bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Sensitivity RDX Obtained From Bachmann RDX
Authors: Spyckerelle Christian , Eck Geneviève , Sjöberg Per , Amnéus Anna‐Maria
Published: February 2008

In recent years much interest has been generated in a quality of reduced sensitivity RDX (RS‐RDX), like I‐RDX® which, when incorporated in cast cure and even pressable plastic bonded explosives (PBX compositions), can confer reduced shock sensitivity as measured through gap test. At crystal level, lot of work has been done to try to determine which property or properties may explain the behaviour of the corresponding cast PBX composition. But up to now, and despite an international inter‐laboratory comparison (Round Robin) of seven lots of RDX from five different manufacturers conducted from 2003 to 2005, even if some techniques lead to interesting results, there is no dedicated specification to apply to RS‐RDX. This quality (I‐RDX®) has proved to retain its low sensitivity even after ageing, which does not seem to be the case for standard RDX produced by the Bachmann process (when re‐crystallized under I‐RDX conditions in order to obtain RS‐RDX). It has been shown that the higher sensitivity of RDX produced by the Bachmann process, or the evolution of sensitivity after ageing of RS‐RDX produced from Bachmann RDX may be linked to the presence of octogen (HMX) during the crystallization process. In order to check such hypothesis, low HMX content RDX produced by the Bachmann process has been prepared and evaluated in cast PBX composition (PBX N 109). Results of the characterization of such quality of RDX and its evaluation in cast PBX composition as well as ageing behaviour are presented and discussed; there are indications that removal of HMX from Bachmann RDX may lead to RS‐RDX, which retains its RS character even after ageing.
RDX and HMX with Reduced Sensitivity Towards Shock Initiation–RS‐RDX and RS‐HMX
Authors: Hammer Johansen Øyvind , Digre Kristiansen Jørn , Gjersøe Richard , Berg Alf , Halvorsen Terje , Smith Kjell‐Tore , Nevstad Gunnar Ove
Published: February 2008

Reduced Sensitivity RDX (RS‐RDX) has received a lot of attention and interest from the explosive community in the recent years. There are several producers of RS‐RDX, most of them using a direct nitration (Woolwich process) for the RDX synthesis, while Chemring Nobel uses the Bachmann process. The processes for obtaining the RS properties probably differ between the various producers. Chemring Nobel has also developed an HMX quality that shows Reduced Sensitivity (RS‐HMX) of different particle size distributions. The shock sensitivity is at the same level as for RS‐RDX in comparable compositions. Reduced shock sensitivity has been obtained for RS‐RDX and Reduced Sensitivity (RS‐HMX) in both pressable and cast‐cured compositions. By using a pressable composition, it is possible to get the results from a BICT gap test faster than from a cast‐cured composition that has to go through a curing process. Chemring Nobel in cooperation with FFI have performed an extensive accelerated ageing testing of RS‐RDX produced by the Bachmann process. The samples have been aged at 60 and 70 °C and the shock sensitivity tested by two different gap tests. The results demonstrate that the Chemring Nobel RS‐RDX retain the insensitivity towards shock during ageing and show no degradation at all. Accelerated ageing testing of RS‐HMX has also been performed and shows no degradation in the shock sensitivity.
Reduced Sensitivity RDX (RS‐RDX) in Pressed Formulations: Respective Effects of Intra‐Granular Pores, Extra‐Granular Pores and Pore Sizes
Authors: Borne Lionel , Mory Julien , Schlesser Franck
Published: February 2008

Reduced sensitivity RDX (RS‐RDX) particles are now available from several manufacturers. But a clear understanding of this reduced sensitivity behavior is not yet available. RS‐RDX particles are usually employed in cast formulations to reduce their shock sensitivity. The use of RS‐RDX in pressed formulations is more recent and does not always give reduced sensitivity formulations.
Particle Size Modification of Thermally Stable Secondary Explosives for IM Applications
Authors: Parker Adam , Claridge Robert P. , Hamid Javid , Proud William G.
Published: February 2008

As well as improving the survivability of weapons and platforms, insensitive munitions (IM) reduce both casualty rates and mission losses. Their use also leads to improved safety during storage and transportation. For a munition to fulfil IM criteria, each of its energetic sub‐sections must be IM compliant. The initiator and explosive train are the most critical of these sub‐systems as their safety and reliability are of paramount importance if the weapon is to be suitable for service use, yet they are generally the most difficult part of a weapon to protect from inadvertent initiation. As part of an ongoing study into initiation methods suitable for use in IM systems, an investigation into the behaviour of energetic materials when impacted by laser‐driven flyers was performed. Laser‐based detonators exhibit increased safety characteristics over conventional initiation methods as they can be based on insensitive secondary explosives rather than sensitive primary explosives. Also, they are less susceptible to accidental initiation due to an external hazard threat. Single pulses from a high‐powered Q‐switched Nd:YAG laser were used to launch flyers from substrate‐backed aluminium films to velocities up to 6 km s−1 across a short stand‐off to impact explosive targets. Several novel energetic materials have been selected for investigation as potential candidates for inclusion within flyer‐based initiation systems and explosive train applications. The materials are of interest due to their increased thermal stability and power output over conventional explosives currently in service. Attempts were made to increase the flyer responsiveness of the materials by tuning their particle size using ultrasound. The effect of particle size on the initiation threshold energy was investigated for three materials.
Solution structure, antibacterial activity, and expression profile of Manduca sexta moricin
Authors: Dai Huaien , Rayaprolu Subrahmanyam , Gong Yuxi , Huang Rudan , Prakash Om , Jiang Haobo
Published: February 2008

In response to wounding or infection, insects produce a battery of antimicrobial peptides (AMPs) and other defense molecules to kill the invading pathogens. To study their structures, functions, and transcriptional regulation, we synthesized Manduca sexta moricin, a 42‐residue peptide (GKIPVKAIKQAGKVIGKGLRAINIAGTTHDVVSFFRPKKKKH, 4539 Da). The compound exhibited potent antimicrobial activities against a broad spectrum of Gram‐positive and Gram‐negative bacteria with a minimum inhibitory concentration of 1.4 µM. The mRNA levels of M. sexta moricin increased substantially in fat body and hemocytes after the larvae were challenged with bacterial cells. We determined the solution structure of this AMP by two‐dimensional 1H1H ‐nuclear magnetic resonance spectroscopy. The tertiary structure is composed of an eight‐turn α‐helix spanning almost the entire peptide. Insights of relationships between the structure and function are also presented. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Isolation and characterization of a C12‐lipopeptide produced byBacillus subtilisHSO 121
Authors: Liu Xiang‐Yang , Yang Shi‐Zhong , Mu Bo‐Zhong
Published: February 2008

A new lipopeptide with C12fatty acid has been isolated from the cell broth ofBacillus subtilisHSO121 by chromatographic methods, which is believed to be the homologue of lipopeptides. The fatty acid portion was methylated and analyzed by GC/MS, ESI Q‐TOF MS and1H‐NMR. The peptide portion, of which the amino acid composition was obtained by HPLC combined with a phenyl isothiocyanate (PITC) derivatization methods, was analyzed by ESI Q‐TOF MS. Comparing the obtained results with surfactin C13showed that the new lipopeptide has a peptide moiety similar to that of surfactin and the difference exists in the fatty acid portion, which is an iso‐C12β‐hydroxy fatty acid. The critical micelle concentration (CMC) of this new homologue is estimated to be 6.27 × 10−5mol/l in 10 mmol/l phosphate buffer solution (PBS, pH 8.0) at 30 °C, and the surface tension at CMC (γCMC) achieved is as little as 27.71 mN/m. The hemolytic activities of the C12‐lipopeptide on 2% human erythrocytes showed a HC50of 26.5 µmol/l. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
High‐throughput solid‐phase permethylation of glycans prior to mass spectrometry
Authors: Kang Pilsoo , Mechref Yehia , Novotny Milos V.
Published: February 2008

Permethylation of glycans prior to their mass spectrometric determination has now become a time‐honored methodology in glycoconjugate analysis due to the advantage of a simultaneous analysis of neutral and acidic glycans as well as enhanced sensitivity and easier tandem mass spectrometry interpretation. While the different solvent extraction‐based versions of this method often suffice in different structural studies, they are generally less satisfactory in the quantitative determinations aiming at minor quantities of the analyzed materials. To overcome these difficulties, we recently introduced a solid‐phase capillary permethylation technique (Kang et al., Rapid Commun. Mass Spectrom. 2005; 19: 3421) for microscale determination. Here, we describe a very useful high‐throughput extension of the solid‐phase methodology utilizing spin columns packed with sodium hydroxide beads. This procedure has been thoroughly optimized to match the analytical performance parameters of the previously used capillary technique. As demonstrated with a high‐precision glycomic profiling analysis of human blood serum, this methodological improvement offers simplicity and reproducibility, allowing the complete permethylation of 12–18 samples in less than 20 min. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous use of gas chromatography/ion trap mass spectrometry ‐ electron capture detection to improve the analysis of bromodiphenyl ethers in biological and environmental samples
Authors: Wang Dongli , Atkinson Shannon , Hoover‐Miller Anne , Shelver Weilin L. , Li Qing X.
Published: February 2008

Bromodiphenyl ethers (BDEs) are a class of synthetic flame retardants and are widely present in the environment. Analysis of higher BDE congeners has proven to be a challenge. We report the development of a method that enhances their analysis by splitting the eluent of a gas chromatograph (GC) between an electron capture detector (ECD) and an ion trap mass spectrometer (ITMS): 1:10, ECD:ITMS. This allowed the quantitation of the lower molecular weight (MW) BDE congeners (Br1–Br7) with the ITMS and of the higher MW BDEs (Br8–Br10) with the highly sensitive ECD. The IT temperature, ionization mode, and MS/MS parameters (excitation amplitude and stability parameter) were optimized. This method took the advantages of the best detector for the different BDE homologues and was suitable for the analysis of BDEs in environmental and biological samples. Average recoveries were 52–112% for BDEs from spiked sand samples and 57–126% from spiked lard samples after accelerated solvent extraction followed by silica gel and alumina column clean‐up. Average recoveries ranged from 51% to 130% for 13C‐labeled BDEs spiked in the real and in matrix samples. The method detection limits for specific congeners were 0.18–120 pg/g of the BDEs in animal tissue samples, and 0.05–40 pg/g in soil and indoor dust samples. The utility of the method was demonstrated by analyzing actual harbor seal blubber, indoor dust and soil samples. The concentration of each BDE ranged from non‐detectable (nd) to 41 ng/g in the dry soil sample, nd to 1042 ng/g in the indoor dust, nd to 15 ng/g wet weight in the Alaskan harbor seal blubber sample, and 0.02 to 11 ng/µL of the identified 23 of the 42 breakdown products from BDE‐209 after zerovalent iron treatment. Finally, an interlaboratory comparison showed high correspondence between the GC/ITMS‐ECD method and a GC high‐resolution MS system for the analysis of BDEs in soil samples. Copyright © 2008 John Wiley & Sons, Ltd.
Dehydroalanine derived from cysteine is a common post‐translational modification in human serum albumin
Authors: Bar‐Or Raphael , Rael Leonard T. , Bar‐Or David
Published: February 2008

The conversion of a cysteine residue into dehydroalanine (DHA) in proteins was previously described. This post‐translational modification (PTM) can be generated artificially as a result of heat and an alkaline environment. The presence of this PTM on human serum albumin (HSA) in plasma collected from healthy volunteers and critically ill patients as well as in commercially available HSA was studied. Using liquid chromatography/mass spectrometry (LC/MS) and matrix‐assisted laser desorption/ionization tandem mass spectrometry (MALDI‐MS/MS) methods, a fragment containing DHA was identified in the trypsin digest of commercial HSA and isolated HSA from plasma. The sequence (RPC*FSALEVDETYVPK) corresponded to the expected molecular mass and fragmentation pattern of a tryptic peptide of HSA where the cysteine residue (cys487) was modified to DHA. The presence of this common PTM of HSA has potential effects on ligand binding to HSA, plasma clearance of this oxidized form of HSA, protein‐protein interactions, and oxidation‐reduction potential. Copyright © 2008 John Wiley & Sons, Ltd.
Cellular proteins detected in HIV‐1
Authors: Ott David E.
Published: February 2008

It has been known for some time that HIV‐1 virions contain cellular proteins in addition to proteins encoded by the viral genome. Recent studies have vastly increased the number of host proteins detected in HIV‐1. This review summarises the current findings on several cellular proteins present in these virions, including some functional studies on their potential roles in the viral replication cycle and pathogenesis. Because retroviruses require extensive assistance from host proteins and pathways, the data from biochemical characterisations of HIV‐1 serve as an important starting point for understanding the role of cellular proteins that act in or influence the biology of HIV‐1. Additionally, a better understanding of the interactions between cellular proteins and viral components might provide more targets for anti‐HIV therapeutic intervention and provide for a better understanding of how HIV‐1 alters the immune system. The extensive study of HIV‐1 has already brought new insights to the fields of immunology and vaccine science. In the same way, knowledge of viral‐‐cellular protein interactions might assist our understanding of important cellular pathways. Copyright © 2008 John Wiley & Sons, Ltd.
Stability‐ and performance‐robustness tradeoffs: MIMO mixed‐µvscomplex‐µ design
Authors: Vasconcelos J. F. , Athans M. , Fekri S. , Silvestre C. , Oliveira P.
Published: February 2008

We present a non‐trivial case study designed to highlight some of the practical issues that arise when using mixed‐µ or complex‐µ robust synthesis methodologies. By considering a multi‐input multi‐output three‐cart mass–spring–dashpot (MSD) with uncertain parameters and dynamics, it is demonstrated that optimized performance (disturbance‐rejection) is reduced as the level of uncertainty in one or two real parameters is increased. Comparisons are made (a) in the frequency domain, (b) by RMS values of key signals and (c) in time‐domain simulations. The mixed‐µ controllers designed are shown to yield superior performance as compared with the classical complex‐µ design. The singular value decomposition analysis shows the directionality changes resulting from different uncertainty levels and from the use of different frequency weights. The nominal and marginal stability regions of the closed‐loop system are studied and discussed, illustrating how stability margins can be extended at the cost of reducing performance. Copyright © 2008 John Wiley & Sons, Ltd.
Insulator nanocapillary production from biological sample
Authors: Bereczky R. J. , Tökési K. , Varga D. , Zhang Z. M. , Ding Z. J.
Published: February 2008

Diatoms are unicellular microscopic organisms with silicon dioxide‐based cylindrical‐shaped skeletons, enveloped with an organic material composed of essentially polysaccharides and proteins. By removing the organic compounds from the diatom, we present an alternative method for the preparation of insulating nanocapillaries. The lengths of the capillaries are about 100 µm and the diameters of the regularly structured pores are about 200 nm. Moreover, we confirm with measurements by XPS that the shell of the Pennales diatoms contains mostly SiO2. Copyright © 2008 John Wiley & Sons, Ltd.
Growth and adhesion of biphasic crystalline–amorphous Sm/FeTaN magnetic nanospheroids on a Ta surface
Authors: Cefalas A. C. , Kovač J. , Sarantopoulou E. , Dražić G. , Kollia Z. , Kobe S.
Published: February 2008

The adhesion strength of magnetic films of intermetallic alloys on different substrates specifies their long‐term magnetic functionality, among other physicochemical characteristics of the films. Nanospheroids of Sm/FeTaN intermetallic alloys were grown from the Sm13.8 Fe82.2 Ta4.0 target by pulse laser deposition at 157 nm. The high‐temperature, liquefied nanodroplets were formed in the plume. They eventually solidified on the surface of a Ta substrate covered with a thin Ta/O layer in the form of biphasic nanospheroids, consisting of a crystalline nucleus surrounded by an amorphous mantle. Such nanostructures exhibit a ferromagnetic response because the oxidization of the inner crystalloid nucleus, which specifies the magnetic properties, is prevented by the amorphous spheroid mantle. The strength of adhesion of the nanodroplets on the Ta substrate was inversely proportional to the Sm/Fe concentration. The nanodroplets with high Sm/Fe concentration were bound on the Ta substrate with a large average contact angle of ∼161.4° due to the strong intermolecular forces in the alloy. The nanodroplets with low Sm/Fe concentration exhibited hydrophilic binding, and they were strongly attached to the Ta substrate with an average contact angle of 11.3° . Magnetic force microscopy measurements revealed that the magnetic response of the nanospheroids was proportional to the contact angle. Copyright © 2008 John Wiley & Sons, Ltd.
An aspect‐oriented software architecture for code mobility
Authors: Lobato Cidiane , Garcia Alessandro , Romanovsky Alexander , Lucena Carlos
Published: February 2008

Mobile agents have come forward as a technique for tackling the complexity of open distributed applications. However, the pervasive nature of code mobility implies that it cannot be modularized using only object‐oriented (OO) concepts. In fact, developers frequently evidence the presence of mobility scattering in their system's modules. Despite these problems, they usually rely on OO application programming interfaces (APIs) offered by the mobility platforms. Such classical API‐oriented designs suffer a number of architectural restrictions, and there is a pressing need for empowering developers with an architectural framework supporting a flexible incorporation of code mobility in the agent applications. This work presents an aspect‐oriented software architecture, called ArchM, ensuring that code mobility has an enhanced modularization and variability in agent systems, and is straightforwardly introduced in otherwise stationary agents. It addresses OO APIs' restrictions and is independent of specific platforms and applications. An ArchM implementation also overcomes fine‐grained problems related to mobility tangling and scattering at the implementation level. The usefulness and usability of ArchM are assessed within the context of two case studies and through its composition with two mobility platforms. Copyright © 2008 John Wiley & Sons, Ltd.
Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas
Authors: Zheng Hua-chuan , Li Xiao-han , Hara Takuo , Masuda Shinji , Yang Xiang-hong , Guan Yi-fu , Takano Yasuo
Published: February 2008

To investigate the pathobiological behaviors of gastric mixed-type (MT) carcinomas and gastric carcinogenesis, the clinicopathological characteristics of MT carcinomas were analyzed and compared with intestinal-type (IT) and diffuse-type (DT) carcinomas. The expression of Ki-67, caspase-3, p53, fragile histine triad (FHIT), maspin, extracellular matrix metalloproteinase inducer (EMMPRIN), vascular growth factor (VEGF), MUC-2, 4, 5AC and 6, CD44, E-cadherin, β-catenin, and phosphorylated glycogen synthase kinase 3β-ser9 (P-GSK3β-ser9) was examined on tissue microarrays using immunohistochemistry. It was found that MT carcinomas exhibited large size, deep invasion, frequent local invasion, and lymph node metastasis in comparison with IT and DT carcinomas (p < 0.05). All the markers except MUC-5AC showed higher expression in IT than DT carcinomas (p < 0.05). The expression of maspin, EMMPRIN, VEGF, MUC-4, and membrane E-cadherin was stronger in MT intestinal than diffuse component (p < 0.05). Immunoreactivities to Ki-67, EMMPRIN, and VEGF were weaker in IT carcinoma than in the MT intestinal portion (p < 0.05), while the opposite was true for CD44, MUC-2, and MUC-6 (p < 0.05). The MT diffuse component displayed a higher expression of FHIT, VEGF, and P-GSK3β-ser9 than DT carcinoma (p < 0.05). The accumulative survival rate of the IT carcinoma patients was higher than the other types (p < 0.05). The invasive depth, venous invasion, lymph node, peritoneal or liver metastasis, and Lauren's classification were independent prognostic factors for gastric carcinomas (p < 0.05). These findings suggested that MT carcinomas were also indicated to be more aggressive than IT and DT carcinomas. Significant differences were observed in the proliferation, apoptosis, angiogenesis, mucin secretion, and cell adhesion between IT and DT carcinomas, whereas only a few of these characteristics showed differences between the MT intestinal and diffuse parts, thus suggesting that both the MT components might originate from the stem cells with similar genetic traits, but follow different histogenic pathways.
Impact of a Genetic Diagnosis of a Mitochondrial Disorder 5–17 Years After the Death of an Affected Child
Authors: Sexton A. C. , Sahhar M. , Thorburn D. R. , Metcalfe S. A.
Published: February 2008

This study used in‐depth interviews to explore the experiences of parents who were re‐contacted with new genetic results many years after the death of a child with a mitochondrial disorder. At the time of their child's illness, parents had consented to a tissue sample being taken to help with diagnosis of a suspected mitochondrial disorder, and subsequently further DNA testing identified the genetic cause. Parents did not express negative feelings about being re‐contacted with new information, and hoped that continuing research might help other families. Positive aspects included relief from feelings of guilt over the cause of the child's disorder, and having accurate genetic information available for surviving children. Difficult emotional and psychosocial implications included contradictions to previous beliefs about inheritance, deciding how and when to communicate information to surviving children, and coping with new fears for the mother's health if a gene located in the mitochondrial DNA was identified. In half of the families the new results significantly altered the parents’ understanding of the inheritance pattern. This study highlights the impact of new genetic information offered after a delay of several years, which has the potential to re‐open feelings of grief and uncertainty and can present a new inheritance scenario for which research participants or their families are unprepared. Health professionals involved in conveying genetic research results can help to support families through this process.
Prolonged‐release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients
Authors: Hanna Magdi , O'Brien Cathy , Wilson Margaret C.
Published: February 2008

Background: Neuropathic pain remains one of the most challenging pain syndromes; under‐diagnosed, poorly managed and associated with significant co‐morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose‐related adverse events.

Aims: This randomized, double‐blind, placebo‐controlled study assessed the potential benefit of adding oxycodone (OxyContin® tablets) to gabapentin. The primary endpoint was to evaluate the analgesic efficacy of co‐administration of gabapentin and prolonged‐release oxycodone, whilst also evaluating the use of escape medication, sleep quality and global assessment of pain.

Methods: Three hundred and thirty eight patients with moderate to severe painful diabetic neuropathy despite receiving their maximum tolerated dose of gabapentin, had oral prolonged‐release oxycodone or placebo tablets added to their therapy for up to 12weeks.

Results: Oxycodone–gabapentin reduced pain score by 33% from baseline to end of treatment. The overall treatment effect was greater with oxycodone–gabapentin than with placebo–gabapentin (P=0.007). Oxycodone–gabapentin also significantly improved pain relief vs gabapentin alone (P=0.003). Oxycodone–gabapentin co‐administration was associated with less escape medication use (P=0.03) and fewer nights of disturbed sleep (P<0.05). Discontinuations due to lack of therapeutic effect were much lower (14% vs 54%) with oxycodone–gabapentin. The commonly seen opiate‐induced adverse events were not exacerbated by the combination of oxycodone and gabapentin.

Conclusions: This study provides the first evidence that co‐administration of prolonged‐release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy.
Antinociceptive effects of high dose remifentanil in male methadone‐maintained patients
Authors: Hay Justin L. , White Jason M. , Bochner Felix , Somogyi Andrew A.
Published: February 2008

The treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross‐tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone‐maintained subjects in a dose‐dependent manner. Eight chronic methadone‐maintained subjects attended the testing session approximately 20h after their normal methadone dose (range 50–110mgday−1). Following a 20min saline infusion, subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5μgkg−1min−1, each for 20min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine–benzedrine group scale (MBG). Results showed dose‐dependent increase in cold pressor tolerance time from baseline of 15.6±3.5 (mean±SEM)s up to 77.3±24.7s during this dosing protocol. During the infusion typical μ‐opioid receptor agonist side effects were observed, but with no withdrawal. Methadone‐maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20–30 higher than required for the treatment of acute pain in opioid‐naïve patients.
Prevalence study of the lungworm Aelurostrongylus abstrusus in stray cats of Portugal
Authors: Payo-Puente Pablo , Botelho-Dinis M. , Urueña Ana Maria Carvaja , Payo-Puente Miren , Gonzalo-Orden José M. , Rojo-Vazquez Francisco A.
Published: February 2008

In this study we have investigated the prevalence of aelurostrongylosis, one of the most common feline pulmonary parasitic diseases, in cats from the north-west region of Portugal. For this purpose, 97 faecal samples were collected from cats at risk of being infected by Aelurostrongylus abstrusus in an animal shelter and in a municipal facility. Using the Baermann–Wetzel coprological technique, faecal shedding of first stage larvae (L1) was detected in 17.4% of the cats. Based on this result, it can be concluded that this lungworm infection seems to be common among feral cats in the north-west region of Portugal, in spite of the fact that clinical aelurostrongylosis is not frequently diagnosed by feline practitioners in the area. This parasitic disease should be included in the differential diagnosis of cats presenting with coughing or dyspnoea, and it also should be extended to asymptomatic animals with pulmonary nodules detected by image diagnosis.
Model-Based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone
Authors: Chen Andy B. , Hamamura Kazunori , Wang Guohua , Xing Weirong , Mohan Subburaman , Yokota Hiroki , Liu Yunlong
Published: February 2008

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both “anabolic responses of mechanical loading” and “BMP-mediated osteogenic signaling”? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
Reconstruction of Pathways Associated with Amino Acid Metabolism in Human Mitochondria
Authors: Guda Purnima , Guda Chittibabu , Subramaniam Shankar
Published: February 2008

We have used a bioinformatics approach for the identification and reconstruction of metabolic pathways associated with amino acid metabolism in human mitochondria. Human mitochondrial proteins determined by experimental and computational methods have been superposed on the reference pathways from the KEGG database to identify mitochondrial pathways. Enzymes at the entry and exit points for each reconstructed pathway were identified, and mitochondrial solute carrier proteins were determined where applicable. Intermediate enzymes in the mitochondrial pathways were identified based on the annotations available from public databases, evidence in current literature, or our MITOPRED program, which predicts the mitochondrial localization of proteins. Through integration of the data derived from experimental, bibliographical, and computational sources, we reconstructed the amino acid metabolic pathways in human mitochondria, which could help better understand the mitochondrial metabolism and its role in human health.
Prediction of Protein-Protein Interactions Using Protein Signature Profiling
Authors: Mahdavi Mahmood A. , Lin Yen-Han
Published: February 2008

Protein domains are conserved and functionally independent structures that play an important role in interactions among related proteins. Domain-domain interactions have been recently used to predict protein-protein interactions (PPI). In general, the interaction probability of a pair of domains is scored using a trained scoring function. Satisfying a threshold, the protein pairs carrying those domains are regarded as “interacting”. In this study, the signature contents of proteins were utilized to predict PPI pairs in Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens. Similarity between protein signature patterns was scored and PPI predictions were drawn based on the binary similarity scoring function. Results show that the true positive rate of prediction by the proposed approach is approximately 32% higher than that using the maximum likelihood estimation method when compared with a test set, resulting in 22% increase in the area under the receiver operating characteristic (ROC) curve. When proteins containing one or two signatures were removed, the sensitivity of the predicted PPI pairs increased significantly. The predicted PPI pairs are on average 11 times more likely to interact than the random selection at a confidence level of 0.95, and on average 4 times better than those predicted by either phylogenetic profiling or gene expression profiling.
Computational Prediction of Rice (Oryza Sativa) miRNA Targets
Authors: Archak Sunil , Nagaraju J.
Published: February 2008

Bioinformatic approaches have complemented experimental efforts to inventorize plant miRNA targets. We carried out global computational analysis of rice (Oryza sativa) transcriptome to generate a comprehensive list of putative miRNA targets. Our predictions (684 unique transcripts) showed that rice miRNAs mediate regulation of diverse functions including transcription (41%), catalysis (28%), binding (18%), and transporter activity (11%). Among the predicted targets, 61.7% hits were in coding regions and nearly 72% targets had a solitary miRNA hit. The study predicted more than 70 novel targets of 34 miRNAs putatively regulating functions like stress-response, catalysis, and binding. It was observed that more than half (55%) of the targets were conserved between O. sativa indica and O. sativa japonica. Members of 31 miRNA families were found to possess conserved targets between rice and at least one of other grass family members. About 44% of the unique targets were common between two dissimilar miRNA prediction algorithms. Such an extent of cross-species conservation and algorithmic consensus confers confidence in the list of rice miRNA targets predicted in this study.
Construction, Characterization, and Chromosomal Mapping of a Fosmid Library of the White-Cheeked Gibbon (Nomascus Leucogenys)
Authors: Chen Liping , Ye Jianping , Liu Yan , Wang Jinghuan , Su Weiting , Yang Fengtang , Nie Wenhui
Published: February 2008

Gibbons have experienced extensive karyotype rearrangements during evolution and represent an ideal model for studying the underlying molecular mechanism of evolutionary chromosomal rearrangements. It is anticipated that the cloning and sequence characterization of evolutionary chromosomal breakpoints will provide vital insights into the molecular force that has driven such a radical karyotype reshuffle in gibbons. We constructed and characterized a high-quality fosmid library of the white-cheeked gibbon (Nomascus leucogenys) containing 192,000 non-redundant clones with an average insert size of 38 kb and 2.5-fold genome coverage. By end sequencing of 100 randomly selected fosmid clones, we generated 196 sequence tags for the library. These end-sequenced fosmid clones were then mapped onto the chromosomes of the white-cheeked gibbon by fluorescence in situ hybridization, and no spurious chimeric clone was detected. BLAST search against the human genome showed a good correlation between the number of hit clones and the number of chromosomes, an indication of unbiased chromosomal distribution of the fosmid library. The chromosomal distribution of the mapped clones is also consistent with the BLAST search result against human and white-cheeked gibbon genomes. The fosmid library and the mapped clones will serve as a valuable resource for further studying gibbons’ chromosomal rearrangements and the underlying molecular mechanism as well as for comparative genomic study in the lesser apes.
Transcriptome and Proteome Expressions Involved in Insulin Resistance in Muscle and Activated T-Lymphocytes of Patients with Type 2 Diabetes
Authors: Stentz Frankie B. , Kitabchi Abbas E.
Published: February 2008

We analyzed the genes expressed (transcriptomes) and the proteins translated (proteomes) in muscle tissues and activated CD4+ and CD8+ T-lymphocytes (T-cells) of five Type 2 diabetes (T2DM) subjects using Affymetrix microarrays and mass spectrometry, and compared them with matched non-diabetic controls. Gene expressions of insulin receptor (INSR), vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 (IRS-1), IRS-2, glucose transporter 4 (GLUT4), and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls. However, there was greater than two-fold gene upregulation of plasma cell glycoprotein-1, tumor necrosis factor α (TNFα), and gluconeogenic enzymes in T2DM than in controls. The gene silencing for INSR or TNFα resulted in the inhibition or stimulation of GLUT4, respectively. Proteome profiles corresponding to molecular weights of the above translated transcriptomes showed different patterns of changes between T2DM and controls. Meanwhile, changes in transcriptomes and proteomes between muscle and activated T-cells of T2DM were comparable. Activated T-cells, analogous to muscle cells, expressed insulin signaling and glucose metabolism genes and gene products. In conclusion, T-cells and muscle in T2DM exhibited differences in expression of certain genes and gene products relative to non-diabetic controls. These alterations in transcriptomes and proteomes in T2DM may be involved in insulin resistance.
Mycobacterial PE_PGRS Proteins Contain Calcium-Binding Motifs with Parallel β-Roll Folds
Authors: Bachhawat Nandita , Singh Balvinder
Published: February 2008

The PE_PGRS family of proteins unique to mycobacteria is demonstrated to contain multiple calcium-binding and glycine-rich sequence motifs GGXGXD/NXUX. This sequence repeat constitutes a calcium-binding parallel β-roll or parallel β-helix structure and is found in RTX toxins secreted by many Gram-negative bacteria. It is predicted that the highly homologous PE_PGRS proteins containing multiple copies of the nona-peptide motif could fold into similar calcium-binding structures. The implication of the predicted calcium-binding property of PE_PGRS proteins in the light of macrophage-pathogen interaction and pathogenesis is presented.
FASMA: A Service to Format and Analyze Sequences in Multiple Alignments
Authors: Costantini Susan , Colonna Giovanni , Facchiano Angelo M.
Published: February 2008

Multiple sequence alignments are successfully applied in many studies for understanding the structural and functional relations among single nucleic acids and protein sequences as well as whole families. Because of the rapid growth of sequence databases, multiple sequence alignments can often be very large and difficult to visualize and analyze. We offer a new service aimed to visualize and analyze the multiple alignments obtained with different external algorithms, with new features useful for the comparison of the aligned sequences as well as for the creation of a final image of the alignment. The service is named FASMA and is available at http://bioinformatica.isa.cnr.it/FASMA/.
Homotopy theory of well-generated algebraic triangulated categories
Authors: Tabuada Gonçalo
Published: February 2008

For every regular cardinal α, we construct a cofibrantly generated Quillen model structure on a category whose objects are essentially dg categories which are stable under suspensions, cosuspensions, cones and α-small sums.

Using results of Porta, we show that the category of well-generated (algebraic) triangulated categories in the sense of Neeman is naturally enhanced by our Quillen model category.
Relative pairing in cyclic cohomology and divisor flows
Authors: Lesch Matthias , Moscovici Henri , Pflaum Markus J.
Published: February 2008

We construct invariants of relative K-theory classes of multiparameter dependent pseudodifferential operators, which recover and generalize Melrose's divisor flow and its higher odd-dimensional versions of Lesch and Pflaum. These higher divisor flows are obtained by means of pairing the relative K-theory modulo the symbols with the cyclic cohomological characters of relative cycles constructed out of the regularized operator trace together with its symbolic boundary. Besides giving a clear and conceptual explanation to the essential features of the divisor flows, namely homotopy invariance, additivity and integrality, this construction allows to uncover the previously unknown even-dimensional counterparts. Furthermore, it confers to the totality of these invariants a purely topological interpretation, that of implementing the classical Bott periodicity isomorphisms in a manner compatible with the suspension isomorphisms in both K-theory and in cyclic cohomology. We also give a precise formulation, in terms of a natural Clifford algebraic suspension, for the relationship between the higher divisor flows and the spectral flow.
Tolosa–Hunt syndrome misdiagnosed as sinusitis complication
Authors: Lachanas V A , Karatzias G T , Tsitiridis I , Panaras I , Sandris V G
Published: February 2008

Objective:

Tolosa–Hunt syndrome is a rare condition of painful ophthalmoplegia combined with ipsilateral ocular motor nerve palsies, caused by non-specific granulomatous inflammation in the cavernous sinus, superior orbital fissure or orbit. A case of Tolosa–Hunt syndrome misdiagnosed as sinusitis orbital complication is reported.

Case report:

A patient suffering from left periorbital pain, upper eyelid oedema and ptosis, and horizontal diplopia, diagnosed as sinusitis orbital complication, was referred to our department. Clinical evaluation revealed only a left VIth nerve paresis. Haematological studies, cerebrospinal fluid tests and computed tomography scanning were negative. A magnetic resonance imaging (MRI) scan showed enhancement of the left cavernous sinus. Corticosteroid therapy was commenced, and within three days all symptoms disappeared. A diagnosis of Tolosa–Hunt syndrome was made. Follow-up MRI studies were normal.

Conclusion:

Tolosa–Hunt syndrome, although rare, is a nosological entity that otolaryngologists must bear in mind. Magnetic resonance imaging studies are essential in the diagnosis and follow up of these patients, in order to avoid a mistaken Tolosa–Hunt syndrome diagnosis.
Change in hearing during ‘wait and scan’ management of patients with vestibular schwannoma
Authors: Stangerup S-E , Caye-Thomasen P , Tos M , Thomsen J
Published: February 2008

Aim:

To evaluate hearing changes during ‘wait and scan’ management of patients with vestibular schwannoma.

Subjects:

Over a 10-year period, 636 patients have prospectively been allocated to ‘wait and scan’ management, with annual magnetic resonance scanning and audiological examination.

Results:

At the time of diagnosis, 334 patients (53 per cent) had good hearing and speech discrimination of better than 70 per cent; at the end of the 10-year observation period, this latter percentage was 31 per cent. In 17 per cent of the patients, speech discrimination at diagnosis was 100 per cent; of these, 88 per cent still had good hearing at the end of the observation period. However, in patients with even a small initial speech discrimination loss, only 55 per cent maintained good hearing at the end of the observation period.

Conclusion:

After comparing the hearing results of hearing preservation surgery and of radiation therapy with those of ‘wait and scan’ management, it appears that, in vestibular schwannoma patients with a small tumour and normal speech discrimination, the main indication for active treatment should be established tumour growth.
Re-operation for secondary hyperparathyroidism
Authors: Debruyne F , Geuens G , Vander Poorten V , Delaere P
Published: February 2008

Objective:

In cases of re-operation for secondary hyperparathyroidism, to evaluate the extent to which the location of recurrent hyperplasia was predicted by (1) operative data from the first intervention, and (2) pre-operative imaging (before the re-operation).

Methods:

The files of 18 patients undergoing surgery for recurrent secondary hyperparathyroidism were reviewed. The surgical findings were compared both with the report of the initial operation and with the results of pre-operative imaging (i.e. ultrasonography, Mibi scintigraphy or computed tomography).

Results:

The location of the recurrent hyperplasia corresponded with the data for the primary intervention in about one-third of patients. There was a partial correlation in one-third of patients, and no correlation at all in one-third. Pre-operative imaging enabled better prediction of the location of recurrent disease.

Conclusion:

Surgeons should have both sources of information at their disposal when planning a re-intervention for secondary hyperparathyroidism. However, in our series, the predictive value of imaging was superior to that of information deduced from the previous surgical record.
Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck
Authors: Choi Y J , Chung J S , Shin H-J , Cho G J , Wang S G , Lee B J , Cho B M , Joo Y D , Sohn C H
Published: February 2008

Objective:

This study was performed to assess the efficacy and safety profile of combination treatment with S-1 and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck.

Design:

Eligibility criteria comprised: histologically confirmed squamous cell carcinoma of the head and neck; stage three or four disease with no evidence of distant metastasis; evaluable lesions; adequate organ function; age 20–80 years; and a performance status of two or less. Cisplatin was infused over one hour on day one (75 mg/m2) and S-1 was administered orally for 14 consecutive days (days two to 15). The dosages of S-1 were calculated according to the patients' body surface area: 50 mg twice a day (body surface area <1.5 m2) or 60 mg twice a day (body surface area >1.5 m2). Each course was repeated every three weeks. After two courses, tumour response was evaluated by computed tomography and laryngoscopy. If a response was evident (either complete or partial), the patient received one more course of chemotherapy, before undergoing radical treatment such as radiotherapy or surgery.

Results:

All 30 patients were assessable for toxicity, and 29 patients for treatment response. The overall response was 89.7 per cent (complete response: nine; partial response: 17). The two-year estimated overall survival rate was 79.2 per cent. Adverse reactions occurred 128 times during 81 courses in the 30 cases. The most common grade three to four adverse event was neutropenia, which occurred in eight patients. Cases of non-haematological grade three or four toxicity included nausea and vomiting in four patients, stomatitis in two and diarrhoea in one.

Conclusion:

S-1 plus cisplatin combination chemotherapy is effective against locally advanced squamous cell carcinoma of the head and neck, with only mild toxicity.