children were asked to discriminate between Southern and Northern accented French in a sentence categorization task. It was found that these children were not able to reliably distinguish between these native variations of their own language, but were able to distinguish between their own accent and a strong foreign accent in Experiment 2. These findings were also replicated using a speaker discrimination task in Experiment 3, where children were asked to detect pairs of speakers sharing the same accent amongst speaker pairs with different accents. Whilst these experiments have shown that 5‐ to 6‐year‐old children do not use non‐familiar regional accents as a discriminatory cue, they are able to perceive the differences between accents, as demonstrated in the AX task used in Experiment 4. The factors underlying the relative lack of awareness for a regional accent as opposed to a foreign accent in childhood are discussed, especially regarding the amount of exposure and the learnability of both types of accents.
Motion prediction and the velocity effect in children
Authors: Benguigui Nicolas , Broderick Michael P. , Baurès Robin , Amorim Michel‐Ange
Published: July 2008

In coincidence‐timing studies, children have been shown to respond too early to slower stimuli and too late to faster stimuli. To examine this velocity effect, children aged 6, 7.5, 9, 10.5, and adults were tested with two different velocities in a prediction‐motion task which consisted of judging, after the occlusion of the final part of its path, the moment of arrival of a moving stimulus towards a specified position. A similar velocity effect, resulting in later responses for the faster velocities than for the slower, was found primarily in the three younger groups of children (for the longer occlusion conditions: 600–1,320 milliseconds). However, this effect was not seen in all children in these groups. Individual analyses showed that this velocity effect, when present, is linked to the use of distance rather than time information, or to the confusion between these in extrapolating the occluded trajectories. The tendency to use one type of information or the other is a good predictor of accuracy and variability in this task and a good indicator of the development stage of the participants. Across development, children tend to initially use distance information with poor accuracy but relative consistency in responses. In a second stage, they use time and distance information alternatively across trials trying to find a better source of information with still poor accuracy and now great variability. In a final stage, they use time information to reach consistency and accuracy in their responses. This chronology follows the stages proposed by Savelesbergh and Van der Kamp (2000) explaining development with an initial stage of ‘freezing’ non‐optimal relationships between information and movement, then a ‘freeing’ stage during which new solutions are searched for, and finally an ‘exploiting’ stage with an optimal relationship between information and movement.
PCR-Based Analysis of Differentially Methylated Regions of GNAS Enables Convenient Diagnostic Testing of Pseudohypoparathyroidism Type Ib
Authors: Weinhaeusel Andreas , Thiele Susanne , Hofner Manuela , Hiort Olaf , Noehammer Christa
Published: July 2008

Background: Pseudohypoparathyroidism type Ib (PHPIb) is characterized by parathyroid hormone (PTH) resistance, which can lead to hypocalcemia, hyperphosphatemia, and increased serum PTH. The disorder is caused by mutations in regulatory regions of the GNAS gene (GNAS complex locus) that lead to interferences in the methylation status of alternative GNAS promoters, such as exon A/B, NESP55, and XLα-s. PHPIb comprises disorders that show distinctive changes in methylation status but share the same clinical phenotype: (a) loss of methylation only at exon A/B of the GNAS gene and involving no other obvious epigenetic abnormalities [e.g., those caused by heterozygous microdeletions in the STX16 (syntaxin 16) region and found in many patients with autosomal dominant (AD) PHPIb]; (b) methylation abnormalities at several differentially methylated regions (DMRs), which are observed in most patients with sporadic PHPIb and some families with AD PHPIb.

Methods: To permit early and reliable diagnosis of suspected PHPIb, we designed methylation-sensitive restriction enzyme–based and bisulfite deamination–based PCR tests for exon A/B and NESP55 DMRs.

Results: Both PCR strategies permit proper methylation testing of GNAS and NESP55 DMRs and elucidate different disease subtypes. We have identified a novel microsatellite repeat polymorphism within GNAS exon A/B, and pedigree analyses have shown its presence to be conclusive evidence for familial disease.

Conclusions: We provide a simple diagnostic test for PHPIb, an imprinting disorder caused by different molecular changes within the GNAS complex locus. PHPIb, a complex and diagnostically challenging clinical phenotype, can be treated successfully by taking steps before the manifestation of symptoms to avoid clinical complications in affected patients or asymptomatic members of affected families who show positive results in genetic tests.
Comparison between Immunoturbidimetry, Size-Exclusion Chromatography, and LC-MS to Quantify Urinary Albumin
Authors: Shaikh Aisha , Seegmiller Jesse C , Borland Timothy M , Burns Bradley E , Ladwig Paula M , Singh Ravinder J , Kumar Rajiv , Larson Timothy S , Lieske John C
Published: July 2008

Background: The accurate and precise measurement of urinary albumin is critical, since even minor increases are diagnostically sensitive indicators of renal disease, cardiovascular events, and risk for death. To gain insights into potential measurement biases, we systematically compared urine albumin measurements performed by LC-MS, a clinically available immunoturbidimetric assay, and size-exclusion HPLC.

Methods: We obtained unused clinical urine samples from 150 patients who were stratified by degrees of albuminuria (<20 mg/L, 20–250 mg/L, >250 mg/L) as determined by the immunoturbidimetric assay used in our clinical laboratory (Roche Hitachi 912). Urine albumin was then remeasured via LC-MS and HPLC (Accumin™) assays.

Results: The immunoturbidimetric assay, calibrated using manufacturer-supplied serum-derived calibrators (Diasorin), underestimated albumin compared with LC-MS. After calibration with purified HSA, this immunoturbidimetric assay correlated well with LC-MS. HPLC overestimated albumin compared with both LC-MS and immunoturbidimetry. The current LC-MS and HPLC assays both performed poorly at concentrations <20 mg/L.

Conclusions: Efforts are needed to establish gold-standard traceable calibrators for clinical assays. LC-MS is a specific method to quantify albumin in native urine when concentrations exceed 20 mg/L, and therefore could be employed for standardization among assays.
Hydrogen-bonded frameworks in molecular metal-organic crystals: the network approach
Authors: Baburin Igor A.
Published: July 2008

Supramolecular architectures in molecular metal-organic crystals with three-dimensional networks of hydrogen bonds have been studied from the topological point of view. 636 hydrogen-bonded frameworks have been classified into 78 types of three-dimensional nets. It is shown that the resulting type of a framework is predetermined by prevailing octahedral coordination of metals in complexes that leads to the preference of 6-and 8-coordinated net topologies and those framework types compatible with the inversion symmetry of a complex. The study of molecular packings in metal-organic crystals with three-dimensional hydrogen-bonded frameworks and in those without hydrogen bonding has confirmed the trend to form close-packed motifs, irrespective of the presence of hydrogen bonds. Finally, a comparative analysis of organic and metal-organic hydrogen-bonded molecular frameworks as well as valence-bonded metal-organic frameworks is presented.
Ca2NaSiO4F: a new monoclinic polymorph
Authors: Krüger Hannes , Kahlenberg Volker
Published: July 2008

The crystal structure of a new monoclinic Ca2NaSiO4F polymorph was determined by single crystal X-ray diffraction methods. It crystallises in space group P21/c, unit cell parameters are a = 13.5385(8), b = 7.1338(4), c = 10.6689(6) Å and β = 113.231(4)°, with Z = 8. The crystals show twinning by pseudo merohedry. Monoclinic dicalcium sodium fluoride silicate is a superstructure of a previously known orthorhombic compound of the same composition. A re-investigation of the orthorhombic Ca2NaSiO4F revealed weak diffuse X-ray scattering, which shows a relation to the monoclinic superstructure. Furthermore, both compounds exhibit additional twinning by partial merohedry interrelated with a hexagonal pseudo symmetry. The sixfold pseudo symmetry originates from chains of face-sharing anion-centred coordination polyhedra of fluorine atoms, which are octahedrally coordinated by mixed Ca/Na sites. Main deviations from hexagonal symmetry are caused by the arrangement of the isolated silicate tetrahedra.
Na8.25Y1.25Si6O18 and its family of zwölfer ring silicates
Authors: Többens Daniel M. , Kahlenberg Volker , Kaindl Reinhard , Sartory Bernhard , Konzett Jürgen
Published: July 2008

The crystal structure of a sodium yttrium silicate with nominal composition Na9YSi6O18 was determined from laboratory X-ray powder diffraction. The actual composition of the crystals was found to be Y-enriched, and a corrected nominal composition of Na8.25Y1.25Si6O18 was established. The compound is cubic with space group Pa−3 and unit cell parameter of a = 15.120 Å. The structure consists of twelve-membered rings of corner-connected SiO4-tetrahedra, which are arranged around the 3-fold axes of the structure. It is isostructural with K4SrGe3O9 and Na4CaSi3O9. A profound disorder results from the absence of any stochiometric composition. The existence of a simultaneous occurrence of two different conformations of the rings relates to the various ordered and disordered cation positions in the structure. Micro-Raman spectra obtained from the polycrystalline material confirm the observed disorder. A model explaining the conformational variations appearing in this structure type was derived from a systematic comparison of isostructural compounds.
Investigation of anhydrous metal(II) nitrates. I. Syntheses and crystal structures of Mg(NO3)2, Co(NO3)2 and Ni(NO3)2, with a stereochemical discussion
Authors: Giester Gerald , Lengauer Christian L. , Wildner Manfred , Zemann Josef
Published: July 2008

Mg(NO3)2, Co(NO3)2 and Ni(NO3)2 were obtained as tiny crystals by dehydration of melts of the respective hydrates in the range 410–450 K. Structure determinations and refinements are based on single crystal X-ray data (CCD area detector) measured at 120–370 K. Crystal parameters at 120 K: Mg(NO3)2: R−3, a = 10.474(1), c = 38.782(4) Å, Z = 36, R
1 = 0.028; Co(NO3)2: R−3, a = 10.445(1), c = 12.769(2) Å, Z = 12, R
1 = 0.019; Ni(NO3)2: R−3, a = 10.332(1), c = 12.658(2) Å, Z = 12, R
1 = 0.025. Co(NO3)2 and Ni(NO3)2 are isotypic; the structure of Mg(NO3)2 is closely related, although it is not simply a stacking variant – it forms a new structure type. In all three compounds the MO6 octahedra share all corners with the NO3 groups to form framework structures; any edge sharing is thereby avoided. The geometries of the structures are also discussed in relation to a simple theoretical cubic structure (space group Pa−3) with the same connection pattern of the MO6 and NO3 building units. Neither X-ray single crystal and powder work nor differential thermoanalytical investigations indicated polymorphism in the temperature range investigated.
Crystal structure and thermal analysis of new mononuclear nickel (II) complexes with NNN type pyrazolyl ligands and halids
Authors: Taştekin Mustafa , Durmuş Sefa , Şahin Ertan , Arici Cengiz , Emregül Kaan Cebesoy , Atakol Orhan
Published: July 2008

Mononuclear Ni(II) complexes of Bis-2,6(pyrazolyl)pyridine(pp), 2(1-pyrazolyl)-6-(3,5-dimethylpyrazol-1-yl)pyridine(mpp) and bis-2,6(3,5-dimethyl-pyrazolyl-1yl)pyridine(dmpp) were prepared in MeOH : H2O mixtures. The complexes were characterized using elemental analysis, IR spectroscopy, X-ray diffraction and thermal analysis. The molecular structure of [Nidmpp(H2O)2Br]Br was evaluated and the Ni(II) ion was found to be in a distorted octahedral coordination environment. One of the halogen ions was found to coordinate the Ni(II) ion whereas the other ion does not coordinate and forms hydrogen bonds with the water molecules situated on the neighboring complex molecules, resulting in a supramolecular arrangement. Thermogravimetric results showed three coordinated water molecules in the pp and mpp complexes. Conductometric and potentiometric studies of the complexes showed 2 and 1 turning points, respectively.
What is a co-crystal – and does it matter?
Authors: Parkin Andrew , Gilmore Christopher J. , Wilson Chick C.
Published: July 2008

The debate about the definition of the term co-crystal is a distraction from the quality of molecular solid-state science being published.
Inclusion body myositis pathomechanism and therapy
Authors: Váncsa Andrea , Dankó Katalin
Published: July 2008

Az inclusiós testes myositis az idiopathiás inflammatorikus myopathiák vakuólaképződéssel járó formái közé tartozik, azok 15–28%-át képezi. Fontos a korai felismerés, mert alattomosan progrediáló betegségről van szó, és a már kialakult izomatrófia nehezen kezelhető. Ötven év felett a leggyakoribb krónikus progresszív izombetegség. Patomechanizmusában egyrészt degeneratív folyamatok, a béta-amyloid-lerakódás játszik szerepet, másrészt a polymyositishez hasonlóan autoinvazív klonális CD8+-T-lymphocyták által mediált celluláris citotoxicitás. A két eltérő patomechanizmust jól szemlélteti a biopsziás mintákban jelen lévő vakuolizált izomrostok, illetve a gyulladásos sejtek által körülvett, nem vakuolizált izomrostok párhuzamos jelenléte. Az MHC-I/CD8 komplex mint specifikus immunmarker bevezetésre került az újonnan kidolgozott diagnosztikus kritériumrendszerben, ez segít elkülöníteni az egyéb izomdisztrófiákban észlelhető aspecifikus gyulladástól. Klinikailag a distalis és proximális izmok érintettsége, légzőizom-gyengeség, dysphagia jellemzi, interstitialis tüdőbetegség nem jellemző. Általában terápiarezisztens, ennek magyarázata lehet a degeneratív folyamatok túlsúlya. Emiatt kortikoszteroid- és egyéb immunszuppresszív terápia sok esetben csak biokémiai választ eredményez, amelyet klinikai válasz nem kísér. A betegség diagnózisa, illetve differenciáldiagnózisa különösen nagy kihívást jelent a gyakorló klinikus számára, tekintettel a specifikus immunhisztokémiai hátteret igénylő diagnosztikus nehézségekre. Az újabb terápiás támadáspontok, kostimulatorikus molekulák elleni antitestek, anticitokin-terápia alkalmazása további előrelépést nyújthat a betegek életminőségének javításában.
New trends in lipidology: the increasing role of HDL-cholesterol
Authors: Paragh György , Harangi Mariann , Márk László
Published: July 2008

A korábbi epidemiológiai tanulmányok eredményei azt igazolták, hogy a HDL-koleszterin a cardiovascularis megbetegedések önálló rizikófaktora, plazmaszintjének emelése a cardiovascularis prevenció egyik fontos eleme. A HDL-nek a reverz koleszterintranszportban betöltött központi szerepe mellett egyéb kedvező biológiai, az érelmeszesedés elleni védőhatása is van. Ezek közé tartozik az antioxidáns, az antiinflammatorikus, az antitrombotikus/profibrinolitikus és a vazoprotektív hatás. A jelenlegi ajánlások az agresszív életmódváltást, a niacin, a fibrátok, a statinok vagy ezek kombinációját javasolják a HDL-koleszterin-szint emelésére. Emellett számos új, a HDL-re épülő terápiás eljárás tesztelése történt meg az utóbbi években, illetve van folyamatban. Idetartoznak a nikotinsav-származékok új formái, illetve receptoragonistái, a CETP-inhibitorok, a kannabinoid-1-receptor-antagonisták, a PPAR-agonisták, az LXR/FXR receptoragonisták és az apoA1- és/vagy foszfolipidterápia. Jelen közleményünkben áttekintjük a korábbi klinikai tanulmányokat, epidemiológiai megfigyeléseket, alapkutatásokat, illetve a legfontosabb új terápiás eljárásokkal végzett klinikai vizsgálatok eredményeit.
IFATS Collection: Using Human Adipose-Derived Stem/Stromal Cells for the Production of New Skin Substitutes
Authors: Trottier Valérie , Marceau-Fortier Guillaume , Germain Lucie , Vincent Caroline , Fradette Julie
Published: July 2008

The ability to harvest and culture stem cell populations from various human postnatal tissues is central to regenerative medicine applications, including tissue engineering. The discovery of multipotent mesenchymal stem cells within the stromal fraction of adipose tissue prompted their use for the healing and reconstruction of many tissues. Here, we examined the influence of adipose-derived stem/stromal cells (ASCs) on skin's regenerative processes, from a tissue engineering perspective. Using a self-assembly approach, human skin substitutes were produced. They featured a stromal compartment containing human extracellular matrix endogenously produced from either dermal fibroblasts or adipose-derived stem/stromal cells differentiated or not toward the adipogenic lineage. Human keratinocytes were seeded on each stroma and cultured at the air-liquid interface to reconstruct a bilayered skin substitute. These new skin substitutes, containing an epidermis and a distinctive stroma devoid of synthetic biomaterial, displayed characteristics similar to human skin. The influence of the type of stromal compartment on epidermal morphogenesis was assessed by the evaluation of tissue histology, the expression of key protein markers of the epidermal differentiation program (keratin [K] 14, K10, transglutaminase), the expression of dermo-epidermal junction components (laminins, collagen VII), and the presence of basement membrane and hemidesmosomes. Our findings suggest that adipose-derived stem/stromal cells could usefully substitute dermal fibroblasts for skin reconstruction using the self-assembly method. Finally, by exploiting the adipogenic potential of ASCs, we also produced a more complete trilayered skin substitute consisting of the epidermis, the dermis, and the adipocyte-containing hypodermis, the skin's deepest layer.

Disclosure of potential conflicts of interest is found at the end of this article.
In Vivo Osteoprogenitor Potency of Human Stromal Cells from Different Tissues Does Not Correlate with Expression of POU5F1 or Its Pseudogenes
Authors: Kaltz Nikolas , Funari Alessia , Hippauf Sandra , Delorme Bruno , Noël Danièle , Riminucci Mara , Jacobs Volker R. , Häupl Thomas , Jorgensen Christian , Charbord Pierre , Peschel Christian , Bianco Paolo , Oostendorp Robert A.J.
Published: July 2008

Expression of “stemness” markers is widely used as a predictor of stem cell properties of mesenchymal stem cells (MSC). Here, we show that bone marrow-derived (BM)-MSC show stem cell-like behavior in vivo; that is, they form ossicles with formation of bone, formation of adipocytes, and establishment of the murine hematopoietic microenvironment. Multipotent umbilical vein-derived stromal cells (UVSC), on the other hand, do not form bone, nor do they give rise to adipocytes in vivo. Despite these differences in stem-cell-like behavior, BM-MSC and UVSC express the two transcripts variants of POU5F1 at a similar level. Also, we found that in BM-MSC and UVSC, POU5F1 is detectable. However, more than 89% of the POU5F1 transcripts correspond to the POU5F1P1, -P3, or -P4 pseudogene. Despite low-level expression of POU5F1, we were unable to precipitate POU5F1 protein in either BM-MSC or UVSC. These results demonstrate that MSC stemness does not correlate to expression of POU5F1 transcripts or its pseudogenes.

Disclosure of potential conflicts of interest is found at the end of this article.
A Reservoir of Brown Adipocyte Progenitors in Human Skeletal Muscle
Authors: Crisan Mihaela , Casteilla Louis , Lehr Lorenz , Carmona Mamen , Paoloni-Giacobino Ariane , Yap Solomon , Sun Bin , Léger Bertrand , Logar Alison , Pénicaud Luc , Schrauwen Patrick , Cameron-Smith David , Russell Aaron Paul , Péault Bruno , Giacobino Jean-Paul
Published: July 2008

Brown adipose tissue uncoupling protein-1 (UCP1) plays a major role in the control of energy balance in rodents. It has long been thought, however, that there is no physiologically relevant UCP1 expression in adult humans. In this study we show, using an original approach consisting of sorting cells from various tissues and differentiating them in an adipogenic medium, that a stationary population of skeletal muscle cells expressing the CD34 surface protein can differentiate in vitro into genuine brown adipocytes with a high level of UCP1 expression and uncoupled respiration. These cells can be expanded in culture, and their UCP1 mRNA expression is strongly increased by cell-permeating cAMP derivatives and a peroxisome-proliferator-activated receptor-γ (PPARγ) agonist. Furthermore, UCP1 mRNA was detected in the skeletal muscle of adult humans, and its expression was increased in vivo by PPARγ agonist treatment. All the studies concerning UCP1 expression in adult humans have until now been focused on the white adipose tissue. Here we show for the first time the existence in human skeletal muscle and the prospective isolation of progenitor cells with a high potential for UCP1 expression. The discovery of this reservoir generates a new hope of treating obesity by acting on energy dissipation.

Disclosure of potential conflicts of interest is found at the end of this article.
Pheochromocytoma: Current Approaches and Future Directions
Authors: Adler Joel T. , Meyer-Rochow Goswin Y. , Chen Herbert , Benn Diana E. , Robinson Bruce G. , Sippel Rebecca S. , Sidhu Stan B.
Published: July 2008

Learning Objectives

After completing this course, the reader should be able to: Use current practice methods in the diagnosis of pheochromocytomas.Employ current practice methods in the treatment of pheochromocytomas.Evaluate the current molecular research that contributes to the treatment of pheochromocytomas.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality of life. While medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Improved medical management and surgical techniques and an increased understanding of hereditary disease have improved the outcome of pheochromocytoma patients with benign disease; however, the outcome of patients with malignant disease remains poor. In this review, we discuss the presentation, diagnosis, management, and future directions in the management of this disease.