bluuebunny/crossref_metadata_2025 huggingface dataset:
The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells
Authors: Marteijn Jurgen A.F. , van Emst Liesbeth , Erpelinck-Verschueren Claudia A.J. , Nikoloski Gorica , Menke Aswin , de Witte Theo , Löwenberg Bob , Jansen Joop H. , van der Reijden Bert A.
Published: August 2005

Protein ubiquitination plays important roles in a variety of basic cellular processes. Proteins are ubiquitinated by E2-E3 ubiquitin ligase complexes. Depending on the type of ubiquitin chain conjugated, proteins are either targeted for degradation by the proteasome or their activity is specifically altered. We describe a novel conserved nuclear protein, Triad1 (2 RING [really interesting new gene] fingers and DRIL [double RING finger linked] 1), which is strongly induced during myeloid differentiation. Triad1 contains a TRIAD motif that harbors 2 RING finger structures. Triad1 binds the E2 ubiquitin-conjugating enzyme UbcH7 as well as ubiquitinated proteins and supports the formation of ubiquitin chains that are recognized by the proteasome. The biologic function of Triad1 in myelopoiesis was studied by performing granulocyte-macrophage colony-forming unit (CFU-GM) assays using retrovirally transduced primary murine bone marrow cells. Triad1 severely inhibited myeloid colony formation. In contrast, 2 Triad1 RING finger point mutants that failed to bind UbcH7 did not affect colony formation. Moreover, proteasome inhibition counteracted the inhibition of colony formation exerted by wild-type Triad1. In liquid cultures, Triad1 did not influence differentiation but strongly inhibited proliferation resulting in a G0/G1 accumulation. We conclude that proteasomal degradation of proteins that are ubiquitinated by Triad1 affects the clonogenic growth of primary myeloid progenitor cells.
The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT
Authors: David Ebenezer , Sun Shi-Yong , Waller Edmund K. , Chen Jing , Khuri Fadlo R. , Lonial Sagar
Published: August 2005

The identification of signaling pathways critical to myeloma growth and progression has yielded an array of novel agents with clinical activity. Multiple myeloma (MM) growth is IL-6 dependent, and IL-6 is secreted in an autocrine/paracrine fashion with signaling via the Ras/Raf/mitogen-activated protein kinase (MAPK) pathway. We hypothesized that combining a Ras pathway inhibitor (lonafarnib, SCH66336) with a proteasome inhibitor (bortezomib, Velcade, PS-341) would enhance myeloma-cell killing. MM cell lines and primary human cells were used to test either single agent bortezomib, lonafarnib, or the combination on MM signaling and apoptosis. Combination therapy induced synergistic tumor-cell death in MM cell lines and primary MM plasma cells. Cell death was rapid and associated with increased caspase 3, 8, and 9 cleavage and concomitant down-regulation of p-AKT. Down-regulation of p-AKT was seen only in combination therapy and not seen with either single agent. Cells transfected with constitutively active p-AKT, wild-type AKT, or Bcl-2 continued to demonstrate synergistic cell death in response to the combination. The order of addition was critically important, supporting bortezomib followed by lonafarnib as the optimal schedule. The combination of a proteasome inhibitor and farnesyl transferase inhibitor demonstrates synergistic myeloma-cell death and warrants further preclinical and clinical studies.
Assessing health centre systems for guiding improvement in diabetes care
Authors: Si Damin , Bailie Ross , Connors Christine , Dowden Michelle , Stewart Allison , Robinson Gary , Cunningham Joan , Weeramanthri Tarun
Published: August 2005

Background

Aboriginal people in Australia experience the highest prevalence of diabetes in the country, an excess of preventable complications and early death. There is increasing evidence demonstrating the importance of healthcare systems for improvement of chronic illness care. The aims of this study were to assess the status of systems for chronic illness care in Aboriginal community health centres, and to explore whether more developed systems were associated with better quality of diabetes care.

Methods

This cross-sectional study was conducted in 12 Aboriginal community health centres in the Northern Territory of Australia. Assessment of Chronic Illness Care scale was adapted to measure system development in health centres, and administered by interview with health centre staff and managers. Based on a random sample of 295 clinical records from attending clients with diagnosed type 2 diabetes, processes of diabetes care were measured by rating of health service delivery against best-practice guidelines. Intermediate outcomes included the control of HbA1c, blood pressure, and total cholesterol.

Results

Health centre systems were in the low to mid-range of development and had distinct areas of strength and weakness. Four of the six system components were independently associated with quality of diabetes care: an increase of 1 unit of score for organisational influence, community linkages, and clinical information systems, respectively, was associated with 4.3%, 3.8%, and 4.5% improvement in adherence to process standards; likewise, organisational influence, delivery system design and clinical information systems were related to control of HbA1c, blood pressure, and total cholesterol.

Conclusion

The state of development of health centre systems is reflected in quality of care outcome measures for patients. The health centre systems assessment tool should be useful in assessing and guiding development of systems for improvement of diabetes care in similar settings in Australia and internationally.
Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481]
Authors:   The FIELD Study Investigators
Published: August 2005

Objective

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics.

Research design and methods

FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred.

Results

About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of <5%, but nearly all had a 5-year stroke risk of <10%. Despite this, half of the cohort were obese (BMI > 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%).

After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%).

Conclusion

The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
Monitoring protein stability in vivo
Authors: Ignatova Zoya
Published: August 2005

Reduced protein stability in vivo is a prerequisite to aggregation. While this is merely a nuisance factor in recombinant protein production, it holds a serious impact for man. This review focuses on specific approaches to selectively determine the solubility and/or stability of a target protein within the complex cellular environment using different detection techniques. Noninvasive techniques mapping folding/misfolding events on a fast time scale can be used to unravel the complexity and dynamics of the protein aggregation process and factors altering protein solubility in vivo. The development of approaches to screen for folding and solubility in vivo should facilitate the identification of potential components that improve protein solubility and/or modulate misfolding and aggregation and may provide a therapeutic benefit.
On the number of founding germ cells in humans
Authors: Zheng Chang-Jiang , Luebeck E Georg , Byers Breck , Moolgavkar Suresh H
Published: August 2005

Background

The number of founding germ cells (FGCs) in mammals is of fundamental significance to the fidelity of gene transmission between generations, but estimates from various methods vary widely. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women.

Results

The germline-development model derives from the assumption that oogonial proliferation in the embryonic stage starts with a founding cells at t = 0 and that the subsequent proliferation can be defined as a simple stochastic birth process. It follows that the population size X(t) at the end of germline expansion (around the 5th month of pregnancy in humans; t = 0.42 years) is a random variable with a negative binomial distribution. A formula based on the expectation and variance of this random variable yields a moment-based estimate of a that is insensitive to the progressive reduction in oocyte numbers due to their utilization and apoptosis at later stages of life. In addition, we describe an algorithm for computing the maximum likelihood estimation of the FGC population size (a), as well as the rates of oogonial division and loss to apoptosis. Utilizing both of these approaches to evaluate available oocyte-counting data, we have obtained an estimate of a = 2 – 3 for Homo sapiens.

Conclusion

The estimated number of founding germ cells in humans corresponds well with values previously derived from chimerical or mosaic mouse data. These findings suggest that the large variation in oocyte numbers between individual women is consistent with a smaller founding germ cell population size than has been estimated by cytological analyses.
Baculovirus-mediated promoter assay and transcriptional analysis of white spot syndrome virus orf427 gene
Authors: Lu Liqun , Wang Hai , Manopo Ivanus , Yu Li , Kwang Jimmy
Published: August 2005

Background

White spot syndrome virus (WSSV) is an important pathogen of the penaeid shrimp with high mortalities. In previous reports, Orf427 of WSSV is characterized as one of the three major latency-associated genes of WSSV. Here, we were interested to analyze the promoter of orf427 and its expression during viral pathogenesis.

Results

in situ hybridization revealed that orf427 was transcribed in all the infected tissues during viral lytic infection and the translational product can be detected from the infected shrimp. A time-course RT-PCR analysis indicated that transcriptional products of orf427 could only be detected after 6 h post virus inoculation. Furthermore, a baculovirus-mediated promoter analysis indicated that the promoter of orf427 failed to express the EGFP reporter gene in both insect SF9 cells and primary shrimp cells.

Conclusion

Our data suggested that latency-related orf427 might not play an important role in activating virus replication from latent phase due to its late transcription during the lytic infection.
Introduction to Bayesian methods III: use and interpretation of Bayesian tools in design and analysis
Authors: Berry Donald A
Published: August 2005

The Bayesian approach and several of its advantages in drug and medical device development are described. One advantage from the perspective of analysis is that it provides a methodology for synthesizing information. However, taking a Bayesian approach to designing clinical trials is potentially more valuable than using this approach in analyzing trial results. Bayesian methodology provides a mechanism for updating what is known as results accumulate during a trial. Such updating can be incorporated completely explicitly and prospectively. An important way in which the Bayesian approach can be used is in calculating the predictive probability distribution of future results on the basis of current results. I show how to exploit predictive distributions in adapting to results that accumulate during the course of a trial. Possible adaptations including decreasing or increasing sample size, dropping treatment arms, and modifying the randomization proportions to the various arms depending on the interim results. Consequences of taking a Bayesian approach to clinical trial design are efficiency, better treatment of patients in the trial, and greater precision regarding the primary endpoints. An example of the last of these is Bayesian modeling of the relationship between early and longer term endpoints. Such modeling also enables earlier decision making. Case studies 2 and 3 deal with trials that were shorter and smaller, respectively, because of such modeling.
Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1
Authors: Yu Tianzheng , Fox Randall J. , Burwell Lindsay S. , Yoon Yisang
Published: August 2005

Mitochondrial fission is a highly regulated process mediated by a defined set of protein factors and is involved in the early stage of apoptosis. In mammals, at least two proteins, the dynamin-like protein DLP1/Drp1 and the mitochondrial outer membrane protein hFis1, participate in mitochondrial fission. The cytosolic domain of hFis1 contains six α-helices that form two tetratricopeptide repeat (TPR) motifs. Overexpression of hFis1 induces DLP1-mediated fragmentation of mitochondria, suggesting that hFis1 is a limiting factor in mitochondrial fission by recruiting cytosolic DLP1. In the present study, we identified two regions of hFis1 that are necessary for correct fission of mitochondria. We found that the TPR region of hFis1 participates in the interaction with DLP1 or DLP1-containing complex and that the first helix (α1) of hFis1 is required for mitochondrial fission presumably by regulating DLP1-hFis1 interaction. Misregulated interaction between DLP1 and hFis1 by α1 deletion induced mitochondrial swelling, in part by the mitochondrial permeability transition, but significantly delayed cell death. Our data suggest that hFis1 is a main regulator of mitochondrial fission, controlling the recruitment and assembly of DLP1 during both normal and apoptotic fission processes.
Tensile and Compressive Properties of the Medial Rabbit Meniscus
Authors: Sweigart M A , Athanasiou K A
Published: August 2005

Quantification of the material properties of the meniscus is of paramount importance, creating a ‘gold-standard’ reference for future tissue engineering research. The purpose of this study was to determine the compressive and circumferential tensile properties in the rabbit meniscus. Creep and recovery indentation experiments were performed on the meniscus using a creep indentation apparatus and analysed via a finite element optimization method to determine the compressive material properties at six topographical locations. Tensile properties of samples taken circumferentially from the rabbit meniscus were also examined. Results show that the femoral side of the anterior portion exhibits the highest aggregate modulus (510 ± 100 kPa) and shear modulus (240 ± 40 kPa), while the lowest aggregate modulus (120 ± 30 kPa) and shear modulus (60 ± 20 kPa) were found on the femoral side of the posterior location. Values of 156.6 ± 48.9 MPa for Young's modulus and of 21.6 ± 7.0 MPa for the ultimate tensile strength of were found from the tensile samples, which are similar to the values found in other animal models. These baseline values of material properties will be of help in future tissue engineering efforts.
Molecular basis for RNA kink-turn recognition by the h15.5K small RNP protein
Authors: SZEWCZAK LARA B. WEINSTEIN , GABRIELSEN J. SCOTT , DEGREGORIO SUZANNE J. , STROBEL SCOTT A. , STEITZ JOAN A.
Published: August 2005

The interaction between box C/D small nucleolar (sno)RNAs and the 15.5K protein nucleates snoRNP assembly. Many eukaryotic snoRNAs contain two potential binding sites for this protein, only one of which appears to be utilized in vivo. The binding site conforms to the consensus for a kink-turn motif. We have investigated the molecular basis for selection of one potential site over the other using in vitro mobility shift assays and nucleotide analog interference mapping of Xenopus U25 snoRNA and of a circularly permuted form. We find that preferential binding of human 15.5K is not dependent on the proximity of RNA ends, but instead appears to require a structural context beyond the kink-turn itself. Direct analysis of the energetic contributions to binding made by 18 functional groups within the kink-turn identified both backbone atoms and base functionalities as key for interaction. An intramolecular RNA–RNA contact via a 2′-hydroxyl may supercede a putative Type I A-minor interaction in stabilizing the RNA–protein complex.
Far-IR Spectroscopy of Ammonium and Oxonium Complexes of 18-Crown-6
Authors: McKenna William P. , Eyring Edward M.
Published: August 2005

The far-IR spectra for NH4+ and H3O+ complexes with 18-crown-6 have been obtained and the hydrogen-bond vibrational mode vσ has been assigned. These results illustrate the suitability of far-IR spectroscopy for exploring crown ether molecular ion interactions.
Quantitative Analysis of Two-Dimensional Fluorescence Spectra via Fourier-Transform-Based Correlation Analysis
Authors: Rossi Thomas M. , Warner Isiah M.
Published: August 2005

Two-dimensional Fourier-transform-based correlation analysis methods are discussed with application to excitation-emission matrices (EEMs). Quantitative analysis of single and multicomponent EEMs in the presence of noise is explored with the use of synthetic and real data. The algorithms developed are then used with a video fluorometer (VF) to study the kinetics of the photodecomposition of acridine. The precision of the kinetic data generated by correlation analysis of EEMs is found to be greater than the precision of data obtained simultaneously by HPLC monitoring of the photodecomposition process.
The Significance of Temperature and Solvent Effects upon Infrared Spectra and Group Frequencies
Authors: Nyquist R. A.
Published: August 2005

Infrared spectra recorded of the same material at variable temperatures are shown to be useful in the making of vibrational assignments and in the elucidation of molecular structure. Functional groups such as OH, NH2, and C=O in compounds whose spectra have been recorded in CS2 solution exhibit group frequencies which shift with change in temperature. Both variable-temperature and solution-phase studies are shown to be helpful in establishing that a compound exists as rotational isomers. Temperature changes are shown to vary the rotational isomer concentrations. The effect of temperature on difference tones, Fermi resonance, and in the breakdown of the selection rules is also demonstrated.
The Concentrations of Calcium Buffering Proteins in Mammalian Cochlear Hair Cells
Authors: Hackney Carole M. , Mahendrasingam Shanthini , Penn Andrew , Fettiplace Robert
Published: August 2005

Calcium buffers are important for shaping and localizing cytoplasmic Ca2+transients in neurons. We measured the concentrations of the four main calcium-buffering proteins (calbindin-D28k, calretinin, parvalbumin-α, and parvalbumin-β) in rat cochlear hair cells in which Ca2+signaling is a central element of fast transduction and synaptic transmission. The proteins were quantified by calibrating immunogold tissue counts against gels containing known amounts of each protein, and the method was verified by application to Purkinje cells in which independent estimates exist for some of the protein concentrations. The results showed that, in animals with fully developed hearing, inner hair cells had\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{1}{10}\) \end{document}of the proteinaceous calcium buffer of outer hair cells in which the cell body contained parvalbumin-β (oncomodulin) and calbindin-D28k at levels equivalent to 5 mmcalcium-binding sites. Both proteins were partially excluded from the hair bundles, which may permit fast unbuffered Ca2+regulation of the mechanotransducer channels. The sum of the calcium buffer concentrations decreased in inner hair cells and increased in outer hair cells as the cells developed their adult properties during cochlear maturation. The results suggest that Ca2+has distinct roles in the two types of hair cell, reflecting their different functions in auditory transduction. Ca2+is used in inner hair cells primarily for fast phase-locked synaptic transmission, whereas Ca2+may be involved in regulating the motor capability underlying cochlear amplification of the outer hair cell. The high concentration of calcium buffer in outer hair cells, similar only to skeletal muscle, may protect against deleterious consequences of Ca2+loading after acoustic overstimulation.
Existing Motor State Is Favored at the Expense of New Movement during 13-35 Hz Oscillatory Synchrony in the Human Corticospinal System
Authors: Gilbertson Thomas , Lalo Elodie , Doyle Louise , Di Lazzaro Vincenzo , Cioni Beatrice , Brown Peter
Published: August 2005

Oscillations in local field potentials in the β-frequency band (13-35 Hz) are a pervasive feature of human and nonhuman primate motor cortical areas. However, the function of such synchronous activity across populations of neurons remains unknown. Here, we test the hypothesis that β activity may promote existing motor set and posture while compromising processing related to new movements. Three experiments were performed. First, healthy subjects were instructed to make reaction time movements of the outstretched index finger in response to imperative cues triggered by transient increases in corticospinal synchrony, as evidenced by phasic elevations of β-frequency band microtremor and intermuscular synchrony. Second, healthy subjects were instructed to resist a stretch to the index finger triggered in the same way. Finger acceleration in the reaction time task and transcortical components of the stretch reflex were measured and compared with those elicited by random cue or stretch presentation. Finally, we sought a correlation between finger acceleration in the reaction time task and cortical synchrony directly measured from the electrocorticogram in two patients undergoing functional neurosurgery. We demonstrate that movements are slowed and transcortical responses to stretch are potentiated during periods of elevated β-band cortical synchrony. The results suggest that physiological periods of β synchrony are associated with a cortical state in which postural set is reinforced, but the speed of new movements impaired. The findings are of relevance to Parkinson's disease, in which subcortical and cortical β-band synchronization is exaggerated in the setting of increased tone and slowed movements.
On low dimensional case in the fundamental asset pricing theorem with transaction costs
Authors: Grigoriev Pavel G.
Published: August 2005

The well-known Harrison–Plisse theorem claims that in the classical discrete time model of the financial market with finite Ω there is no arbitrage iff there exists an equivalent martingale measure. The famous Dalang–Morton–Willinger theorem extends this result for an arbitrary Ω. Kabanov and Stricker [KS01] generalized the Harrison–Pliska theorem for the case of the market with proportional transaction costs. Nevertheless the corresponding extension of the Kabanov and Stricker result to the case of non-finite Ω fails, the corresponding counter-example with 4 assets was constructed by Schachermayer [S04].

The main result of this paper is that in the special case of 2 assets the Kabanov and Stricker theorem can be extended for an arbitrary Ω. This is quite a surprising result since the corresponding cone of hedgeable claims ÂT is not necessarily closed.
Functional Connection Between the Clb5 Cyclin, the Protein Kinase C Pathway and the Swi4 Transcription Factor in Saccharomyces cerevisiae
Authors: Queralt Ethel , Igual J Carlos
Published: August 2005

The rsf12 mutation was isolated in a synthetic lethal screen for genes functionally interacting with Swi4. RSF12 is CLB5. The clb5 swi4 mutant cells arrest at G2/M due to the activation of the DNA-damage checkpoint. Defects in DNA integrity was confirmed by the increased rates of chromosome loss and mitotic recombination. Other results suggest the presence of additional defects related to morphogenesis. Interestingly, genes of the PKC pathway rescue the growth defect of clb5 swi4, and pkc1 and slt2 mutations are synthetic lethal with clb5, pointing to a connection between Clb5, the PKC pathway, and Swi4. Different observations suggest that like Clb5, the PKC pathway and Swi4 are involved in the control of DNA integrity: there is a synthetic interaction between pkc1 and slt2 with rad9; the pkc1, slt2, and swi4 mutants are hypersensitive to hydroxyurea; and the Slt2 kinase is activated by hydroxyurea. Reciprocally, we found that clb5 mutant is hypersensitive to SDS, CFW, latrunculin B, or zymolyase, which suggests that, like the PKC pathway and Swi4, Clb5 is related to cell integrity. In summary, we report numerous genetic interactions and phenotypic descriptions supporting a close functional relationship between the Clb5 cyclin, the PKC pathway, and the Swi4 transcription factor.
Replication Origin of Mitochondrial DNA in Insects
Authors: Saito Shigeru , Tamura Koichiro , Aotsuka Tadashi
Published: August 2005

The precise position of the replication origin (OR) of mtDNA was determined for insect species belonging to four different orders (four species of Drosophila, Bombyx mori, Triborium castaneum, and Locusta migratoria, which belong to Diptera, Lepidoptera, Coleoptera, and Orthoptera, respectively). Since the free 5′ ends of the DNA strands of mtDNA are interpreted as the OR, their positions were mapped at 1-nucleotide resolution within the A + T-rich region by using the ligation-mediated PCR method. In all species examined, the free 5′ ends were found within a very narrow range of several nucleotides in the A + T-rich region. For four species of Drosophila, B. mori, and T. castaneum, which belong to holometabolous insects, although the OR's were located at different positions, they were located immediately downstream of a series of thymine nucleotides, the so-called T-stretch. These results strongly indicate that the T-stretch is involved in the recognition of the OR of mtDNA at least among holometabolous insects. For L. migratoria (hemimetabolous insect), on the other hand, none of the long stretches of T's was found in the upstream portion of the OR, suggesting that the regulatory sequences involved in the replication initiation process have changed through insect evolution.
Fractal fragmentation theory for size effects of quasi-brittle materials in compression
Authors: Carpinteri A. , Pugno N.
Published: August 2005

Size effects on dissipated energy density and strength for quasi-brittle materials in compression are analysed theoretically and experimentally herein. By using a fractal fragmentation approach the dissipated energy density of a structural element under compression is deduced. In addition, the dissipated energy density and the strength for geometrically similar structural elements under compression, by varying their size, are obtained. Finally, a comparison between theoretical predictions and experimental results is presented for plane as well as fibre-reinforced concrete. The size effects on dissipated energy density and compressive strength are captured by the proposed model in a satisfactory way.
Protein–nucleic acid recognition: Statistical analysis of atomic interactions and influence of DNA structure
Authors: Lejeune Diane , Delsaux Nicolas , Charloteaux Benoît , Thomas Annick , Brasseur Robert
Published: August 2005

We analyzed structural features of 11,038 direct atomic contacts (either electrostatic, H‐bonds, hydrophobic, or other van der Waals interactions) extracted from 139 protein–DNA and 49 protein–RNA nonhomologous complexes from the Protein Data Bank (PDB). Globally, H‐bonds are the most frequent interactions (∼50%), followed by van der Waals, hydrophobic, and electrostatic interactions. From the protein viewpoint, hydrophilic amino acids are over‐represented in the interaction databases: Positively charged amino acids mainly contact nucleic acid phosphate groups but can also interact with base edges. From the nucleotide point of view, DNA and RNA behave differently: Most protein–DNA interactions involve phosphate atoms, while protein–RNA interactions involve more frequently base edge and ribose atoms. The increased participation of DNA phosphate involves H‐bonds rather than salt bridges. A statistical analysis was performed to find the occurrence of amino acid–nucleotide pairs most different from chance. These pairs were analyzed individually. Finally, we studied the conformation of DNA in the interaction sites. Despite the prevalence of B‐DNA in the database, our results suggest that A‐DNA is favored in the interaction sites. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Structural insights into the cellular retinaldehyde‐binding protein (CRALBP)
Authors: Liu Tianyun , Jenwitheesuk Ekachai , Teller David C. , Samudrala Ram
Published: August 2005

Cellular retinaldehyde‐binding protein (CRALBP) is an essential protein in the human visual cycle without a known three‐dimensional structure. Previous studies associate retinal pathologies to specific mutations in the CRALBP protein. Here we use homology modeling and molecular dynamics methods to investigate the structural mechanisms by which CRALBP functions in the visual cycle. We have constructed two conformations of CRALBP representing two states in the process of ligand association and dissociation. Notably, our homology models map the pathology‐associated mutations either directly in or adjacent to the putative ligand‐binding cavity. Furthermore, six novel residues have been identified to be crucial for the hinge movement of the lipid‐exchange loop in CRALBP. We conclude that the binding and release of retinoid involve large conformational changes in the lipid‐exchange loop at the entrance of the ligand‐binding cavity. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Mean Entropies
Authors: Lavenda B. H.
Published: August 2005

Entropies are expressed in terms of mean values, and not as weighted arithmetic means of their generating functions, which result in pseudo-additive entropies. The Shannon entropy corresponds to the logarithm of the inverse of the geometric mean, while the Rényi entropy, more generally, to the logarithm of the inverse of power means of order τ < 1. Translation invariance of the means relates to mean code lengths, while their homogeneity translates them into entropies: the arithmetic and exponential means correspond to the Shannon and Rényi entropies, respectively, under the Kraft equality. While under the Kraft inequality, the entropies are lower bounds to the mean code lengths. Means of any order cannot be expressed as escort averages because such averages contradict the fact that the means are monotonically increasing functions of their order. Exponential entropies are shown to be measures of the extent of a distribution. The probability measure and the incomplete probability distribution are shown to be the ranges of continuous and discrete sample spaces, respectively. Comparison is made with Boltzmann's principle.
Evolution of the electronic structure of Be clusters
Authors: Cerowski V. , Rao B. K. , Khanna S. N. , Jena P. , Ishii Soh , Ohno Kaoru , Kawazoe Yoshiyuki
Published: August 2005

Using a modified symbiotic genetic algorithm approach and many-body interatomic potential derived from first principles, we have calculated equilibrium geometries and binding energies of the ground-state and low-lying isomers of Be clusters containing up to 41 atoms. Molecular-dynamics study was also carried out to study the frequency of occurrence of the various geometrical isomers as these clusters are annealed during the simulation process. For a selected group of these clusters, higher-energy isomers were more often found than their ground-state structures due to large catchment areas. The accuracy of the above ground-state geometries and their corresponding binding energies were verified by carrying out separate ab initio calculations based on molecular-orbital approach and density-functional theory with generalized gradient approximation for exchange and correlation. The atomic orbitals were represented by a Gaussian 6-311G** basis, and the geometry optimization was carried out using the GAUSSIAN 98 code without any symmetry constraint. While the ground-state geometries and their corresponding binding energies obtained from ab initio calculations do not differ much from those obtained using the molecular-dynamics approach, the relative stability of the clusters and the energy gap between the highest occupied and the lowest unoccupied molecular orbitals show significant differences. The energy gaps, calculated using the density-functional theory, show distinct shell closure effects, namely, sharp drops in their values for Be clusters containing 2, 8, 20, 34, and 40 electrons. While these features may suggest that small Be clusters behave free-electron-like and, hence, are metallic, the evolution of the structure, binding energies, coordination numbers, and nearest-neighbor distances do not show any sign of convergence towards the bulk value. We also conclude that molecular-dynamics simulation based on many-body interatomic potentials may not always give the correct picture of the evolution of the structure and energetics of clusters although they may serve as a useful tool for obtaining starting geometries by efficiently searching a large part of the phase space.
Spatial distribution of the velocity distribution function of Fe atoms in a magnetron sputtering plasma source
Authors: Shibagaki K. , Nafarizal N. , Sasaki K.
Published: August 2005

We examined the spatial distribution of the velocity distribution function of Fe atoms in a conventional dc magnetron sputtering source by laser-induced fluorescence (LIF) imaging spectroscopy. By measuring the Doppler broadening of the excitation spectrum of LIF, we evaluated the velocity distribution function of Fe at many positions in the discharge space. By calculating the first- and second-order moments of the velocity distribution function, we obtained two-dimensional maps of the average velocity and the effective temperature in the r-z plane of the cylindrically symmetric magnetron discharge. The map of the average velocity clearly indicates that Fe atoms have fast velocity in the region adjacent to the target at a low discharge pressure such as 3 mTorr, while at a high gas pressure such as 20 mTorr, the average velocity of Fe atoms is almost zero in the entire discharge space. On the other hand, it has been found from the map of the effective temperature that the velocity distribution function observed at 3 mTorr has a broad width corresponding to approximately 8×104K in the bright plasma near the target.
Subwavelength imaging by a flat cylindrical lens using optimized negative refraction
Authors: Lu Zhaolin , Chen Caihua , Schuetz Christopher A. , Shi Shouyuan , Murakowski Janusz A. , Schneider Garrett J. , Prather Dennis W.
Published: August 2005

We experimentally demonstrate subwavelength imaging by a “flat cylindrical” lens using negative refraction. A two-dimensional photonic crystal whose dispersion at the second band provides group velocity opposite to the phase velocity for electromagnetic waves is employed to realize the flat lens, and the working frequency is chosen so that the effective refractive index is approximately equal to −1.0. Experiment demonstrated the imaging of a point source in both amplitude and phase in the millimeter-wave regime. By measuring the field distributions in the object plane and image plane, we observed amplification of evanescent waves and subwavelength size image. The image of two incoherent sources with subwavelength distance showed two resolvable spots, which served to further verify subwavelength resolution.
A Local Housing Market Model with Spatial Interaction and Land-Use Planning Controls
Authors: Leishman Chris , Bramley Glen
Published: August 2005

There have been relatively few attempts to construct local housing market models in the United Kingdom—particularly models with an explicit treatment of land supply. In this paper we report the results of a pilot study designed to test the practicability of estimating a system of equations which describe housing market dynamics at the local level. Former district council areas in Central Scotland are used as a proxy for local housing markets within a region, thereby providing a panel dataset. A simple supply — demand system with separate equations for inward and outward household migration is modelled using two-stage least squares. The empirical results are varied, with some equations and coefficients performing more closely in line with prior expectations than others. House price levels are explained largely with reference to household income, socioeconomic status, and past levels of house price growth. Higher price levels and higher deprivation diminish inward migration. There are also suggestions in the results that higher rates of new-build supply partly cause higher inward migration. The rate of outward migration increases with ethnicity and wealth and decreases with deprivation. The empirical performance of the new-build supply equation is poor although the results do yield some interesting insights. House building output generally decreases as the proportion of ‘small’ sites in the land supply increases. There is also evidence that house building output decreases as land supply in neighbouring areas increases. We conclude the paper by outlining further directions for modelling prices, supply, and migration at local housing market level. In particular, the case is made for further work involving the collection of wider and longer panel datasets and for extending the pilot study work beyond Scotland.
Obesity and Adenomatous Polyps of the Sigmoid Colon
Authors: Shinchi Koichi , Kono Suminori , Honjo Satoshi , Todoroki Isao , Sakurai Yutaka , Imanishi Koji , Nishikawa Hiroshi , Ogawa Shinsaku , Katsurada Mitsuhiko , Hirohata Tomio
Published: August 2005

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self‐defense officials who received a retirement health examination at three hospitals of the Self‐Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist‐hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (<5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut‐off points. There was a significant two‐fold elevation in the overall adenoma risk among men at the highest BMI level (≥26.95) compared with those at the lowest level (<22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR: odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4–5.9) for the highest (≥0.958) versus lowest (<0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95%CI 1.5–7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.
Different Roles of 8‐Hydroxyguanine Formation and 2‐Thiobarbituric Acid‐reacting Substance Generation in the Early Phase of Liver Carcinogenesis Induced by a Choline‐deficient, l‐Amino Acid‐defined Diet in Rats
Authors: Nakae Dai , Mizumoto Yasushi , Yoshiji Hitoshi , Andoh Nobuaki , Horiguchi Kohsuke , Shiraiwa Kazumi , Kobayashi Eisaku , Endoh Takehiro , Shimoji Naoshi , Tamura Kazutoshi , Tsujiuchi Toshifumi , Denda Ayumi , Konishi Yoichi
Published: August 2005

The present study was performed to assess the roles of hepatocellular oxidative damage to DNA and constituents other than DNA in rat liver carcinogenesis caused by a choline‐deficient, l‐amino acid‐defined (CDAA) diet by examining the effects of the antioxidant N, N′‐diphenyl‐p‐phenylenediamine (DPPD). The parameters used for cellular oxidative damage were the level of 8‐hydroxyguanine (8‐OHGua) for DNA and that of 2‐thiobarbituric acid‐reacting substance (TBARS) for constituents other than DNA. A total of 40 male Fischer 344 rats, 6 weeks old, were fed the CDAA diet for 12 weeks with or without DPPD (0.05, 0.10 or 0.20%) or butylated hydroxytoluene (BHT, 0.25%). In the livers of the rats, the numbers and sizes of glutathione S‐transferasc (EC 2.5.1.18) placental form (GSTP)‐ and/or γ‐glutamyltransferase (GGT, EC 2.3.2.2)‐positive lesions and levels of 8‐OHGua and TBARS were determined. The GSTP‐positive lesions of 0.08 mm2 or larger were all stained positively for GGT as well in cross‐sectional area, whereas the smaller lesions were generally negative for GGT. DPPD and BHT reduced the size of the GSTP‐positive lesions without affecting their total numbers. At the same time, they reduced TBARS generation without affecting 8‐OHGua formation in DNA. The present results indicate that oxidative DNA damage (represented by 8‐OHGua formation) and damage to constituents other than DNA (represented by TBARS generation) may play different roles in rat liver carcinogenesis caused by the CDAA diet; the former appears to be involved in the induction of phenotypically altered hepatocyte populations while the latter may be related to the growth of such populations.
Different Incidence of Loss of Heterozygosity on Chromosome 16q between Intraductal Papilloma and Intracystic Papillary Carcinoma of the Breast
Authors: Tsuda Hitoshi , Uei Yoshio , Fukutomi Takashi , Hirohashi Setsuo
Published: August 2005

Loss of heterozygosity (LOH) on chromosome 16q was examined in DNA isolated from 11 intraductal papillomas and 12 intracystic papillary adenocarcinomas of the breast. Such LOH was detected in 8 (67%) out of 12 intracystic papillary adenocarcinomas, and in 7 (64%) of 11 of these adenocarcinomas of low grade atypia (Grade 1), whereas it was not detected in 11 intraductal papillomas. Therefore, inactivation of tumor‐suppressor genes on chromosome 16q was suggested to be involved in acquisition of malignant phenotype rather than in tumorigenesis in mammary gland epithelial cell. Examination of LOH on I6q should he helpful for differential diagnosis of intracystic papillary tumors.
Synergistic Antimetastatic Effects of Lentinan and Interleukin 2 with Pre‐ and Post‐operative Treatments
Authors: Hamuro Junji , Takatsuki Fumihiko , Suga Tetsuya , Kikuchi Tomoko , Suzuki Manabu
Published: August 2005

The antimetastatic activity of a combination of lentinan and interleukin 2 (IL‐2) was evaluated against spontaneously metastatic 3‐methylcholanthrene‐induced DBA/2.MC.CS.T fibrosarcoma. Although pre‐operative treatment with either IL‐2 or lentinan alone exerted little effect on the reduction of lung metastasis colony numbers (7.1% or 28.4% reduction, respectively), the combination exhibited a synergistic effect (85% reduction). Furthermore, 3 of 13 mice given the pre‐operative combination treatment achieved complete cure, while no mice given saline did. Although the post‐operative combination treatment also reduced the colony number (71% reduction), it caused little prolongation of survival and no mouse achieved complete cure. Synergistic effects were observed between pre‐ and post‐operative treatments with lentinan and IL‐2: 8 of 12 mice were completely cured. The anti‐metastatic activity was abolished in mice treated simultaneously with antibodies to CD4 and CDS antigens, whereas either CD4, CDS, or NK1.1 antibody alone was ineffective. Analysis of the cellular mechanism involved in the antimetastatic activity revealed the involvement of a tumor‐associated antigen‐specific delayed‐type hypersensitivity response. These data suggest that the life‐prolonging effect of the combination of lentinan and IL‐2 is mediated by antigen‐specific T cells and that the combination of pre‐ and post‐operative therapy with lentinan and IL‐2 may be effective to prevent cancer recurrence and metastasis after surgical resection.
Detection of Hepatic Micrometastasis in Pancreatic Adenocarcinoma Patients by Two‐stage Polymerase Chain Reaction/Restriction Fragment Length Polymorphism Analysis
Authors: Inoue Soichiro , Nakao Akimasa , Kasai Yasushi , Harada Akio , Nonami Toshiaki , Takagi Hiroshi
Published: August 2005

Hepatic metastasis and retroperitoneal recurrence generally are considered to be the two primary modes of recurrence in pancreatic cancer. The goal of this study was to determine if patients with pancreatic adenocarcinoma have hepatic and peritoneal micrometastasis at operation. Pancreatic adenocarcinomas are known to have a high incidence of K‐ras gene mutations. Liver tissue specimens were obtained from 30 patients (17 with pancreatic adenocarcinoma and 13 with other diseases) with a hiopsy needle at operation. Peritoneal washings were obtained during operation from 20 patients with pancreatic adenocarcinoma. Two‐stage polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to detect K‐ras oncogene mutation at codon 12. Thirteen of 17 pancreatic adenocarcinoma patients had K‐ras gene mutations in the liver, whereas all 13 patients with other diseases did not. However, only two of 20 pancreatic adenocarcinoma patients revealed K‐ras gene mutation in peritoneal lavage fluids. These results indicate the feasibility of detecting hepatic micrometastasis in patients with pancreatic adenocarcinoma, and imply that PCR/ RFLP analysis may be of value in the diagnosis, treatment and follow‐up of hepatic metastasis of pancreatic adenocarcinoma.