bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of synapses in the entorhinal‐dentate gyrus pathway following repeated induction of electroshock seizures in the rat
Authors: Cardoso Armando , Assunção Marco , Andrade José P. , Pereira Pedro A. , Madeira M. Dulce , Paula‐Barbosa Manuel M. , Lukoyanov Nikolai V.
Published: August 2007

The goal of this study was to answer the question of whether repeated administration of electroconvulsive shock (ECS) seizures causes structural changes in the entorhinal‐dentate projection system, whose neurons are known to be particularly vulnerable to seizure activity. Adult rats were administered six ECS seizures, the first five of which were spaced by 24‐hr intervals, whereas the last two were only 2 hr apart. Stereological approaches were employed to compare the total neuronal and synaptic numbers in sham‐ and ECS‐treated rats. Golgi‐stained material was used to analyze dendritic arborizations of the dentate gyrus granule cells. Treatment with ECS produced loss of neurons in the entorhinal layer III and in the hilus of the dentate gyrus. The number of neurons in the entorhinal layer II, which provides the major source of dentate afferents, and in the granular layer of the dentate gyrus, known to receive entorhinal projections, remained unchanged. Despite this, the number of synapses established between the entorhinal layer II neurons and their targets, dentate granule cells, was reduced in ECS‐treated rats. In addition, administration of ECS seizures produced atrophic changes in the dendritic arbors of dentate granule cells. The total volumes of entorhinal layers II, III, and V–VI were also found to be reduced in ECS‐treated rats. By showing that treatment with ECS leads to partial disconnection of the entorhinal cortex and dentate gyrus, these findings shed new light on cellular processes that may underlie structural and functional brain changes induced by brief, generalized seizures. © 2007 Wiley‐Liss, Inc.
The nature and practice of strategic planning in Egypt
Authors: Elbanna Said
Published: August 2007

This paper aims to fill a gap in the literature of strategic management by providing a profile of organizations working in Egypt regarding their practice of strategic planning. Based upon responses from 120 organizations, the respondents have a positive attitude towards strategic planning.

There are relatively few significant differences in the findings between manufacturing and service organizations compared with the differences between local and foreign organizations and also between small and large organizations. Unexpectedly, a high percentage of the respondents are not familiar with some of what are seen as the traditional tools of strategic management.

Copyright © 2007 John Wiley & Sons, Ltd.
The Oil‐Absorbing Property of Polyhydroxyalkanoate Films and its Practical Application: A Refreshing New Outlook for an Old Degrading Material
Authors: Sudesh Kumar , Loo Ching‐Yee , Goh Lay‐Koon , Iwata Tadahisa , Maeda Mizuo
Published: August 2007

Polyhydroxyalkanoates (PHAs) have attracted the attention of academia and industry because of their plastic‐like properties and biodegradability. However, practical applications as a commodity material have not materialized because of their high production cost and unsatisfactory mechanical properties. PHAs are also believed to have high‐value applications as an absorbable biomaterial for tissue engineering and drug‐delivery devices because of their biocompatibility. However, research in these areas is still in its very early stages. The main problem faced by proponents of PHAs is the lack of a niche area where PHAs will be the most desired material in terms of its function during use rather than because of its eco‐friendly virtues after use. Here, we report on the oil‐absorbing property of PHA films and its potential applications. By comparing with some of the existing commercial products, the potential application of PHAs as cosmetic oil‐blotting films is revealed for the first time. Besides having the ability to rapidly absorb and retain oil, PHA films also have a natural oil‐indicator property, showing obvious changes in opacity following oil absorption. Surface analysis revealed that the surface structures such as porosity and smoothness exert great influence on the rapid oil‐absorption properties of the PHA films. These newly discovered properties could be exploited to create a niche area for the practical applications of PHAs.

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Analyte‐Induced Aggregation of a Water‐Soluble Conjugated Polymer for Fluorescent Assay of Oxalic Acid
Authors: Sun Huan , Feng Fude , Yu Minghui , Wang Shu
Published: August 2007

An assay method has been developed to detect oxalic acid from other structurally similar dicarboxylic acids using a cationic polythiophene derivative (PFT). Upon adding oxalic acid, the PFT can be cross‐linked through the bifunctional diacids of oxalic acid to form tense interpolymer π‐stacking aggregation, which results in the fluorescence self‐quenching of the PFT. Upon adding other dicarboxylic acids with a longer tether, loose interpolymer π‐stacking aggregation forms and the PFT fluorescence is less quenched. The fluorescence analysis was carried out in solution for the aggregates prior to precipitation. As a result of the short tether of oxalic acid, the unique fluorescent response from the PFT/oxalic acid assembly can be used to detect oxalic acid.

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Prediction of the Bivariate Molecular Weight‐Long Chain Branching Distribution in High‐Pressure Low‐Density Polyethylene Autoclaves
Authors: Krallis Apostolos , Pladis Prokopis , Kiparissides Costas
Published: August 2007

In the present study a population balance approach is described to follow the time evolution of bivariate molecular weight‐long chain branching (MW‐LCB) distributions in high pressure low density polyethylene autoclaves. The model formulation is based on a sectional grid method, the so‐called fixed pivot technique (FPT). According to this method, the ‘live’ and ‘dead’ polymer chain populations are assigned to a selected number of discrete points. Then, the resulting dynamic discrete‐continuous molar species equations for ‘live’ and ‘dead’ polymer chains are solved at the specified grid points. It is shown that a very good agreement exists between theoretical results and experimental data which proves the capability of the FPT method in calculating the joint MW‐LCB distribution for branched polymers.

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Spinodal Decomposition in Ternary Systems with Significantly Different Component Diffusivities
Authors: Alfarraj Abdulrahman A. , Nauman E. Bruce
Published: August 2007

A numerical method for simulating spinodal decomposition in ternary systems with order‐of‐magnitude differences in diffusion coefficients is presented. The method has been partially verified by molecular dynamic simulations and gives results equivalent to the standard technique when the diffusivities are equal. A two‐dimensional simulation of an asymmetric polymer/polymer/polymer system reproduces an experimentally observed bimodal distribution of dispersed‐phase particle sizes. The ripening exponent for the larger particles is near the expected value of 0.33, but that for the smaller particles is only about 0.1. The method was also used for a polymer/polymer/solvent system.

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Uncertainty and choice: the challenges of pharmaceutical efficacy, safety, and cost
Authors: Scherer F.M.
Published: August 2007

This paper addresses the role of uncertainty in challenges confronting the US pharmaceutical industry and its regulators. It begins with a macroeconomic overview, showing how rising health care costs, including rising ethical drug costs, squeeze the wage and salary share of national income. It addresses the claim that pharmaceutical companies' new drug pipelines are drying up. Taking a stochastic approach, it shows that both the trend of new medical entity approvals and the trend of pharmaceutical company gross margins can be explained as random walks—the latter as a result of sampling from a highly skew distribution. It then focuses on problems of ascertaining efficacy and especially low‐probability adverse effects from clinical trial samples of acceptable size. Noting the need for post‐NDA surveillance of adverse effects and observing the incentive failures that occur at that stage, it proposes two new approaches to identifying adverse reactions. Copyright © 2007 John Wiley & Sons, Ltd.
Entry and competition in generic biologics
Authors: Grabowski Henry G. , Ridley David B. , Schulman Kevin A.
Published: August 2007

Patents for several blockbuster biological products are expected to expire soon. The Food and Drug Administration is examining whether biologics can and should be treated like pharmaceuticals with regard to generics. In contrast with pharmaceuticals, which are manufactured through chemical synthesis, biologics are manufactured through fermentation, a process that is more variable and costly. Regulators might require extensive clinical testing of generic biologics to demonstrate equivalence to the branded product. The focus of the debate on generic biologics has been on legal and health concerns, but there are important economic implications. We combine a theoretical model of generic biologics with regression estimates from generic pharmaceuticals to estimate market entry and prices in the generic biologic market. We find that generic biologics will have high fixed costs from clinical testing and from manufacturing, so there will be less entry than would be expected for generic pharmaceuticals. With fewer generic competitors, generic biologics will be relatively close in price to branded biologics. Policy makers should be prudent in estimating financial benefits of generic biologics for consumers and payers. We also examine possible government strategies to promote generic competition. Copyright © 2007 John Wiley & Sons, Ltd.
Benefits and costs of newer drugs: an update
Authors: Lichtenberg Frank R.
Published: August 2007

In previous work, we found strong evidence to support the hypothesis that the replacement of older drugs by new drugs resulted in reductions in total medical expenditures. In this study, we update and extend our previous study of the effect of drug age—years since FDA approval—on total medical expenditure, in several respects: (1) the unit of analysis is a medical condition, rather than a prescription; (2) the sample is much larger, including data for 3 years, rather than 1 year; (3) we obtain estimates for the Medicare population as well as for the entire population; and (4) within the Medicare population, we examine the effect of drug age on Medicare expenditure as well as on expenditure by all payers.

The estimates indicate that, in the entire population, a reduction in the age of drugs utilized reduces non‐drug expenditure 7.2 times as much as it increases drug expenditure. For example, reducing the mean age of drugs used to treat a condition from 15 years to 5.5 years is estimated to increase prescription drug spending by $18 but reduce other medical spending by $129, yielding a $111 net reduction in total health spending. Most of the savings are due to reductions in hospital expenditure ($80) and in physician office‐visit expenditures ($24).

In the Medicare population, a reduction in the age of drugs utilized reduces non‐drug expenditure by all payers (i.e. Medicare and various forms of Medicare supplemental insurance, Medicare for dually eligible individuals and Medicare beneficiaries' out of pocket payments) 8.3 times as much as it increases drug expenditure; it reduces Medicare non‐drug expenditure 6.0 times as much as it increases drug expenditure. About two‐thirds of the non‐drug Medicare cost reduction is due to reduced hospital costs. The remaining third is approximately evenly divided between reduced Medicare home health care cost and reduced Medicare office‐visit cost.

We also show that Medicare enrollees with private prescription drug coverage tend to use newer drugs than those without such coverage: the mean age of drugs used by Medicare enrollees with private Rx insurance is about 9% lower than the mean age of drugs used by Medicare enrollees without either private or public Rx insurance. Copyright © 2007 John Wiley & Sons, Ltd.
Rx Roulette: combatting counterfeit pharmaceuticals in developing nations
Authors: Lybecker Kristina M.
Published: August 2007

The debate over access to medicines has principally centered on pharmaceutical patents and prohibitively high drug prices. Although a less recognized problem, counterfeit pharmaceuticals are certainly a more insidious barrier to access. Pharmaceutical counterfeiting is an invisible threat, not only by nature, but also because the industry has historically downplayed it. However, that has changed. Pharmaceutical firms now not only readily concede counterfeiting is a threat to their business, but in some cases publicly address their strategies and the anticounterfeiting technologies in use and development. Acknowledging the problem has benefited the industry because it alters the ways in which firms are able to combat counterfeiting, allowing them to more overtly confront the problem. In addition, it allows them to better partner with governments and health advocates since their incentives are aligned in efforts to prevent counterfeiting. In light of the more public and more aggressive campaign against counterfeiting, it is important to examine the variety of strategies firms may utilize to prevent their sale. Through a theoretical model of the market in a representative developing country, several anticounterfeiting strategies are considered. Some strategies appear to be more effective than others in the battle against fake drugs. Copyright © 2007 John Wiley & Sons, Ltd.
The cost of biopharmaceutical R&D: is biotech different?
Authors: DiMasi Joseph A. , Grabowski Henry G.
Published: August 2007

The costs of developing the types of new drugs that have been pursued by traditional pharmaceutical firms have been estimated in a number of studies. However, similar analyses have not been published on the costs of developing the types of molecules on which biotech firms have focused. This study represents a first attempt to get a sense for the magnitude of the R&D costs associated with the discovery and development of new therapeutic biopharmaceuticals (specifically, recombinant proteins and monoclonal antibodies [mAbs]).

We utilize drug‐specific data on cash outlays, development times, and success in obtaining regulatory marketing approval to estimate the average pre‐tax R&D resource cost for biopharmaceuticals up to the point of initial US marketing approval (in year 2005 dollars). We found average out‐of‐pocket (cash outlay) cost estimates per approved biopharmaceutical of $198 million, $361 million, and $559 million for the preclinical period, the clinical period, and in total, respectively. Including the time costs associated with biopharmaceutical R&D, we found average capitalized cost estimates per approved biopharmaceutical of $615 million, $626 million, and $1241 million for the preclinical period, the clinical period, and in total, respectively. Adjusting previously published estimates of R&D costs for traditional pharmaceutical firms by using past growth rates for pharmaceutical company costs to correspond to the more recent period to which our biopharmaceutical data apply, we found that total out‐of‐pocket cost per approved biopharmaceutical was somewhat lower than for the pharmaceutical company data ($559 million vs $672 million). However, estimated total capitalized cost per approved new molecule was nearly the same for biopharmaceuticals as for the adjusted pharmaceutical company data ($1241 million versus $1318 million). The results should be viewed with some caution for now given a limited number of biopharmaceutical molecules with data on cash outlays, different therapeutic class distributions for biopharmaceuticals and for pharmaceutical company drugs, and uncertainty about whether recent growth rates in pharmaceutical company costs are different from immediate past growth rates. Copyright © 2007 John Wiley & Sons, Ltd.
Refining Gerschgorin disks through new criteria for nonsingularity
Authors: Peña J. M.
Published: August 2007

New criteria for nonsingular matrices are provided. These criteria generalize strict diagonal dominance and they are also applied to derive new inclusion sets for the eigenvalues of a matrix. Results on exclusion sets are also presented. Copyright © 2007 John Wiley & Sons, Ltd.
Nostalgia and giving to charity: a conceptual framework for discussion and research
Authors: Merchant Altaf , Ford John
Published: August 2007

Academic work involving nostalgia has shown it to evoke a basket of emotions. This paper proposes a conceptual model that links nostalgia to charitable giving. We argue that the nostalgia evoked by certain NPOs (not‐for‐profit organizations) is likely to have a bearing on both emotional and familial utility derived by the donor. This in turn is likely to drive the donor commitment to the NPO. Thus by evoking nostalgia, certain NPOs are likely to emotionally engage their current and potential donors, which could facilitate the creation of long‐term intimate relationships between them and their donors. However, the extent to which the NPO can evoke nostalgia is likely to depend upon the nostalgia proneness of the donor, the emotional importance of the past experiences evoked by the NPO, and the characteristics of the NPO such as the extent to which the NPO can alleviate the feelings of alienation, discontinuity, and the need for authenticity experienced by the donor. The paper provides a series of research propositions and proposes a research agenda.

Copyright © 2007 John Wiley & Sons, Ltd.
Preconceptional and prenatal screening for fragile X syndrome: Experience with 40 000 tests
Authors: Berkenstadt Michal , Ries‐Levavi Liat , Cuckle Howard , Peleg Leah , Barkai Gad
Published: August 2007

Objectives

To determine the carrier frequency of fragile X syndrome, and the rate of expansion from premutation (PM) carrier to full mutation (FM) fetus.

Methods

Results were analyzed on women with no family history of fragile X syndrome, or who were PM/FM carriers, who were tested between January 1994 and June 2004.

PM was defined 55–199 repeats, FM above 200.

Results

Out of 40 079 women screened, 5 FM and 255 PM carriers were detected. There was no significant difference in carrier frequency between those with versus those without family history of mental retardation or developmental abnormalities: 1 in 128 (28/3596) versus 1 in 157 (232/36 483). However, the median of repeats differed significantly: 58 and 66 repeats, respectively, (P < 0.0001). Invasive prenatal diagnosis was carried out in 370 pregnancies (7 FM and 363 PM). Thirty FM fetuses were detected. There was a lower expansion rate in cases without a family history: 10% (17/169 PMs) compared to 50% (11/22 PMs) in those with a history, but this could be accounted for by the difference in allele size.

Conclusion

There is now sufficient information on screening parameters and prenatal diagnosis of fragile X syndrome to offer testing to women of reproductive age. Copyright © 2007 John Wiley & Sons, Ltd.
Methods, algorithms and tools in computational proteomics: A practical point of view
Authors: Matthiesen Rune
Published: August 2007

Computational MS‐based proteomics is an emerging field arising from the demand of high throughput analysis in numerous large‐scale experimental proteomics projects. The review provides a broad overview of a number of computational tools available for data analysis of MS‐based proteomics data and gives appropriate literature references to detailed description of algorithms. The review provides, to some extent, discussion of algorithms and methods for peptide and protein identification using MS data, quantitative proteomics, and data storage. The hope is that it will stimulate discussion and further development in computational proteomics. Computational proteomics deserves more scientific attention. There are far fewer computational tools and methods available for proteomics compared to the number of microarray tools, despite the fact that data analysis in proteomics is much more complex than microarray analysis.
Surfactant‐assisted specific‐acid catalysis of Diels–Alder reactions in aqueous media
Authors: Mubofu Egid B. , Engberts Jan B.F.N.
Published: August 2007

Surfactant‐assisted specific‐acid catalysis (SASAC) for Diels–Alder reactions of dienophiles 1 and 4 with cyclopentadiene 2 in aqueous media at 32 °C was studied. This study showed that acidified anionic surfactants (pH 2) such as sodium dodecyl sulfate (SDS) and linear alkylbenzene sulfonic acid (LAS) accelerate Diels—Alder reactions. Conversely, under similar reaction conditions (pH 2) these reactions are inhibited by (acidified) cationic surfactants such as dodecyltrimethylammonium bromide (DTAB), dodecyldimethylammonium bromide (DDAB), and dodecylmethylammonium bromide (DMAB). A modest rate acceleration resulting from the surfactant hydrogen‐bonding capacity is also recorded for the Diels–Alder reaction of naphthoquinones (6) with cyclopentadiene (2) in aqueous media at 32 °C. Copyright © 2007 John Wiley & Sons, Ltd.
The nature of the electronic factor governing diastereofacial selectivity in remotely substituted (X) 2‐adamantyl cations: 5‐X versus 4‐X substitution
Authors: Adcock William , Trout Neil A.
Published: August 2007

A limited series of 4eq‐substituted (X) 2‐methyleneadamantanes (6, YCH2, XF, Cl, Br, I, and SnMe3) has been synthesized and diastereoselectivities for their hydrochlorination (HCl/CH2Cl2) have been determined. Diastereoselectivities for the fluorination (DAST/CH2Cl2) of secondary alcohol mixtures, obtained from the hydride reduction of the precursor ketones (6,YO) to the alkenes, have also been measured. A comparison of this selectivity data for nucleophilic trapping of 4eq‐substituted (X) 2‐adamantyl cations (4, RH and Me) with the corresponding information for 5‐substituted (X) 2‐adamantyl cations (1, RH and Me) has revealed important distinctions between the two series. In particular, whereas extended hyperconjugative effects appear to be the predominant electronic effect governing facial selectivity in the 5,2‐series, electrostatic influences prevail in the 4,2‐disposition. Copyright © 2007 John Wiley & Sons, Ltd.
Polymeric nanocomposites containing polyhedral oligomeric silsesquioxanes prepared via frontal polymerization
Authors: Mariani Alberto , Alzari Valeria , Monticelli Orietta , Pojman John A. , Caria Giuseppe
Published: August 2007

Frontal polymerization (FP) has been successfully applied, for the first time, to obtain polymeric nanocomposites containing polyhedral oligomeric silsesquioxanes (POSS) in an amine‐cured epoxy matrix. Variations of maximum temperature (Tmax) and front velocity (Vf) have been studied. A comparison of these products with the corresponding materials, obtained by the classical batch polymerization technique, demonstrated that FP allows a higher degree of conversion than batch polymerization. The products have been characterized in terms of their thermal behavior with DSC analysis. SEM and X‐ray analyses revealed the morphology and the structures of the nanocomposites. The nanocomposites obtained by FP have the same characteristics of those synthesized, in much longer times, by batch polymerization. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4514–4521, 2007
UV‐photodimerization in uracil‐substituted dendrimers for high density data storage
Authors: Lohse Brian , Vestberg Robert , Ivanov Mario T. , Hvilsted Søren , Berg Rolf H. , Ramanujam P. S. , Hawker Craig J.
Published: August 2007

Two series of uracil‐functionalized dendritic macromolecules based on poly (amidoamine) PAMAM and 2,2‐bis(hydroxymethylpropionic acid) bis‐MPA backbones were prepared and their photoinduced (2π+2π) cycloaddition reactions upon exposure to UV light at 257 nm examined. Dendrimers up to 4th generation were synthesized and investigated as potential materials for high capacity optical data storage with their dimerization efficiency compared to uracil as a reference compound. This allows the impact of increasing the generation number of the dendrimers, both the number of chromophores, as well as the different steric environments, on the performance of each series of dendrimers to be investigated. The (uracil)12‐[G‐2]‐bis‐MPA and (uracil)8‐[G‐1]‐PAMAM were observed to have high dimerization efficiency in solution with different behavior being observed for the PAMAM and bis‐MPA dendrimers. The dendrimers with the best dimerization efficiency in solution were then examined in the solid state as thin films cast on quartz plates, and their film qualities along with their photodimerization performance studied. High quality films with a transmission response of up to 70% in 55 s. when irradiated at 257 nm with an intensity of 70 mW/cm2 could be obtained suggesting future use as recording media for optical data storage. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4401–4412, 2007
Ozone Formation in a Coaxial DC Corona Discharge under Carbon Dioxide Gas Flow
Authors: Országh Juraj , Skalný Ján D. , Mason Nigel J.
Published: August 2007

Ozone formation has been monitored in DC corona discharges fed by pure carbon dioxide in a flowing regime. Ozone concentrations have been measured for both positive and negative polarities of the discharge. Several different electrical parameters of the discharge have been measured. The onset voltage in the positive corona is approximately 1 kV higher than in a similar negative discharge, however, the maximum ozone concentration and total discharge current were found to be higher in the negative corona discharge. The gas flow rate is shown to influence the CV characteristics within a negative corona but, in contrast, only a marginal effect of flow rate was observed in positive corona. The mobility of both negative and positive charge carriers in the drift region of the discharges have been derived from CV characteristics.

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Hazard assessment of potential periglacial debris flows based on GIS‐based spatial modelling and geophysical field surveys: a case study in the Swiss Alps
Authors: Kneisel C. , Rothenbühler C. , Keller F. , Haeberli W.
Published: August 2007

Combined geomorphological and geophysical approaches were used to perform a hazard assessment of potential periglacial debris flow. Possible debris flow initiation zones were identified within a GIS‐based model and located based on geomorphic attributes which contribute the most to this type of instability. In permafrost‐affected alpine environments, these include the extent and location of ground ice and permafrost. In a potential debris flow‐starting zone in the Upper Engadine (moraine/debris rock glacier complex Boval) two‐dimensional electrical resistivity surveys were used to detect the presence/absence of permafrost and to estimate active‐layer depth. The results show that the moraine complex represents a periglacial debris reservoir which consists of frozen and unfrozen debris. The ice‐bonded part of the moraine is largely protected from sudden destabilisation and retrogressive erosion can be assumed to be limited. However, future degradation or loss of permafrost in the lower parts of the debris rock glacier would increase the amount of erodible debris and generally reduce mechanical stability. Copyright © 2007 John Wiley & Sons, Ltd.
Proteomic profiling of animal models mimicking skeletal muscle disorders
Authors: Doran Philip , Gannon Joan , O'Connell Kathleen , Ohlendieck Kay
Published: August 2007

Over the last few decades of biomedical research, animal models of neuromuscular diseases have been widely used for determining pathological mechanisms and for testing new therapeutic strategies. With the emergence of high‐throughput proteomics technology, the identification of novel protein factors involved in disease processes has been decisively improved. This review outlines the usefulness of the proteomic profiling of animal disease models for the discovery of new reliable biomarkers, for the optimization of diagnostic procedures and the development of new treatment options for skeletal muscle disorders. Since inbred animal strains show genetically much less interindividual differences as compared to human patients, considerably lower experimental repeats are capable of producing meaningful proteomic data. Thus, animal model proteomics can be conveniently employed for both studying basic mechanisms of molecular pathogenesis and the effects of drugs, genetic modifications or cell‐based therapies on disease progression. Based on the results from comparative animal proteomics, a more informed decision on the design of clinical proteomics studies could be reached. Since no one animal model represents a perfect pathobiochemical replica of all of the symptoms seen in complex human disorders, the proteomic screening of novel animal models can also be employed for swift and enhanced protein biochemical phenotyping.
Nine steps to proteomic wisdom: A practical guide to using protein‐protein interaction networks and molecular pathways as a framework for interpreting disease proteomic profiles
Authors: Isserlin Ruth , Emili Andrew
Published: August 2007

A major aim of proteomic profiling of disease is to uncover the mechanistic basis of a given pathology. High‐throughput experimental techniques continue to advance rapidly, but are still plagued by high rates of false negatives, false positives, and other spurious findings. By reducing a disease profile to a subset of differentially expressed proteins and determining functional over‐representation, one can often make a reasonable first‐pass assessment as to what might be happening in disease. Integrating mRNA expression patterns together with prior knowledge of protein‐protein interaction networks and biological pathway information goes a step further, providing clues into the core processes that are aberrant in the disease state, and indicating which cellular functions are activated or repressed as a maladaptive pathophysiological response. This multi‐step framework allows one to hypothesize as to possible cause and effect of pathology, and highlights potentially instructive pathways or sub‐networks for subsequent experimental validation. Indeed, efficiently exploiting data regarding the myriad of physical and genetic interactions among expressed gene products, in parallel with the systematic sampling of genetic variation among diverse human populations, promises to revolutionize our current understanding of disease action at a deeper molecular level.
Exploring the proteome of meningococcal outer membrane vesicle vaccines
Authors: Wheeler Jun X. , Vipond Caroline , Feavers Ian M.
Published: August 2007

Neisseria meningitidis, one of the principal causes of bacterial meningitis and septicemia, continues to present a challenge for vaccine developers. While significant progress has been made in the development and implementation of conjugate vaccines, which are based on the capsular polysaccharide of the organism, this approach has failed to produce a vaccine against organisms expressing a serogroup B capsule. The completion of the first meningococcal genome sequences in 2000 provided new ways of meeting this challenge. One approach has been to learn more about meningococcal biology and pathogenesis through exploring its proteome. This article reviews the results of ten recent studies of the meningococcal proteome and compares the different methodologies employed. Not surprisingly, given the renewed impetus to develop a comprehensive vaccine and the continuing clinical development of outer membrane vesicle vaccines, many of these studies focus on the proteome of the outer membrane fraction. As in other areas of proteome research, the direct comparison of data from different studies is hampered by the lack of standardization of separation technologies and data formats. Nevertheless, proteomic analysis, especially when combined with detailed knowledge of meningococcal population structures, represents a powerful tool in the development of vaccines against this important pathogen.
Lysosomal proteomics and disease
Authors: Sleat David E. , Jadot Michel , Lobel Peter
Published: August 2007

A recent trend in proteomic studies has been to analyze macromolecular complexes such as subcellular organelles instead of complete cells or tissues. This “divide and conquer” approach circumvents some of the formidable problems associated with whole proteome analyses and allows focus on a subset of proteins that may be involved in a particular process or disease of interest. One organelle that has been the focus of considerable attention in proteomic studies is the lysosome, an acidic, membrane‐delimited compartment that plays an essential role in the degradation and recycling of biological macromolecules. Lysosomal proteomics have been driven in part by the well‐established involvement of this organelle in numerous human diseases, but also by the availability of approaches to selectively visualize and/or isolate subsets of lysosomal proteins. In terms of clinical application, proteomic studies of the lysosome have led to the identification of gene defects in three human hereditary diseases. This review summarizes past progress, current limitations and future directions in the field of lysosomal proteomics.
Thermal Decomposition of NTO: An Explanation of the High Activation Energy
Authors: Sinditskii Valery P. , Smirnov Sergei P. , Egorshev Viacheslav Yu.
Published: August 2007

Burning rate characteristics of the low‐sensitivity explosive 5‐nitro‐1,2,4‐triazol‐3‐one (NTO) have been investigated in the pressure interval of 0.1–40 MPa. The temperature distribution in the combustion wave of NTO has been measured at pressures of 0.4–2.1 MPa. Based on burning rate and thermocouple measurements, rate constants of NTO decomposition in the molten layer at 370–425 °C have been derived from a condensed‐phase combustion model (k=8.08⋅1013⋅exp(−19420/T) s−1. NTO vapor pressure above the liquid (ln P=−9914.4/T+14.82) and solid phases (ln P=−12984.4/T+20.48) has been calculated. Decomposition rates of NTO at low temperatures have been defined more exactly and it has been shown that in the interval of 180–230 °C the decomposition of solid NTO is described by the following expression: k=2.9⋅1012⋅exp(−20680/T). Taking into account the vapor pressure data obtained, the decomposition of NTO in the gas phase at 240–250 °C has been studied. Decomposition rate constants in the gaseous phase have been found to be comparable with rate constants in the solid state. Therefore, a partial decomposition in the gas cannot substantially increase the total rate. High values of the activation energy for solid‐state decomposition of NTO are not likely to be connected with a sub‐melting effect, because decomposition occurs at temperatures well below the melting point. It has been suggested that the abnormally high activation energy in the interval of 230–270 °C is a consequence of peculiarities of the NTO transitional process rather than strong bonds in the molecule. In this area, the NTO molecule undergoes isomerization into the aci‐form, followed by C3‐N2 heterocyclic bond rupture. Both processes depend on temperature, resulting in an abnormally high value of the observed activation energy.
Serum PSA half‐life as a predictor of survival for hormone‐refractory prostate cancer patients: Modelization using a standardized set of response criteria
Authors: Banu Eugeniu , Banu Adela , Medioni Jacques , Levy Eric , Thiounn Nicolas , Mejean Arnaud , Andrieu Jean‐Marie , Oudard Stephane
Published: August 2007

OBJECTIVE

Changes of serum prostate‐specific antigen (PSA) during chemotherapy have been validated as a marker of response for hormone‐refractory prostate cancer (HRPC) patients. We retrospectively established new response criteria to assess the risk of death.

METHODS

Two hundred fifty‐six chemonaive HRPC patients treated with chemotherapy were included in the analysis. According to PSA half‐life (HL) dynamics, three response categories were defined: responders (R), late‐progressors (LP) and initial‐progressors (IP), that were compared with Working Group (WG) criteria. PSA HL time to failure (TTF) and overall survival (OS) were estimated and compared between HT categories. Multivariate regression analysis was performed to isolate the impact on OS of these response categories. A new predictor of survival, delta‐time PSA interval (ΔT) was described.

RESULTS

PSA HL categories were strongly related with WG criteria (P = 0.0001). PSA HL TTF differed among PSA HL categories: 4.2, 2.3, and 0.9 months for R, LP, and IP patients, respectively, and their respective median OS were 27, 19.7, and 12.3 months (P = 0.0001). For ΔT ≥ 3 versus <3 months, median OS significantly differed: 24.9 months versus 13.2 months (P = 0.0001).

CONCLUSIONS

PSA HL dynamics during chemotherapy were able to accurately predict survival, earlier than WG‐defined progression criteria. This criterion should be prospectively evaluated in randomized trials for HRPC patients in order to better estimate the risk of death. Prostate 67: 1543–1549, 2007. © 2007 Wiley‐Liss, Inc.
A prospective randomized trial comparing contrast‐enhanced targeted versus systematic ultrasound guided biopsies: Impact on prostate cancer detection
Authors: Mitterberger Michael , Horninger Wolfgang , Pelzer Alexandre , Strasser Hannes , Bartsch Georg , Moser Patrizia , Halpern Ethan J. , Gradl Johann , Aigner Friedrich , Pallwein Leo , Frauscher Ferdinand
Published: August 2007

BACKGROUND

We performed a prospective randomized trial comparing 5 contrast‐enhanced color Doppler (CECD) ultrasound (US) targeted biopsy cores to 10 gray‐scale US guided systematic biopsy (SB) cores to determine the impact on the cancer detection rate.

METHODS

We prospectively randomized 100 prostate specific antigen (PSA) screening volunteers with an elevated PSA (≥1.25 ng/ml and free‐to‐total PSA < 18%) to undergo contrast‐enhanced targeted or SB. Contrast‐enhanced targeted biopsies with a limited number of five cores were performed into hypervascular areas of the peripheral zone (PZ) during administration of the US contrast agent SonoVue® (Bracco, Italy). A subjective grading of the vascularity from 0 to 3 was used: grade 0, no color signal; 1, low density; 2, medium density; and 3, high density of color signals. Ten SBs were obtained in a standard spatial distribution. Cancer detection rates were compared in the groups.

RESULTS

Cancer was detected in 16/50 subjects (32%) by targeted biopsy, and in 13/50 patients (26%) with SB. The cancer detection rate was significantly better for the targeted approach (P < 0.04, McNemar). The detection rate for targeted biopsy cores (15.6% or 39/250 cores) was significantly better than for SB cores (6.8% or 34/500 cores, P < 0.001, McNemar).

CONCLUSIONS

CECD targeted biopsy detected more cancers than SB with a reduced number of biopsy cores. Prostate 67: 1537–1542, 2007. © 2007 Wiley‐Liss, Inc.
Are aromatic carbon donor hydrogen bonds linear in proteins?
Authors: Nanda Vikas , Schmiedekamp Ann
Published: August 2007

Proteins fold and maintain structure through the collective contributions of a large number of weak, noncovalent interactions. The hydrogen bond is one important category of forces that acts on very short distances. As our knowledge of protein structure continues to expand, we are beginning to appreciate the role that weak carbon‐donor hydrogen bonds play in structure and function. One property that differentiates hydrogen bonds from other packing forces is propensity for forming a linear donor‐hydrogen‐acceptor orientation. To ascertain if carbon‐donor hydrogen bonds are able to direct acceptor linearity, we surveyed the geometry of interactions specifically involving aromatic sidechain ring carbons in a data set of high resolution protein structures. We found that while donor–acceptor distances for most carbon donor hydrogen bonds were tighter than expected for van der Waals packing, only the carbons of histidine showed a significant bias for linear geometry. By categorizing histidines in the data set into charged and neutral sidechains, we found only the charged subset of histidines participated in linear interactions. B3LYP/6‐31G**++ level optimizations of imidazole and indole–water interactions at various fixed angles demonstrates a clear orientation dependence of hydrogen bonding capacity for both charged and neutral sidechains. We suggest that while all aromatic carbons can participate in hydrogen bonding, only charged histidines are able to overcome protein packing forces and enforce linear interactions. The implications for protein modeling and design are discussed. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Thermal annealing effects on the TL response of beta‐irradiated HPHT Ib type synthetic diamond
Authors: Preciado‐Flores S. , Meléndrez R. , Chernov V. , Soto‐Puebla D. , Pedroza‐Montero M. , Barboza‐Flores M.
Published: August 2007

It is known that room temperature beta‐irradiated Ib type diamond generates a non‐reproducible TL glow curve shape, due to mobility of the impurity‐vacancy (I –V) and interstitials (I) defects in the 30–800 °C temperature range. This situation may hinder the use of this type of diamond material in dose assessment applications. The recurring heating of the Ib type diamond sample changes the defects concentration and consequently the intensity of the TL glow peaks associated to the characteristic temperature annealing stages. In the present work we have performed thermal annealing (TA) treatment on an Ib type diamond in the 100–800 °C range previous to beta irradiation. It was observed that after the 800 °C annealing treatment the TL glow curve showed 3–5% reproducibility, in contrast to the non‐reproducible TL observed in non‐annealed diamond, and remained the same after two months of successive TL read outs. Moreover, the 800 °C annealing treatment assured a linear integrated TL dose behavior, a significant improvement over non‐annealed samples that could facilitate the employment of Ib type synthetic diamond in dosimetric applications. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Radiation hardness of diamond and silicon sensors compared
Authors: de Boer Wim , Bol Johannes , Furgeri Alex , Müller Steffen , Sander Christian , Berdermann Eleni , Pomorski Michal , Huhtinen Mika
Published: August 2007

The radiation hardness of silicon charged particle sensors is compared with single crystal and polycrystalline diamond sensors, both experimentally and theoretically. It is shown that for Si‐ and C‐sensors, the NIEL hypothesis, which states that the signal loss is proportional to the Non‐Ionizing Energy Loss, is a good approximation to the present data. At incident proton and neutron energies well above 0.1 GeV the radiation damage is dominated by the inelastic cross section, while at non‐relativistic energies the elastic cross section prevails. The smaller inelastic nucleon‐carbon cross section and the light nuclear fragments imply that at high energies diamond is an order of magnitude more radiation hard than silicon, while at energies below 0.1 GeV the difference becomes significantly smaller. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thermal conductivity of CoSb3 nano‐composites grown via a novel solvothermal nano‐plating technique
Authors: Ji X. , He J. , Alboni P. , Su Z. , Gothard N. , Zhang B. , Tritt Terry M. , Kolis J. W.
Published: August 2007

We have utilized a solvothermal nano‐plating technique to grow nano‐structured CoSb3 directly onto the surface of micron‐sized CoSb3 particles that were subsequently hot pressed and densified into a homogeneous skutterudite nano‐composite. We herein present results for three samples: a bulk sample to serve as a reference, and two samples with solvothermally grown nano‐structures of 5 wt% and 20 wt%, respectively. All three samples used the same bulk starting materials. The thermal conductivity was measured via two independent techniques (steady state and laser flash) and both show a systematic reduction in the thermal conductivity with an increasing amount of nano‐structures. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Deep‐level characterization of emissive interface states in Alq3‐based OLEDs
Authors: Nakano Yoshitaka , Noda Koji , Fujikawa Hisayoshi , Morikawa Takeshi
Published: August 2007

We have succesfully investigated emissive interface states in fabricated indium‐tin‐oxide (ITO)/N,N′‐di‐1‐naphthyl‐N,N′‐diphenyl‐1,1′‐biphenyl‐4,4′diamine (α‐NPD)/tris(8‐hydroxyquinoline) aluminum (Alq3)/LiF/Al organic light‐emitting diodes (OLEDs) by a modified deep‐level optical spectroscopy (DLOS) technique. In the vicinity of the α‐NPD/Alq3 emissive interface, a discrete trap level was found to be located at ∼1.77 eV below the conduction band of Alq3, in addition to band‐to‐band transitions of carriers from α‐NPD to Alq3. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM
Authors: Park Hae‐Ran , Jo Sung‐Kee , Jung Uhee , Yee Sung‐Tae
Published: August 2007

The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol‐insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1‐like function, but not the Th2‐like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN‐γ and IgG2a production, and conversely a reduced IL‐4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL‐12p70. However, HemoHIM restored the IL‐12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans. Copyright © 2007 John Wiley & Sons, Ltd.
Improvement of the duty cycle of an orthogonal acceleration time‐of‐flight mass spectrometer using ion gates
Authors: Brenton A. G. , Krastev T. , Rousell D. J. , Kennedy M. A. , Craze A. S. , Williams C. M.
Published: August 2007

A method to control the duty cycle of a time‐of‐flight mass spectrometer is described. The method relies on one or more ion gates placed in the beam path that have the function to transmit or stop the beam. These ion gates can switch from the open state to the closed state in tens of nanoseconds and effectively select portions of the mass range. The method is useful in circumstances where recording the complete mass spectrum is not an essential requirement, for example, in the analysis of known compounds where sensitivity and speed of operation are more important. It will be of benefit for applications in separation sciences with techniques involving fast chromatographic separations, where hundreds of mass spectra may be required per second. In such circumstances analytical identification may require only a limited number of masses (or mass regions) to be continuously monitored. Improvement of the duty cycle is particularly important for orthogonal‐acceleration time‐of‐flight (oa‐TOF) mass spectrometry instruments whose performance suffers from a low duty cycle. The duty cycle is not a constant for an instrument design but is a mass‐dependent function and is least for smaller masses. The method described here is capable of raising the duty cycle to 100%. A theory is developed for one or more ion gate arrangements, for both linear‐ and reflectron‐TOF systems. For a two‐gate system the relationship between the positions of the first and second gates is described by a ‘2/3 rule’. Experimental results are shown for one‐gate and two‐gate operation, both in linear and in reflectron modes of operation, on an oa‐TOF system built in‐house. Copyright © 2007 John Wiley & Sons, Ltd.