bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive hyperplasias,precancerous and malignant lesions of the oral mucosa
Authors: Krahl Dieter , Altenburg Andreas , Zouboulis Christos C. 
Published: February 2008

SummaryThe oral cavity contains many organs and tissues compressed in a small area. Accordingly oral tumors have a wide variety of appearances. Reactive hyper‐plastic lesions include epulis,morsicatio,traumatic ulcer or palatal hyperplasia. These benign lesions must be separated clinically and histologically from precancerous and neoplastic lesions. In leukoplakia,the individual risk can be estimated by clinical signs. Nevertheless histopathology is mandatory because precancerous lesions usually precede or accompany most oral cancers. Amalgam tattoo,oral nevi and melanoacanthoma have to be considered as differential diagnoses of oral melanoma. Accurate clinico‐pathological diagnosis is mandatory to insure appropriate therapy. Oral soft tissue tumors such as Kaposi sarcoma and multiple mucosal neuromas in MEN 2b require interdisciplinary management. Diseases affecting the minor salivary glands which may be encountered by dermatologists include mucocele, necrotizing sialometa‐plasia,and tumors such as pleomorphic adenoma.
Oral Delivery of 1,3‐Dicyclohexylurea Nanosuspension Enhances Exposure and Lowers Blood Pressure in Hypertensive Rats
Authors: Ghosh Sarbani , Chiang Po‐Chang , Wahlstrom Jan L. , Fujiwara Hideji , Selbo Jon G. , Roberds Steven L. 
Published: February 2008

Abstract:  Cytochrome P450‐derived epoxyeicosatrienoic acids (EET) are biologically active metabolites of arachidonic acid that have potent effects on renal vascular reactivity and tubular ion transport and have been implicated in the control of blood pressure. EETs are hydrolyzed to their less active diols, dihydroxyeicosatrienoic acids (DHET), by the enzyme soluble epoxide hydrolase (sEH). 1,3‐Dicyclohexylurea (DCU), a potent sEH inhibitor, lowers systemic blood pressure in spontaneously hypertensive rats when dosed intraperitoneally. However, DCU has poor aqueous solubility, posing a challenge for in vivo oral delivery. To overcome this limitation, we formulated DCU in a nanosuspension using wet milling. Milling reduced particle size, increasing the total surface area by approximately 40‐fold. In rats chronically infused with angiotensin II, the DCU nanosuspension administered orally twice daily for 4 days produced plasma exposures an order of magnitude greater than unmilled DCU and lowered blood pressure by nearly 30 mmHg. Consistent with the mechanism of sEH inhibition, DCU increased plasma 14,15‐EET and decreased plasma 14,15‐DHET levels. These data confirm the antihypertensive effect of sEH inhibition and demonstrate that greatly enhanced exposure of a low‐solubility compound is achievable by oral delivery using a nanoparticle drug delivery system.
Influence ofCYP2C19*18andCYP2C19*19Alleles on Omeprazole 5‐Hydroxylation:In vitroFunctional Analysis of Recombinant Enzymes Expressed inSaccharomyces cerevisiae
Authors: Hanioka Nobumitsu , Tsuneto Yumi , Saito Yoshiro , Maekawa Keiko , Sawada Jun‐ichi , Narimatsu Shizuo 
Published: February 2008

Abstract: Omeprazole is one of the most widely used proton pump inhibitors for the treatment of gastric acid‐related disorders. The major metabolic pathway of omeprazole is 5‐hydroxylation, which is catalysed by CYP2C19. In this study, the effect ofCYP2C19*18andCYP2C19*19alleles on omeprazole 5‐hydroxylation was studied using recombinant CYP2C19 enzymes of wild‐type (CYP2C19.1B having Ile331Val) and variants (CYP2C19.18 having Arg329His/Ile331Val and CYP2C19.19 Ser51Gly/Ile331Val) expressed in yeast cells. TheKmvalue for omeprazole 5‐hydroxylation of CYP2C19.1B was 1.46 µM. TheKmvalue of CYP2C19.19 was significantly higher (1.5‐fold) than that of CYP2C19.1B.VmaxandVmax/Kmvalues for omeprazole 5‐hydroxylation of CYP2C19.1B on the basis of cytochrome P450 protein level were 8.09 pmol/min./pmol CYP and 5.45 µl/min./pmol CYP, respectively. TheVmaxvalue of CYP2C19.19 was significantly higher (1.8‐fold) than that of CYP2C19.1B, whereas theVmax/Kmvalue was comparable to that of CYP2C19.1B. In contrast,Km,VmaxandVmax/Kmvalues of CYP2C19.18 were similar to those of CYP2C19.1B. These results suggest thatCYP2C19*19allele decreases the affinity between CYP2C19 enzyme and the substrate in omeprazole metabolism.
Interleukin‐10 and interferon‐gamma gene polymorphisms in patients with nasopharyngeal carcinoma
Authors: Farhat K. , Hassen E. , Gabbouj S. , Bouaouina N. , Chouchane L. 
Published: February 2008

SummaryNasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin‐10 (IL‐10) is known to reduce the production of interferon‐gamma (IFN‐γ), we supposed that genetic differences in IL‐10 and IFN‐γ expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL‐10 and IFN‐γ with NPC. Different IL‐10 –1082 G/A and IFN‐γ+874 Τ/Α genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL‐10 and IFN‐γ polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL‐10 and IFN‐γ do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.
Characterization, expression and evolution analysis of Toll‐like receptor 1 gene in pufferfish (Tetraodon nigroviridis)
Authors: Wu X‐Y. , Xiang L‐X. , Huang L. , Jin Y. , Shao J‐Z. 
Published: February 2008

SummaryThe Toll‐like receptor (TLR) family is a pathogen‐associated molecular pattern recognition receptor family that plays key roles in the activation of innate immune system. As an important member of TLRs, TLR1 is involved in the recognition of triacylated lipoproteins and mycobacterial products by binding to TLR2 to form a heterodimer. Although partial sequences of TLR1 has been predicted in Fugu and Danio by bioinformatics, the molecular cloning and characterization of this gene in fish still remains largely unclear. Here we report the full‐length sequence of TLR1 gene in the pufferfish (Tetraodon nigroviridis), providing experimental evidence to its existence in fish. The cloned Tetraodon TLR1 (TnTLR1) cDNA exhibited 2587 bp in length and contains a 122‐bp 5′ untranslated region (UTR), a 2391‐bp open reading frame and a 74‐bp 3′ UTR. Expression of TLR1 transcripts in most selected tissues were detected at lower levels; however, the transcripts in spleen was markedly increased (threefold) after stimulation with lipopolysaccharide, indicating that TLR1 in fish may be involved in the inflammatory responses to bacterial endotoxin or Gram‐negative bacteria infection. Gene organization of TnTLR1 is similar to mammalian and avian, and a high degree of conservation of chromosome synteny exists between them. The protein sequence shares 33.7–77.3% identity with known TLR1 members. Phylogenetic analysis grouped TnTLR1 with other fish TLRs on a separated branch, excluded from mammalian and avian TLR1s. TnTLR1 with 796 amino acids has a calculated molecular mass of 90.69 kDa and a theoretical pI of 8.43. Structurally, TnTLR1 has a Toll/interleukin‐1 receptor (TIR) domain, a transmembrane domain and leucine‐rich repeat domain which are the hallmarks of TLR family. Phylogenetic analysis provided evidence that the TnTLR1 was very close to mammalian TLR1, TLR6 and TLR10 and seemed to be their common ancestor. This report of the full‐length TLR1 gene in Tetraodon will provide us further insights into the study of both function and evolution of fish TLRs as a whole.
Microcalorimetry: a response to challenges in modern biotechnology
Authors: Krell Tino 
Published: February 2008

SummaryAlmost any process in life is accompanied by heat changes which can be monitored by isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Both techniques are now established tools in fundamental research but over the last decade a clear tendency towards more problem‐driven applications is noted. This review aims at summarizing these problem‐oriented applications of microcalorimetry and the solutions both techniques can provide to problems in biotechnology. The biotechnological issues to which microcalorimetry has been successfully applied are as diverse as rational drug design, overcoming drug resistance, optimization of long‐term stability of proteins, estimation of the bioavailability of drugs, control of complex pharmaceutical products or the optimization of gene delivery efficiency. The main limitation of microcalorimetry, which is the relatively large amounts of sample necessary for analysis, is less important in the biotechnology sector which frequently uses large‐scale produced bulk products for analysis. The recently developed high‐throughput DSC and ITC microcalorimeters will additionally reduce the labour intensity of these techniques. Due to the precision of microcalorimetric analyses and the versatility of processes which can be studied, it is expected that ITC and DSC will soon be key technologies in biotechnological research.
Poly‐3‐hydroxyalkanoate synthases from Pseudomonas putida U: substrate specificity and ultrastructural studies
Authors: Arias Sagrario , Sandoval Angel , Arcos Mario , Cañedo Librada M. , Maestro Beatriz , Sanz Jesús M. , Naharro Germán , Luengo José M. 
Published: February 2008

SummaryThe substrate specificity of the two polymerases (PhaC1 and PhaC2) involved in the biosynthesis of medium‐chain‐length poly‐hydroxyalkanoates (mcl PHAs) in Pseudomonas putida U has been studied in vivo. For these kind of experiments, two recombinant strains derived from a genetically engineered mutant in which the whole pha locus had been deleted (P. putida U Δpha) were employed. These bacteria, which expresses only phaC1 (P. putida U Δpha pMC‐phaC1) or only phaC2 (P. putida U Δpha pMC‐phaC2), accumulated different PHAs in function of the precursor supplemented to the culture broth. Thus, the P. putida U Δpha pMC‐phaC1 strain was able to synthesize several aliphatic and aromatic PHAs when hexanoic, heptanoic, octanoic decanoic, 5‐phenylvaleric, 6‐phenylhexanoic, 7‐phenylheptanoic, 8‐phenyloctanoic or 9‐phenylnonanoic acid were used as precursors; the highest accumulation of polymers was observed when the precursor used were decanoic acid (aliphatic PHAs) or 6‐phenylhexanoic acid (aromatic PHAs). However, although it synthesizes similar aliphatic PHAs (the highest accumulation was observed when hexanoic acid was the precursor) the other recombinant strain (P. putida U Δpha pMC‐phaC2) only accumulated aromatic PHAs when the monomer to be polymerized was 3‐hydroxy‐5‐phenylvaleryl‐CoA. The possible influence of the putative three‐dimensional structures on the different catalytic behaviour of PhaC1 and PhaC2 is discussed.
Development of a LytE‐based high‐density surface display system in Bacillus subtilis
Authors: Chen Chyi‐Liang , Wu Sau‐Ching , Tjia Wai Mui , Wang Christopher L. C. , Lohka Manfred J. , Wong Sui‐Lam 
Published: February 2008

SummaryThe three N‐terminal, tandemly arranged LysM motifs from a Bacillus subtilis cell wall hydrolase, LytE, formed a cell wall‐binding module. This module, designated CWBMLytE, was demonstrated to have tight cell wall‐binding capability and could recognize two classes of cell wall binding sites with fivefold difference in affinity. The lower‐affinity sites were approximately three times more abundant. Fusion proteins with β‐lactamase attached to either the N‐ or C‐terminal end of CWBMLytE showed lower cell wall‐binding affinity. The number of the wall‐bound fusion proteins was less than that of CWBMLytE. These effects were less dramatic with CWBMLytE at the N‐terminal end of the fusion. Both CWBMLytE and β‐lactamase were essentially functional whether they were at the N‐ or C‐terminal end of the fusion. In the optimal case, 1.2 × 107 molecules could be displayed per cell. As cells overproducing CWBMLytE and its fusions formed filamentous cells (with an average of nine individual cells per filamentous cell), 1.1 × 108β‐lactamase molecules could be displayed per filamentous cell. Overproduced CWBMLytE and its fusions were distributed on the entire cell surface. Surface exposure and accessibility of these proteins were confirmed by immunofluorescence microscopy.
Microbial whole‐cell arrays
Authors: Elad Tal , Lee Jin Hyung , Belkin Shimshon , Gu Man Bock 
Published: February 2008

SummaryThe coming of age of whole‐cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines – the whole‐cell array. In the present review, we highlight the state‐of‐the‐art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high‐performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis and – most importantly – enhanced long‐term maintenance of viability and activity on the fabricated biochips.
Injury trends in sanctioned mixed martial arts competition: a 5-year review from 2002 to 2007
Authors: Ngai K M , Levy F , Hsu E B 
Published: February 2008

Background:Professional mixed martial arts (MMA) competition is a full-contact sport that has risen rapidly in popularity in recent years. However, there is limited information regarding the incidence of competition injuries after sanctioning by an athletic commission.Methods:We conducted a retrospective cohort study to examine MMA injury patterns during a 5 year period after sanctioning in the state of Nevada. Data from all regulated MMA competitions during the study period from March 2002 to September 2007 (1270 fight exposures) was obtained. Injury odds ratios were calculated by conditional logistic regression on match outcome, age, weight, and fight experience, using a pair-matched case-control design (n = 464) and by multiple logistic regression on match outcome, age, fight experience, weight, combat minutes, and scheduled rounds.Results:During the 635 professional MMA matches, 300 of the 1270 athletes sustained documented injuries with an injury rate of 23.6 per 100 fight participations. Most common reported injuries were lacerations and upper limb injuries. Severe concussion rate was 15.4 per 1000 athlete exposures, or 3% of all matches. No deaths or critical sports-related injuries resulted from any of the regulated matches during the study period. Age, weight and fight experience did not statistically increase the likelihood of injuries after controlling for other covariates.Conclusions:Injury rates in regulated professional MMA competition are similar to other combat sports; the overall risk of critical sports-related injury seems to be low. Additional study is warranted to achieve a better understanding of injury trends and ways to further lower injury risk in MMA.
A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength
Authors: Myer Gregory , Brent Jensen , Ford Kevin , Hewett Timothy 
Published: February 2008

Objectives:The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength.Methods:Twenty-one (TMNT n=14: 15.4 ± 1.4 yrs, 170.5 ± 5.0 cm, 64.1 ± 8.5 kg; CTRL n =7: 16.0 ± 1.7 yrs, 173.4 ± 10.0 cm, 63.9 ± 5.3 kg; p>0.05) high school female volleyball players were recruited to participate in this study. Fourteen participated in TNMT protocol (2 X/wk) over a ten week period in addition to their standard off-season strength training (1X/wk). Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured prior to and after TNMT.Results:A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% dominant leg: 46.6 ± 10.1 to 52.9 ± 11.4 ft-lbs and 17.1% in the non-dominant leg: 46.1 ± 10.4 to 54.0 ± 10.7 ft-lbs; p = 0.01). There was no difference in the control group in pre- versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p=0.57) or knee flexion (p=0.57) strength.Conclusions:Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower extremity alignment and decrease loads resulting from increased trunk displacement during sports activities.
Physically Realistic Motion Synthesis in Animation
Authors: Ngo J. Thomas , Marks Joe 
Published: February 2008

Motion-synthesis problems arise in the creation of physically realistic animations involving autonomous characters. Trpically characters are required to perform goal tasks, subject to physical law and other constraints on their motion. Witkin and Kass (1988) dubbed this class of problems “Spacetime Constraints“ (SC) and presented results for specific problems involving an articulated figure. Their approach was based on a procedure for the local optimization of an initial approximate trajectory supplied by the user. Unfortunately, SC problems are typically multimodal and discontinuous, and the number of decision alternatives available at each time step can be exponential in the number of degrees of freedom in the system. Thus, constructing even coarse trajectories for subsequent optimization can be difficult. We present an algorithm that constructs such trajectories de novo, without directive input from the user. Rather than use a time-series representation, which might be appropriate for local optimization, our algorithm uses a stimulus-response model. Locomotive skills appropriate for the given articulated figure are acquired through repeated testing of (simulated) reality. Our initial implementation, which chooses stimulus-response parameters using a parallel genetic algorithm, succeeds in finding good, novel solutions for a test suite of SC problems involving unbranched 2-D linkages.
Mutation-Crossover Isomorphisms and the Construction of Discriminating Functions
Authors: Culberson Joseph C. 
Published: February 2008

We compare the search power of crossover and mutation in genetic algorithms. Our discussion is framed within a model of computation using search space structures induced by these operators. Isomorphisms between the search spaces generated by these operators on small populations are identified and explored. These are closely related to the binary reflected Gray code. Using these we generate discriminating functions that are hard for one operator but easy for the other and show how to transform from one case to the other. We use these functions to provide theoretical evidence that traditional GAs use mutation more effectively than crossover, but dispute claims that mutation is a better search mechanism than crossover. To the contrary, we show that methods that exploit crossover more effectively can be designed and give evidence that these are powerful search mechanisms. Experimental results using GIGA, the Gene Invariant Genetic Algorithm, and the well-known GENESIS program support these theoretical claims. Finally, this paper provides the initial approach to a different method of analysis of GAs that does not depend on schema analysis or the notions of increased allocations of trials to hyperplanes of above-average fitness. Instead it focuses on the search space structure induced by the operators and the effect of a population search using them.
A Derandomized Approach to Self-Adaptation of Evolution Strategies
Authors: Ostermeier Andreas , Gawelczyk Andreas , Hansen Nikolaus 
Published: February 2008

Comparable to other optimization techniques, the performance of evolution strategies (ESs) depends on a suitable choice of internal strategy control parameters. Apart from a fixed setting, ESs facilitate an adjustment of such parameters within a self-adaptation process. For step-size control in particular, various adaptation concepts have been evolved early in the development of ESs. These algorithms mostly work very efficiently as long as the scaling of the parameters to be optimized is known. If the scaling is not known, the strategy has to adapt individual step-sizes for all the parameters. In general, the number of necessary step-sizes (variances) equals the dimension of the problem. In this case, step-size adaptation proves to be difficult, and the algorithms known are not satisfactory. The algorithm presented in this paper is based on the well-known concept of mutative step-size control. Our investigations indicate that the adaptation by this concept declines due to an interaction of the random elements involved. We show that this weak point of mutative step-size control can be avoided by relatively small changes in the algorithm. The modifications may be summarized by the word “derandomization.” The derandomized scheme of mutative step-size control facilitates a reliable self-adaptation of individual step-sizes.
An Overview of Evolutionary Algorithms in Multiobjective Optimization
Authors: Fonseca Carlos M. , Fleming Peter J. 
Published: February 2008

The application of evolutionary algorithms (EAs) in multiobjective optimization is currently receiving growing interest from researchers with various backgrounds. Most research in this area has understandably concentrated on the selection stage of EAs, due to the need to integrate vectorial performance measures with the inherently scalar way in which EAs reward individual performance, that is, number of offspring. In this review, current multiobjective evolutionary approaches are discussed, ranging from the conventional analytical aggregation of the different objectives into a single function to a number of population-based approaches and the more recent ranking schemes based on the definition of Pareto optimality. The sensitivity of different methods to objective scaling and/or possible concavities in the trade-off surface is considered, and related to the (static) fitness landscapes such methods induce on the search space. From the discussion, directions for future research in multiobjective fitness assignment and search strategies are identified, including the incorporation of decision making in the selection procedure, fitness sharing, and adaptive representations.